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The FDA approved naratriptan for the acute treatment of migraine with or without aura in adults. Naratriptan selectively suppresses neurotransmission from sensory fibers through inhibitor of neuropeptide transmitter release. It's in a class of medications called selective serotonin receptor agonists, which is used to treat migraines and cluster headaches.
The medication works by narrowing blood vessels around the brain, which stops pain signals from being sent to the brain, and stops the release of certain natural substances that can cause symptoms of migraine.

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pronounced as (nar' a trip tan)

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Naratriptan is used to treat the symptoms of migraine headaches (severe, throbbing headaches that sometimes are accompanied by nausea and sensitivity to sound or light). Naratriptan is in a class of medications called selective serotonin receptor agonists. It works by narrowing blood vessels around the brain, stopping pain signals from being sent to the brain, and stopping the release of certain natural substances that cause pain, nausea, and other symptoms of migraine. Naratriptan does not prevent migraine attacks or reduce the number of headaches you have.

Naratriptan comes as a tablet to take by mouth. It is usually taken at the first sign of a migraine headache. If your symptoms improve after you take naratriptan but return after 4 hours or longer, you may take a second tablet. However, if your symptoms do not improve after you take naratriptan, do not take a second tablet before calling your doctor. Your doctor will tell you the maximum number of tablets you may take in a 24-hour period. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take naratriptan exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

You may take your first dose of naratriptan in a doctor's office or other medical facility where you can be monitored for serious reactions.

Call your doctor if your headaches do not get better or occur more frequently after taking naratriptan.

If you take naratriptan more often or for longer than the recommended period of time, your headaches may get worse or may occur more frequently. You should not take naratriptan or any other headache medication for more than 10 days per month. Call your doctor if you need to take naratriptan to treat more than four headaches in a 1-month period.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

Before taking naratriptan,

tell your doctor and pharmacist if you are allergic to naratriptan any other medications, or any of the ingredients in naratriptan tablets. Ask your pharmacist for a list of the ingredients.

do not take naratriptan if you have taken any of the following medications in the past 24 hours: other selective serotonin receptor agonists such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), rizatriptan (Maxalt), sumatriptan (Imitrex, in Treximet), or zolmitriptan (Zomig); or ergot-type medications such as bromocriptine (Parlodel), cabergoline, dihydroergotamine (D.H.E. 45, Migranal), ergoloid mesylates (Hydergine), ergonovine (Ergotrate), ergotamine (Cafergot, Ergomar), methylergonovine (Methergine), methysergide (Sansert), and pergolide (Permax).

tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements and herbal products you are taking or plan to take. Be sure to mention any of the following: acetaminophen (Tylenol); antidepressants such as amitriptyline (Elavil), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Adapin, Sinequan), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); aspirin and other nonsteroidal anti-inflammatory medications (NSAIDS) such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn); oral contraceptives (birth control pills); selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine, paroxetine (Paxil), and sertraline (Zoloft); and selective serotonin/norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine (Pristiq), duloxetine (Cymbalta), sibutramine (Meridia), and venlafaxine (Effexor). Also tell your doctor or pharmacist if you are taking the following medications or have stopped taking them within the past two weeks: isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl), and tranylcypromine (Parnate). Your doctor may need to change the doses of your medications or monitor you more carefully for side effects.

tell your doctor if you have or have ever had heart disease; a heart attack; angina (chest pain); irregular heartbeats; stroke or 'mini-stroke'; circulation problems such as varicose veins, blood clots in the legs, Raynaud's disease (problems with blood flow to the fingers, toes, ears, and nose), or ischemic bowel disease (bloody diarrhea and stomach pain caused by decreased blood flow to the intestines); Your doctor may tell you not to take naratriptan.

tell your doctor if you smoke or are overweight; if you have or have ever had high blood pressure, diabetes, high cholesterol, or kidney or liver disease; if you have gone through menopause (change of life); or if any family members have or have ever had heart disease or stroke.

tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you plan to be sexually active while you are taking this medication, talk to your doctor about effective methods of birth control. If you become pregnant while taking naratriptan, call your doctor.

you should know that naratriptan may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.

talk to your doctor about your headache symptoms to make sure they are caused by migraine. Naratriptan should not be used to treat certain types of migraine headaches (hemiplegic or basilar migraines) or other types of headaches (such as cluster headaches).

Naratriptan may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment:

tightness, pain, pressure, or heaviness in the chest, throat, neck, or jaw

rapid, pounding, or irregular heartbeat

shortness of breath

breaking out in a cold sweat

lightheadedness

weakness or numbness or an arm or leg

slow or difficult speech

difficulty breathing or swallowing

swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs

hoarseness

hives

rash

itching

sudden or severe stomach pain

bloody diarrhea

constipation

vomiting

paleness or blue color of fingers or toes

pain, burning, or tingling in the hands or feet

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online ( http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website ( http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location - one that is up and away and out of their sight and reach. http://www.upandaway.org

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

Symptoms of overdose may include the following:

Keep all appointments with your doctor. Your blood pressure should be checked regularly.

You should keep a headache diary by writing down when you have headaches and when you take naratriptan.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Last Revised - 10/15/2015

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pronounced as (nar' a trip tan) To use the sharing features on this page, please enable JavaScript. Naratriptan is used to treat the symptoms of migraine headaches (severe, throbbing headaches that sometimes are accompanied by nausea and sensitivity to sound or light). Naratriptan is in a class of medications called selective serotonin receptor agonists.

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Telmisartan is used as a hypertensive drug and to treat high blood pressure.

It blocks the binding of angiotensin II to the AT1 receptor in many tissues, which in turn blocks the vasoconstrictor and aldosterone, effectively causing blood vessels to relax.  It is part of the class of medications called Angiotensin II receptor antagonists.

The manufacturer has claimed that Telmisartan is superior to other ARB drugs due to its ability in reducing fasting plasma glucose. Data does prove this statement (Consequently, it can be concluded, when Telmisartan test and reference product show bioequivalence as in study 1040, that the products could be considered therapeutically equivalent and should be similar in terms of efficacy and safety. The difference in Telmisartan Cmax of up to 30% can therefore be considered irrelevant in terms of efficacy and safety) and is reported within a detailed report (which includes properly designed trials).
https://www.ema.europa.eu/en/documents/assessment-report/telmisartan-actavis-epar-public-assessment-report_en.pdf

The cost of telmisartan is about $26.84 – $127.25 for 30 tablets. While I do think this drug can be helpful, it may be way too expensive for those who cannot afford it (since the tablets usually are sold for prices in the higher end) and cannot be worth it if there are other substitutes that are cheaper (which there are).

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Raloxifene (Evista) is FDA-approved to be indicated for the prevention and treatment of osteoporosis as well as the reduction in risk of invasive breast cancer for postmenopausal women when treated for osteoporosis. This form of hormone therapy, acting through the binding of estrogen receptors, is specialized to postmenopausal women, so it is not approved to be used for those in premenopausal. Considering that Raloxifene is mainly used for the treatment of osteoporosis, with a positive side effect being the reduction of invasive breast cancer, I would say the cost is fair for the patient when compared to other osteoporosis medications. Raloxifene is about $96 for thirty 60mg tablets, while other osteoporosis medications, though only taken weekly and/or monthly, typically cost over $100 for 4-5 smaller tablets. If the patient is being prescribed raloxifene for reducing the risk of invasive breast cancer, however, it would be better to research alternate medications with that main specific purpose to be cost effective.

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What are the "FDA-approved" and "unapproved" indications for this drug?
Since the drug Mezlocillin is a type of penicillin, it is permitted by the FDA to be used on anyone who has a bacterial infection. Currently, it is being used as various therapies for those who have had respiratory infections or urinary infections.

What is the mechanism of its therapeutic effect? Is this drug a member of an established class, or is it a brand new form of therapy?
Mezlocillin is an ampicillin-derived penicillin meaning it is part of the penicillin family. It binds to the bacterial penicillin-binding protein and mediates it.

What is the appropriate standard against which to compare it? Why? Is this comparator another drug, a surgical procedure, or …?
One would be able to compare this drug to penicillin, or specifically penicillin V. They are both drugs that are able to bind to bacterial penicillin-binding protein. The difference is that mezlocillin only targets bacterial infections whereas penicillin v is also able to respond to staph infections and strep infections as well. Penicillin is able to be taken orally and on the other hand mezlocillin patients did not respond well to an oral version and had to stick with intravenous injections. This limitation lead to the discontinuation of the drug in the United States.

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Valsartan is a medication that is used to treat high blood pressure and is compared to other medications. In an FDA press release, officials stated when valsartan was prioritized, they were finding other medication that was able to do the same function. (#3)
The cost for a number of 90-days is around $100-150, varying based on where you buy it from. While this definitely is a pricey tablet, there are cheaper, albeit lesser-effective options such as losartan. (#5)
Circling around how it works, valsartan is aimed at helping ease hypertension, or high blood pressure - when the heart has to work harder to pump blood throughout the body. Taking this drug allows for substances that restrict blood vessels and block them. This relaxes the blood vessels, so with a lower blood pressure, the heart is able to pump blood through the boy easier. (#2)

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- Sirolimus is used to suppress the body's immune system to prevent the body from rejecting an organ transplant, specifically kidney transplants. It is an immunosuppressant, and is often combined with other immunosuppressants when treating an organ transplant.
- Sirolimus is often compared to another immunosuppressant drug known as tacrolimus, which does the same job.
- Although both sirolimus and tacrolimus have the same effect, patients have to take tacrolimus for the rest of their life, but sirolimus only needs consistent monitoring.

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Sirolimus may increase the risk that you will develop an infection or cancer, especially lymphoma (cancer of a part of the immune system) or skin cancer. To reduce your risk of skin cancer, plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen during your treatment. If you experience any of the following symptoms, call your doctor immediately: fever, sore throat, chills, frequent or painful urination, or other signs of infection; new sores or changes on the skin; night sweats; swollen glands in the neck, armpits, or groin; unexplained weight loss; trouble breathing; chest pain; weakness or tiredness that does not go away; or pain, swelling, or fullness in the stomach.

Sirolimus may cause serious side effects or death in patients who have had liver or lung transplants. This medication should not be given to prevent rejection of liver or lung transplants.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests to check your body's response to sirolimus.

Talk to your doctor about the risks of taking sirolimus.

Sirolimus is used in combination with other medications to prevent rejection of kidney transplants. Sirolimus is in a class of medications called immunosuppressants. It works by suppressing the body's immune system.

Sirolimus comes as a tablet and a solution (liquid) to take by mouth. It is usually taken once a day, either always with food or always without food. To help you remember to take sirolimus, take it around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take sirolimus exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the tablets whole; do not split, chew, or crush them.

Your doctor will probably adjust your dose of sirolimus during your treatment, usually not more than once every 7 to 14 days.

Continue to take sirolimus even if you feel well. Do not stop taking sirolimus without talking to your doctor.

Sirolimus solution may develop a haze when refrigerated. If this happens, let the bottle stand at room temperature and gently shake it until the haze goes away. The haze does not mean that the medication is damaged or unsafe to use.

To use the bottles of solution, follow these steps:

1. Open the solution bottle. On first use, insert the plastic tube with stopper tightly into the bottle until it is even with the top of the bottle. Do not remove from the bottle once inserted.

2. For each use, tightly insert one of the amber syringes, with the plunger fully pushed in, into the opening in the plastic tube.

3. Draw up the amount of solution your doctor has prescribed by gently pulling out the plunger of the syringe until the bottom of the black line of the plunger is even with the correct mark on the syringe. Keep the bottle upright. If bubbles form in the syringe, empty the syringe into the bottle and repeat this step.

4. Empty the syringe into a glass or plastic cup containing at least 2 ounces (60 milliliters [1/4 cup]) of water or orange juice. Do not use apple juice, grapefruit juice, or other liquids. Stir vigorously for 1 minute and drink immediately.

5. Refill the cup with at least 4 ounces (120 milliliters [1/2 cup]) of water or orange juice. Stir vigorously and drink the rinse solution.

6. Dispose of the used syringe.

If you need to carry a filled syringe with you, snap a cap onto the syringe and put the syringe in the carrying case. Use the medication in the syringe within 24 hours.

Sirolimus also is used sometimes to treat psoriasis. Talk to your doctor about the possible risks of using this medication for your condition.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Before taking sirolimus,

tell your doctor and pharmacist if you are allergic to sirolimus, any other medications, or any of the ingredients in sirolimus tablets or solution. Ask your pharmacist for a list of the ingredients.

tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking. Be sure to mention any of the following: aminoglycoside antibiotics such as amikacin, gentamicin, kanamycin, neomycin (Neo-Fradin, Neo-Rx), streptomycin, and tobramycin (Tobi); amphotericin B (Abelcet, AmBisome, Amphocin, Fungizone); angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik); antifungals such as clotrimazole (Lotrimin), fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), and voriconazole (Vfend); bromocriptine (Cycloset, Parlodel); cimetidine (Tagamet); cisapride (Propulsid) (not available in the U.S.); clarithromycin (Biaxin); danazol (Danocrine); diltiazem (Cardizem, Dilacor, Tiazac); erythromycin (E.E.S., E-Mycin, Erythrocin); HIV protease inhibitors such as indinavir (Crixivan) and ritonavir (Norvir, in Kaletra); certain medications for cholesterol; medications for seizures such as carbamazepine (Tegretol), phenobarbital (Luminal), and phenytoin (Dilantin); metoclopramide (Reglan); nicardipine (Cardene); rifabutin (Mycobutin); rifampin (Rifadin, Rimactane); rifapentine (Priftin); telithromycin (Ketek); troleandomycin (TAO) (not available in the U.S.); and verapamil (Calan, Covera, Isoptin, Verelan). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.

if you are taking cyclosporine (Neoral) soft gelatin capsules or solution, take them 4 hours before sirolimus.

tell your doctor what herbal products you are taking, especially St. John's wort.

tell your doctor if you have or have ever had high cholesterol or triglycerides or liver disease.

tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. You should use an effective method of birth control before starting to take sirolimus, while taking sirolimus, and for 12 weeks after stopping sirolimus. If you become pregnant while taking sirolimus, call your doctor.

if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking sirolimus.

do not have any vaccinations without talking to your doctor.

Avoid drinking grapefruit juice while taking this medication.

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Sirolimus may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them or those listed in the IMPORTANT WARNING section, call your doctor immediately:

unusual bleeding or bruising

cough

swollen, red, cracked, scaly skin

hives

rash

itching

difficulty breathing or swallowing

swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs

hoarseness

Sirolimus may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online ( http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store tablets at room temperature and away from light, excess heat, and moisture (not in the bathroom). Keep liquid medication in the refrigerator, away from light, closed tightly, and dispose of any unused medication one month after the bottle is opened. Do not freeze. If needed, you may store the bottles for up to 15 days at room temperature.

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website ( http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location - one that is up and away and out of their sight and reach. http://www.upandaway.org

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Last Revised - 02/15/2016

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Sirolimus may increase the risk that you will develop an infection or cancer, especially lymphoma (cancer of a part of the immune system) or skin cancer. To reduce your risk of skin cancer, plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen during your treatment.

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-What are the FDA approved and unapproved indications of benazepril?
It is FDA approved for the treatment of hypertension and to lower blood pressure. It works to relax blood vessels so blood can flow more easily. It is not approved for people younger than 6 years old and those that suffer from dehydration, has low sodium in the blood, and others should not take benazepril.
-What is the mechanism of it's therapeutic effect? Is this drug a member of an established class, or is it a brand new form of therapy?
Benazepril blocks the substance in the body that makes blood vessels tighten. It is part of the Angiotensin Converting Enzyme Inhibitors drug class.
-What is the cost to the patient (per treatment or per time period, if appropriate)? Do you think it is worth the price? Why or why not?
The cost to the patient for Benazepril is $22 for 30, 10 mg tablets, meaning around 74 cents per unit. This drug is also covered by a lot of health insurance plans so I think it is worth it.

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Moxifloxacin is a medication used to treat bacterial conjunctivitis, also known as pink eye, which is an infection of the membrane that effects the inside of the eyelids and and surface of the eye. The FDA approves of moxifloxacin as a topical ophthalmic solution. However, this drug is unapproved for intraocular administration. It is not available as an over-the-counter medication and has to be prescribed in 5ml or 10ml bottles; each one would cost an average of $115 per bottle, making it a fairly expensive eye drop medication. Moxifloxacin works by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV, which results in a separation of bacterial DNA, thereby inhibiting cell replication.

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Chemical Image: (Click to enlarge)

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use MOXIFLOXACIN TABLETS safely and effectively. See full prescribing information for MOXIFLOXACIN TABLETS.

MOXIFLOXACIN tablets, for oral use
Initial U.S. Approval: 1999

WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS and EXACERBATION OF MYASTHENIA GRAVIS
See full prescribing information for complete boxed warning

Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together (5.1) including:

Tendinitis and tendon rupture (5.2)

Peripheral Neuropathy (5.3)

Central nervous system effects (5.4)

Discontinue moxifloxacin hydrochloride immediately and avoid the use of fluoroquinolones, including moxifloxacin hydrochloride, in patients who experience any of these serious adverse reactions (5.1)

Fluoroquinolones, including moxifloxacin hydrochloride, may exacerbate muscle weakness in patients with myasthenia gravis. Avoid moxifloxacin hydrochloride in patients with known history of myasthenia gravis (5.5).

Because fluoroquinolones, including moxifloxacin hydrochloride, have been associated with serious adverse reactions (5.1 to 5.14), reserve moxifloxacin hydrochloride for use in patients who have no alternative treatment options for the following indications:

Acute bacterial sinusitis (1.6)

Acute bacterial exacerbation of chronic bronchitis (1.7)

RECENT MAJOR CHANGES

Dosage and Administration ( 2.2) 5/2020

INDICATIONS AND USAGE

Moxifloxacin tablets are a fluoroquinolone antibacterial indicated for treating infections in adults 18 years of age and older caused by designated susceptible bacteria, in the conditions listed below:

Community Acquired Pneumonia (1.1)

Skin and Skin Structure Infections: Uncomplicated (1.2) and Complicated (1.3)

Complicated Intra-Abdominal Infections (1.4)

Plague (1.5)

Acute Bacterial Sinusitis (1.6)

Acute Bacterial Exacerbation of Chronic Bronchitis (1.7)

To reduce the development of drug-resistant bacteria and maintain the effectiveness of moxifloxacin tablets and other antibacterial drugs. Moxifloxacin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. ( 1.8)

DOSAGE AND ADMINISTRATION

Type of Infection

Dose Every 24 hours

Duration (days)

No dosage adjustment in patients with renal or hepatic impairment. (8.6, 8.7)

DOSAGE FORMS AND STRENGTHS

Tablets: 400 mg moxifloxacin (3.1)

CONTRAINDICATIONS

Known hypersensitivity to moxifloxacin tablets or other quinolones (4, 5.8)

WARNINGS AND PRECAUTIONS

Prolongation of the QT interval and isolated cases of torsade de pointes has been reported. Avoid use in patients with known prolongation, proarrhythmic conditions such as clinically significant bradycardia or acute myocardial ischemia, hypokalemia, hypomagnesemia, and with drugs that prolong the QT interval. (5.6, 7.5, 8.5)

Hypersensitivity and other serious reactions: Serious and sometimes fatal reactions, including anaphylactic reactions, may occur after first or subsequent doses of moxifloxacin hydrochloride. Discontinue moxifloxacin hydrochloride at first sign of skin rash, jaundice or any other sign of hypersensitivity. (5.7, 5.8)

Clostridioides difficile-Associated Diarrhea: Evaluate if diarrhea occurs. (5.10)

ADVERSE REACTIONS

Most common reactions (3% or greater) were nausea, diarrhea, headache, and dizziness. ( 6)

To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Interacting Drug

Interaction

Multivalent cation-containing products including: antacids, sucralfate, multivitamins

Decreased moxifloxacin hydrochloride absorption. Take moxifloxacin tablet at least 4 hours before or 8 hours after these products. ( 2.2, 7.1, 12.3)

Warfarin

Anticoagulant effect enhanced. Monitor prothrombin time/INR, and bleeding. ( 6, 7.2, 12.3)

Class IA and Class III antiarrhythmics:

Proarrhythmic effect may be enhanced. Avoid concomitant use. ( 5.6, 7.5)

Antidiabetic agents

Carefully monitor blood glucose. ( 5.12, 7.3)

USE IN SPECIFIC POPULATIONS

Pregnancy: Based on animal data may cause fetal harm. (8.1)

Geriatrics: Increased risk for severe tendon disorders further increased by concomitant corticosteroid therapy and increased risk of prolongation of the QT interval. (5.1, 5.6, 8.5)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide

1.1 Community Acquired Pneumonia

Moxifloxacin tablets are indicated in adult patients for the treatment of Community Acquired Pneumonia caused by susceptible isolates of Streptococcus pneumoniae (including multi-drug resistant Streptococcus pneumoniae [MDRSP]), Haemophilus influenzae, Moraxella catarrhalis, methicillin-susceptible Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Clinical Studies (14.3)].

MDRSP isolates are isolates resistant to two or more of the following antibacterial drugs: penicillin (minimum inhibitory concentrations [MIC] ≥ 2 mcg/mL), 2nd generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole.

1.4 Complicated Intra-Abdominal Infections

Moxifloxacin tablets are indicated in adult patients for the treatment of Complicated Intra-Abdominal Infections (cIAI) including polymicrobial infections such as abscess caused by susceptible isolates of Escherichia coli, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides thetaiotaomicron, or Peptostreptococcus species [see Clinical Studies (14.6)].

1.6 Acute Bacterial Sinusitis

Because fluoroquinolones, including moxifloxacin tablets, have been associated with serious adverse reactions [see Warnings and Precautions (5.1 to 5.14)] and for some patients ABS is self-limiting, reserve moxifloxacin tablets for treatment of ABS in patients who have no alternative treatment options.

1.7 Acute Bacterial Exacerbation of Chronic Bronchitis

Moxifloxacin tablets are indicated in adult patients for the treatment of Acute Bacterial Exacerbation of Chronic Bronchitis (ABECB) caused by susceptible isolates of Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, methicillin-susceptible Staphylococcus aureus, or Moraxella catarrhalis [see Clinical Studies (14.2)].

2.1 Dosage in Adult Patients

The dose of moxifloxacin is 400 mg (orally) once every 24 hours. The duration of therapy depends on the type of infection as described in Table 1.

a) Due to the designated pathogens [see Indications and Usage (1)].
b) Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician
c) Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis.

Type of Infectiona

Dose Every 24 hours

Plague ( 1.5)C

400 mg

10 to 14

Conversion of Intravenous to Oral Dosing in Adults

Intravenous formulation is indicated when it offers a route of administration advantageous to the patient (for example, patient cannot tolerate an oral dosage form). When switching from intravenous to oral formulation, no dosage adjustment is necessary. Patients whose therapy is started with moxifloxacin hydrochloride injection may be switched to moxifloxacin tablets when clinically indicated at the discretion of the physician.

2.2 Important Administration Instructions

With Multivalent Cations

With Food

Moxifloxacin tablets can be taken with or without food, drink fluids liberally.

Missed Doses

If a dose is missed, it should be taken anytime but not later than 8 hours prior to the next scheduled dose. If less than 8 hours remain before the next dose, the missed dose should not be taken and treatment should be continued as prescribed with the next scheduled dose. Double doses should not be taken to compensate for a missed dose.

3 DOSAGE FORMS AND STRENGTHS

3.1 Moxifloxacin Tablets, USP

Modified capsule shaped, dull red, film-coated tablets debossed with E-18 on one side and plain on the other side containing 400 mg moxifloxacin.

Moxifloxacin tablets are contraindicated in persons with a history of hypersensitivity to moxifloxacin or any member of the quinolone class of antibacterials [see Warnings and Precautions (5.8)].

5 WARNINGS AND PRECAUTIONS

5.1 Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects

Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). These reactions can occur within hours to weeks after starting moxifloxacin hydrochloride. Patients of any age or without pre-existing risk factors have experienced these adverse reactions [see Warnings and Precautions (5.2, 5.3, 5.4)].

Discontinue moxifloxacin hydrochloride immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including moxifloxacin hydrochloride, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones.

5.2 Tendinitis and Tendon Rupture

Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with an increased risk of tendinitis and tendon rupture in all ages [see Warnings and Precautions (5.1) and Adverse Reactions (6.2)]. This adverse reaction most frequently involves the Achilles tendon, and has also been reported with the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendons. Tendinitis or tendon rupture can occur within hours or days of starting moxifloxacin or as long as several months after completion of therapy. Tendinitis and tendon rupture can occur bilaterally.

5.3 Peripheral Neuropathy

Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with an increased risk of peripheral neuropathy. Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving fluoroquinolones including moxifloxacin hydrochloride. Symptoms may occur soon after initiation of moxifloxacin hydrochloride and may be irreversible in some patients [see Warnings and Precautions (5.1) and Adverse Reactions (6.1, 6.2)].

Discontinue moxifloxacin hydrochloride immediately if the patient experiences symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness or other alterations of sensation including light touch, pain, temperature, position sense, and vibratory sensation. Avoid fluoroquinolones, including moxifloxacin hydrochloride, in patients who have previously experienced peripheral neuropathy.

5.4 Central Nervous System Effects

Psychiatric Adverse Reactions [see

Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with an increased risk of psychiatric adverse reactions, including: toxic psychosis, hallucinations, or paranoia; depression or suicidal thoughts or acts; anxiety, agitation, or nervousness; confusion, delirium, disorientation, or disturbances in attention; insomnia or nightmares; memory impairment. These adverse reactions may occur following the first dose. If these reactions occur in patients receiving moxifloxacin hydrochloride, discontinue moxifloxacin hydrochloride immediately and institute appropriate measures Adverse Reactions (6.1, 6.2)].

Central Nervous System Adverse Reactions

Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with an increased risk of seizures (convulsions), increased intracranial pressure (including pseudotumor cerebri), dizziness, and tremors. As with all fluoroquinolones, use moxifloxacin hydrochloride with caution in patients with known or suspected CNS disorders (for example, severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold. These adverse reactions may occur following the first dose. If these reactions occur in patients receiving moxifloxacin hydrochloride, discontinue moxifloxacin hydrochloride immediately and institute appropriate measures [see Drug Interactions (7.4) Adverse Reactions (6.1, 6.2), and Patient Counseling Information (17)].

5.5 Exacerbation of Myasthenia Gravis

Fluoroquinolones, including moxifloxacin hydrochloride, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. Postmarketing serious adverse reactions, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Avoid moxifloxacin hydrochloride in patients with known history of myasthenia gravis.

5.6 QT Prolongation

Moxifloxacin hydrochloride has been shown to prolong the QT interval of the electrocardiogram in some patients. Following oral dosing with 400 mg of moxifloxacin hydrochloride the mean (± SD) change in QTc from the pre-dose value at the time of maximum drug concentration was 6 msec (± 26) (n = 787). Following a course of daily intravenous dosing (400 mg; 1 hour infusion each day) the mean change in QTc from the Day 1 pre-dose value was 10 msec (±22) on Day 1 (n = 667) and 7 msec (± 24) on Day 3 (n = 667).

Avoid moxifloxacin hydrochloride in patients with the following risk factors due to the lack of clinical experience with the drug in these patient populations:

Known prolongation of the QT interval

Ventricular arrhythmias including torsade de pointes because QT prolongation may lead to an increased risk for these conditions

Ongoing proarrhythmic conditions, such as clinically significant bradycardia and acute myocardial ischemia,

Uncorrected hypokalemia or hypomagnesemia

Class IA (for example, quinidine, procainamide) or Class III (for example, amiodarone, sotalol) antiarrhythmic agents

Other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants

In patients with mild, moderate, or severe liver cirrhosis, metabolic disturbances associated with hepatic insufficiency may lead to QT prolongation. Monitor ECG in patients with liver cirrhosis treated with moxifloxacin hydrochloride [see Clinical Pharmacology (12.3)].

The magnitude of QT prolongation may increase with increasing concentrations of the drug or increasing rates of infusion of the intravenous formulation. Therefore, the recommended dose or infusion rate should not be exceeded.

In premarketing clinical trials, the rate of cardiovascular adverse reactions was similar in 798 moxifloxacin hydrochloride and 702 comparator treated patients who received concomitant therapy with drugs known to prolong the QTc interval. No excess in cardiovascular morbidity or mortality attributable to QTc prolongation occurred with moxifloxacin hydrochloride treatment in over 15,500 patients in controlled clinical studies, including 759 patients who were hypokalemic at the start of treatment, and there was no increase in mortality in over 18,000 moxifloxacin tablet treated patients in a postmarketing observational study in which ECGs were not performed.

5.7 Other Serious and Sometimes Fatal Adverse Reactions

Other serious and sometimes fatal adverse reactions, some due to hypersensitivity, and some due to uncertain etiology, have been reported in patients receiving therapy with fluoroquinolones, including moxifloxacin hydrochloride. These reactions may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following:

Fever, rash, or severe dermatologic reactions (for example, toxic epidermal necrolysis, Stevens-Johnson syndrome)

Vasculitis; arthralgia; myalgia; serum sickness

Allergic pneumonitis

Interstitial nephritis; acute renal insufficiency or failure

Hepatitis; jaundice; acute hepatic necrosis or failure

Anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities

Discontinue moxifloxacin hydrochloride immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity and institute supportive measures.

5.10 Clostridioides difficile-Associated Diarrhea

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

5.12 Blood Glucose Disturbances

As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycemia and hyperglycemia have been reported with moxifloxacin hydrochloride. In moxifloxacin hydrochloride-treated patients, dysglycemia occurred predominantly in elderly diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (for example, sulfonylurea) or with insulin. Severe cases of hypoglycemia resulting in coma or death have been reported. In diabetic patients, careful monitoring of blood glucose is recommended. If a hypoglycemic reaction occurs, discontinue moxifloxacin hydrochloride and initiate appropriate therapy immediately [see Adverse Reactions (6.1), Drug Interactions (7.3)] and Patient Counseling Information (17).

5.13 Photosensitivity/Phototoxicity

Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (for example, burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, "V" area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of fluoroquinolones, including moxifloxacin hydrochloride, after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Moxifloxacin hydrochloride should be discontinued if phototoxicity occurs [see Clinical Pharmacology (12.2)].

The following serious and otherwise important adverse reactions are discussed in greater detail in the warnings and precautions section of the label:

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to moxifloxacin hydrochloride in 14981 patients in 71 active controlled Phase II to IV clinical trials in different indications [see Indications and Usage (1)]. The population studied had a mean age of 50 years (approximately 73% of the population was less than 65 years of age), 50% were male, 63% were Caucasian, 12% were Asian and 9% were Black. Patients received moxifloxacin 400 mg once daily oral, intravenous, or sequentially (intravenous followed by oral). Treatment duration was usually 6 to 10 days, and the mean number of days on therapy was 9 days.

Discontinuation of moxifloxacin due to adverse reactions occurred in 5% of patients overall, 4% of patients treated with 400 mg PO, 4% with 400 mg intravenous and 8% with sequential therapy 400 mg oral/intravenous. The most common adverse reactions (>0.3%) leading to discontinuation with the 400 mg oral doses were nausea, diarrhea, dizziness, and vomiting. The most common adverse reaction leading to discontinuation with the 400 mg intravenous dose was rash. The most common adverse reactions leading to discontinuation with the 400 mg intravenous/oral sequential dose were diarrhea, pyrexia.

Adverse reactions occurring in 1% of moxifloxacin hydrochloride-treated patients and less common adverse reactions, occurring in 0.1 to 1% of moxifloxacin hydrochloride-treated patients, are shown in Tables 2 and Table 3, respectively. The most common adverse drug reactions (3%) are nausea, diarrhea, headache, and dizziness.

System Organ Class

Adverse Reactions

Diarrhea

6

Vomiting

2

Constipation

2

Abdominal pain

2

Dyspepsia

1

Dizziness

3

System Organ Class

Adverse Reactions

Eosinophilia

Neutropenia

Thrombocytopenia

Leukopenia

Leukocytosis

Palpitations

Tachycardia

Angina pectoris

Cardiac failure

Cardiac arrest

Bradycardia

Tinnitus

Abdominal discomfort

Flatulence

Abdominal distention

Gastritis

Gastroesophageal reflux disease

Chest pain

Asthenia

Pain

Malaise

Infusion site extravasation

Edema

Chills

Chest discomfort

Facial pain

Vaginal infection

Fungal infection

Gastroenteritis

Gamma-glutamyltransferase increased

Blood alkaline phosphatase increased

Electrocardiogram QT prolonged

Blood lactate dehydrogenase increased

Blood amylase increased

Lipase increased

Blood creatinine increased

Blood urea increased

Hematocrit decreased

Prothrombin time prolonged

Eosinophil count increased

Activated partial thromboplastin time prolonged

Blood triglycerides increased

Blood uric acid increased

Anorexia

Hyperlipidemia

Decreased appetite

Dehydration

Pain in extremity

Arthralgia

Muscle spasms

Musculoskeletal pain

Somnolence

Tremor

Lethargy

Paresthesia

Hypoesthesia

Syncope

Confusional state

Agitation

Depression

Nervousness

Restlessness

Hallucination

Disorientation

Dysuria

Asthma

Wheezing

Bronchospasm

Pruritus

Hyperhidrosis

Erythema

Urticaria

Dermatitis allergic

Night sweats

Hypotension

Phlebitis

Laboratory Changes

Changes in laboratory parameters, which are not listed above and which occurred in 2% or more of patients and at an incidence greater than in controls included: increases in mean corpuscular hemoglobin (MCH), neutrophils, white blood cells (WBCs), prothrombin time (PT) ratio, ionized calcium, chloride, albumin, globulin, bilirubin; decreases in hemoglobin, red blood cells (RBCs), neutrophils, eosinophils, basophils, glucose, oxygen partial pressure (pO2), bilirubin, and amylase. It cannot be determined if any of the above laboratory abnormalities were caused by the drug or the underlying condition being treated.

6.2 Postmarketing Experience

Table 4 below lists adverse reactions that have been identified during post-approval use of moxifloxacin hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

7 DRUG INTERACTIONS

7.4 Nonsteroidal Anti-Inflammatory Drugs

The concomitant administration of a nonsteroidal anti-inflammatory drug (NSAID) with a fluoroquinolone, including moxifloxacin hydrochloride, may increase the risks of CNS stimulation and convulsions [see Warnings and Precautions (5.4)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no available human data establishing a drug associated risk with the use of moxifloxacin.

Based on animal studies with moxifloxacin, moxifloxacin hydrochloride may cause fetal harm. Moxifloxacin did not cause fetal malformations when administered to pregnant rats (IV and oral), rabbits (IV), and monkeys (oral) at exposures that were 0.24 to 2.5 times of those at the human clinical dose (400 mg/day moxifloxacin hydrochloride). However, when moxifloxacin was administered to rats and rabbits during pregnancy and throughout lactation (rats only) at doses associated with maternal toxicity, decreased neonatal body weights, increased incidence of skeletal variations (rib and vertebra combined), and increased fetal loss were observed (see Data). Advise pregnant women of the potential risk to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

Animal reproductive and development studies were done in rats, rabbits and cynomolgus macaques. Moxifloxacin did not cause fetal malformations when administered to pregnant rats during organogenesis (gestation days 6 to 17) at oral doses as high as 500 mg/kg/day or 0.24 times the maximum recommended human dose based on systemic exposure (AUC), but decreased fetal body weights and slightly delayed fetal skeletal development were observed. Intravenous administration of 80 mg/kg/day (approximately 2 times the maximum recommended human dose based on body surface area) to pregnant rats resulted in maternal toxicity and a marginal effect on fetal and placental weights and the appearance of the placenta (Gestation days 6 to 17). Fetal malformations were not observed at intravenous doses as high as 80 mg/kg/day (approximately 2 times the maximum recommended human dose based on body surface area) in litters of pregnant rats that received moxifloxacin during organogenesis (Gestation days 6 to 17). Intravenous administration of 20 mg/kg/day (approximately equal to the maximum recommended human oral dose based upon systemic exposure) to pregnant rabbits during organogenesis (gestation days 6 to 20) resulted in decreased fetal body weights and delayed fetal skeletal ossification. When rib and vertebral malformations were combined, there was an increased fetal and litter incidence of these effects in rabbits. Signs of maternal toxicity in rabbits at this dose included mortality, abortions, marked reduction of food consumption, decreased water intake, body weight loss and hypoactivity. Fetal malformations were not observed when pregnant cynomolgus macaques were given oral doses as high as 100 mg/kg/day (2.5 times the maximum recommended human dose based upon systemic exposure) during organogenesis (gestation days 20 to 50). An increased incidence of smaller fetuses was observed at 100 mg/kg/day in macaques. In a pre- and postnatal development study conducted in rats given oral doses from Gestation day 6, throughout gestation and rearing to Postpartum day 21, effects observed at 500 mg/kg/day (0.24 times the maximum recommended human dose based on systemic exposure (AUC)) included slight increases in duration of pregnancy and prenatal loss, reduced pup birth weight and decreased neonatal survival. Treatment-related maternal mortality occurred during gestation at 500 mg/kg/day in this study.

8.2 Lactation

Risk Summary

It is not known if moxifloxacin is present in human milk. Based on animal studies in rats, moxifloxacin may be excreted in human milk (see Data). When a drug is present in animal milk, it is likely that the drug will be present in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for moxifloxacin hydrochloride and any potential adverse effects on the breastfed child from moxifloxacin hydrochloride or from the underlying maternal condition.

Data

In lactating rats given a single oral dose of 4.59 mg/kg moxifloxacin (approximately 9 times less than the recommended human dose based on body surface area) 8 days postpartum, there was very low excretion of substance-related radioactivity into the milk, amounting to approximately 0.03% of the dose.

8.4 Pediatric Use

Effectiveness in pediatric patients and adolescents less than 18 years of age has not been established. Moxifloxacin hydrochloride causes arthropathy in juvenile animals. Limited information on the safety of moxifloxacin hydrochloride in 301 pediatric patients is available from the cIAI trial [see Boxed Warning, Warnings and Precautions (5.11) and Nonclinical Toxicology (13.2)].

Active Controlled Trial in Complicated Intra-Abdominal Infection (cIAI)

The safety and efficacy of moxifloxacin hydrochloride in pediatric patients for the treatment of cIAI has not been demonstrated.

Pediatric patients 3 months to <18 years of age (mean age of 12 ± 4 years) were enrolled in a single randomized, double-blind, active controlled trial in cIAI including appendicitis with perforation, abscesses and peritonitis.

Pediatric patients were randomized (2:1) to receive either moxifloxacin hydrochloride or comparator. This study enrolled 451 patients who received study medication, 301 treated with moxifloxacin, and 150 with comparator. Of the 301 pediatric patients treated with moxifloxacin hydrochloride, 15 were below the age of 6 years and 286 were between the ages of 6 to <18 years.

Patients received sequential intravenous/oral moxifloxacin hydrochloride or comparator (intravenous ertapenem followed by oral amoxicillin/clavulanate) for 5 to 14 days (mean duration was 9 days with a range of 1 to 24 days).

The overall adverse reaction profile in pediatric patients was comparable to that of adult patients. The most frequently occurring adverse reactions in pediatric patients treated with moxifloxacin hydrochloride were QT prolongation 9.3% (28/301), vomiting, 6.6% (20/301), diarrhea 3.7% (11/301), arthralgia 3.0% (9/301), and phlebitis 2.7% (8/301) (see Table 5). Discontinuation of study drug due to an adverse reaction was reported in 5.3% (16/301) of moxifloxacin hydrochloride-treated patients versus 1.3% (2/150) of comparator-treated patients. The adverse reaction profile of moxifloxacin hydrochloride or comparator was similar across all age groups studied.

System Organ Class

Adverse Reactions

Clinical response was assessed at the test-of-cure visit (28 to 42 days after end of treatment). The clinical response rates observed in the modified intent to treat population were 83.9% (208/248) for moxifloxacin hydrochloride and 95.5% (127/133) for comparator; see Table 6.

mITT Population1

N = 248

N = 133

8.5 Geriatric Use

Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients [see Warnings and Precautions (5.9) ].

In controlled multiple-dose clinical trials, 23% of patients receiving oral moxifloxacin hydrochloride were greater than or equal to 65 years of age and 9% were greater than or equal to 75 years of age. The clinical trial data demonstrate that there is no difference in the safety and efficacy of oral moxifloxacin hydrochloride in patients aged 65 or older compared to younger adults.

In trials of intravenous use, 42% of moxifloxacin hydrochloride patients were greater than or equal to 65 years of age, and 23% were greater than or equal to 75 years of age. The clinical trial data demonstrate that the safety of intravenous moxifloxacin hydrochloride in patients aged 65 or older was similar to that of comparator-treated patients. In general, elderly patients may be more susceptible to drug-associated effects of the QT interval. Therefore, moxifloxacin hydrochloride should be avoided in patients taking drugs that can result in prolongation of the QT interval (for example, class IA or class III antiarrhythmics) or in patients with risk factors for torsade de pointes (for example, known QT prolongation, uncorrected hypokalemia) [see Warnings and Precautions (5.6), Drug Interactions (7.5), and Clinical Pharmacology (12.3)].

Single oral overdoses up to 2.8 g were not associated with any serious adverse events. In the event of acute overdose, empty the stomach and maintain adequate hydration. Monitor ECG due to the possibility of QT interval prolongation. Carefully observe the patient and give supportive treatment. The administration of activated charcoal as soon as possible after oral overdose may prevent excessive increase of systemic moxifloxacin exposure. About 3% and 9% of the dose of moxifloxacin, as well as about 2% and 4.5% of its glucuronide metabolite are removed by continuous ambulatory peritoneal dialysis and hemodialysis, respectively.

Moxifloxacin hydrochloride is a synthetic antibacterial agent for oral administration. Moxifloxacin, a fluoroquinolone, is available as the monohydrochloride salt of 1-cyclopropyl-7-[(S,S)-2,8-diazabicyclo[4.3.0]non-8-yl]-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3 quinoline carboxylic acid. It is a slightly yellow to yellow powder or crystals, slightly hygroscopic substance with a molecular weight of 437.9. Its molecular formula is C21H24FN3O4*HCl and its chemical structure is as follows:

11.1 Moxifloxacin Tablets, USP

Moxifloxacin tablets, USP are available as film-coated tablets containing 400 mg moxifloxacin (equivalent to 436.33 mg moxifloxacin hydrochloride USP).

The inactive ingredients are hypromellose, iron oxide red, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, sodium starch glycolate, and titanium dioxide.

12.1 Mechanism of Action

Moxifloxacin hydrochloride is a member of the fluoroquinolone class of antibacterial agents [see Microbiology (12.4)].

12.2 Pharmacodynamics

Photosensitivity Potential [see

A study of the skin response to ultraviolet (UVA and UVB) and visible radiation conducted in 32 healthy volunteers (8 per group) demonstrated that moxifloxacin hydrochloride does not show phototoxicity in comparison to placebo. The minimum erythematous dose (MED) was measured before and after treatment with moxifloxacin (200 mg or 400 mg once daily), lomefloxacin (400 mg once daily), or placebo. In this study, the MED measured for both doses of moxifloxacin were not significantly different from placebo, while lomefloxacin significantly lowered the MED Warnings and Precautions (5.13)] .

12.3 Pharmacokinetics

Absorption

Moxifloxacin, given as an oral tablet, is well absorbed from the gastrointestinal tract. The absolute bioavailability of moxifloxacin is approximately 90 percent. Co-administration with a high fat meal (that is, 500 calories from fat) does not affect the absorption of moxifloxacin.

Consumption of 1 cup of yogurt with moxifloxacin does not affect the rate or extent of the systemic absorption (that is, area under the plasma concentration time curve (AUC).

a) Range of means from different studies

Healthy (n = 372)

3.1 ± 1

36.1 ± 9.1

11.5 to 15.6a

a) Range of means from different studies
b) Expected Cmax (concentration obtained around the time of the end of the infusion)

Healthy young male/female (n = 56)

3.9 ± 0.9

39.3 ± 8.6

8.2 to 15.4a

Plasma concentrations increase proportionately with dose up to the highest dose tested (1200 mg single oral dose). The mean (± SD) elimination half-life from plasma is 12 ± 1.3 hours; steady-state is achieved after at least three days with a 400 mg once daily regimen.

Mean Steady-State Plasma Concentrations of Moxifloxacin Obtained With Once Daily Dosing of 400 mg Either Orally (n = 10) or by Intravenous Infusion (n = 12)

Distribution

Moxifloxacin is approximately 30 to 50% bound to serum proteins, independent of drug concentration. The volume of distribution of moxifloxacin ranges from 1.7 to 2.7 L/kg. Moxifloxacin is widely distributed throughout the body, with tissue concentrations often exceeding plasma concentrations. Moxifloxacin has been detected in the saliva, nasal and bronchial secretions, mucosa of the sinuses, skin blister fluid, subcutaneous tissue, skeletal muscle, and abdominal tissues and fluids following oral or intravenous administration of 400 mg. Moxifloxacin concentrations measured post-dose in various tissues and fluids following a 400 mg oral or intravenous dose are summarized in Table 9. The rates of elimination of moxifloxacin from tissues generally parallel the elimination from plasma.

a) All moxifloxacin concentrations were measured 3 hours after a single 400 mg dose, except the abdominal tissue and exudate concentrations which were measured at 2 hours post-dose and the sinus concentrations which were measured 3 hours post-dose after 5 days of dosing.
b) N = 5
c) N = 7
d) N = 12
e) Reflects only non-protein bound concentrations of drug.

Tissue or Fluid

N

Plasma Concentration (mcg/mL)

Tissue or Fluid Concentration (mcg/mL or mcg/g)

Tissue Plasma Ratio

Subcutaneous Tissue

6

2.3 ± 0.4d

0.9 ± 0.3e

0.4 ± 0.6

Skeletal Muscle

6

2.3 ± 0.4d

0.9 ± 0.2e

0.4 ± 0.1

Metabolism

Approximately 52% of an oral or intravenous dose of moxifloxacin is metabolized via glucuronide and sulfate conjugation. The cytochrome P450 system is not involved in moxifloxacin metabolism, and is not affected by moxifloxacin. The sulfate conjugate (M1) accounts for approximately 38% of the dose, and is eliminated primarily in the feces. Approximately 14% of an oral or intravenous dose is converted to a glucuronide conjugate (M2), which is excreted exclusively in the urine. Peak plasma concentrations of M2 are approximately 40% those of the parent drug, while plasma concentrations of M1 are generally less than 10% those of moxifloxacin.

In vitro studies with cytochrome (CYP) P450 enzymes indicate that moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2.

Excretion

Approximately 45% of an oral or intravenous dose of moxifloxacin is excreted as unchanged drug (~20% in urine and ~25% in feces). A total of 96% ± 4% of an oral dose is excreted as either unchanged drug or known metabolites. The mean (± SD) apparent total body clearance and renal clearance are 12 ± 2 L/hr and 2.6 ± 0.5 L/hr, respectively.

Pharmacokinetics in Specific Populations

Geriatric

Gender

Following oral administration of 400 mg moxifloxacin daily for 10 days to 23 healthy males (19 to 75 years) and 24 healthy females (19 to 70 years), the mean AUC and Cmax were 8% and 16% higher, respectively, in females compared to males. There are no significant differences in moxifloxacin pharmacokinetics between male and female subjects when differences in body weight are taken into consideration.

A 400 mg single dose study was conducted in 18 young males and females. The comparison of moxifloxacin pharmacokinetics in this study (9 young females and 9 young males) showed no differences in AUC or Cmax due to gender. Dosage adjustments based on gender are not necessary.

Race

Steady-state moxifloxacin pharmacokinetics in male Japanese subjects were similar to those determined in Caucasians, with a mean Cmax of 4.1 mcg/mL, an AUC24 of 47 mcg*h/mL, and an elimination half-life of 14 hours, following 400 mg p.o. daily.

Renal Insufficiency

The pharmacokinetic parameters of moxifloxacin are not significantly altered in mild, moderate, severe, or end-stage renal disease. No dosage adjustment is necessary in patients with renal impairment, including those patients requiring hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD).

In a single oral dose study of 24 patients with varying degrees of renal function from normal to severely impaired, the mean peak concentrations (Cmax) of moxifloxacin were reduced by 21% and 28% in the patients with moderate (CLCR≥ 30 and ≤ 60 mL/min) and severe (CLCR<30 mL/min) renal impairment, respectively. The mean systemic exposure (AUC) in these patients was increased by 13%. In the moderate and severe renally impaired patients, the mean AUC for the sulfate conjugate (M1) increased by 1.7-fold (ranging up to 2.8-fold) and mean AUC and Cmax for the glucuronide conjugate (M2) increased by 2.8-fold (ranging up to 4.8-fold) and 1.4-fold (ranging up to 2.5-fold), respectively [see Use in Specific Populations (8.6)].

Oral administration of 400 mg QD moxifloxacin for 7 days to patients on HD or CAPD produced mean systemic exposure (AUCss) to moxifloxacin similar to that generally seen in healthy volunteers. Steady-state Cmax values were about 22% lower in HD patients but were comparable between CAPD patients and healthy volunteers. Both HD and CAPD removed only small amounts of moxifloxacin from the body (approximately 9% by HD, and 3% by CAPD). HD and CAPD also removed about 4% and 2% of the glucuronide metabolite (M2), respectively.

Hepatic Insufficiency

No dosage adjustment is recommended for mild, moderate, or severe hepatic insufficiency (Child-Pugh Classes A, B, or C). However, due to metabolic disturbances associated with hepatic insufficiency, which may lead to QT prolongation, moxifloxacin hydrochloride should be used with caution in these patients [see Warnings and Precautions (5.6) and Use in Specific Populations (8.7)].

In 400 mg single oral dose studies in 6 patients with mild (Child-Pugh Class A) and 10 patients with moderate (Child-Pugh Class B) hepatic insufficiency, moxifloxacin mean systemic exposure (AUC) was 78% and 102%, respectively, of 18 healthy controls and mean peak concentration (Cmax) was 79% and 84% of controls.

Drug-Drug Interactions

The following drug interactions were studied in healthy volunteers or patients.

Antacids and iron significantly reduced bioavailability of moxifloxacin, as observed with other fluoroquinolones [see Drug Interactions (7.1)].

Calcium, digoxin, itraconazole, morphine, probenecid, ranitidine, theophylline, cyclosporine and warfarin did not significantly affect the pharmacokinetics of moxifloxacin. These results and the data from in vitro studies suggest that moxifloxacin is unlikely to significantly alter the metabolic clearance of drugs metabolized by CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2 enzymes.

Moxifloxacin had no clinically significant effect on the pharmacokinetics of atenolol, digoxin, glyburide, itraconazole, oral contraceptives, theophylline, cyclosporine and warfarin. However, fluoroquinolones, including moxifloxacin hydrochloride, have been reported to enhance the anticoagulant effects of warfarin or its derivatives in the patient population [see Drug Interactions (7.2)].

Antacids [see

When moxifloxacin (single 400 mg tablet dose) was administered two hours before, concomitantly, or 4 hours after an aluminum/magnesium-containing antacid (900 mg aluminum hydroxide and 600 mg magnesium hydroxide as a single oral dose) to 12 healthy volunteers there was a 26%, 60% and 23% reduction in the mean AUC of moxifloxacin, respectively. Moxifloxacin should be taken at least 4 hours before or 8 hours after antacids containing magnesium or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc, or didanosine buffered tablets for oral suspension or the pediatric powder for oral solution Dosage and Administration (2.2) and Drug Interactions (7.1)].

Atenolol

In a crossover study involving 24 healthy volunteers (12 male; 12 female), the mean atenolol AUC following a single oral dose of 50 mg atenolol with placebo was similar to that observed when atenolol was given concomitantly with a single 400 mg oral dose of moxifloxacin. The mean Cmax of single dose atenolol decreased by about 10% following co-administration with a single dose of moxifloxacin.

Calcium

Twelve healthy volunteers were administered concomitant moxifloxacin (single 400 mg dose) and calcium (single dose of 500 mg Ca++ dietary supplement) followed by an additional two doses of calcium 12 and 24 hours after moxifloxacin administration. Calcium had no significant effect on the mean AUC of moxifloxacin. The mean Cmax was slightly reduced and the time to maximum plasma concentration was prolonged when moxifloxacin was given with calcium compared to when moxifloxacin was given alone (2.5 hours versus 0.9 hours). These differences are not considered to be clinically significant.

Digoxin

No significant effect of moxifloxacin (400 mg once daily for two days) on digoxin (0.6 mg as a single dose) AUC was detected in a study involving 12 healthy volunteers. The mean digoxin Cmax increased by about 50% during the distribution phase of digoxin. This transient increase in digoxin Cmax is not viewed to be clinically significant. Moxifloxacin pharmacokinetics were similar in the presence or absence of digoxin. No dosage adjustment for moxifloxacin or digoxin is required when these drugs are administered concomitantly.

Glyburide

In diabetics, glyburide (2.5 mg once daily for two weeks pretreatment and for five days concurrently) mean AUC and Cmax were 12% and 21% lower, respectively, when taken with moxifloxacin (400 mg once daily for five days) in comparison to placebo. Nonetheless, blood glucose levels were decreased slightly in patients taking glyburide and moxifloxacin in comparison to those taking glyburide alone, suggesting no interference by moxifloxacin on the activity of glyburide. These interaction results are not viewed as clinically significant.

Iron [see

When moxifloxacin tablets were administered concomitantly with iron (ferrous sulfate 100 mg once daily for two days), the mean AUC and Cmax of moxifloxacin was reduced by 39% and 59%, respectively. Moxifloxacin should only be taken more than 4 hours before or 8 hours after iron products Dosage and Administration (2.2) and Drug Interactions (7.1)].

Itraconazole

In a study involving 11 healthy volunteers, there was no significant effect of itraconazole (200 mg once daily for 9 days), a potent inhibitor of cytochrome P4503A4, on the pharmacokinetics of moxifloxacin (a single 400 mg dose given on the 7th day of itraconazole dosing). In addition, moxifloxacin was shown not to affect the pharmacokinetics of itraconazole.

Morphine

No significant effect of morphine sulfate (a single 10 mg intramuscular dose) on the mean AUC and Cmax of moxifloxacin (400 mg single dose) was observed in a study of 20 healthy male and female volunteers.

Oral Contraceptives

A placebo-controlled study in 29 healthy female subjects showed that moxifloxacin 400 mg daily for 7 days did not interfere with the hormonal suppression of oral contraception with 0.15 mg levonorgestrel/0.03 mg ethinylestradiol (as measured by serum progesterone, FSH, estradiol, and LH), or with the pharmacokinetics of the administered contraceptive agents.

Probenecid

Probenecid (500 mg twice daily for two days) did not alter the renal clearance and total amount of moxifloxacin (400 mg single dose) excreted renally in a study of 12 healthy volunteers.

Ranitidine

No significant effect of ranitidine (150 mg twice daily for three days as pretreatment) on the pharmacokinetics of moxifloxacin (400 mg single dose) was detected in a study involving 10 healthy volunteers.

Theophylline

No significant effect of moxifloxacin (200 mg every twelve hours for 3 days) on the pharmacokinetics of theophylline (400 mg every twelve hours for 3 days) was detected in a study involving 12 healthy volunteers. In addition, theophylline was not shown to affect the pharmacokinetics of moxifloxacin. The effect of co-administration of 400 mg once daily of moxifloxacin with theophylline has not been studied.

Warfarin [see

No significant effect of moxifloxacin (400 mg once daily for eight days) on the pharmacokinetics of R- and S-warfarin (25 mg single dose of warfarin sodium on the fifth day) was detected in a study involving 24 healthy volunteers. No significant change in prothrombin time was observed. However, fluoroquinolones, including moxifloxacin hydrochloride, have been reported to enhance the anticoagulant effects of warfarin or its derivatives in the patient population Adverse Reactions (6.2) and Drug Interactions (7.2)].

12.4 Microbiology

Mechanism of Action

The bactericidal action of moxifloxacin results from inhibition of the topoisomerase II (DNA gyrase) and topoisomerase IV required for bacterial DNA replication, transcription, repair, and recombination.

Resistance

The mechanism of action for fluoroquinolones, including moxifloxacin, is different from that of macrolides, beta-lactams, aminoglycosides, or tetracyclines; therefore, microorganisms resistant to these classes of drugs may be susceptible to moxifloxacin. Resistance to fluoroquinolones occurs primarily by a mutation in topoisomerase II (DNA gyrase) or topoisomerase IV genes, decreased outer membrane permeability or drug efflux. In vitro resistance to moxifloxacin develops slowly via multiple-step mutations. Resistance to moxifloxacin occurs in vitro at a general frequency of between 1.8 x 10-9 to < 1 x 10-11 for Gram-positive bacteria.

Cross Resistance

Cross-resistance has been observed between moxifloxacin and other fluoroquinolones against Gram-negative bacteria. Gram-positive bacteria resistant to other fluoroquinolones may, however, still be susceptible to moxifloxacin. There is no known cross-resistance between moxifloxacin and other classes of antimicrobials.

Antimicrobial Activity

Gram-positive bacteria

Enterococcus faecalis

Staphylococcus aureus

Streptococcus anginosus

Streptococcus constellatus

Streptococcus pneumoniae (including multi-drug resistant isolates [MDRSP] **)

Streptococcus pyogenes

Gram-negative bacteria

Enterobacter cloacae

Escherichia coli

Haemophilus influenzae

Haemophilus parainfluenzae

Klebsiella pneumoniae

Moraxella catarrhalis

Proteus mirabilis

Yersinia pestis

Anaerobic bacteria

Bacteroides fragilis

Bacteroides thetaiotaomicron

Clostridium perfringens

Peptostreptococcus species

Other microorganisms

Chlamydophila pneumoniae

Mycoplasma pneumoniae

Gram-positive bacteria

Staphylococcus epidermidis

Streptococcus agalactiae

Streptococcus viridans group

Gram-negative bacteria

Citrobacter freundii

Klebsiella oxytoca

Legionella pneumophila

Anaerobic bacteria

Fusobacterium species

Prevotella species

Susceptibility Tests Methods

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals to determine the carcinogenic potential of moxifloxacin have not been performed.

Moxifloxacin was not mutagenic in 4 bacterial strains (TA 98, TA 100, TA 1535, TA 1537) used in the Ames Salmonella reversion assay. As with other fluoroquinolones, the positive response observed with moxifloxacin in strain TA 102 using the same assay may be due to the inhibition of DNA gyrase. Moxifloxacin was not mutagenic in the CHO/HGPRT mammalian cell gene mutation assay. An equivocal result was obtained in the same assay when v79 cells were used. Moxifloxacin was clastogenic in the v79 chromosome aberration assay, but it did not induce unscheduled DNA synthesis in cultured rat hepatocytes. There was no evidence of genotoxicity in vivo in a micronucleus test or a dominant lethal test in mice.

Moxifloxacin had no effect on fertility in male and female rats at oral doses as high as 500 mg/kg/day, approximately 12 times the maximum recommended human dose based on body surface area) or at intravenous doses as high as 45 mg/kg/day, approximately equal to the maximum recommended human dose based on body surface area). At 500 mg/kg orally there were slight effects on sperm morphology (head-tail separation) in male rats and on the estrous cycle in female rats.

13.2 Animal Toxicology and/or Pharmacology

Fluoroquinolones have been shown to cause arthropathy in immature animals. In studies in juvenile dogs oral doses of moxifloxacin 30 mg/kg/day or more (approximately 1.5 times the maximum recommended human dose based upon systemic exposure) for 28 days resulted in arthropathy. There was no evidence of arthropathy in mature monkeys and rats at oral doses up to 135 and 500 mg/kg/day, respectively.

Moxifloxacin at an oral dose of 300 mg/kg did not show an increase in acute toxicity or potential for CNS toxicity (for example, seizures) in mice when used in combination with NSAIDs such as diclofenac, ibuprofen, or fenbufen. Some fluoroquinolones have been reported to have proconvulsant activity that is exacerbated with concomitant use of NSAIDs.

A QT-prolonging effect of moxifloxacin was found in dog studies, at plasma concentrations about five times the human therapeutic level. The combined infusion of sotalol, a Class III antiarrhythmic agent, with moxifloxacin induced a higher degree of QTc prolongation in dogs than that induced by the same dose (30 mg/kg) of moxifloxacin alone. Electrophysiological in vitro studies suggested an inhibition of the rapid activating component of the delayed rectifier potassium current (IKr) as an underlying mechanism.

No signs of local intolerability were observed in dogs when moxifloxacin was administered intravenously. After intra-arterial injection, inflammatory changes involving the peri-arterial soft tissue were observed suggesting that intra-arterial administration of moxifloxacin hydrochloride should be avoided.

14 CLINICAL STUDIES

14.1 Acute Bacterial Sinusitis

In a controlled double-blind study conducted in the U.S., moxifloxacin tablets (400 mg once daily for ten days) were compared with cefuroxime axetil (250 mg twice daily for ten days) for the treatment of acute bacterial sinusitis. The trial included 457 patients valid for the efficacy analysis. Clinical success (cure plus improvement) at the 7 to 21 day post-therapy test of cure visit was 90% for moxifloxacin hydrochloride and 89% for cefuroxime.

An additional non-comparative study was conducted to gather bacteriological data and to evaluate microbiological eradication in adult patients treated with moxifloxacin 400 mg once daily for seven days. All patients (n = 336) underwent antral puncture in this study. Clinical success rates and eradication/presumed eradication rates at the 21 to 37 day follow-up visit were 97% (29 out of 30) for Streptococcus pneumoniae, 83% (15 out of 18) for Moraxella catarrhalis, and 80% (24 out of 30) for Haemophilus influenzae.

14.2 Acute Bacterial Exacerbation of Chronic Bronchitis

Moxifloxacin tablets (400 mg once daily for five days) were evaluated for the treatment of acute bacterial exacerbation of chronic bronchitis in a randomized, double-blind, controlled clinical trial conducted in the U.S. This study compared moxifloxacin hydrochloride with clarithromycin (500 mg twice daily for 10 days) and enrolled 629 patients. Clinical success was assessed at 7 to 17 days post-therapy. The clinical success for moxifloxacin hydrochloride was 89% (222/250) compared to 89% (224/251) for clarithromycin.

PATHOGEN

Moxifloxacin Hydrochloride

Clarithromycin

The microbiological eradication rates (eradication plus presumed eradication) in moxifloxacin hydrochloride treated patients were Streptococcus pneumoniae 100%, Haemophilus influenzae 89%, Haemophilus parainfluenzae 100%, Moraxella catarrhalis 85%, Staphylococcus aureus 94%, and Klebsiella pneumoniae 85%.

14.3 Community Acquired Pneumonia

A randomized, double-blind, controlled clinical trial was conducted in the U.S. to compare the efficacy of moxifloxacin tablets (400 mg once daily) to that of high-dose clarithromycin (500 mg twice daily) in the treatment of patients with clinically and radiologically documented community acquired pneumonia. This study enrolled 474 patients (382 of whom were valid for the efficacy analysis conducted at the 14 to 35 day follow-up visit). Clinical success for clinically evaluable patients was 95% (184/194) for moxifloxacin hydrochloride and 95% (178/188) for high dose clarithromycin.

A randomized, double-blind, controlled trial was conducted in the U.S. and Canada to compare the efficacy of sequential intravenous/oral moxifloxacin 400 mg once a day for 7 to 14 days to an intravenous/oral fluoroquinolone control (trovafloxacin or levofloxacin) in the treatment of patients with clinically and radiologically documented community acquired pneumonia. This study enrolled 516 patients, 362 of whom were valid for the efficacy analysis conducted at the 7 to 30 day post-therapy visit. The clinical success rate was 86% (157/182) for moxifloxacin hydrochloride therapy and 89% (161/180) for the fluoroquinolone comparators.

An open-label ex-U.S. study that enrolled 628 patients compared moxifloxacin tablets to sequential intravenous/oral amoxicillin/clavulanate (1.2 gram intravenously every 8 hours/625 mg orally every 8 hours) with or without high-dose intravenous/oral clarithromycin (500 mg twice a day). The intravenous formulations of the comparators are not FDA approved. The clinical success rate at Day 5 to 7 for moxifloxacin hydrochloride therapy was 93% (241/258) and demonstrated superiority to amoxicillin/clavulanate ± clarithromycin (85%, 239/280) [95% C.I. of difference in success rates between moxifloxacin and comparator (2.9%, 13.2%)]. The clinical success rate at the 21 to 28 days post-therapy visit for moxifloxacin hydrochloride was 84% (216/258), which also demonstrated superiority to the comparators (74%, 208/280) [95% C.I. of difference in success rates between moxifloxacin and comparator (2.6%, 16.3%)].

The clinical success rates by pathogen across four CAP studies are presented in Table 11.

PATHOGEN

Moxifloxacin Hydrochloride

Community Acquired Pneumonia caused by Multi-Drug Resistant Streptococcus pneumoniae (MDRSP)*

Moxifloxacin hydrochloride was effective in the treatment of community acquired pneumonia (CAP) caused by multi-drug resistant Streptococcus pneumoniae MDRSP* isolates. Of 37 microbiologically evaluable patients with MDRSP isolates, 35 patients (95%) achieved clinical and bacteriological success post-therapy. The clinical and bacteriological success rates based on the number of patients treated are shown in Table 12.

a) n = number of patients successfully treated; N = number of patients with MDRSP (from a total of 37 patients)
b) n = number of patients successfully treated (presumed eradication or eradication); N = number of patients with MDRSP (from a total of 37 patients)
c) One patient had a respiratory isolate that was resistant to penicillin and cefuroxime but a blood isolate that was intermediate to penicillin and cefuroxime. The patient is included in the database based on the respiratory isolate.
d) Azithromycin, clarithromycin, and erythromycin were the macrolide antimicrobials tested.

Screening Susceptibility

Clinical Success

Bacteriological Success

n/Na

%

n/Nb

%

Penicillin-resistant

21/21

100%c

21/21

100%c

2nd generation cephalosporin-resistant

25/26

96%c

25/26

96%c

Not all isolates were resistant to all antimicrobial classes tested. Success and eradication rates are summarized in Table 13.

a) One patient had a respiratory isolate resistant to 5 antimicrobials and a blood isolate resistant to 3 antimicrobials. The patient was included in the category resistant to 5 antimicrobials.

Clinical Success

Bacteriological Eradication Rate

Resistant to 3 antimicrobials

10/11 (90.9%)a

10/11 (90.9%)a

Resistant to 5 antimicrobials

7/7 (100%)a

7/7 (100%)a

14.5 Complicated Skin and Skin Structure Infections

Two randomized, active controlled trials of cSSSI were performed. A double-blind trial was conducted primarily in North America to compare the efficacy of sequential intravenous/oral moxifloxacin 400 mg once a day for 7 to 14 days to an intravenous/oral beta-lactam/beta-lactamase inhibitor control in the treatment of patients with cSSSI. This study enrolled 617 patients, 335 of which were valid for the efficacy analysis. A second open-label International study compared moxifloxacin 400 mg once a day for 7 to 21 days to sequential intravenous/oral beta-lactam/beta-lactamase inhibitor control in the treatment of patients with cSSSI. This study enrolled 804 patients, 632 of which were valid for the efficacy analysis. Surgical incision and drainage or debridement was performed on 55% of the moxifloxacin hydrochloride treated and 53% of the comparator treated patients in these studies and formed an integral part of therapy for this indication. Success rates varied with the type of diagnosis ranging from 61% in patients with infected ulcers to 90% in patients with complicated erysipelas. These rates were similar to those seen with comparator drugs. The overall success rates in the evaluable patients and the clinical success by pathogen are shown in Tables 14 and 15.

a) of difference in success rates between Moxifloxacin and comparator (Moxifloxacin - comparator)

Study

95% Confidence Intervala

a) methicillin susceptibility was only determined in the North American Study

Pathogen

106/129 (82.2%)

120/137 (87.6%)

14.6 Complicated Intra-Abdominal Infections

Two randomized, active controlled trials of cIAI were performed. A double-blind trial was conducted primarily in North America to compare the efficacy of sequential intravenous/oral moxifloxacin 400 mg once a day for 5 to 14 days to intravenous/piperacillin/tazobactam followed by oral amoxicillin/clavulanic acid in the treatment of patients with cIAI, including peritonitis, abscesses, appendicitis with perforation, and bowel perforation. This study enrolled 681 patients, 379 of which were considered clinically evaluable. A second open-label international study compared moxifloxacin 400 mg once a day for 5 to 14 days to intravenous ceftriaxone plus intravenous metronidazole followed by oral amoxicillin/clavulanic acid in the treatment of patients with cIAI. This study enrolled 595 patients, 511 of which were considered clinically evaluable. The clinically evaluable population consisted of subjects with a surgically confirmed complicated infection, at least 5 days of treatment and a 25 to 50 day follow-up assessment for patients at the Test of Cure visit. The overall clinical success rates in the clinically evaluable patients are shown in Table 16.

Study

Moxifloxacin Hydrochloride
n/N (%)

Comparator
n/N (%)

95% Confidence Intervala

a) of difference in success rates between moxifloxacin hydrochloride and comparator (moxifloxacin hydrochloride - comparator)
b) Excludes 2 patients who required additional surgery within the first 48 hours.
c) NA - not applicable

Abscess

40/57 (70.2%)

49/63 (77.8%)b

NAc

14.7 Plague

Efficacy studies of moxifloxacin hydrochloride could not be conducted in humans with pneumonic plague for ethical and feasibility reasons. Therefore, approval of this indication was based on an efficacy study conducted in animals and supportive pharmacokinetic data in adult humans and animals.[see

A randomized, blinded, placebo-controlled study was conducted in an African Green Monkey (AGM) animal model of pneumonic plague. Twenty AGM (10 males and 10 females) were exposed to an inhaled mean (± SD) dose of 100 ± 50 LD50 (range 92 to 127 LD50) of Yersinia pestis (CO92 strain) aerosol. The minimal inhibitory concentration (MIC) of moxifloxacin for the Y. pestis strain used in this study was 0.06 mcg/mL. Development of sustained fever for at least 4 hours duration was used as the trigger for the initiation of 10 days of treatment with either a humanized regimen of moxifloxacin or placebo. All study animals were febrile and bacteremic with Y. pestis prior to the initiation of study treatment. Ten of 10 (100%) of the animals receiving the placebo succumbed to disease between 83 to 139 h (mean 115 ± 19 hours) post treatment. Ten of 10 (100%) moxifloxacin-treated animals survived for the 30-day period after completion of the study treatment. Compared to the placebo group, mortality in the moxifloxacin group was significantly lower (difference in survival: 100% with a two-sided 95% exact confidence interval [66.3%, 100%], p-value<0.0001).

The mean plasma concentrations of moxifloxacin associated with a statistically significant improvement in survival over placebo in an AGM model of pneumonic plague are reached or exceeded in human adults receiving the recommended oral and intravenous dosage regimens. The mean (± SD) peak plasma concentration (Cmax) and total plasma exposure defined as the area under the plasma concentration-time curve (AUC) in human adults receiving 400 mg intravenously were 3.9 ± 0.9 mcg/mL and 39.3 ± 8.6 mcg*h/mL, respectively 0-24 in AGM following one- day administration of a humanized dosing regimen simulating the human AUC0-24 at a 400 mg dose were 4.4 ± 1.5 mcg/mL and 22 ± 8.0 mcg·h/mL, respectively. Clinical Pharmacology (12.3)]. The mean (± SD) peak plasma concentration and AUC

How Supplied16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 Moxifloxacin Tablets, USP

Moxifloxacin Tablets, USP are available as modified capsule shaped, dull red film-coated tablets containing 400 mg moxifloxacin. The tablet is debossed with E-18 on one side and plain on the other side.

Bottles of 30NDC 65862-603-30
Bottles of 1,000 NDC 65862-603-99
Cartons of 50 (5 x 10) Unit-dose TabletsNDC 65862-603-55

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Avoid high humidity.

Advise the patient to read the FDA-approved patient labeling ( Medication Guide)

Serious Adverse Reactions

Advise patients to stop taking moxifloxacin hydrochloride if they experience an adverse reaction and to call their healthcare provider for advice on completing the full course of treatment with another antibacterial drug.

Inform patients of the following serious adverse reactions that have been associated with moxifloxacin hydrochloride or other fluoroquinolone use:

Disabling and potentially irreversible serious adverse reactions that may occur together: Inform patients that disabling and potentially irreversible serious adverse reactions, including tendinitis and tendon rupture, peripheral neuropathies, and central nervous system effects, have been associated with use of moxifloxacin hydrochloride and may occur together in the same patient. Inform patients to stop taking moxifloxacin hydrochloride immediately if they experience an adverse reaction and to call their healthcare provider.

Tendinitis and Tendon Rupture: Instruct patients to contact their healthcare provider if they experience pain, swelling, or inflammation of a tendon, or weakness or inability to use one of their joints; rest and refrain from exercise; and discontinue moxifloxacin hydrochloride treatment. Symptoms may be irreversible. The risk of severe tendon disorder with fluoroquinolones is higher in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants.

Peripheral Neuropathies: Inform patients that peripheral neuropathies have been associated with moxifloxacin hydrochloride use, symptoms may occur soon after initiation of therapy and may be irreversible. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness and/or weakness develop, immediately discontinue moxifloxacin hydrochloride and tell them to contact their physician.

Central nervous system effects (for example, convulsions, dizziness, lightheadedness, increased intracranial pressure): Inform patients that convulsions have been reported in patients receiving fluoroquinolones, including moxifloxacin hydrochloride. Instruct patients to notify their physician before taking this drug if they have a history of convulsions. Inform patients that they should know how they react to moxifloxacin hydrochloride before they operate an automobile or machinery or engage in other activities requiring mental alertness and coordination. Instruct patients to notify their physician if persistent headache with or without blurred vision occurs.

Exacerbation of Myasthenia Gravis: Instruct patients to inform their physician of any history of myasthenia gravis. Instruct patients to notify their physician if they experience any symptoms of muscle weakness, including respiratory difficulties.

Hypersensitivity Reactions: Inform patients that moxifloxacin hydrochloride can cause hypersensitivity reactions, even following a single dose, and to discontinue the drug at the first sign of a skin rash, hives or other skin reactions, a rapid heartbeat, difficulty in swallowing or breathing, any swelling suggesting angioedema (for example, swelling of the lips, tongue, face, tightness of the throat, hoarseness), or other symptoms of an allergic reaction.

Hepatotoxicity: Inform patients that severe hepatotoxicity (including acute hepatitis and fatal events) has been reported in patients taking moxifloxacin hydrochloride. Instruct patients to inform their physician if they experience any signs or symptoms of liver injury including: loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of the skin and eyes, light colored bowel movements or dark colored urine.

Aortic aneurysm and dissection: Inform patients to seek emergency medical care if they experience sudden chest, stomach, or back pain.

Diarrhea: Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, instruct patients to contact their physician as soon as possible.

Prolongation of the QT Interval: Instruct patients to inform their physician of any personal or family history of QT prolongation or proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia; if they are taking any Class IA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents. Instruct patients to notify their physician if they have any symptoms of prolongation of the QT interval, including prolonged heart palpitations or a loss of consciousness.

Blood Glucose Disturbances: Inform the patients that if they are diabetic and are being treated with insulin or an oral hypoglycemic agent and a hypoglycemic reaction occurs, they should discontinue moxifloxacin hydrochloride and consult a physician.

Photosensitivity/Phototoxicity: Inform patients that photosensitivity/phototoxicity has been reported in patients receiving fluoroquinolones. Inform patients to minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while taking quinolones. If patients need to be outdoors while using quinolones, instruct them to wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. If a sunburn-like reaction or skin eruption occurs, instruct patients to contact their physician.

Antibacterial Resistance

Inform patients that antibacterial drugs including moxifloxacin hydrochloride should only be used to treat bacterial infections. They do not treat viral infections (for example, the common cold). When moxifloxacin hydrochloride is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by moxifloxacin hydrochloride or other antibacterial drugs in the future.

Administration Instructions

Inform patients that moxifloxacin tablets may be taken with or without food. Advise patients drink fluids liberally.

Inform patients that moxifloxacin tablets should be taken at least 4 hours before or 8 hours after multivitamins (containing iron or zinc), antacids (containing magnesium or aluminum), sucralfate, or didanosine buffered tablets for oral suspension or the pediatric powder for oral solution.

Advise patients that if a dose is missed, it should be taken anytime but not later than 8 hours prior to the next scheduled dose. If less than 8 hours remain before the next dose, the missed dose should not be taken and treatment should be continued as prescribed with the next scheduled dose. Double doses should not be taken to compensate for a missed dose.

Plague Studies

Inform patients given moxifloxacin hydrochloride for plague that efficacy studies could not be conducted in humans for feasibility reasons. Therefore, approval for plague was based on efficacy studies conducted in animals.

Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides

MEDICATION GUIDE

Moxifloxacin Tablets, USP

(mox'' i flox' a sin)

for oral use

Rx only

Read the Medication Guide that comes with moxifloxacin tablets before you start taking them and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about moxifloxacin tablets?

Moxifloxacin tablets is in a class of antibiotics called fluoroquinolones. Moxifloxacin tablets can cause serious side effects that can happen at the same time and could result in death. If you get any of the following serious side effects, you should stop taking moxifloxacin tablets and get medical help right away. Talk with your healthcare provider about whether you should continue to take moxifloxacin tablets.

1. Tendon rupture or swelling of the tendon (tendinitis).

Tendon problems can happen in people of all ages who take moxifloxacin tablets. Tendons are tough cords of tissue that connect muscles to bones. Symptoms of tendon problems may include:
Pain, swelling, tears and inflammation of tendons including the back of the ankle (Achilles), shoulder, hand, or other tendon sites.

The risk of getting tendon problems while you take moxifloxacin tablets is higher if you:

Are over 60 years of age.

Are taking steroids (corticosteroids).

Have had a kidney, heart or lung transplant.

Tendon problems can happen in people who do not have the above risk factors when they take moxifloxacin tablets.

Other reasons that can increase your risk of tendon problems can include:

Physical activity or exercise.

Kidney failure.

Tendon problems in the past, such as in people with rheumatoid arthritis (RA).

Stop taking moxifloxacin tablets immediately and call your healthcare provider right away at the first sign of tendon pain, swelling or inflammation. Stop taking moxifloxacin tablets until tendinitis or tendon rupture has been ruled out by your healthcare provider. Avoid exercise and using the affected area. The most common area of pain and swelling is in the Achilles tendon at the back of your ankle. This can also happen with other tendons.

Talk to your healthcare provider about the risk of tendon rupture with continued use of moxifloxacin tablets. You may need a different antibiotic that is not a fluoroquinolone to treat your infection.

Tendon rupture can happen while you are taking or after you have stopped taking moxifloxacin tablets. Tendon ruptures can happen within hours or days after taking moxifloxacin tablets and have happened up to several months after people have stopped taking their fluoroquinolone.

Stop taking moxifloxacin tablets immediately and get medical help right away if you get any of the following signs or symptoms of a tendon rupture:

Hear or feel a snap or pop in a tendon area.

Bruising right after an injury in a tendon area.

Unable to move the affected area or put weight on the area.

2. Changes in sensation and possible nerve damage (Peripheral Neuropathy). Damage to the nerves in arms, hands, legs, or feet can happen in people who take fluoroquinolones, including moxifloxacin tablets. Stop taking moxifloxacin tablets immediately and talk to your healthcare provider right away if you get any of the following symptoms of peripheral neuropathy in your arms, hands, legs, or feet:

pain

tingling

weakness

burning

numbness

Moxifloxacin tablets may need to be stopped to prevent permanent nerve damage.

3. Central Nervous System (CNS) effects . Seizures have been reported in people who take fluoroquinolone antibiotic medicines, including moxifloxacin tablets. Tell your healthcare provider if you have a history of seizures before you start taking moxifloxacin tablets. CNS side effects may happen as soon as after taking the first dose of moxifloxacin tablets. Stop taking moxifloxacin tablets immediately and talk to your healthcare provider right away if you get any of these side effects, or other changes in mood or behavior:

seizures

hear voices, see things, or sense things that are not there (hallucinations)

feel restless

tremors

feel anxious or nervous

confusion

depression

trouble sleeping

nightmares

feel lightheaded or dizzy

feel more suspicious (paranoia)

suicidal thoughts or acts

headaches that will not go away (with or without blurred vision)

4. Worsening of myasthenia gravis (a disease which causes muscle weakness). Fluoroquinolones like moxifloxacin tablets may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Tell your healthcare provider if you have a history of myasthenia gravis. Moxifloxacin tablets should not be used in people who have a history of myasthenia gravis. Call your healthcare provider right away if you have any worsening muscle weakness or breathing problems.

See the section "What are the possible side effects of moxifloxacin tablets?" for more information about side effects.

What are moxifloxacin tablets?

Moxifloxacin tablets are a fluoroquinolone antibiotic medicine used to treat certain types of infections caused by certain germs called bacteria in adults 18 years or older. These bacterial infections include:

Community Acquired Pneumonia

Uncomplicated Skin and Skin Structure Infections

Complicated Skin and Skin Structure Infections

Complicated Intra-Abdominal Infections

Plague

Acute Bacterial Sinusitis

Acute Bacterial Exacerbation of Chronic Bronchitis

Moxifloxacin tablets should not be used in people with acute bacterial sinusitis or acute bacterial exacerbation of chronic bronchitis if there are other treatment options available.

Studies of moxifloxacin tablets for use in the treatment of plague were done in animals only, because plague could not be studied in people.

It is not known if moxifloxacin tablet is safe and works in people under 18 years of age. Children have a higher chance of getting bone, joint, and tendon (musculoskeletal) problems while taking fluoroquinolone antibiotic medicines.

Sometimes infections are caused by viruses rather than by bacteria. Examples include viral infections in the sinuses and lungs, such as the common cold or flu. Antibiotics, including moxifloxacin tablets, do not kill viruses.

Call your healthcare provider if you think your condition is not getting better while you are taking moxifloxacin tablets.

Who should not take moxifloxacin tablets?

Do not take moxifloxacin tablets if you have ever had an allergic reaction to moxifloxacin, other fluoroquinolone antibiotics, or any of the ingredients in moxifloxacin tablets. Ask your healthcare provider if you are not sure. See the end of this Medication Guide for a complete list of ingredients in moxifloxacin tablets.

What should I tell my healthcare provider before taking moxifloxacin tablets?

See "What is the most important information I should know about moxifloxacin tablets?"

Tell your healthcare provider about all your medical conditions, including if you:

Have tendon problems. Moxifloxacin tablets should not be used in people who have a history of tendon problems.

Have a disease that causes muscle weakness (myasthenia gravis). Moxifloxacin tablets should not be used in people who have a history of myasthenia gravis.

Have central nervous system problems (such as epilepsy).

Have nerve problems. Moxifloxacin tablets should not be used in people who have a history of a nerve problem called peripheral neuropathy.

Have or anyone in your family has an irregular heartbeat, especially a condition called "QT prolongation".

Have low blood potassium (hypokalemia).

Have a slow heartbeat (bradycardia).

Have a history of seizures.

Have kidney problems.

Have rheumatoid arthritis (RA) or other history of joint problems.

Are pregnant or plan to become pregnant. It is not known if moxifloxacin tablets will harm your unborn baby.

Are breastfeeding or plan to breastfeed. It is not known if moxifloxacin hydrochloride passes into breast milk. You and your healthcare provider should decide whether you will take moxifloxacin tablets or breastfeed.

Have diabetes or problems with low blood sugar (hypoglycemia).

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, herbal and dietary supplements. Moxifloxacin tablets and other medicines can affect each other causing side effects.

Especially tell your healthcare provider if you take:

A Non-Steroidal Anti-Inflammatory Drug (NSAID). Many common medicines for pain relief are NSAIDs. Taking an NSAID while you take moxifloxacin tablets or other fluoroquinolones may increase your risk of central nervous system effects and seizures.

A blood thinner (warfarin, Coumadin, Jantoven).

A medicine to control your heart rate or rhythm (antiarrhythmic). See "What are the possible side effects of moxifloxacin tablets?"

An anti-psychotic medicine.

A tricyclic antidepressant.

An oral anti-diabetes medicine or insulin.

Erythromycin.

A water pill (diuretic).

A steroid medicine. Corticosteroids taken by mouth or by injection may increase the chance of tendon injury. See "What is the most important information I should know about moxifloxacin tablets?"

Certain medicines may keep moxifloxacin tablets from working correctly. Take moxifloxacin tablets either 4 hours before or 8 hours after taking these products:

An antacid, multivitamin, or other product that has magnesium, aluminum, iron, or zinc

Sucralfate (Carafate)

Didanosine oral suspension or solution

Ask your healthcare provider if you are not sure if any of your medicines are listed above.

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

How should I take moxifloxacin tablets?

Take moxifloxacin tablets 1 time each day exactly as prescribed by your healthcare provider.

Take moxifloxacin tablets at about the same time each day.

Moxifloxacin tablets can be taken with or without food.

If you miss a dose of moxifloxacin tablets and it is:

8 hours or more until your next scheduled dose, take your missed dose right away. Then take the next dose at your regular time.

less than 8 hours until your next scheduled dose, do not take the missed dose. Take the next dose at your regular time.

Do not take 2 doses of moxifloxacin tablets to make up for a missed dose. If you are not sure about when to take moxifloxacin tablets after a missed dose, ask your doctor or pharmacist.

Drink plenty of fluids while taking moxifloxacin tablets.

Do not skip any doses, or stop taking moxifloxacin tablets even if you begin to feel better, until you finish your prescribed treatment, unless:

You have tendon problems. See "What is the most important information I should know about moxifloxacin tablets?").

You have nerve problems. See "What is the most important information I should know about moxifloxacin tablets?"

You have central nervous system problems. See "What is the most important information I should know about moxifloxacin tablets?"

You have a serious allergic reaction (see "What are the possible side effects of moxifloxacin tablets?"), or your healthcare provider tells you to stop taking moxifloxacin tablets.

This will help make sure that all of the bacteria are killed and lower the chance that the bacteria will become resistant to moxifloxacin tablets. If this happens, moxifloxacin tablets and other antibiotic medicines may not work in the future.

If you take too much moxifloxacin hydrochloride, call your healthcare provider or get medical help immediately.

What should I avoid while taking moxifloxacin tablets?

Moxifloxacin tablets can make you feel dizzy and lightheaded. Do not drive, operate machinery, or do other activities that require mental alertness or coordination until you know how moxifloxacin tablets affect you.

Avoid sunlamps, tanning beds, and try to limit your time in the sun. Moxifloxacin tablets can make your skin sensitive to the sun (photosensitivity) and the light from sunlamps and tanning beds. You could get severe sunburn, blisters or swelling of your skin. If you get any of these symptoms while taking moxifloxacin tablets, call your healthcare provider right away. You should use a sunscreen and wear a hat and clothes that cover your skin if you have to be in sunlight.

What are the possible side effects of moxifloxacin tablets?

Moxifloxacin tablets can cause side effects that may be serious or even cause death, including:

See "What is the most important information I should know about moxifloxacin tablets?"

Serious heart rhythm changes (QT prolongation and torsade de pointes). Tell your healthcare provider right away if you have a change in your heartbeat (a fast or irregular heartbeat), or if you faint. Moxifloxacin tablets may cause a rare heart problem known as prolongation of the QT interval. This condition can cause an abnormal heartbeat and can be very dangerous. The chances of this event are higher in people:

Who are elderly

With a family history of prolonged QT interval

With low blood potassium (hypokalemia)

Who take certain medicines to control heart rhythm (antiarrhythmics)

Serious allergic reactions. Allergic reactions can happen in people taking fluoroquinolones, including moxifloxacin tablets, even after only 1 dose. Stop taking moxifloxacin tablets and get emergency medical help right away if you get any of the following symptoms of a severe allergic reaction:

Hives

Trouble breathing or swallowing

Swelling of the lips, tongue, face

Throat tightness, hoarseness

Fast heartbeat

Faint

Yellowing of the skin or eyes. Stop taking moxifloxacin tablets and tell your healthcare provider right away if you get yellowing of your skin or white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to moxifloxacin tablets (a liver problem).

Skin rash. Skin rash may happen in people taking moxifloxacin tablets even after only 1 dose. Stop taking moxifloxacin tablets at the first sign of a skin rash and call your healthcare provider. Skin rash may be a sign of a more serious reaction to moxifloxacin tablets.

Aortic aneurysm and dissection. Tell your healthcare provider if you have ever been told that you have a swelling of the large artery that carries blood from the heart to the body (aortic aneurysm). Get emergency medical help right away if you have sudden chest, stomach, or back pain.

Intestine infection (Pseudomembranous colitis). Pseudomembranous colitis can happen with most antibiotics, including moxifloxacin tablets. Call your healthcare provider right away if you get watery diarrhea, diarrhea that does not go away, or bloody stools. You may have stomach cramps and a fever. Pseudomembranous colitis can happen 2 or more months after you have stopped taking moxifloxacin tablets.

Changes in blood sugar. People who take moxifloxacin tablets and other fluoroquinolone medicines with oral anti-diabetes medicines or with insulin can get low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia). Follow your healthcare provider's instructions for how often to check your blood sugar. If you have diabetes and you get low blood sugar while taking moxifloxacin tablets, stop taking moxifloxacin tablets and call your healthcare provider right away. Your antibiotic medicine may need to be changed.

Sensitivity to sunlight (photosensitivity). See "What should I avoid while taking moxifloxacin tablets?" The most common side effects of moxifloxacin tablets include:

nausea

diarrhea

headache

dizziness

These are not all the possible side effects of moxifloxacin tablets. Tell your healthcare provider about any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store moxifloxacin tablets?

Store moxifloxacin tablets at 20° to 25°C (68° to 77°F).

Keep moxifloxacin tablets away from moisture (humidity).

Keep moxifloxacin tablets and all medicines out of the reach of children.

General Information about the safe and effective use moxifloxacin tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use moxifloxacin tablets for a condition for which it is not prescribed. Do not give moxifloxacin tablets to other people, even if they have the same symptoms that you have. They may harm them.

This Medication Guide summarizes the most important information about moxifloxacin tablets. If you would like more information about moxifloxacin tablets, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about moxifloxacin tablets that is written for health professionals.

What are the ingredients in moxifloxacin tablets?

Active ingredient: moxifloxacin hydrochloride

Inactive ingredients: hypromellose, iron oxide red, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, sodium starch glycolate, and titanium dioxide.

Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides

Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520

Manufactured by:
Aurobindo Pharma Limited
Hyderabad-500 038, India

All brands listed are the trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited.

For more information call Aurobindo Pharma USA, Inc. at 1-866-850-2876.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Revised: 06/2020

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 400 mg (30 Tablet Bottle)

NDC 65862-603-30 PHARMACIST: Dispense the Medication Guide
Rx only
Moxifloxacin Tablets, USP
400 mg

AUROBINDO 30 Tablets
provided separately to each patient.

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 400 mg Blister Carton (5 x 10 Unit-dose)

NDC 65862-603-55 PHARMACIST: Dispense the Medication Guide provided separately to each
Rx only
Moxifloxacin Tablets, USP
400 mg

AUROBINDO 50 (5 x 10) Unit-dose Tablets
patient.

MOXIFLOXACIN HYDROCHLORIDE
moxifloxacin hydrochloride tablet, film coated

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Strength

MOXIFLOXACIN HYDROCHLORIDE (MOXIFLOXACIN)

MOXIFLOXACIN

400 mg

Inactive Ingredients

Ingredient Name

Strength

Product Characteristics

Contains

Marketing Information

Marketing Category

Application Number or Monograph Citation

Marketing Start Date

Marketing End Date

ANDA

ANDA202632

03/04/2014

Labeler - Aurobindo Pharma Limited (650082092)

Establishment

Name

Address

ID/FEI

Operations

Aurobindo Pharma Limited

650381903

ANALYSIS, MANUFACTURE

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Antibacterial (Quinolone)

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Moxifloxacin Hydrochloride - Tablet (film coated) | NIH

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Chemical Image: (Click to enlarge) HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use MOXIFLOXACIN TABLETS safely and effectively. See full prescribing information for MOXIFLOXACIN TABLETS. MOXIFLOXACIN tablets, for oral use Initial U.S.

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- Caspofungin was approved by the FDA by working to treat invasive aspergillosis or yeast infections found in adult and pediatric patients (around 3 months of age and older) who are known to be intolerant of other types of therapies. Treating such infections in the blood, stomach, lungs and esophagus, it helps to care for certain fungal infections that were not previously successful with other medications.
In terms of the non-approved FDA indications, this includes the patient getting Oropharyngeal candidiasis (thrush), infectious arthritis, and the possibility of cardiovascular system infections.
- With the medication, it works in blocking or stopping the synthesis of the fungal cell wall component beta-(1,3)-D-glucan. Caspofungin utilizes the non-competive inhibition of the enzyme β(1,3)-d-glucan synthase, allowing for the medication to therefore reduce the activity of said enzyme and bind well to the enzyme regardless of if or not it has already found a substrate. It is part of the new class of antifungal agents, the echinocandins, and works almost like a new form of therapy because of its novel mechanism of action.
- The cost feels appropriate as the medication works to be solely administered by the IV route as they are poorly bioavailable for oral usage. Due to it being a new form of treatment and the IV infusion needing to be carefully looked after so it takes for over an hour, it requires attention to not administer it co-infused with other medications. Due to it's relatively low incidence of adverse effects, I would consider it a worthy investment for the patients if one is struggling with untreated fungal infections.

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Caspofungin - StatPearls - NCBI Bookshelf

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Caspofungin is a drug in the echinocandins class of medications used to manage and treat several medical conditions. These conditions include febrile neutropenia, candida infections, invasive candidiasis, esophageal candidiasis, and invasive aspergillosis. This activity reviews the mechanism of acti…

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Meloxicam is a severe painkiller that is FDA approved as it's been supported with a Phase 3 safety study. It serves it's purpose as a painkiller but does have many side effects that are rare affecting 2% of people who use it.

Meloxicam is about $2 for 100mg with only 7.5 mg dosages each day, it's an inexpensive drug. Since meloxicam is cheap and serves its purpose, it's a worthwhile medication.

Meloxicam is an NSAID (nonsteroidal anti-inflammatory drug) that can be taken as an oral tablet or pill, and can also be injected as a liquid intravenously. How it works is it blocks a chemical called cyclo-oxygenase (COX) enzymes that produce prostaglandin which cause inflammation or pain.

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Benazepril is newer drug that has been approved to help with treatment for people with Hypertension or high-blood pressure. Benazepril works by decreasing certain chemicals that tighten bloodstreams, which helps create a smoother and easier blood flow through the body. The drug is in the class ACE Inhibitors or angiotensin-converting enzyme inhibitors. The price for Benazepril changes vastly from brand to generic name prices. The average price for a brand-name bottle of 20mg prescription of Benazepril is about $20, but generic bottles do go for a cheaper prices, which doesn't cause many financial problems. While the medication does treat hypertension if you have a history of angioedema, liver, kidney, or heart problems you should not be taking this medication as it may be fatal. In addition to that if your are pregnant or 6 years or younger it is not recommended for consumption of the medication.

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Perindopril inhibits angiotensin-converting enzymes (ACE) by relaxing the blood vessels and decreasing blood volume. It allows the blood to move much more smoothly by preventing the production of naturally-produced chemicals that tighten blood vessels. Perindopril is in a class of ACE inhibitors.
FDA approved indications for perindopril include hypertension and for those with coronary heart disease. Some contraindications for perindopril include angioedema or any history of hereditary angioedema.
The cost of 30, 4mg tablets of perindopril is about $72. This is not a relatively overly-expensive drug, and it may be covered by certain insurance companies.

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Prescription lansoprazole is used to treat the symptoms of gastroesophageal reflux disease (GERD). Based on the Drug History at FDA, it was first identified in 1995, had new dosage form three times, and a new manufacturer once. Cost of the medication (oral delayed release capsules) is around $26 for a supply of 30 capsules. The oral tablet, disengrating is 15 mg starts from $545.46 for 100. It seems to be worth the price since 55% of people claimed to have positive effects.

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Prescription lansoprazole is used to treat the symptoms of gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and possible injury of the esophagus (the tube between the throat and stomach) in adults and children 1 year of age and older. Prescription lansoprazole is used to treat the damage from GERD in adults and children 1 year of age and older. Prescription lansoprazole is used to allow the esophagus to heal and prevent further damage to the esophagus in adults with GERD. Prescription lansoprazole is also used to treat ulcers (sores in the lining of the stomach or intestine), to prevent more ulcers from developing in adults whose ulcers have already healed, and to decrease the risk that adults who are taking nonsteroidal anti-inflammatory drugs (NSAIDs) will develop ulcers. Prescription lansoprazole is also used to treat conditions where the stomach produces too much acid, such as Zollinger-Ellison syndrome in adults. Prescription lansoprazole is also used in combination with other medications to treat and prevent stomach ulcers caused by a certain type of bacteria ( H. pylori) in adults. Nonprescription (over-the-counter) lansoprazole is used to treat frequent heartburn (heartburn that occurs two or more days per week) in adults. Lansoprazole is in a class of medications called proton pump inhibitors. It works by decreasing the amount of acid made in the stomach.

Prescription lansoprazole comes as a delayed-release (releases the medication in the intestine to prevent break-down of the medication by stomach acids) capsule and as a delayed-release orally disintegrating (dissolving) tablet to take by mouth. Nonprescription lansoprazole comes as a delayed-release capsule to take by mouth. Prescription lansoprazole is usually taken once a day, before a meal. When taken in combination with other medications to eliminate H. pylori, prescription lansoprazole is taken twice a day (every 12 hours) or three times a day (every 8 hours), before a meal, for 10 to 14 days. Nonprescription lansoprazole is usually taken once a day, in the morning before eating for 14 days. If needed, additional 14-day treatments may be repeated, not more often than once every 4 months. Take lansoprazole at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take lansoprazole exactly as directed. Do not take more or less of it or take it more often or for a longer time than prescribed by your doctor or stated on the package. Tell your doctor if you have taken nonprescription lansoprazole for a longer period of time than stated on the package.

Swallow the prescription capsules whole; do not split, chew, or crush them. If you have difficulty swallowing capsules, you may open the capsule, sprinkle the granules on 1 tablespoon of applesauce, Ensure ® pudding, cottage cheese, yogurt, or strained pears and swallow the mixture immediately without chewing. You can also open a capsule and pour the contents into 2 ounces (60 milliliters) of orange juice, apple juice or tomato juice, mix briefly, and swallow immediately. After you swallow the mixture, rinse the glass with some additional juice and drink immediately. Then rinse the glass with juice at least two more times and drink the juice to be sure that you wash all the medication out of the glass.

Swallow the nonprescription capsules whole with a glass of water. Do not split, chew, or crush them.

Do not break, cut or chew the orally disintegrating tablets. Place a tablet on your tongue and wait up to one minute for it to dissolve. After the tablet dissolves, swallow it with or without water. If you cannot swallow the tablet, you may place it in an oral syringe, draw up 4 mL of water for a 15 mg tablet or 10 mL of water for a 30-mg tablet, shake the syringe gently to dissolve the tablet, and squirt the contents into your mouth immediately. Then draw an additional 2 mL of water into the syringe, shake gently, and squirt that water into your mouth. Do not swallow the mixture more than 15 minutes after you dissolve the tablet.

The capsule contents and orally disintegrating tablets can both be given through a feeding tube. If you have a feeding tube, ask your doctor how you should take the medication. Follow these directions carefully.

Do not take nonprescription lansoprazole for immediate relief of heartburn symptoms. It may take 1 to 4 days for you to feel the full benefit of the medication. Call your doctor if your symptoms get worse or do not improve after 14 days or if your symptoms return sooner than 4 months after you finish your treatment. Do not take nonprescription lansoprazole for longer than 14 days or treat yourself with lansoprazole more often than once every 4 months without talking to your doctor.

Continue to take lansoprazole even if you feel well. Do not stop taking prescription lansoprazole without talking to your doctor. If your condition does not improve or gets worse, call your doctor.

Ask your doctor or pharmacist for a copy of the manufacturer's information for the patient.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Before taking lansoprazole,

tell your doctor and pharmacist if you are allergic to lansoprazole, any other medications, or any of the ingredients in lansoprazole capsules or orally disintegrating tablets. Ask your doctor or pharmacist for a list of the ingredients.

tell your doctor if you are taking rilpivirine (Edurant, in Complera, Odefsey). Your doctor will probably tell you not to take lansoprazole if you are taking this medication.

tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: certain antibiotics, including anticoagulants (blood thinners) such as warfarin (Coumadin), atazanavir (Reyataz), dasatinib (Sprycel), digoxin (Lanoxicaps, Lanoxin), diuretics ('water pills'), erlotinib (Tarceva), iron supplements, itraconazole (Onmel, Sporonox), ketoconazole (Nizoral), lopinavir/ritonavir (Kaletra), methotrexate (Trexall, Xatmep), mycophenolate mofetil (Cellcept), nelfinavir (Viracept), nilotinib (Tasigna), rifampin (Rifadin, in Rifater), ritonavir (Norvir, in Viekira XR), saquinavir (Invirase), tacrolimus (Prograf), theophylline (Theo-24, TheoChron), and voriconazole (Vfend). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.

tell your doctor what herbal products you are taking, especially St. John's wort. Your doctor may tell you not to take St. John's wort while taking lansoprazole.

if you are taking sucralfate (Carafate), take it at least 30 minutes after you take lansoprazole.

tell your doctor if you have or have ever had a low level of magnesium in your blood, low levels of vitamin B-12 in your body, osteoporosis, an autoimmune disease (condition in which the body attacks its own organs, causing swelling and loss of function) such as systemic lupus erythematosus, or liver disease.

if you plan to take nonprescription lansoprazole, first tell your doctor if your heartburn has lasted 3 months or longer or if you have experienced any of the following symptoms: lightheadedness, sweating, or dizziness along with your heartburn; chest pain or shoulder pain; shortness of breath or wheezing; pain that spreads to your arms, neck, or shoulders; unexplained weight loss; nausea; vomiting, especially if the vomit is bloody; stomach pain; difficulty swallowing food or pain when you swallow food; or black or bloody stools. You may have a more serious condition that cannot be treated with a nonprescription medication.

tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking lansoprazole, call your doctor.

if you are 70 years of age or older, do not take this medication for a longer period of time than recommended on the product label or by your doctor.

if you have phenylketonuria (PKU, an inherited condition in which a special diet must be followed to prevent damage to your brain that can cause severe intellectual disability), you should know that the orally disintegrating tablets may contain aspartame, which forms phenylalanine.

Unless your doctor tells you otherwise, continue your normal diet.

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your dosing schedule. Do not take a double dose to make up for a missed one.

Lansoprazole may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:

rash

blistering or peeling skin

hives

swelling of the eyes, face, lips, mouth, tongue, or throat

difficulty breathing or swallowing

hoarseness

increased or decreased urination, blood in urine, fatigue, nausea, loss of appetite, fever, rash, or joint pain

irregular, fast, or pounding heartbeat

excessive tiredness

dizziness

lightheadedness

muscle spasms, cramps, or weakness

jitteriness

uncontrollable shaking of a part of the body

seizures

severe diarrhea with watery stools, stomach pain, or fever that does not go away

rash on cheeks or arms that is sensitive to sunlight

Lansoprazole may cause other side effects. Call your doctor if you have any unusual problems while you are taking the medication.

People who take proton pump inhibitors such as lansoprazole may be more likely to fracture their wrists, hips, or spine than people who do not take one of these medications. People who take proton pump inhibitors may also develop fundic gland polyps (a type of growth on the stomach lining). These risks are highest in people who take high doses of one of these medications or take them for 1 year or longer. Talk to your doctor about the risk of taking lansoprazole.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online ( http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location - one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website ( http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

Keep all appointments with your doctor and the laboratory. Your doctor may order certain laboratory tests before and during your treatment, especially if you have severe diarrhea.

Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking lansoprazole.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Last Revised - 01/15/2022

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Prescription lansoprazole is used to treat the symptoms of gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and possible injury of the esophagus (the tube between the throat and stomach) in adults and children 1 year of age and older.

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Citalopram is an FDA-approved antidepressant, only found in tablet dosage form. It has also been used for non-FDA-approved uses such as for panic disorders, OCD, alcohol use disorder, and coronary arteriosclerosis. Citalopram is thought to work by increasing serotonin levels in the brain, and belongs to a class of medicines called selective serotonin reuptake inhibitors (SSRIs). Citalopram can be compared to other SSRIs such as escitalopram and fluoxetine, since they all serve the same purpose of increasing serotonin.

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Miglitol had been approved as supplementary to diet and exercise in order to ameliorate glycemic control for type 2 diabetic adults. It is an oral medication belonging to the class of drugs called alpha-glucosidase inhibitors. It usually taken 3 times day per meal. The cost of for 30 25mg tablets is around $137. I think it isn't worth the price as it doesn't lower your A1C. There are other medications that are more effective.

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REALLY LOW BLOOD SUGAR (HYPOGLYCEMIA)

Risk factors: Use of other blood sugar-lowering medications | Poor kidney function

Glyset (miglitol) can cause really low blood sugar if you're taking it with other drugs to control your diabetes (like insulin or sulfonylureas). Make sure you have glucose tablets or gel to treat low blood sugar since foods that have sucrose won't work with Glyset (miglitol).

KIDNEY PROBLEMS

Glyset (miglitol) is not recommended for people with poor kidney function. Talk to your provider if you've had problems with your kidneys before. They'll probably give you a different medication.

STOMACH AND INTESTINE PROBLEMS

Risk factors: Inflammatory bowel disease | Ulcers | Bowel obstruction or blockage | Trouble absorbing or digesting food

Don't use Glyset (miglitol) if you've had problems with your intestines, like inflammatory bowel disease, ulcers or blockages, or you have problems with digesting or absorbing food. Talk to your provider about choosing a different medication.

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Glyset (miglitol): Basics, Side Effects & Reviews

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Risk factors: Use of other blood sugar-lowering medications | Poor kidney function Glyset (miglitol) can cause really low blood sugar if you're taking it with other drugs to control your diabetes (like insulin or sulfonylureas). Make sure you have glucose tablets or gel to treat low blood sugar since foods that have sucrose won't work with Glyset (miglitol).

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1. The NDA for this particular drug was not approved at first due to insufficient evidence of its effectiveness and the lack of consistency in treatments varying from men to women. Once approved, the FDA narrowed the target patients from both genders to only males over 18.
2. Balsalazide is a generic drug established to be part of the class of aminosalicylates: which decreases swelling in the colon.
5. The cost of balsalazide varies from 50 - 200+ dollars. I believe that this is not worth the price. There are various other aminosalicytes that do the job and are significantly cheaper. For example, sulfasalazine is another drug from the same group costing only about 15 - 55 dollars.

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By Abbigail Tago
What is the cost to the patient (per treatment or per time period, if appropriate)? Do you think it is worth the price? Why or why not?
The cost is about $13 for 60 tablets so it is relatively inexpensive for the job that it does. You do not need to take a large amount of tablets over a short period of time so the 60 tablets should go a long way.
What is the mechanism of its therapeutic effect? Is this drug a member of an established class, or is it a brand new form of therapy?
Meloxicam works by blocking the effects of the COX or cyclo-oxygenase enzyme, and dulls the pain receptors in the injured area. By blocking the natural course of action the body takes when injured it reduces the swelling and pain for the patient. Meloxicam is a nonsteroidal anti-inflammatory drug, the same type of drug as Advil and Tylenol.
What are the "FDA-approved" and "unapproved" indications for this drug?
The FDA has approved meloxicam for the use against osteoarthritis, rheumatoid arthritis, and juvenile rheumatoid arthritis. It is a prescription drug and cannot be used on patients who have asthma, urticaria, or anyone who has had an adverse reaction to a drug in the anti-inflammatory class.

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-When injected IP, Tyloxapol blocks plasma lipolytic activity, which causes the breakdown of triglyceride-rich lipoproteins
-One use of Tyloxapol is to clear the upper and lower airways, so in way it can be compared to that of an inhaler, however Tyloxapol is used to clear mucus or pus stuck in the airways.
-100 Mg of Tyloxapol runs for about $100 USD, while 500 Mg of it runs for about $300 USD. Considering there are easier ways to get what Tyloxapol does quicker and more effeciently, I think that the price is unreasonable.

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-The FDA has approved tramadol to be used and indicated for the treatment of moderate to moderately severe chronic pain in adults. It will be used for patients who require treatment for an extended period of time. On the other hand, the FDA does not approve of using tramadol on children and has restricted and strong discourages women who are breastfeeding to use it
-The manufacturer claims that tramadol is a safer opioid. When comparing it to ibuprofen, there was an actual scientific trial done to see results (described on pubmed.gov). Eighty patients who had lower abdomen problems were split into two groups: one taking ibuprofen and one taking tramadol. The results were that both regimens were well tolerated and there were no significant differences. The experiment concluded that oral tramadol is safe and effective. However, after doing further research, tramadol is only safe in a controlled state. It is very easy to overdose on tramadol and there are very bad side effects which could be fatal.
-The cost of tramadol is about $50 for 60 tablets and the price can even be covered if you carry insurance. It is relatively inexpensive so I think it is worth the price compared to other types of pain medications.

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Nizatidine is used to treat and prevent ulcers and other conditions that make too much stomach acid. Nizatidine can be found for about $70 for 60, 150mg capsules, which could be pretty expensive, but is worth the price because its effective.

Nizatidine inhibits the binding of histamine to the H2-receptors on the gastric basolateral membrane of parietal cells, which helps reduce basal and nocturnal gastric acid secretions. This drug belongs to the known class H2 blockers.

Nizatidine can be compared to esomeprazole , which is also used to treat frequent heartburn and too much stomach acid. This drug can be used to treat gastroesophageal reflux disease (GERD). It can also lower the risk of bleeding after endoscopy in patients with ulcers.

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Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location - one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website ( http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

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Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

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Zaleplon is around 21$ for ten capsules of it with each capsule containing around 10mg of the drug it self. I think its worth it at this price because all through the price is a little high the family of drugs that this medicine falls under is relatively new, and the low amount given is because of the addictive possibility.

Zaleplon is proven to help with insomnia in the short term which is FDA approved however it does also come with the risk of addiction as well as that it cant help you stay asleep, only fall asleep.

Zaleplon is a part of the Nonbenzodiazepine class of sedatives. These are a relatively new class of drugs for sedative purposes and they are normally used for the short term treatment of insomnia.

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Sonata Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD

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Find patient medical information for Sonata oral on WebMD including its uses, side effects and safety, interactions, pictures, warnings and user ratings.

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Cilostazol is a selective inhibitor of phosphodiesterase type 3 (PDE3) with therapeutic focus on increasing cAMP. Cilostazol improves the flow of blood through the blood vessels. It is used to reduce leg pain caused by poor circulation making it possible to walk farther before having to rest because of leg pain. The cost for cilostazol oral tablet 100 mg is around $33 for a supply of 50, depending on the pharmacy you visit. I personally do think that it is worth it, as according to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663440/, taking 100 mg of cilostazol twice a day led to a 76% improvement in maximal walking distance from the baseline compared with a 20% improvement for the placebos. According to The American Journal of Medicine, when compared to its competitor, "Cilostazol was significantly better than pentoxifylline or placebo for increasing walking distances in patients with intermittent claudication, but was associated with a greater frequency of minor side effects." It is more effective, but more likely to give you minor side effecs.

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Abstract

Peripheral arterial disease (PAD) is a major health problem affecting millions of patients worldwide. Many will suffer from intermittent claudication (IC), which leads to marked impairment of quality of life (QoL). Besides surgical and endovascular interventions to improve limb-specific outcomes, pharmacotherapy is an effective tool in the treatment of IC. Cilostazol, a Federal Drug Administration-approved medication for the treatment of IC, has demonstrated consistent efficacy in improving exercise capacity and overall health-related QoL. This manuscript will review the pharmacokinetics, safety, and efficacy of cilostazol in the treatment of patients with IC as well as compare this agent with other proven non-invasive therapies for PAD.

Keywords: peripheral arterial disease, cilostazol, intermittent claudication, supervised exercise therapy

Introduction

Peripheral arterial disease (PAD) is most commonly due to atherosclerosis, affects millions of patients worldwide, and is associated with significant morbidity and mortality (). PAD is defined as an obstruction of the infra-renal abdominal aorta and lower extremity arteries that reduces arterial flow during exercise and/or at rest. Intermittent claudication (IC) is the most common symptom in patients with PAD and is associated with exercise-induced discomfort in the muscles, relieved with rest; this may lead to marked impairment of quality of life (QoL) and daily activities. However, IC is one symptom. Many patients have limited walking distance (atypical claudication) but do deny IC, ie, fatigue or tired or aching legs. Investigators have found that peak walking distance, peak walking time, and peak heart rate are all significantly reduced in PAD patients versus healthy controls (Hiatt et al 1992).

Following the general principle that more intense activities require greater oxygen consumption, the requirement for oxygen consumption in a healthy person increases from 4 mL/kg/min at rest to approximately 7 mL/kg/min for self-care, 9 mL/kg/min for house-cleaning, 13 mL/kg/min for dancing, 14 mL/kg/min for golf, 24 mL/kg/min for jogging, and 31 mL/kg/min for marathon running (Ainsworth et al 2000). Considering that the peak oxygen capacity for an individual with PAD rarely exceeds 14.8 ± 0.8 mL/kg/min (Hiatt et al 1992), it appears that even when working at maximum capacity, many PAD patients may lack the ability to complete the activities of daily life. Subjects with IC exhibited a mean exercise duration of 10.6 minutes, which was approximately half that demonstrated by age-matched controls (p < 0.05) (Hiatt et al 1987). In addition, the PAD-associated deficits in exercise performance were accompanied by a roughly 50% decline in oxygen capacity, indicating that the level of impairment in PAD is comparable to that associated with class III congestive heart failure ().

A number of drugs () have been tested for IC therapy, with mostly disappointing results. Among the multitude of failed pharmacotherapies, prostaglandins appeared to have promising potential more than a decade ago but more recently have been shown to have only modest efficacy (). Antiplatelet medications, serotonin blockers, and vasodilators have also been studied, but thus far none have demonstrated significant benefits for patients with IC (). In the US, two agents have been approved for such an indication (cilostazol and pentoxifylline), but only cilostazol has demonstrated consistent efficacy in both extending exercise capacity and improving QoL (Beebe et al 1999; Dawson et al 2000; Money et al 1998). As a result, cilostazol may be the most clinically effective pharmacologic option for IC in US patients. This manuscript will provide an overview of the pharmacology, metabolism, safety, and efficacy of cilostazol in the treatment of patients with typical IC and will compare this agent to other proven, non-invasive therapies for PAD.

Pharmacology

Cilostazol () was approved by the Federal Drug Administration (FDA) in 1999 for the treatment of IC (Kumar and Bhattacharya 2007). It became available in generic form in 2006. It is a reversible selective inhibitor of phosphodiesterase (PDE) type III. Similar to other members of its class, one of the primary effects of cilostazol is an increase in cyclic adenosine monophosphate (cAMP) in platelets, vascular smooth muscle, endothelial cells, and other PDE-III-rich cells, which may lead to a number of beneficial outcomes (). Among these potential benefits, cilostazol has been shown to inhibit platelet activation/aggregation, reduce thrombosis, enhance vasodilation (Chapman and Goa 2003), and induce nitric oxide (NO) production (Hashimoto et al 2006) as well as inhibit smooth muscle cell proliferation (Takahashi et al 1992; Hayashi et al 2000), increase limb blood flow (Elam et al 1998), increase plasma high-density lipoprotein-cholesterol (HDL-C) (Lee et al 2001) and reduce plasma triglyceride levels (Elam et al 1998), potentiate angiogenesis (Lee et al 2001), and reduce inflammation (Agrawal et al 2007). Although the exact mechanism for cilostazol's benefits in IC remains unknown, any of these properties could potentially contribute to the symptomatic efficacy associated with this pharmacologic agent.

Table 2

Inhibits platelet activation and aggregation

Reduces thrombosis

Inhibits smooth muscle cell contraction

Inhibits smooth muscle cell proliferation

Increases limb blood flow

Increases plasma high density lipoprotein-cholesterol levels

Reduces plasma triglyceride levels

Potentiates angiogenesis

Reduces inflammation

In vitro and/or ex vivo studies using platelets from healthy volunteers, in patients with atherosclerosis and in patients with cerebrovascular disease, have shown that cilostazol reversibly inhibits the primary and secondary stages of platelet aggregation (Chapman and Goa 2003). Cilostazol has also been found to be superior to aspirin in suppressing platelet aggregation ex vivo and to have some effects on platelet function more potent than the antiplatelet drug ticlopidine (Ikeda et al 1987). Cilostazol has been shown to reduce platelet aggregation without prolonging bleeding time (Tamai et al 1999). While selectively inhibiting the function of human platelets, cilostazol does not affect the production of prostacyclin and does not inhibit the function of vascular endothelial cells (Tani et al 1992). Cilostazol also produces vasodilatation by inhibiting smooth muscle cell contraction secondary to the elevation of cAMP levels and the blocking of calcium ion release (Chapman and Goa 2003). Cilostazol has also been shown to induce NO production by activating endothelial nitric oxide synthase (eNOS) (Hashimoto et al 2006).

Cilostazol has been shown to inhibit neointimal hyperplasia and restore endothelial function after balloon injury to the carotid artery of rats by inhibiting vascular smooth muscle cell growth, thus stimulating the production of hepatocyte growth factor in rapidly regenerating endothelial cells (Aoki et al 2001).

Cilostazol also has beneficial effects on lipids. After 12 weeks of therapy with cilostazol, a 10% increase in HDL-C and a 15% decrease in plasma triglycerides have been noted (Elam et al 1998; Lee et al 2001). These beneficial changes with cilostazol were evident at 2 weeks for HDL-C and 4 weeks for triglycerides and persisted throughout the 12 weeks of therapy. There were no significant effects on low-density lipoprotein-cholesterol (LDL-C) or total cholesterol, but there was an increase of 6% in apolipoprotein A levels (Elam et al 1998, Lee et al 2001). More interestingly, in animal models of myocardial infarction (MI), cilostazol in combination with the potent statin atorvastatin had synergistic effects on nitric oxide production and reduction of MI size (Manickavasagam et al 2007). Cilostazol may potentiate angiogenesis and has been shown to increase vascular endothelial growth factors levels, which were significantly related to improved levels of exercise tolerance (Lee et al 2001).

Additionally, in hypertensive patients with type 2 diabetes mellitus, inflammatory markers - such as highly-sensitive C reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), total leukocyte count, and plasma malondialdehyde - have been shown to be elevated, suggesting high levels of inflammation and oxidative stress. Cilostazol has been shown to reduce these inflammatory markers (Agrawal et al 2007). In a randomized, open, add-on preventive controlled trial specifically assessing the effects of cilostazol on inflammatory markers, 60 hypertensive patients ≥45 years of age with diabetes mellitus were recruited. Cilostazol 100 mg 2×/day was given to 30 patients in addition to their standard medical treatment. At the 1-month follow-up, the cilostazol group showed significant (p < 0.001) reductions in hs-CRP (24%), ESR (39%), total leukocyte count (13%), and plasma malondialdehyde (18%).

Metabolism

Cilostazol is taken orally, and maximal plasma concentration of the drug is observed at 2.7 hours after the final administration, reaching its steady state within 96 hours (Bramer et al 1999). Cilostazol is highly bound to plasma proteins, primarily albumin, and has a free fraction of up to 5% in patients with IC (Bramer et al 1999). It is metabolized by the hepatic enzyme CYP3A4 and to a lesser extent CYP2C19, primarily by oxidative metabolism to numerous metabolites (Bramer et al 1997). The main metabolites identified include dehydrocilostazol and monohydroxycilostazol, which have inhibitory effects on platelet aggregation (Bramer et al 1997).

Safety

A black box warning indicates that cilostazol should be avoided in patients with congestive heart failure. The warning does not specify the heart failure classification or the degree of severity that should be avoided. This warning was imposed by the FDA because of the prior experience of chronic oral milrinone therapy (another PDE-III inhibitor) in patients with heart failure (Packer et al 1991). Regarding cardiovascular events and mortality, the risks associated with cilostazol seem to be numerically comparable to placebo. In an analysis that included the entire cilostazol safety database in addition to 4 trials conducted outside the US (), no significant differences were found between cilostazol- and placebo-treated groups in rates of MI, stroke, or cardiovascular death during follow-up (). Moreover, in two trials the distribution of total cardiovascular morbidity and mortality was actually higher in the placebo group (8%) than among patients receiving either 50 mg 2×/day (6%) or 100 mg 2×/day (7%) doses of cilostazol (). Thus, cilostazol seems to be a relatively safe alternative for IC therapy, offering an acceptable risk-benefit profile for patients with this condition. However, because of the existing black box warning against giving cilostazol to patients with congestive heart failure, the authors do not recommend prescribing cilostazol to such patients with IC.

Similar to other drugs in its class, cilostazol is associated with a fairly high frequency of non-life threatening adverse effects, particularly headaches, which may occur as a result of its vasodilatory properties. Headaches occurred in 443 of 1374 patients (32%) treated with cilostazol compared with 40 of 355 (11%) treated with the other approved therapy for IC, pentoxifylline, and 127 of 973 (13%) treated with placebo (). In addition, more patients in the cilostazol group than in the pentoxifylline and placebo groups reported diarrhea (17% versus 8% and 7%, respectively), abnormal stools (14% versus 5% and 4%, respectively), peripheral edema (7% versus 4% and 4%, respectively), and palpitations (9% versus 2% and 1%, respectively).

A large (n = 1439) ongoing, long-term, post-marketing clinical study conducted in the US, Japan and other Asian countries, South America, and the UK from 1999 through 2003 recently concluded (). Patients exposed to marketed formulations of cilostazol were evaluated to measure spontaneously reported adverse events. At the end of the study, 872 treatment-emergent adverse events were reported. A total of 773 events were considered serious and 99 non-serious according to FDA definitions. Of these, 61 events in 41 cases were considered drug related by the study investigators. Treatment-related serious adverse events occurring with the greatest frequency included congestive heart failure (14 cases; 2%), gastrointestinal hemorrhage (6 cases; 1%), atrial fibrillation (4 cases; <1%), diarrhea (3 cases; <1%), and dyspnea (3 cases; <1%). At total of 572 events were considered unexpected. Of the 872 serious and non-serious events observed, 181 required the discontinuation of cilostazol due to adverse events. The most frequent adverse events requiring discontinuation were congestive heart failure (26 cases; 2%), diarrhea (15 cases; 1%), and headaches (14 cases; 1%).

Efficacy

Once the goals of risk factor modification for patients with PAD have been met, the focus of PAD management shifts from general cardio-protection to treatment strategies specific for the clinical manifestations of PAD such as IC. There are consistent data supporting the efficacy of cilostazol for IC. In one the of most important studies included in the agent's New Drug Application, 698 patients with moderate to severe IC were randomized to a standard dose of cilostazol 100 mg 2×/day, a standard dose of pentoxifylline (400 mg 3×/day), or placebo (3×/day) for a period of 24 weeks. By the end of the study, patients included in the cilostazol group had shown a 54% improvement in maximal walking distance from the baseline compared with increases of 30% in the pentoxifylline group (p < 0.05) and 34% in the placebo group (p < 0.05) () (Dawson et al 2000). Earlier trials have demonstrated a dose-response relationship with cilostazol. In one study (Beebe et al 1999), IC patients who received cilostazol 100 mg 2×/day for 24 weeks increased their maximal walking distance by 51% over the baseline, whereas those who received a 50 mg 2×/day dose showed an increase of only 38% compared to baseline values (p < 0.001 for both doses versus placebo) (). In a second trial, the net improvement in maximal walking distance over placebo was 21% with cilostazol 100 mg 2×/day compared to 7% for cilostazol 50 mg 2×/day. Notably, patients in both the 50 mg and 100 mg cilostazol groups showed improvements in global measures of physical functioning compared to placebo-treated patients (p < 0.05) (Strandness et al 1998). Collectively, more than 2,700 IC patients were investigated in eight clinical trials with variable results, but there was a consistent trend toward improvement with cilostazol over placebo. Dawson et al (1998) and Money et al (1998) have shown a significant improvement in maximal walking distance in those who received cilostazol 100 mg 2×/day compared with those who received placebo. Recently, a meta-analysis from six phase III cilostazol trials (Regensteiner et al 2002) with study durations of 12 to 24 weeks found a net benefit of the drug in both the constant workload treadmill and graded treadmill tests. Among the 749 patients who had been evaluated with a constant workload treadmill test, cilostazol 100 mg 2×/day was associated with a 76% improvement in maximal walking distance from the baseline compared with a 20% improvement for placebo (p < 0.0001). Similarly, 895 patients evaluated with a graded treadmill test showed a 40% maximal walking distance improvement with cilostazol 100 mg 2×/day compared with a 20% increase with placebo (p < 0.05) (). When data for both types of treadmill protocols were combined, cilostazol 100 mg 2×/day demonstrated superiority over placebo in both maximal walking distance (p < 0.05) and pain-free walking distance values (p < 0.05). Furthermore, cilostazol demonstrated efficacy on several pain and physical dimensions on the Short Form-36 physical functioning scores and Walking Impairment Questionnaire, indicating that the drug's beneficial effects on exercise capacity are indeed accompanied by meaningful improvements in QoL. The beneficial effects of cilostazol were statistically superior to placebo as early as 4 weeks following treatment onset. However, the therapeutic effects of cilostazol were seen to improve progressively as study duration increased. In clinical practice, 12 to 24 weeks should be expected as a typical waiting period for improvement to occur.

In a randomized, placebo-controlled study, patients receiving either cilostazol 100 mg 2×/day, pentoxifylline 400 mg 3×/day, or placebo were monitored for 24 weeks with cross-over to placebo after that period. When these patients were followed up for an additional 6 weeks, those in the cilostazol treatment group demonstrated a significant loss of treatment benefit after the change (p < 0.05) (Cleanthis et al 2005), whereas there was no significant change following pentoxifylline therapy.

Interestingly, cilostazol has also been shown to provide long-term vessel patency after percutaneous transluminal angioplasty (PTA) in hemodialysis patients with PAD (Ishii et al 2008). In a recent Japanese study assessing lower extremity arterial patency rates 5 years after initial PTA, 193 hemodialysis patients with 372 consecutive lesions underwent successful PTA and were randomized to receive either cilostazol 100 mg 2×/day in conjunction with standard medical treatment (71 patients with 130 lesions) or standard medical therapy without cilostazol (122 patients with 242 lesions). After 5 years, the patency rate was 52% in the cilostazol group and 33% in the control group (p < 0.05). Moreover, in the Cilostazol for Restenosis Trial (Douglas et al 2005), 750 patients with successful coronary bare metal stent implantation were randomized to receive either cilostazol 100 mg 2×/day or placebo for 6 months in additional to aspirin and clopidogrel 75 mg daily. At 6 months, the cilostazol group had a 36% relative risk reduction in the restenosis rate compared with those who received placebo, as determined by quantitative coronary angiography. Furthermore, in the Cilostazol for Diabetic Patients in Drug-Eluting Stent Trial (Ahn et al 2008), 280 patients successfully underwent coronary stenting and were randomized to receive either aspirin and cilostazol or aspirin and clopidogrel. After a mean follow-up of 7.1 months, 237 patients underwent repeat coronary angiography; those randomized to receive aspirin and cilostazol had a 50% decrease in the incidence of restenosis compared to those who received aspirin and clopidogrel. The trial concluded that combination therapy with aspirin and cilostazol for the prevention of restenosis is comparable and may even be superior to that of aspirin and clopidogrel in diabetic patients who undergo drug-eluting stent implantation.

Supervised exercise rehabilitation is an effective and safe intervention that has been demonstrated to improve the walking distance of patients with IC. Multiple controlled trials have demonstrated that both walking distance until the onset of claudication and absolute claudication distance improve in patients who receive supervised exercise rehabilitation. One meta-analysis of 21 studies found that patients who were treated with supervised exercise rehabilitation had a 180% increase in distance walked until the onset of claudication compared with a 40% increase in control group individuals. Similarly, the absolute distance walked increased by 130% in patients who received supervised exercise rehabilitation compared with a 30% increase among those who did not (Gardner and Poehlman 1995). Another meta-analysis of 10 randomized trials comprising 250 patients with IC found that initial maximal walking time increased by approximately 150% in patients treated with exercise rehabilitation compared with control group individuals (Leng et al 2000). Overall, supervised exercise therapy has been shown to be very effective in improving maximal treadmill walking distance (Milani and Lavie 2007) ().

Conclusions

In summary, cilostazol remains the only drug thus far proven to demonstrate consistent benefits in clinical trials in patients with IC. In addition to limb-specific outcomes, cilostazol has also been shown to provide pleotropic effects; these may provide additional clinical benefits, but clinical trials are needed to validate such effects. Finally, studies are also needed to compare the effects of cilostazol and supervised exercise training in patients with IC to either therapy by itself.

Footnotes
Disclosures
None of the authors report conflicts of interest.

References

Bramer SL, Tata PNV, Mallikaarjun S. Disposition of 14 C-cilostazol after single dose administration to healthy human subjects. Phar Res. 1997;14(11 Suppl):S612. [Google Scholar]

Ishii H, Kumada Y, Toriyama T, et al. Cilostazol improves long-term patency after percutaneous transluminal angioplasty in hemodialysis patients with peripheral artery disease. Clin J Am Soc Nephrol. 2008;3:1034-40. [[PMC free article] [PubMed] Google Scholar]

Strandness DE, Dalman R, Panian S, et al. Two doses of cilostazol versus placebo in the treatment of claudication: results of a randomized, multicenter trial. Circulation. 1998;98(17 Suppl 1):1-12. [Google Scholar]

# data[].attributes.attachment_link.title
Safety and efficacy of cilostazol in the management of intermittent claudication

# data[].attributes.attachment_link.description
Peripheral arterial disease (PAD) is a major health problem affecting millions of patients worldwide. Many will suffer from intermittent claudication (IC), which leads to marked impairment of quality of life (QoL). Besides surgical and endovascular interventions to improve limb-specific outcomes, pharmacotherapy is an effective tool in the treatment of IC.

# data[].attributes.body
By modifying its inactivation threshold of voltage-dependent sodium channels, Zonisamide is able to reduce sustained high-frequency repetitive firing of action potentials. Zonisamide also inhibits low-threshold T-type calcium channels in neurons, which can possibly stop/slow the spread of seizure discharge across cells.
The drug is indicated as am adjunctive therapy in partial seizure treatment for adults with epilepsy.
About 100 units of Zonisamide will cost $34-56 and and it takes approximately 2 weeks for it to take effect. I believe it is worth it because it was proven to be highly effective in treating partial seizures.

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How to take and store Zonisamide?

Follow your doctor's directions. Call if you have any questions. Usually, your doctor will tell you to start by taking no more than 100 mg each day. After a while the doctor may tell you to take a larger dose to get better control of your seizures. Usually the doctor will tell you to take all the capsules at one time, or perhaps to take capsules twice a day.

Swallow each capsule whole. Don't bite it or break it open. It's OK to take Zonisamide either with food or without food, but it's important to take it the same way day after day.

Drink plenty of liquids every day. Doing this may help to prevent kidney stones, a serious problem that affects a small number of people who take Zonisamide.

Don't take more than the doctor prescribes. Be sure to use only the amount of Zonisamide that your doctor prescribes. Be especially careful if you get a new prescription for a different size of capsule. Don't just continue to take the same number of pills as before.

If you think you've taken one or two extra capsules, call your doctor for advice. For a larger overdose, call your local poison control center or emergency room right away, unless you have special directions from the doctor.

Don't stop taking Zonisamide or change the number of capsules you take without talking to your doctor first. Stopping any seizure medicine all at once can cause a serious problem called status epilepticus.

Store Zonisamide capsules at room temperature, protected from dampness and light. Keep them where children can't get them.

If you forget a dose, take it as soon as you remember. If it is almost time for the next dose, delay that dose for a few hours instead of taking two doses very close together. If you take Zonisamide only once a day, allow an interval of about 12 hours before taking the second dose, and then start a 24-hour schedule again the next day. If you're not sure about what to do, call the doctor's office for advice.

Do your best to follow the doctor's directions. If you forget doses often, it may be a good idea to get a special pillbox or watch with an alarm to remind you.

Taking the right amount of seizure medicine on time every single day is the most important step in preventing seizures!

How does Zonisamide affect the brain?

Brain cells need to work (fire) at a certain rate to function normally. During a seizure, brain cells are forced to work much more rapidly than normal. Zonisamide helps prevent brain cells from working as fast as a seizure requires them to. In this way, seizures can be stopped when they are just beginning.

How does the body digest Zonisamide?

After medicine is swallowed, it must be absorbed into the blood so it can move throughout the body. The process of absorbing, digesting, and excreting a medicine or food is called metabolism. The way the body metabolizes a particular medicine affects how often it must be taken. It also determines whether it will interact with other medicines or be affected by liver disease or kidney disease.

Zonisamide is broken down (digested) in the liver. People with liver disease must be cautious about taking it. Other people also need to be careful if they take other medicines that are digested in the liver, as many are.

Because zonisamide is eliminated from the body through the kidneys, the dose may need to be reduced in people with kidney disease.

How well does the Zonisamide work?

Doctors have studied large numbers of people with partial seizures to find out how well zonisamide works. Studies have shown that zonisamide works well when added to other seizure medications. Zonisamide is not a perfect add-on seizure medicine for everyone, however. Sometimes people must try a series of combinations before finding what is best for them.

Some other medicines affect how zonisamide is eliminated from the body, so the dosages may need to be changed with different combinations.

What are the most common side effects of Zonisamide?

Many people who take zonisamide don't report any unwanted side effects. Those who experience undesirable effects most often complain of:

sleepiness or fatigue

dizziness

loss of appetite (it's not unusual to lose several pounds)

upset stomach

headache

agitation or irritability

weight loss

Some less-common side effects are:

poor coordination or tremor

speech problems

poor concentration

itching

vision problems

If you notice any of these problems, call the doctor's office. Sometimes the doctor can help by changing the amount of zonisamide you take or how you take it. Don't stop taking zonisamide or change the amount you take without the doctor's guidance.

You should be careful when you first start taking zonisamide. Make sure you don't have a problem with sleepiness or dizziness when driving or doing anything else that might be dangerous.

Be sure to read about the serious side effects so you will be aware of symptoms that might indicate the beginning of a dangerous reaction to zonisamide. These serious problems are very rare but everyone who takes this medicine should at least be aware of them.

Allergic reactions
Approximately 1 in 20 people who take zonisamide have a red rash within the first few weeks of taking it. If this happens, tell the doctor or nurse right away, to be sure that it's not the beginning of a serious problem. It's rare for the rash to be serious, but don't ignore it. It's often necessary to switch to a different seizure medicine

What are the most serious side effects of Zonisamide?

Very few people have serious reactions to Zonegran. If you take it, you should be aware of them, however, so you and your family can recognize them. Here's a list of warning signs that may be the start of one of these problems:

If you notice any of these symptoms, call your doctor right away:

Rash

Fever, sore throat, sores in your mouth, or easy bruising (could mean a blood problem)

Sudden back pain, pain in the stomach area, pain when urinating, or bloody or dark urine (could mean a kidney stone)

Decreased sweating or rise in body temperature, especially for a child

Depression

Thoughts that are unusual for you

If you notice mood changes with Zonegran, speak to your doctor or nurse. A slight reduction in the dosage may improve your frame of mind. If you had a history of depression before starting Zonegran, your doctor may consider other treatments such as antidepressants or referral to a counselor or psychiatrist.

Rashes
The rash may take various forms, from small red spots or blotches on the surface of the skin to large blisters. It may be preceded or accompanied by itchiness. When you first start taking Zonegran (specifically during the first 2 to 4 weeks), watch closely for any signs of a rash. Alert your doctor if you detect changes in your skin. If a rash progresses, you may develop a fever or a feeling of sickness. Occasionally, fever comes before the rash.

Blood disorders
A few people have developed blood disorders called aplastic anemia and agranulocytosis while taking zonisamide. The numbers are so small that not much can be said about a possible relationship, but you should tell the doctor if you develop symptoms such as fever, sores in your mouth, or easy bruising.

Kidney stones
Kidney stones occurred in about 1 in 80 people, usually after taking Zonegran for 6 to 12 months. Most people who get kidney stones have had kidney stones before. Contact your doctor immediately if you develop symptoms that could indicate a kidney stone, such as sudden back pain, abdominal pain, or blood in the urine. Drinking more fluids may reduce the risk of stone formation. This is especially important if you or someone in your family has had kidney stones, because your risk is greater.

Decreased sweating
An effect reported only in children is decreased sweating leading to high body temperature, even heatstroke. This effect is quite rare, but parents of children or teenagers taking Zonegran should be watchful, especially in summer.

Depression or psychosis
Tell your doctor if you feel depressed or have thoughts that are unusual for you while you're taking Zonegran. This is unusual but can happen.

A complete list of all reactions to Zonegran can be found in the package insert, but it is important to remember that only a tiny number of people have any of these serious problems.

On 2/23/2009, the US Food and Drug Administration issued a warning that the antiepileptic medication zonisamide (Zonegran) can cause metabolic acidosis in some patients. Metabolic acidosis is a condition of excess acidity (low pH) in the blood. The condition can manifest with a variety of symptoms, including chest pains, heart racing, rapid breathing, stomach upset, kidney stones, confusion and other symptoms. People who are already prone to have metabolic acidosis from kidney disease or drugs such as acetazolamide (Diamox), certain diabetes drugs or the ketogenic diet may be more prone to develop zonisamide-induced metabolic acidosis. Young people are also more likely to develop the condition. Metabolic acidosis is detected by measuring blood levels of bicarbonate (worrisome if less than 17 mEq/L), sometimes along with arterial blood gas measurement for levels of oxygen, carbon dioxide and acidity. Once diagnosed, the condition usually is treatable, most directly by stopping zonisamide. The FDA recommended that healthcare professionals measure serum bicarbonate before starting treatment and regularly thereafter.

On July 10, 2008, an advisory panel was convened by the Food and Drug Administration (FDA) to review data that the FDA had previously collected from drug studies showing an association between many of the antiepileptic drugs (AEDs) and suicidal ideation and behavior, which together are called suicidality. According to the FDA's Alert, among the patients with epilepsy in these drug studies, 1 out of 1000 people taking the placebo (inactive substance) showed suicidality compared to approximately 3.5 out of 1000 people who took an AED. The FDA advisory panel voted to accept the FDA's data at its meeting on July 10.

Taking antiepileptic medicines may increase the risk of having suicidal thoughts or actions;

Do not make any changes to the medication regimen without first talking with the responsible healthcare professional;

Pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.

Be aware of common warning signs that might be a signal for risk of suicide. Some of these are:

Talking or thinking about wanting to hurt yourself or end your life

Withdrawing from friends and family

Becoming depressed or having your depression get worse

Becoming preoccupied with death and dying

Giving away prized possessions

We again urge patients and families to contact their doctor before stopping an epilepsy medication because this may possibly lead to seizures and worsening of mood.

What else is Zonisamide used for?

Often doctors find that medicines are useful for more than one purpose. It is legal to prescribe medicines for "off-label uses" even though the FDA has not formally approved such use. Off-label uses of zonisamide include: Lennox-Gastaut syndrome, infantile spasms (West syndrome), progressive myoclonic epilepsy (PME).

Who should not take Zonisamide?

The only people who definitely should not take zonisamide are those who are allergic to it or to other medicines in the same family, called sulfonamides. If you have ever been told that you're allergic to sulfa drugs (such as Bactrim or Septra), you should not take zonisamide, or take it only after carefully discussing it with your doctor.

Because zonisamide is metabolized in the liver and eliminated in the urine, people with liver and kidney disease should be treated with caution. The dosage may have to be increased more slowly.

Can Zonisamide be taken with other medicines?

Sometimes one kind of medicine changes the way another kind of medicine works in the body. If two kinds of medicine affect each other, the doctor may prescribe something else or change the amount to be taken.

Your body gets rid of zonisamide quicker if you are also taking certain other seizure medicines, such as:

carbamazepine (Tegretol, Tegretol XR, Carbatrol)

phenobarbital

primidone (Mysoline)

phenytoin (Dilantin, Phenytek)

If this applies to you, your doctor may plan to give you more zonisamide than you would otherwise take.

What are the effects of Zonisamide on Children?

Although the Food and Drug Administration (FDA) has not officially approved zonisamide for children, there have been quite a few research studies in which it has been given to children of various ages (even infants) with generally good results. It has been effective in reducing many types of seizures, especially partial seizures, primarily generalized seizures, absence seizures, infantile spasms, and myoclonic seizures.

Doctors figure out how much medicine to give to young children based mostly on their weight. To keep side effects at a minimum, the doctor probably will prescribe a low dose to start with and increase it slowly. Children usually start with a dose 1 to 2 milligrams (mg) per kilogram (kg) per day. A kilogram equals 2.2 pounds, so a 50-pound child weighs about 23 kilograms and would be started on approximately 25 to 50 mg of zonisamide each day. The doctor would then increase the dosage by a similar amount every 2 weeks, depending on how well the child's seizures are controlled and whether any side effects have appeared. Most children do best at about 8 mg per kg per day (184 mg for a 50-pound child). The highest dose recommended is 12 mg per kg per day.

The most common side effects in studies of children involved problems with thinking or behavior, followed by stomach upset. One dangerous side effect, decreased sweating with fever, occasionally affects young children but not adults. It is quite unusual but is worth watching out for, especially in summer. Parents whose children are given zonisamide should also watch for the other symptoms of rare but serious reactions that are listed on the serious side effects page.

If a woman takes Zonisamide during pregnancy will it hurt the baby?

In the United States, the Food and Drug Administration (FDA) assigns each medication to a Pregnancy Category according to whether it has been proven to be harmful in pregnancy. Zonisamide is listed in Pregnancy Category C. This indicates that caution is advised, but the benefits of the medicine may outweigh the potential risks. Studies in animals have shown some harm to the baby, but there haven't been any good studies of results in women.

Talk to your doctor or another health professional if you are pregnant or plan to become pregnant. We don't yet have enough information to be able to estimate the risk of various types of birth defects that might occur if zonisamide is taken during pregnancy. We also don't know enough to compare the risk with zonisamide to the risk with other seizure medicines. The risk of birth defects is generally higher for women who take more than one seizure medication and for women with a family history of birth defects.

Women who are capable of becoming pregnant should take at least 400 mcg (0.4 mg) of folic acid (folate) daily to help prevent a type of birth defect called a neural tube defect. (The best-known of these is spina bifida, in which the spinal cord is not completely enclosed.) Women at high risk, such as those with a history of this kind of defect in a previous pregnancy, should take 4000 mcg (4 mg) daily, beginning before they become pregnant.

How much zonisamide is passed through breast milk is not known for certain, but the way the body uses it suggests that probably a large portion does enter the milk. If you want to breast-feed your baby, check with your doctor.

What are the effects of Zonisamide on Seniors

The effects of zonisamide on seniors are not that well known yet. In general, seniors are more sensitive to the side effects of seizure medicines. Also, because older people are more likely than young ones to have reduced kidney function, their dose of zonisamide will be lower, since zonisamide leaves the body by the kidneys.

For these reasons, doctors usually start seniors at a low dose and proceed cautiously with any increases.

What are the dose ranges for Zonisamide?

The best amount is the amount that completely controls seizures without causing troublesome side effects. It depends on many factors, which are different for every individual. Follow the doctor's directions. Call if you have any questions.

Zonisamide is usually started at 100 to 200 milligrams per day (mg) for adults. For children, the amount is calculated according to child's weight. Children usually start at 2 to 4 mg per kilogram (kg, about 2.2 pounds) per day, divided into two doses.

Dosages should be increased at 2-week intervals to an ongoing dose of 400 to 600 mg per day for adults and 4 to 8 mg per kg per day for children. Some people may need (and be able to tolerate) higher dosages.

Read the package insert of Zonisamide

In the United States, companies that manufacture medicines are required to publish certain kinds of information about each product. This document is commonly known as a "package insert" because it is usually included with each package of the medicine.

You can also read these documents (also called "prescribing information") online. The U.S. package insert for Zonegran (zonisamide) is found at:

Some of the information may differ in other countries.

To learn how to read and understand a package insert, see " How to read a package insert."

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How to take and store Zonisamide? Follow your doctor's directions. Call if you have any questions. Usually, your doctor will tell you to start by taking no more than 100 mg each day. After a while the doctor may tell you to take a larger dose to get better control of your seizures.