PHRM3012Quiz3 by karlwinckel

22 year old Joan w/ asthma

2018-08-26 06:11:19 UTC

Her asthma is not well controlled. She would like to do something to improve her condition.

She is currently on Seretide MDI 250/25 2 puffs BD.
Seretide contains salmeterol (a long acting beta2 agonist, or LABA) and fluticasone propionate (a corticosteroid)

well...
first of all, from the AMH, we can see that Seretide cannot be used for acute symptom relief of asthma
so OPTION 2 is out.

She is currently on the maximum dose of seretide
From eTG and AMH, highest dose is 500+50 micrograms (= 2 puffs), twice daily.
Dose increase would not be appropriate. So OPTION 1 is out.

eTG suggests:
Montelukast may be considered as add-on therapy in adults and adolescents with severe asthma, ie uncontrolled despite good inhaler technique and adherence

We are not sure whether Joan has good inhaler technique. But we do know that her asthma has never been well controlled, and that she is embarrassed to use it in front of other people (which may indicate poor adherence)
- starting montelukast might be good but we should see if her inhaler technique is good first
- also montelukast has a small risk of causing neuropsychiatric symptoms including depression

Conclusion: Let's assess her inhaler technique before starting an add-on therapy (OPTION 4)

Vaccination service

2018-08-26 06:46:31 UTC

Refer to http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-7
Section 4.7.7 Recommendations

Influenza vaccination is particularly strongly recommended for:

All adults aged ≥65 years

Influenza-associated mortality rates are highest among adults aged ≥65 years. Evidence shows that influenza vaccine reduces hospitalisations from influenza and pneumonia and all-cause mortality in adults ≥65 years of age.

Conclusion: More important to vaccinate the elderly because they have higher morbidity (higher hospitalization rates compared to teenagers, and is only matched by the hospitalization rates in children <5, another high risk group) and mortality rates (OPTION 3)

55 year old Carl w/ HIV

2018-08-26 06:59:28 UTC

Refer to
https://www.hiv-druginteractions.org/

PMHx
mild allergic rhinitis
type 2 diabetes
large proximal deep venous thrombosis (2 months ago)

Medications
Fluticasone nasal spray 200mcg daily (for allergic rhinitis)
Warfarin 5mg daily (INR yesterday =2.3, for DVT)
metformin 1.5g twice daily (for T2DM)

HIV prescriptions
Kaletra (lopinavir with ritonavir)

400/100mg twice daily

Truvada (tenofovir)

1 tablet daily

Put all those drugs into the interaction checker and it seems that Kaletra is the troublemaker

First, none of the HIV meds interact with metformin. That's good news because we can eliminate OPTION 4

Carl is already on his maximum daily dose of metformin, and while kaletra could worsen diabetes (check AMH), we would add on another antihyperglycemic agent rather than further increase his metformin dose. So OPTION 1 is out.

Co-administration of kaletra with warfarin may result in decreased warfarin levels and will require regular INR monitoring on initiation. If my memory serves, DVT maintenance therapy usually goes for 3-12 months so we definitely should not be ceasing warfarin just yet. Instead we will have to resign ourselves to monitor INR and adjust warfarin dose accordingly. OPTION 3 is out.

By the virtue of elimination, OPTION 2 seems to be the answer.
Co-administration of kaletra with fluticasone leads to significant increases in fluticasone exposure (AUC). This will cause a lot of side effects (CUSHINGS!!) if Carl was using a systemic corticosteroid.
He is using a nasal spray (which is has pretty localized action), however he is only using it for mild allergic rhinitis so you could argue that the risks (drug in systemic circulation increase to a level that leads to adverse effects) outweigh the benefits (symptomatic relief of only MILD allergic rhinitis) in this case. I agree with ceasing his nasal spray (maybe recommend something else? antihistamine?) and regularly monitoring INR.

TL;DR: I pick OPTION 2

35 year old Jack w/ HIV

2018-08-26 07:23:47 UTC

Medications
simvastatin 40mg daily for dyslipidaemia.
His last LDL level was 2.2mmol/L and triglycerides were 1.4mmol/L

Target lipid levels for patients taking lipid-modifying therapy (eTG)
LDL < 2mmol/L
TG < 2mmol/L
His levels are pretty good, no other medical conditions, is young...
His absolute CVD risk is probably low. There is no real reason for Jack to be taking statins.
But ignore that since that's not one of the options

The two regimens
1, Atripla (tenofovir) OD

2, emtricitabine + tenofovir + atazanavir + ritonavir

pop the drugs into HIV interaction checker and you will find that atazanavir and ritonavir are contraindicated with simvastatin as it could lead to increased simvastatin levels and subsequent myopathy.
On the other hand, tenofovir does not interact with simvastatin
It is clear which regimen we should pick.

BUT According to the Australian antiretroviral guidelines, initial antiretroviral regimen should include two nucleoside reverse transcriptase inhibitors (NRTIs) plus one of either INSTI, NNRTI or PI

So it is suspect whether a single drug regimen (i.e. Atripla) is adequate.
But in terms of this question, and in terms of the interaction with simastatin, I'm going with OPTION 2

These are some funky trial names

2018-08-26 07:25:09 UTC

TORCH, UPLIFT, FLAME, IMPACT
I wonder if the TORCH and FLAME guys had a collaboration?

Links
TORCH: http://erj.ersjournals.com.ezproxy.library.uq.edu.au/content/24/2/206
UPLIFT:
https://www.ncbi.nlm.nih.gov/pubmed/19317104
FLAME:
https://www.nejm.org/doi/full/10.1056/nejmoa1516385
IMPACT:
https://www.nejm.org/doi/full/10.1056/NEJMoa1713901

TORCH:
compares salmeterol/fluticasone propionate (LABA/ICS) vs placebo on COPD survival (primary endpoint is all cause mortality)
- does not apply to question

UPLIFT:
tiotropium vs placebo on annual rate of decline in FEV1 of COPD
I couldn't get the full text for this one. Tiotropium is a long-acting muscarinic antagonist (LAMA)

FLAME:
compares effects of LABA/LAMA vs LABA/ICS on annual rate of COPD exacerbations

IMPACT:
compares triple therapy (LABA/LAMA/ICS) against dual therapy (LABA/LAMA or LABA/ICS)
on annual rate of COPD exacerbations
- not relevant to the question

Conclusion of the FLAME investigators:
Indacaterol–glycopyrronium (LABA/LAMA) showed not only

noninferiority but also superiority to salmeterol–fluticasone (LABA/ICS) in reducing the annual rate

of all COPD exacerbation

The question asks about this conclusion
"The combination of a LABA/LAMA was shown to results in a reduction in in COPD exacerbations when compared to the combination of LAMA/ICS"

I believe this is a typo, it should be LABA/ICS instead of LAMA/ICS. LAMA/ICS has not been tested in any of the four studies and is definitely not recommended therapy. Usually, it's LABA + something else.

If it was really a typo, then I would pick the FLAME study (OPTION 4)

2018-08-27 23:37:20 UTC

flame and touch guy would have coffee breaks together while doing the research and used to light each others darts :\

35 yr old Jack w/HIV

2018-08-28 08:12:57 UTC

I think Atripla is a combo of tenofovir, emtricitabine and efavirenz (according to the AMH and google). Efavirenz has an interaction with simvastatin as well (can decrease concentration and efficacy)...
I would still pick option 2 but the combo does still have an interaction.

2018-08-29 03:46:42 UTC

Agree w/ reviewing inhaler technique so that she doesn't have to use her inhaler at work regularly

2018-08-29 03:49:25 UTC

Agreed

Note from Karl

karlwinckel85 — 2018-08-29 13:23:02 UTC

It is beyond the scope of this question to compare efficacy of different treatment options for HIV. For this question consider solely drug interations

Note from Karl

karlwinckel85 — 2018-08-29 13:35:32 UTC

Thanks for spotting the typo. I have amended the question stem to LABA/ICS rather than LAMA/ICS. I apologise for this error.

2018-08-30 02:35:50 UTC

2018-08-31 04:57:52 UTC

So we all agree it is FLAME?

2018-08-31 04:58:56 UTC

So Carl should cease the nasal spray and have his INR monitored closer?

2018-08-31 05:00:59 UTC

I think Atripla is more effective due to a drug interaction i.e. option 2?

2018-08-31 06:36:54 UTC

2018-08-31 06:37:17 UTC

Since she is already on max dose ICS would we assume she is at level 4?

2018-08-31 06:38:22 UTC

Straight from Asthma handbook - review technique since she has only had poorly controlled asthma