Brandon Dyson is a board certified pharmacist who created a website to help educate students about the battles of pharmacy school and how to succeed. I’d like to thank him for his guest post below! You can find his website right here – http://www.tldrpharmacy.com/
The Top 5 HIV Clinical Pearls for the NAPLEX
GG is a 36 year old male with a PMH of recently-diagnosed HIV. His medical history is otherwise unremarkable. He presents to the ED feeling lightheaded and short of breath. He is confused and disoriented. He states that he drinks “about” 6 beers per day, but does not smoke or use illicit drugs. His relevant medications include:
- Darunavir [Prezista]
- Ritonavir [Norvir]
- Abacavir/Lamivudine [Epzicom]
This is a classic case of early lactic acidosis caused by the NRTI abacavir. Abacavir is unique among the NRTIs because it is metabolized largely by alcohol dehydrogenase. It’s estimated that chronic alcohol consumption can increase abacavir levels by about 41%. One of the class side effects of all NRTIs is lactic acidosis. This is a rare metabolic condition, but it is a very serious one. The mortality rate is quite high if it’s not caught early.
Need a quick HIV refresher? Below are The Top 5 HIV Clinical Pearls for the NAPLEX.
- Brand names. For starters, you have to know brand names. There’s just no way around it. This is especially true in HIV where there are so many combination pills. What is the most frustrating thing in the world? When you miss a question you knew the answer to because you didn’t know the brand name (trust me on this, I know from experience).
Most, if not all NAPLEX questions will use a drug’s brand name, so be prepared. You might know everything about dolutegravir, abacavir, and lamivudine…..but if you don’t know what Triumeq is, you just missed a question.
2. Renal adjustments. You can actually distill about 95% of what you need to know with renal adjustments in HIV meds to 3 rules:
- All NRTIs need a renal adjustment (EXCEPT abacavir)
- Combination products with cobicistat are not given below a CrCl of 70 ml/min
- All other combination products are not given below a CrCl of 50 ml/min
Ok, they aren’t perfect rules. But they’re a great starting point if you don’t come across HIV that often. here are a couple of other medications (such as nevirapine and maraviroc) that you might adjust in a hemodialysis (HD) patient. But even then, the recommendations get kind of fuzzy. For the most part (and for most patients), you won’t need to make renal adjustments to any of the other drug classes.
How do we handle the combination products in decreased renal function? We break them up into their individual components and adjust each one individually. So for example, let’s say you have a patient taking Atripla (efavirenz/emtricitabine/tenofovir) with a CrCl of 35 ml/min. The efavirenz (an NNRTI) doesn’t need to be adjusted, but the emtricitabine and tenofovir (both NRTIs) do. So you break it up. In this case, you’d give efavirenz 600 mg QHS*, emtricitabine 200 mg q48h, and tenofovir 300 mg q48h.
*Bonus clinical pearl: efavirenz should be taken QHS to minimize CNS effects.
- Opportunistic Infection Prophylaxis. You have 3 big ones to worry about here. Pneumocystis jirovecii pneumonia (PCP), Toxoplasma gondii encephalitis, and Mycobacterium avium complex (MAC). What you need to memorize are the CD4 counts where you’d need to begin prophylaxis, and the drugs we use to prophylax with.
For PCP, we begin prophylaxis when the CD4 count dips below 200. For toxo, the count is 100. And for MAC, the CD4 count is 50. Conveniently, sulfamethoxazole-trimethoprim (SMZ/TMP) covers both PCP and toxoplasma. So when you start a patient on PCP prophylaxis, you are also covering toxo. MAC is covered with either azithromycin (preferred) or clarithromycin. To summarize:
- CD4 < 200 = PCP (SMZ/TMP)
- CD4 < 100 = Toxo (also SMZ/TMP)
- CD4 < 50 = MAC (azithromycin or clarithromycin)
- Drug Interactions. Your biggest concern here is the Protease Inhibitors. Almost all of them are metabolized by CYP3A4. And a lot of them are also inhibitors or inducers of various CYP enzymes. The big one to watch out for is ritonavir. It’s not used for viral efficacy (so if you see it as the only protease inhibitor in an HIV regimen, that regimen is incomplete). Ritonavir is used as a booster (or a “pharmacokinetic enhancer”) because it’s a powerful CYP inhibitor. Always scan the med profile for potential drug interactions when you see ritonavir.
A common scenario to watch out for is statin use with protease inhibitors. There are specifics for each agent, but the general rule is to completely avoid simvastatin and lovastatin in any patient using a protease inhibitor.
Another common interaction is with acid-suppressing agents. There are two HIV drugs to be watchful for here: atazanavir (a protease inhibitor) and rilpivirine (an NNRTI). Both of them are contraindicated with Proton Pump Inhibitors. Increasing the pH of the stomach lowers the bioavailability of the drugs significantly enough to cause treatment failures and resistance.
Atazanavir and rilpivirine can be used with H2 antagonists, but you must separate the dose by 10 – 12 hours. This is a very common inpatient drug interaction, so be on the lookout for it.
- Drugs of Note. There are some individual drugs with unique “personalities” that you should know about for the NAPLEX.
- Abacavir REQUIRES an HLA-B*5701 test before treatment. This is one of the very few pharmacogenomic tests that are required (not just recommended) before administering a drug. If it seems like we are really hammering home points on abacavir it’s because we are. Abacavir is a very common agent. It’s part of several combination pills, including the preferred first-line regimen Triumeq. You need to know abacavir.
- Speaking of pre-treatment requirements, there’s also maraviroc. This drug is notable because it’s the only HIV medication that has a human (not viral) target. It specifically targets a binding protein on your CD4 cells, which prevents HIV from entering. But unfortunately, it only targets one binding protein: the CCR5 receptor. Some patients only have the CCR5 receptor. If that’s the case, maraviroc will work. However, if the patient’s CD4 cells have a CCR4 or a CXCR4 receptor, maraviroc will not work. To prevent this colossal failure (and waste of money) we do a trofile test before hand. This tells you if you have the appropriate binding receptor on your CD4 cells.
- The NNRTI nevirapine is an auto-inducer. You’ve seen this concept before with carbamazepine. Practically speaking, what does that mean? Because the drug induces its own metabolism, you have to scale up the dosing after a couple of weeks. In the case of nevirapine, you double the daily dose 2 weeks after treatment initiation. Incidentally, this is also what you do with carbamazepine.
- Sulfa allergy. The protease inhibitors darunavir, fosamprenavir, and tipranavir all have a caution in patients with a sulfa allergy. It’s not a contraindication, but something to be mindful of.
- Lopinavir/ritonavir and ritonavir liquid formulations both have high alcohol content (>40%). Something to keep in mind when you have a pediatric patient or a patient who cannot take alcohol.