April 30, 2017
Paul E. Sax, M.D., is director of the HIV Program and Division of Infectious Diseases at Brigham and Women's Hospital in Boston.
Since expression of gratitude makes you happier -- hey, I read it on the internet -- and whining does the reverse, I've decided to turn what was going to be a typical rant about dealing with insurance companies into an expression of thanks to a remarkable group of professionals.
Namely, the Doctors of Pharmacy (Pharm.D.'s) who specialize in Infectious Diseases. About whom I am extremely, exceedingly grateful.
And I'm not alone in holding that view -- you'll find it's universal among ID doctors who are lucky enough to work with one or more ID Pharm.D.'s, whether it's as part of an antibiotic stewardship program, an HIV or transplant clinic, or on the inpatient ID consultation service.
Although I could cite numerous examples of how the two primary ID Pharm.D.'s help us out (thank you Dave and Brandon!), here's a recent case from my outpatient practice.
A patient of mine, receiving TAF/FTC, darunavir/cobicistat for HIV treatment, needed a nasal steroid inhaler for seasonal allergies. For the non-HIV specialists, recall that when inhaled, injectable, or even topical corticosteroids are given with these potent cytochrome p450 inhibitors, systemic levels of cortisol can dangerously increase.
Result: Full-blown hypercortisolism (Cushing Syndrome), which usually takes months to resolve and can leave permanent damage. This ritonavir/cobicistat-inhaled steroid interaction is emphatically not one of those EHR alerts to ignore.
So this isn't a simple matter of telling him to go grab whatever over-the-counter spray is on sale at his local CVS or Walgreens. As a result, I sent a prescription to his pharmacy for beclomethasone because it can be safely given without interacting with cobicistat or ritonavir.
Per his insurance pharmacy benefit manager, however, they wouldn't cover the beclomethasone. They sent along an annoying notice about "formulary alternatives", specifically:
... flunisolide spray, fluticasone spray [hey guys at insurance company, this is the WORST POSSIBLE SUGGESTION!], mometasone spray, or triamcinolone spray.
So what to do? Obviously fluticasone would be a terrible option. Furthermore, I've seen iatrogenic hypercortisolism several times after triamcinolone injections, so cross that one off the list too.
What about mometasone? UpToDate has an easy-to-use drug interaction program, and it showed no significant interaction. However, the invaluable University of Liverpool HIV Drug Interactions checker disagreed, and did so strongly (that's their report to the right).
This left flunisolide, which for some reason isn't listed on the Liverpool site. At this point, I needed help with determining whether flunisolide would be safe to administer with cobicistat. Cue up the query to our ID Pharm.D.'s.
Shortly after sending an email, I received the following incredibly helpful response:
Beclomethasone is the only corticosteroid that has been shown to have no clinically significant interaction, likely due to the fact that it is not primarily metabolized by CYP3A4. Flunisolide is also not primarily metabolized by 3A4 and has similar physicochemical properties as beclomethasone (less systemic absorption and more highly protein bound) -- here's a good review. Theoretically it would have the lowest likelihood of an interaction out of the alternatives they recommended, but there are no studies or case reports of flunisolide use with ritonavir or cobicistat. If you decide to prescribe flunisolide, you could start at the initial dose of 2 sprays in each nostril BID, which is half of the maximum dose of 8 sprays in each nostril daily. Let me know if you have any further questions.
Thank you, Brandon!
And to the other ID Pharm.D.'s out there, thanks for the advice on the innumerable other drug interactions, for guidance on dosing in renal failure, for questions about formulations (about which doctors know shockingly little), for interpretation of voriconazole, vancomycin, and aminoglycoside levels, for researching adverse drug effects -- and for the whole gamut of expertise you bring to our specialty.
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