Cobicistat approved as PK booster
September 26, 2014
Cobicistat, a CYP3A inhibitor, has been approved by the FDA to be used as a pharmacokinetic booster for atazanavir and once-daily darunavir. Thus, it can be used as an alternative to ritonavir in these combinations. It already is available as a PK enhancer of elvitegravir in the elvitegravir/cobicistat/tenofovir/emtricitabine coformulation (Stribild). Cobicistat’s brand name is Tybost.
Dosing is as follows:
- cobicistat 150 mg once daily + atazanavir 300 mg once daily
- cobicistat 150 mg once daily + darunavir 800 mg once daily
- cobicistat 150 mg once daily + elvitegravir 150 mg once daily (available in coformulation with tenofovir/emtricitabine)
Cobicistat has not been well studied in combination with other antiretrovirals or other classes of medications and it will be important to consult prescribing information on specific interactions. The approval announcement from the FDA emphasizes that cobicistat should not be considered equivalent to ritonavir from a PK standpoint. Based on the limited information currently available on interactions with other ARVs,
Cobicistat is OKAY to use with:
- once-daily darunavir (800 mg) in patients without darunavir-associated mutations
Cobicistat is NOT OKAY to use with:
- BID darunavir
- protease inhibitors other than atazanavir and once-daily darunavir
- a protease inhibitor + elvitegravir
- efavirenz, etravirine, nevirapine
Interactions with other CYP 3A4 inhibitors or inducers may affect plasma levels of either cobicistat, the co-administered atazanavir or darunavir, or the other drug. Some agents should be avoided, and others should be used with caution.
Symptomatic adverse effects are similar to those of ritonavir: nausea and diarrhea. When cobicistat is given with atazanavir, the risk of icterus is increased. Cobicistat may decrease renal secretion of creatinine, without affecting actual GFR. The FDA recommends that it not be used in combination with tenofovir in patients with CrCl <70 mg/dL. Renal function should be assessed before cobicistat is given (eg, by checking serum creatinine, urine protein, and urine glucose).
Cobicistat has no antiretroviral activity and does not select for resistance mutations.
For further information consult prescribing information, soon to be available at [email protected],
Susa Coffey is medical editor of the NCRC. She is a Professor of Medicine at UCSF in the Division of HIV, Infectious Diseases and Global Medicine and a longtime clinician and educator in the HIV at San Francisco General Hospital clinic (“Ward 86”). She also is medical editor of HIV InSite.