Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
Last Updated: May 22, 2018; Last Reviewed: May 22, 2018
|Cobicistat (COBI, Tybost)
For additional information see Drugs@FDA: https://www.accessdata.fda.gov/scripts/cder/daf/
|Tablets: 150 mg
Fixed-Dose Combination Tablets:
|Dosing Recommendations||Selected Adverse Events|
|Cobicistat is a Pharmacokinetic (PK) Enhancer:
Not Food and Drug Administration (FDA)-Approved for Use in Children Aged <18 Years:
- Metabolism: Cobicistat is an inhibitor of cytochrome P (CYP) 3A4 and a weak inhibitor of CYP2D6. In addition, cobicistat inhibits adenosine triphosphate-dependent transporters, breast cancer resistance protein, and P-glycoprotein (Pgp), and the organic anion transporting polypeptides OAT1B1 and OAT1B3. By inhibiting Pgp intestinal secretion, cobicistat increases the bioavailability of tenofovir alafenamide (TAF) by 2.2-fold, so the 10-mg dose of TAF in Genvoya is equivalent to the 25-mg dose of TAF found in other coformulated, TAF-containing preparations that do not contain cobicistat.1,2 The potential exists for multiple drug interactions when using cobicistat. Before cobicistat is administered, a patient’s medication profile should be carefully reviewed for potential interactions and overlapping toxicities with other drugs.
- While cobicistat and ritonavir are both strong inhibitors of CYP3A4,3 they are not interchangeable,4,5 and administration with either atazanavir or darunavir may result in different drug interactions. Darunavir induces cobicistat clearance and leads to a shorter cobicistat half-life; atazanavir decreases cobicistat clearance and increases cobicistat half-life.6
- Cobicistat is a stronger Pgp inhibitor than ritonavir and therefore has a greater effect than ritonavir on intestinal absorption of drugs that are metabolized by Pgp, like dabigatran.7 Cobicistat boosts dolutegravir concentrations to a greater extent than ritonavir, presumably also due to a Pgp interaction.8
- Dexamethasone induces CYP3A4 and decreases cobicistat half-life, potentially decreasing concentrations of the antiretroviral (ARV) drugs that cobicistat is boosting. Cobicistat inhibits the clearance of corticosteroids whose exposures are significantly increased by CYP3A4 inhibitors (e.g., fluticasone), potentially leading to adrenal suppression or Cushing syndrome.
- More common: Nausea, vomiting, diarrhea, abdominal pain, anorexia.
- Less common (more severe): New onset or worsening of renal impairment when used with tenofovir disoproxil fumarate. Rhabdomyolysis; increased amylase and lipase.
Not applicable. Cobicistat has no antiviral activity. Its sole use is as a pharmacokinetic enhancer of ARV drugs.
Cobicistat alone (as Tybost), or cobicistat coformulated with atazanavir (as Evotaz) or darunavir (as Prezcobix), or as a component of Stribild, is not Food and Drug Administration (FDA)-approved for use in children aged <18 years. Cobicistat as a component of Genvoya is FDA-approved at the adult dose in children aged ≥6 years and weighing ≥25 kg. The safety of cobicistat as a component of Genvoya in this age and weight group suggests the cobicistat component would be safe in other formulations, as well.9
- Ruane PJ, DeJesus E, Berger D, et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of tenofovir alafenamide as 10-day monotherapy in HIV-1-positive adults. J Acquir Immune Defic Syndr. 2013;63(4):449-455. Available at http://www.ncbi.nlm.nih.gov/pubmed/23807155.
- Lepist EI, Phan TK, Roy A, et al. Cobicistat boosts the intestinal absorption of transport substrates, including HIV protease inhibitors and GS-7340, in vitro. Antimicrob Agents Chemother. 2012;56(10):5409-5413. Available at http://www.ncbi.nlm.nih.gov/pubmed/22850510.
- Hossain MA, Tran T, Chen T, Mikus G, Greenblatt DJ. Inhibition of human cytochromes P450 in vitro by ritonavir and cobicistat. J Pharm Pharmacol. 2017;69(12):1786-1793. Available at https://www.ncbi.nlm.nih.gov/pubmed/28960344.
- von Hentig N. Clinical use of cobicistat as a pharmacoenhancer of human immunodeficiency virus therapy. HIV/AIDS. 2016;8:1-16. Available at http://www.ncbi.nlm.nih.gov/pubmed/26730211.
- Tseng A, Hughes CA, Wu J, Seet J, Phillips EJ. Cobicistat versus ritonavir: similar pharmacokinetic enhancers but some important differences. Ann Pharmacother. 2017;51(11):1008-1022. Available at https://www.ncbi.nlm.nih.gov/pubmed/28627229.
- Elliot ER, Amara A, Pagani N, et al. Once-daily atazanavir/cobicistat and darunavir/cobicistat exposure over 72 h post-dose in plasma, urine and saliva: contribution to drug pharmacokinetic knowledge. J Antimicrob Chemother. 2017;72(7):2035-2041. Available at https://www.ncbi.nlm.nih.gov/pubmed/28407075.
- Kumar P, Gordon LA, Brooks KM, et al. Differential influence of the antiretroviral pharmacokinetic enhancers ritonavir and cobicistat on intestinal p-glycoprotein transport and the pharmacokinetic/pharmacodynamic disposition of dabigatran. Antimicrob Agents Chemother. 2017;61(11). Available at https://www.ncbi.nlm.nih.gov/pubmed/28848011.
- Gervasoni C, Riva A, Cozzi V, et al. Effects of ritonavir and cobicistat on dolutegravir exposure: when the booster can make the difference. J Antimicrob Chemother. 2017;72(6):1842-1844. Available at https://www.ncbi.nlm.nih.gov/pubmed/28333266.
- Cobicistat [package insert]. Food and Drug Administration. 2014 Available at http://www.gilead.com/~/media/Files/pdfs/medicines/hiv/tybost/tybost_pi.pdf.