Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.
Last Updated: April 16, 2019; Last Reviewed: April 16, 2019
|Cobicistat (COBI, Tybost)
For additional information see Drugs@FDA: https://www.accessdata.fda.gov/scripts/cder/daf/
|Tablet: 150 mg
Fixed-Dose Combination Tablets:
|Dosing Recommendations||Selected Adverse Events|
|Cobicistat is a Pharmacokinetic Enhancer:
Not Food and Drug Administration (FDA)-Approved for Use in Children and Adolescents Aged <18 Years:
Cobicistat Must be Administered as:
- Metabolism: Metabolism of cobicistat is mainly via cytochrome P450 (CYP) 3A4 and, to a lesser degree, CYP2D6. Cobicistat is a strong inhibitor of CYP3A4 and a weak inhibitor of CYP2D6. Cobicistat also inhibits the breast cancer resistance protein, P-glycoprotein (P-gp), the organic anion transporting polypeptides OATP1B1 and OATP1B3, and multidrug and toxin extrusion 1. Unlike ritonavir, cobicistat does not demonstrate any enzyme-inducing effects. 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.
- Nucleoside reverse transcriptase inhibitors: Cobicistat is a strong P-gp inhibitor; thus, a dose of tenofovir alafenamide (TAF) 10 mg combined with cobicistat produces tenofovir exposures that are similar to those produced by TAF 25 mg without cobicistat.1
- Non-nucleoside reverse transcriptase inhibitors: Efavirenz, etravirine, and nevirapine should not be used with cobicistat.
- Protease inhibitors: Using cobicistat as a dual booster for elvitegravir and darunavir has been studied in people with HIV and people without HIV, and the evidence is conflicting. When elvitegravir plus cobicistat plus darunavir was administered to people without HIV, the Ctrough concentration of elvitegravir was 50% lower than the Ctrough concentration seen in people who received elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (TDF) without darunavir.2 When elvitegravir/cobicistat/emtricitabine/TAF was administered with darunavir to patients with HIV, both darunavir and elvitegravir concentrations were comparable to historic controls.3
- Integrase inhibitors: In one small study, dolutegravir Ctrough concentrations were higher when dolutegravir was administered with darunavir/cobicistat (DRV/c) than when it was administered with darunavir/ritonavir.4 Bictegravir area under the curve increases 74% when bictegravir is administered with DRV/c.5 Increased serum concentrations of corticosteroids can occur when corticosteroids and cobicistat are coadministered; this can lead to clinically significant adrenal suppression. Adrenal suppression occurs regardless of whether the corticosteroids are administered orally or by some other route (e.g., intranasal, inhaled, interlaminar) and regardless of whether the corticosteroids are administered routinely or intermittently. A possible exception is beclomethasone, which appears to be a relatively safe option with inhaled or intranasal administration.6
- More common: Nausea, vomiting, diarrhea, abdominal pain, anorexia.
- Less common (more severe): New onset renal impairment or worsening of renal impairment when used with TDF. Rhabdomyolysis; increased amylase and lipase levels.
Not applicable. Cobicistat has no antiviral activity. Its sole use is as a pharmacokinetic enhancer of antiretroviral drugs.
The Food and Drug Administration (FDA) has not approved the use of cobicistat alone (as Tybost), cobicistat coformulated with atazanavir (as Evotaz) or darunavir (as Prezcobix), or cobicistat as a component of Symtuza in children aged <18 years. Cobicistat, as a component of Stribild, is approved by the FDA at the adult dose for use in children and adolescents aged ≥12 years and weighing ≥35 kg. The Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV recommends limiting use to those with a sexual maturity rating of 4 or 5. Cobicistat, as a component of Genvoya, is approved by the FDA at the adult dose for use in children weighing ≥25 kg.
- Ramanathan S, Wei X, Custudio J, et al. Pharmacokinetics of a novel EVG/COBI/FTC/GS-7340 single tablet regimen. Abstract O-13. Presented at: 13th International Workshop on Clinical Pharmacology of HIV Therapy. 2012. Barcelona, Spain. Available at: http://www.natap.org/2012/pharm/Pharm_24.htm.
- Ramanathan S, Wang H, Szwarcberg J, Kearney BP. Safety/tolerability, pharmacokinetics, and boosting of twice-daily cobicistat administered alone or in combination with darunavir or tipranavir. Abstract abstract P-08. Presented at: 13th International Workshop on Clinical Pharmacology of HIV Therapy. 2012. Barcelona, Spain. Available at: http://www.natap.org/2012/pharm/Pharm_28.htm.
- Gutierrez-Valencia A, Trujillo-Rodriguez M, Fernandez-Magdaleno T, Espinosa N, Viciana P, Lopez-Cortes LF. Darunavir/cobicistat showing similar effectiveness as darunavir/ritonavir monotherapy despite lower trough concentrations. J Int AIDS Soc. 2018;21(2). Available at: https://www.ncbi.nlm.nih.gov/pubmed/29430854.
- 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.
- Zhang H, Custudio J, Wei X, et al. Clinical Pharmacology of the HIV integrase strand transfer inhibitor bictegravir. Abstract 40. Presented at: Conference on Retrovirsues and Opportunistic Infections. 2017. Seattle, Washington. Available at: http://www.croiconference.org/sessions/clinical-pharmacology-hiv-integrase-strand-transfer-inhibitor-bictegravir.
- Saberi P, Phengrasamy T, Nguyen DP. Inhaled corticosteroid use in HIV-positive individuals taking protease inhibitors: a review of pharmacokinetics, case reports and clinical management. HIV Med. 2013;14(9):519-529. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23590676.