Cobicistat has no inherent antiretroviral activity but is a strong CYP3A4 inhibitor that prevents the breakdown of HIV protease inhibitors which are metabolised via the CYP3A pathway, thereby increasing plasma levels of these drugs. It can be used instead of ritonavir in patients taking atazanavir or darunavir for the treatment of HIV-1 infection.
Tybost is available as a film-coated tablet containing 150mg cobicistat, to be taken once daily with food at the same time as atazanavir 300mg or darunavir 800mg.
Prescribers must be aware of the high potential of cobicistat for interaction with other drugs. Cobicistat strongly inhibits CYP3A4 and its use in combination with drugs that are extensively metabolised by this pathway and undergo a high degree of first-pass metabolism is contraindicated. Such drugs include amiodarone, quinidine, statins, alfuzosin, pimozide, sildenafil, oral midazolam and ergot derivatives.
Concomitant use of cobicistat with strong CYP3A4 inducers, such as carbamazepine, phenytoin, phenobarbital, rifampicin and St John's wort, is also contraindicated.
Cobicistat is not recommended for use in combination with drugs that are moderate to weak inhibitors or inducers of CYP3A4 and should be used with caution in patients taking any drug that is metabolised via the CYP3A metabolic pathway.
Cobicistat also inhibits the transporters P-glycoprotein, BCRP, MATE1, OATP1B1 and OATP1B3, and can result in increased plasma concentrations of drugs that are substrates of these transport systems.
Component of quadruple combination tablet
Until the launch of Tybost, cobicistat was available in the UK only as a component of the four-drug combination tablet Stribild, which also includes the integrase inhibitor elvitegravir and the nucleoside reverse transcriptase inhibitors emtricitabine and tenofovir. The inclusion of cobicistat, to prevent the metabolism of elvitegravir, allows Stribild to be given once daily.
Further information: Gilead Sciences