Pharmacokinetic enhancer (booster) for antiretroviral therapy
ATC code: V03AX03 (Cobicistat)
Brand names
Tybost, Evotaz, Prezcobix
Strong reversible inhibitor of CYP3A4 and, to a lesser extent, CYP2D6, MATE1 and P-glycoprotein. Has no antiretroviral activity on its own – it is given only in fixed-dose combinations with darunavir, atazanavir or elvitegravir to raise and sustain their therapeutic concentrations. CYP3A4 inhibition is similar to ritonavir but with less impact on lipids and glycaemia.
First line
Cobicistat is a pharmacokinetic enhancer in first-line antiretroviral therapy for HIV. GeSIDA 2024 recommends cobicistat-based combinations (Symtuza, Genvoya, Evotaz) in patients who need darunavir- or elvitegravir-based regimens with preserved renal function (eGFR > 70 mL/min). Drug-interaction review is mandatory – cobicistat inhibits CYP3A4 and raises levels of most co-administered drugs.
8 pairs found. Sorted from critical to minor.
Mechanism
Cobicistat is a strong CYP3A4 inhibitor. Tybost Section 4.3 strict contraindication with ergot alkaloids.
Symptoms
Fatal ergotism.
Management
Combination contraindicated.
Mechanism
Cobicistat is a strong CYP3A4 inhibitor (similar to ritonavir). Everolimus rises 10+ fold.
Symptoms
Acute immunosuppression.
Management
Combination contraindicated.
Mechanism
Lovastatin is a CYP3A4 sensitive substrate (like simvastatin). Cobicistat causes 30-fold rise. Tybost Section 4.3.
Symptoms
Rhabdomyolysis within 5–10 days.
Management
Combination contraindicated. Pravastatin or rosuvastatin.
Mechanism
Cobicistat is a strong CYP3A4 inhibitor (potency similar to ritonavir). Tybost Section 4.3 strict contraindication with pimozide.
Symptoms
QT prolongation, syncope, torsades de pointes.
Management
Combination contraindicated. For HIV, switch to a regimen without cobicistat (dolutegravir + 2 NRTIs).
Mechanism
Cobicistat inhibits CYP3A4 (quinidine metabolism) and itself prolongs PR via MATE1 inhibition. Quinidine concentration rises, additive QT effect.
Symptoms
QT prolongation, torsades de pointes.
Management
Combination contraindicated.
Mechanism
Strong CYP3A4 inducer. Cobicistat falls 80% – ART failure.
Symptoms
Rising viral load, resistance risk.
Management
Combination contraindicated. TB in HIV patient – dolutegravir-based ARV (double dose with rifampicin).
Mechanism
Cobicistat is a strong CYP3A4 inhibitor. Simvastatin rises 30-fold with fatal rhabdomyolysis risk. Tybost Section 4.3.
Symptoms
Myalgia, weakness, dark urine within 5 days.
Management
Combination contraindicated. Alternative statin: pravastatin 20–40 mg or rosuvastatin 5–10 mg.
Mechanism
Sirolimus is a CYP3A4 sensitive substrate, P-gp substrate, NTI. Cobicistat raises concentration 10+ fold with severe toxicity: nephrotoxicity, hepatotoxicity, cytopenia.
Symptoms
Rising creatinine, thrombocytopenia, hepatitis within days.
Management
Combination contraindicated. For HIV in transplant patient – regimen without cobicistat.
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Cobicistat levels fall by ~50% in the second and third trimesters, risking loss of antiretroviral effect. EMA advises against starting a cobicistat-based regimen in pregnancy; women who conceive on therapy are switched to a ritonavir-boosted regimen.
Breastfeeding by women with HIV is not recommended in Spain irrespective of the regimen, due to vertical transmission risk.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Cobicistat is evaluated for the following indications with varying evidence strength: HIV infection (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of Cobicistat (≥ 1 in 100): Nausea, Diarrhoea, Headache, Rash, Creatinine rise of 0.1–0.15 mg/dL (artefactual, not nephrotoxicity). See the Safety section for uncommon and serious reactions.
FDA category C. Cobicistat levels fall by ~50% in the second and third trimesters, risking loss of antiretroviral effect. EMA advises against starting a cobicistat-based regimen in pregnancy; women who conceive on therapy are switched to a ritonavir-boosted regimen.
Breastfeeding by women with HIV is not recommended in Spain irrespective of the regimen, due to vertical transmission risk.
Cobicistat is contraindicated in: Co-administration with CYP3A4-sensitive drugs (simvastatin, lovastatin, dronedarone, amiodarone at start, cisapride, oral midazolam, pimozide, ergotamine and other ergot alkaloids, sildenafil for pulmonary hypertension); Strong CYP3A4 inducers (rifampicin, phenytoin, phenobarbital, carbamazepine, St John's wort); Severe renal impairment (eGFR < 50 mL/min) for tenofovir disoproxil regimens. Full list in the Safety section.