Darunavir and cobicistat are both inhibitors of the cytochrome P450 3A (CYP3A) isoform. SYMTUZA® should not be coadministered with medicinal products that are highly dependent on CYP3A for clearance and for which increased plasma concentrations are associated with serious and/or life-threatening events.
Darunavir and cobicistat are both substrates of the cytochrome P450 3A (CYP3A) isoform. Coadministration of SYMTUZA® with CYP3A inducers is expected to lower plasma concentrations of darunavir and cobicistat which may lead to loss of efficacy of darunavir and development of resistance.
These recommendations are based on drug interaction trials conducted with the components of SYMTUZA®, as individual agents or in combination, or are predicted interactions. No drug interaction trials have been performed with SYMTUZA® or with all the components administered together.
| Examples of drugs that are contraindicated | |
|---|---|
| Alpha 1-adrenoreceptor antagonist | alfuzosin |
| Anticonvulsants | carbamazepine, phenobarbital, phenytoin |
| Antigout | colchicine in patients with renal and/or hepatic impairment |
| Antimycobacterial | rifampin |
| Antipsychotics | lurasidone, pimozide |
| Cardiac disorders | dronedarone, ivabradine, ranolazine |
| Ergot derivatives | dihydroergotamine, ergotamine, methylergonovine |
| Hepatitis C direct-acting antivirals | elbasvir/grazoprevir |
| Herbal product | St. John’s wort (Hypericum perforatum) |
| Lipid-modifying agents | lomitapide, lovastatin, simvastatin |
| Opioid antagonist | naloxegol |
| PDE-5 inhibitor | sildenafil when used for treatment of pulmonary arterial hypertension |
| Sedatives/hypnotics | midazolam, triazolam |
| Examples of drugs where coadministration is not recommended | |
|---|---|
| Anticoagulant | rivaroxaban |
| Anticonvulsants | eslicarbazepine, oxcarbazepine |
| Antifungal | voriconazole |
| Antimycobacterials | rifabutin, rifapentine |
| Corticosteroids | betamethasone, budesonide, ciclesonide, dexamethasone (systemic), fluticasone, methylprednisolone, mometasone, triamcinolone |
| Hepatitis C direct-acting antivirals | glecaprevir/pibrentasvir |
| Immunosuppressant/neoplastic | everolimus, irinotecan |
| Inhaled beta agonist | salmeterol |
| PDE-5 inhibitor | avanafil |
| Platelet aggregation inhibitors | clopidogrel, ticagrelor |
