Table 3.
Drugs contraindicated or not recommended with darunavir/cobicistat and mechanism of interaction between drugs
| Drug class | Drug within class | Mechanism of interaction | Coadministration recommendation |
|---|---|---|---|
| Non-nucleoside reverse transcriptase inhibitors | Efavirenza, nevirapinea, etravirinea | Induction of CYP3A by NNRTI | Not recommended |
| Antianginal/antiarrhythmic | Amiodarone, bepridil, dronedarone, systemic lidocaine, quinidine, ranolazine | Inhibition of CYP3A by COBI | Contraindicated |
| Anticoagulant/platelet aggregation inhibitor | Apixaban, dabigatran, rivaroxaban ticagrelor | Inhibition of CYP3A/P-gp by COBI | Not recommended (contraindicated with ticagrelor) |
| Anticonvulsants | Carbamazepine, phenobarbital, phenytoin | Induction of CYP3A by anticonvulsants | Contraindicated |
| Antimycobacterials | Rifampicin rifabutina rifapentine | Induction of CYP3A by rifamycins | Contraindicated with rifampicin and not recommended with rifabutin and rifapentine |
| Anti-neoplastics | Everolimus | Inhibition of CYP3A by COBI | Not recommended |
| Antipsychotics/neuroleptics | Pimozide, sertindole, quetiapine | Inhibition of CYP2D6 by COBI | Contraindicated |
| Corticosteroids | Budesonide, fluticasone | Inhibition of CYP3A by COBI | Not recommended |
| Endothelin receptor antagonists | Bosentan | Induction of CYP3A by bosentan | Not recommended |
| Direct-acting antivirals (HCV) | Boceprevir, telaprevir, simeprevir | Multidirectional interaction | Not recommended |
| HMG-CoA reductase inhibitors | Lovastatin, simvastatin | Inhibition of CYP3A by COBI | Contraindicated |
| Inhaled beta-agonists | Salmeterol | Inhibition of CYP3A by COBI | Not recommended |
| Phosphodiesterase 5 inhibitors | Sildenafil (for pulmonary arterial hypertension), avanafil | Inhibition of CYP3A by COBI | Contraindicated |
| Sedatives/hypnotics | Oral midazolam, triazolam | Inhibition of CYP3A by COBI | Contraindicated |
| Ergot derivatives | Dihydroergotamine, ergometrine, ergotamine | Inhibition of CYP3A by COBI | Contraindicated |
| Herbal supplements | Hypericum perforatum (St. John’s wort). | Induction of CYP3A by Hypericum | Contraindicated |
Notes: If CYP3A is inhibited by cobicistat, plasma concentrations of the coadministered drug increase, with the subsequent risk of greater toxicity. If CYP3A is induced by another drug, darunavir and/or cobicistat plasma concentrations decrease, with the subsequent risk of virological failure.
The prescribing recommendations for these drugs differ between darunavir/cobicistat and darunavir/ritonavir. Reproduced from Rezolsta® [prescribing information]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002819/WC500178953.pdf. Accessed August 19, 2016.14
Abbreviations: COBI, cobicistat; CYP, cytochrome P450; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A.