Indications for TYBOST:
HIV-1 infection: to increase systemic exposure of atazanavir (adults and pediatric patients weighing ≥35kg) or darunavir (adults and pediatric patients weighing ≥40kg) for once-daily dosing, in combination with other antiretroviral agents.
Limitations of Use:
Not interchangeable with ritonavir to increase systemic exposure of darunavir 600mg twice daily, fosamprenavir, saquinavir, or tipranavir. Different drug interactions possible when cobicistat and ritonavir given with either atazanavir or darunavir.
Adults and Children:
<12yrs (<35kg): not established (with atazanavir) or (<40kg): not established (with darunavir). Take with food. Must be co-administered at same time as atazanavir or darunavir. ≥12yrs (≥35kg): 150mg once daily with atazanavir 300mg once daily (if treatment-naïve or experienced); or (≥40kg): 150mg once daily with darunavir 800mg once daily (if treatment-naïve or experienced with no darunavir resistance associated substitutions).
Concomitant alfuzosin, ranolazine, dronedarone, carbamazepine, phenobarbital, phenytoin, colchicine (in renal and/or hepatic impairment), rifampin, irinotecan (with atazanavir only), lurasidone, pimozide, ergots, cisapride, St. John’s wort, lomitapide, lovastatin, simvastatin, drospirenone/ethinyl estradiol (with atazanavir only), nevirapine (with atazanavir only), sildenafil (as Revatio for PAH), indinavir (with atazanavir only), triazolam, oral midazolam.
Assess CrCl prior to initiation and during treatment. Renal impairment: consider alternatives that do not require dose adjustments. When concomitant tenofovir disoproxil fumarate (TDF): assess baseline CrCl, urine glucose, urine protein and monitor during treatment; not recommended if CrCl <70mL/min; measure serum phosphorus in patients with or at risk for renal impairment. Severe hepatic impairment. Pregnancy, nursing mothers: not recommended.
See Contraindications. Concomitant nephrotoxic agents with cobicistat + TDF: not recommended. Concomitant darunavir 600mg twice daily or darunavir in combination with efavirenz, nevirapine, etravirine; atazanavir in combination with etravirine or efavirenz (in treatment-experienced); more than 1 antiretroviral that requires PK enhancement, other HIV-1 protease inhibitors (eg, fosamprenavir, saquinavir, tipranavir), rivaroxaban, voriconazole, boceprevir, simeprevir, salmeterol, avanafil: not recommended. Concomitant lopinavir/ritonavir, other ritonavir- or cobicistat-containing fixed-dose combination tabs or regimens: not recommended. May need to adjust dose of dasatinib, nilotinib, colchicine, sildenafil, tadalafil, vardenafil, perphenazine, risperidone, thioridazine, buprenorphine, buprenorphine/naloxone, methadone, tramadol, bosentan, rifabutin, and sedatives/hypnotics; see full labeling. May potentiate apixaban (with atazanavir or darunavir); betrixaban, dabigatran, edoxaban (with atazanavir). Concomitant maraviroc: give maraviroc 150mg twice daily. Concomitant quetiapine: consider alternative antiretrovirals; if necessary, reduce quetiapine to ⅙ of current dose and monitor. Monitor with antiarrhythmics, digoxin, clonazepam, SSRIs, TCAs, trazodone, antifungals, fentanyl, immunosuppressants, other statins (eg, atorvastatin, rosuvastatin), β-blockers, calcium channel blockers. Monitor INR with warfarin. Concomitant antibacterials (eg, clarithromycin, erythromycin, telithromycin), CYP3A-inducing anticonvulsants that are not contraindicated (eg, eslicarbazepine, oxcarbazepine), corticosteroids (eg, oral dexamethasone, betamethasone): consider alternatives. Concomitant vincristine, vinblastine: monitor for hematologic or GI adverse effects. Concomitant hormonal contraceptives: consider additional or alternative (non-hormonal) contraception. Separate dosing with concomitant H2 receptor antagonists, PPIs (not recommended in treatment-experienced), or antacids (at least 2hrs).
Jaundice, rash, ocular icterus, nausea, diarrhea, headache; serum creatinine increase.