Drug information of cobicistat

Mechanism of effect

Cobicistat is a mechanism-based inhibitor of cytochrome P450 3A (CYP3A) isoforms. Inhibition of CYP3A-mediated metabolism by cobicistat increases the systemic exposure of CYP3A substrates atazanavir and darunavir and therefore enables increased anti-viral activity at a lower dosage. Cobicistat does not have any anti-HIV activity on its own. Increasing systemic exposure of anti-retrovirals (ARVs) without increasing dosage allows for better treatment outcomes and a decreased side effect profile.

Pharmacodynamic

Not Available

Pharmacokinetics

Peak Plasma Time: 3.5 hr

Peak Plasma Concentration: 0.99 mcg/mL

Trough Plasma Concentration: 0.03 mcg/mL

AUC: 7.6 mcg•hr/mL

Protein bound: 97-98%

Metabolism

Metabolized by CYP3A4 and CYP2D6 (minor)

Inhibits CYP3A, CYP2D6, p-glycoprotein (P-gp), BCRP, OATP1B1, and OATP1B3

Half-life: 3-4 hr

Excretion: 86.2% feces; 8.2% urine

Dosage

Adult

Pharmacokinetic Enhancer for HIV Treatment

Coadministered with atazanavir

• 150 mg PO qDay with atazanavir 300 mg PO qDay

Coadministered with darunavir

• 150 mg PO qDay with darunavir 800 mg PO qDay

Pediatric

Safety and efficacy not established

Side effects

depression , Insomnia , Diarrhea , Headache , nausea , vomiting , Increased ALT , Increased AST , Hyperbilirubinemia , tiredness , Rash , Ocular icterus , Creatine kinase , Urine RBC, >75 RBC/HPF , Nephropathy , Fanconi syndrome

Interactions

Medroxyprogesterone , Midazolam , Dorzolamide and timolol , saquinavir , Meglumine Compound , Mefloquine , brigatinib , Efavirenz , Copanlisib , Simeprevir , Etravirine , Dabrafenib , Netilmicin , Acalabrutinib , Maraviroc , Halofantrine , Amiodarone , Erythromycin , Everolimus , Irinotecan , Budesonide , Bosentan , silodosin , Venetoclax , tolvaptan , Bepridil , levomethadyl acetate , neratinib , eszopiclone , lurasidone , glasdegib , Ceritinib , Eliglustat , Ruxolitinib , riociguat , conivaptan , Cariprazine , Cobimetinib , Temsirolimus , Naloxegol , Larotrectinib , gilteritinib , midostaurin , elagolix , ivosidenib , Sonidegib , Crizotinib , Cabozantinib , Isavuconazonium , Iloperidone , Pimavanserin , trabectedine , Duvelisib , encorafenib , Alfuzosin , Pazopanib , Palbociclib , Butorphanol , olaparib , Ibrutinib , Triazolam , Lumefantrine / artemether , Darifenacin , red yeast rice , Fostamatinib , Fesoterodine , Ribociclib , Ticagrelor , Guanfacine , Hydrocodone , Fosphenytoin , Ivacaftor , Ivabradine , Mifepristone , Eluxadoline , Alfentanil , Osimertinib , Panobinostat , Lomitapide , Axitinib , dronedarone , eletriptan , mitotane , valbenazine , Rifapentine , Ranolazine , Quetiapine , Toremifene , Quinidine , Oxycodone , Daclatasvir , eplerenone , ergotamine , fentanyl , ergonovine , Rifabutin , Carbamazepine , Colchicine , Solifenacin , Enzalutamide , Flecainide , Rivaroxaban , Nilotinib , Nimodipine , Vardenafil , Vinblastin , Vincristin , Vinorelbine , Fluticasone , Phenobarbital , Phenytoin , Phenylephrine , Lovastatin , Methylprednisolone , Sirolimus , Cisapride , Sildenafil , Cilostazol , Simvastatin , Cyclosporine , Deflazacort , Docetaxel , Dihydroergotamine , Disopyramide , Rifampin , Salmeterol , Propafenone , Primidone , Pimozide , Tamsulosin , Triamcinolone , Thioridazine , Ixazomib , Flibanserin , Avanafil , Edoxaban , Entrectinib , Levomilnacipran , ELBASVIR/GRAZOPREVIR , Abemaciclib , Brexpiprazole , Gefitinib , Dasatinib , Cannabidiol , talazoparib , Macitentan , voxelotor , Capmatinib

Alerts

Cobicistat may cause modest increases in serum creatinine and modest declines in CrCl without affecting renal glomerular function; serum creatinine >0.4 mg/dL from baseline should be closely monitored for renal safety; assess CrCl before administering

CYP inducers may lower systemic exposure of cobicistat and atazanavir or darunavir, resulting in loss of virologic response

Cobicistat is an inhibitor of CYP3A, CYP2D6, p-glycoprotein (P-gp), BCRP, OATP1B1, and OATP1B3; plasma concentration of drugs that are substrates of the aforementioned isoenzymes or transporters may be increased if coadministered with cobicistat

Antiretrovirals that are not recommended

• The following are NOT recommended in combination with cobicistat because dosing recommendations for the combinations have not been established
• Coadministration may result in decreased plasma concentrations of the antiretroviral agents, leading to loss of therapeutic effect and development of resistance
• More than 1 antiretroviral that requires pharmacokinetic enhancement (ie, 2 protease inhibitors or a protease inhibitor in combination with elvitegravir)
• Darunavir in combination with efavirenz, nevirapine, or etravirine
• Atazanavir in combination with etravirine
• Atazanavir in combination with efavirenz in treatment-experienced patients
• Darunavir 600 mg BID
• Other HIV-1 protease inhibitors, including fosamprenavir, saquinavir, or tipranavir
• Stribild fixed-dose combination tablets (elvitegravir, cobicistat, emtricitabine, tenofovir) are not recommended because cobicistat is a component of Stribild
• Cobicistat in combination with lopinavir/ritonavir or regimens containing ritonavir are not recommended, owing to similar effects of cobicistat and ritonavir on CYP3A

Points of recommendation

• Tell all of your health care providers that you take cobicistat. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine interacts with many other drugs. The chance of cobicistat's side effects may be raised or how well cobicistat works may be lowered. The chance of the other drugs' side effects may also be raised. This may include very bad, life-threatening, or deadly side effects. Check with your doctor and pharmacist to make sure that it is safe for you to take cobicistat with all of your other drugs (prescription or OTC, natural products, vitamins).
• This medicine is not a cure for HIV. Stay under the care of your doctor.
• This medicine does not stop the spread of diseases like HIV or hepatitis that are passed through blood or having sex. Do not have any kind of sex without using a latex or polyurethane condom. Do not share needles or other things like toothbrushes or razors. Talk with your doctor.
• Do not run out of cobicistat.
• Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking cobicistat.

Use cobicistat as ordered by your doctor. Read all information given to you. Follow all instructions closely.

For all patients taking cobicistat:

• Take cobicistat with food.
• Take cobicistat at the same time as the other HIV drug you take it with (atazanavir or darunavir).
• Keep taking cobicistat as you have been told by your doctor or other health care provider, even if you feel well.
• It is important that you do not miss or skip a dose of cobicistat during treatment.

When taking cobicistat with atazanavir:

• Do not take antacids within 2 hours before or 2 hours after taking cobicistat.
• If you take cimetidine, dexlansoprazole, esomeprazole, famotidine, lansoprazole, nizatidine, omeprazole, pantoprazole, rabeprazole, or ranitidine, ask your doctor or pharmacist how to take it with cobicistat.

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Related drugs

ritonavir