TYBOST
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TYBOST (TYBOST).
CYP3A inhibitor; increases plasma concentrations of coadministered antiretroviral drugs that are substrates of CYP3A.
| Metabolism | Primarily hepatic via CYP3A4; minor contributions from CYP2D6 and CYP2C9. |
| Excretion | Renal (approx. 8% unchanged) and biliary/fecal (majority as metabolites). |
| Half-life | Terminal elimination half-life is 5.5-7 hours in healthy subjects; clinically, supports once-daily dosing with ritonavir or cobicistat. |
| Protein binding | Approximately 97-98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is 0.3-0.4 L/kg, indicating distribution primarily in extracellular fluid. |
| Bioavailability | Oral bioavailability is not well defined; absorption is at least 70% based on mass balance studies. |
| Onset of Action | Oral: Inhibition of CYP3A occurs within 2-4 hours after a single dose. |
| Duration of Action | CYP3A inhibition persists for 12-24 hours, allowing once-daily dosing as a pharmacokinetic enhancer. |
| Molecular Weight | 625.6 |
150 mg orally once daily, coadministered with a protease inhibitor (atazanavir or darunavir) and an HIV-1 regimen.
| Dosage form | TABLET |
| Renal impairment | Cobicistat (TYBOST) is not recommended in patients with CrCl <70 mL/min when coadministered with tenofovir disoproxil fumarate due to increased tenofovir exposure. For other combinations, no dose adjustment is required for CrCl ≥50 mL/min; insufficient data for CrCl <50 mL/min. |
| Liver impairment | No dose adjustment required for mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Not recommended in severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | Not approved for pediatric patients weighing <35 kg. For patients ≥35 kg, dose as adults: 150 mg orally once daily. |
| Geriatric use | No age-specific dose adjustment recommended. Limited data in patients ≥65 years; dosing should be cautious due to higher frequency of renal or hepatic impairment. |
| 1st trimester | No adequate studies in pregnant women; use only if clearly needed. |
| 2nd trimester | No data; potential for harm unknown; consider risk-benefit. |
| 3rd trimester | No data; potential for harm unknown; consider risk-benefit. |
Clinical note
Comprehensive clinical and safety monograph for TYBOST (TYBOST).
| Placental transfer | Crosses placenta in animals; no human data. |
| Breastfeeding | No data on excretion in human milk; due to potential for adverse effects in nursing infants, discontinue drug or nursing. |
| Lactation Rating | L4: Possibly Hazardous |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to cobicistat or any componentConcomitant use with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious adverse events (e.g., alfuzosin, amiodarone, quinidine, ergot derivatives, cisapride, pimozide, midazolam, triazolam, lovastatin, simvastatin, sildenafil for pulmonary hypertension)
| Precautions | Hepatotoxicity, Renal impairment (contraindicated with CrCl <70 mL/min for tenofovir disoproxil fumarate-containing regimens), Drug interactions due to CYP3A inhibition, Lipid abnormalities |
| Food/Dietary | Take with food to reduce gastrointestinal side effects. Avoid St. John's wort as it may reduce cobicistat levels and lead to treatment failure. No specific food restrictions beyond general healthy diet. |
Loading safety data…
| Teratogenic Risk | Pregnancy Category C. No adequate human studies; animal studies show fetal toxicity at high doses. First trimester: potential for miscarriage; second/third trimester: avoid due to decreased AUC, risking virologic failure. |
| Fetal Monitoring | Monitor HIV viral load, CD4 count, hepatic function (ALT/AST), and renal function (serum creatinine) throughout pregnancy. Assess for potential drug interactions. |
| Fertility Effects | No adverse effects on fertility observed in animal studies; no human data available. |
| Clinical Pearls | Cobicistat is a potent CYP3A4 inhibitor used as a pharmacokinetic booster for HIV protease inhibitors and elvitegravir. Not active against HIV itself. Monitor serum creatinine as cobicistat inhibits tubular secretion of creatinine, causing benign increases without affecting actual GFR. Do not use with drugs highly dependent on CYP3A4 for clearance (e.g., sildenafil for PAH, midazolam, triazolam). Use with caution in patients with severe hepatic impairment. |
| Patient Advice | Take exactly as prescribed with food to improve tolerability. · Do not skip doses or stop without consulting your doctor. · Report any signs of kidney problems (decreased urination, swelling in legs/ankles). · Inform your doctor about all other medications, including over-the-counter and herbal products. · Cobicistat does not cure HIV or prevent transmission; use safer sex practices. |