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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TYBOST (TYBOST).
| Breastfeeding | No data on human milk excretion; M/P ratio unknown. Administer with caution in breastfeeding women; potential for infant CYP3A inhibition. |
| 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 |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concomitant use with drugs highly dependent on CYP3A for clearance (e.g., alfuzosin, cisapride, ergot derivatives, lovastatin, simvastatin, sildenafil for PAH, triazolam, midazolam, pimozide)","Severe hepatic impairment"]
| Precautions | ["Hepatotoxicity","Renal impairment (contraindicated with CrCl <70 mL/min for tenofovir disoproxil fumarate-containing regimens)","Drug interactions due to CYP3A inhibition","Lipid abnormalities"] |
Loading safety data…
| 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. |