VITEKTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VITEKTA (VITEKTA).
VITEKTA (telaprevir) is a direct-acting antiviral agent that inhibits the NS3/4A serine protease of hepatitis C virus (HCV). This protease is essential for the cleavage of the HCV polyprotein into functional proteins required for viral replication. By blocking this enzyme, telaprevir disrupts viral replication and reduces viral load.
| Metabolism | Telaprevir is primarily metabolized by cytochrome P450 (CYP) 3A4 and to a lesser extent by CYP3A5. It is also a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily hepatic metabolism via CYP3A4, with 93% eliminated in feces as metabolites and 1% in urine as unchanged drug. |
| Half-life | Terminal elimination half-life is approximately 12 hours (range 10-14 hours) in healthy subjects, supporting once-daily dosing. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is 1.7 L/kg, indicating extensive tissue penetration and distribution beyond plasma volume. |
| Bioavailability | Oral bioavailability is approximately 70% in healthy subjects under fed conditions; food increases absorption (high-fat meal increases AUC by up to 50%). |
| Onset of Action | Oral: Onset of antiretroviral activity occurs within 2-4 hours after a single dose, with maximal viral suppression achieved by 2-4 weeks. |
| Duration of Action | Antiviral effect persists for 24 hours with once-daily dosing; duration is extended by co-administration with ritonavir or cobicistat due to pharmacokinetic boosting. |
| Molecular Weight | 776.02 |
800 mg orally once daily with food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in patients with severe renal impairment (CrCl <30 mL/min) or end-stage renal disease (ESRD). |
| Liver impairment | Mild (Child-Pugh A): no adjustment. Moderate (Child-Pugh B): not recommended. Severe (Child-Pugh C): contraindicated. |
| Pediatric use | For children aged ≥6 years and weighing ≥25 kg: 800 mg once daily with food. For children weighing 15 to <25 kg: 600 mg once daily with food. Safety and efficacy not established in children <6 years or <15 kg. |
| Geriatric use | No specific dose adjustment required; however, caution due to increased frequency of renal and hepatic impairment, and potential for decreased renal function. Monitor renal function closely. |
| 1st trimester | There are no adequate and well-controlled studies in pregnant women. Animal studies have shown reproductive toxicity. Use only if potential benefit justifies risk to fetus. |
| 2nd trimester | Limited human data; no evidence of major teratogenicity based on available reports. Use if clearly needed. |
| 3rd trimester | No known specific risks in third trimester; however, data are limited. Use with caution. |
Clinical note
Comprehensive clinical and safety monograph for VITEKTA (VITEKTA).
| Placental transfer | Cobicistat is highly bound to plasma proteins and has low molecular weight; limited data suggest minimal placental transfer, but exact degree is unknown. |
| Breastfeeding | It is not known whether cobicistat (VITEKTA) is excreted in human breast milk. Because of the potential for HIV transmission and adverse effects in nursing infants, breastfeeding is not recommended for HIV-infected mothers. |
■ FDA Black Box Warning
None
| Serious Effects |
Concurrent administration with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., alfuzosin, amiodarone, dronedarone, ergot derivatives, lomitapide, lovastatin, simvastatin, oral midazolam, pimozide, sildenafil for pulmonary arterial hypertension, triazolam, and St. John's wort).Severe hepatic impairment (Child-Pugh Class C).
| Precautions | Rash, including severe cases (Stevens-Johnson syndrome, DRESS syndrome) – may require discontinuation; monitor for progression., Anemia, including severe anemia requiring dose reduction or discontinuation of ribavirin., Neutropenia and thrombocytopenia associated with peginterferon alfa; laboratory monitoring required., Pancreatitis (rare but potentially fatal); discontinue if confirmed., Cardiovascular events (e.g., worsening of pre-existing cardiac disease) related to anemia or interferon therapy., Hepatic decompensation in patients with cirrhosis; monitor liver function closely., Drug interactions due to CYP3A4 inhibition; telaprevir is a strong inhibitor of CYP3A4, increasing exposure of many drugs. |
| Food/Dietary |
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| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | VITEKTA (telaprevir) is contraindicated in pregnancy due to teratogenicity observed in animal studies; first-trimester exposure associated with major birth defects including neural tube defects and cardiovascular malformations. Second and third trimester: risk continues with potential fetal harm; use only if benefit justifies risk after thorough counseling. |
| Fetal Monitoring | Pregnancy test required before initiation; monthly pregnancy testing during treatment; immediate ribavirin discontinuation if pregnancy occurs; fetal ultrasound and monitoring for anemia, hepatic function, and viral load. |
| Fertility Effects | Animal studies show testicular degeneration and reduced fertility in males; reversible upon discontinuation. Females: no impairment in fertility observed in rats; human data limited, but possible impact on spermatogenesis. |
| Take VITEKTA with food to enhance absorption (with atazanavir) or with a meal (with darunavir). Avoid St. John's wort, which decreases VITEKTA levels. Grapefruit juice may moderately increase cobicistat exposure; avoid large quantities. |
| Clinical Pearls | VITEKTA (cobicistat) is a pharmacokinetic enhancer, not an antiretroviral; it must be co-administered with atazanavir or darunavir. Monitor renal function closely due to potential for increased serum creatinine via inhibition of tubular secretion, without affecting actual glomerular filtration. Avoid in patients with CrCl <70 mL/min when used with tenofovir disoproxil fumarate due to increased tenofovir exposure. Do not use with rifampin, St. John's wort, or other strong CYP3A inducers. |
| Patient Advice | Take VITEKTA exactly as prescribed, with food to improve absorption. · Do not stop taking VITEKTA without consulting your doctor, as this may lead to loss of HIV control. · Report any symptoms of kidney problems, such as decreased urination, swelling, or flank pain. · VITEKTA does not cure HIV; continue to use barrier protection to prevent transmission. · Inform all healthcare providers that you are taking VITEKTA, especially before starting new medications. |