VIEKIRA XR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIEKIRA XR (VIEKIRA XR).
VIEKIRA XR contains dasabuvir, ombitasvir, paritaprevir, and ritonavir. Dasabuvir inhibits HCV NS5B RNA-dependent RNA polymerase, ombitasvir inhibits NS5A, paritaprevir inhibits NS3/4A protease, and ritonavir boosts paritaprevir levels via CYP3A4 inhibition.
| Metabolism | Dasabuvir: metabolized by CYP2C8, with minor CYP3A4 involvement. Ombitasvir: primarily metabolized by amide hydrolysis. Paritaprevir: metabolized by CYP3A4. Ritonavir: metabolized by CYP3A4 and CYP2D6. |
| Excretion | Daunorubicin is eliminated via hepatic metabolism (daunorubicinol) and biliary excretion; renal excretion accounts for approximately 25% of total clearance, with 15-20% as unchanged drug and 5-10% as metabolites in urine over 72 hours; fecal excretion accounts for about 40% (mainly metabolites). |
| Half-life | Daunorubicin: 24-48 hours; daunorubicinol: 26-50 hours; clinically, the prolonged half-life contributes to cumulative cardiotoxicity risk. |
| Protein binding | Daunorubicin: approximately 50-60% bound to albumin and other plasma proteins. |
| Volume of Distribution | Vd: approximately 1.0-1.5 L/kg (wide tissue distribution, extensive binding to DNA); clinical meaning: high Vd indicates extensive extravascular distribution and tissue accumulation, particularly in heart, kidney, lung, and spleen. |
| Bioavailability | Oral: negligible (not absorbed); IV: 100%. |
| Onset of Action | IV: Antineoplastic effect begins within minutes; clinical response may take days to weeks depending on cell cycle. |
| Duration of Action | Duration of cytotoxic effect is prolonged due to DNA intercalation and free radical formation; effects persist for days to weeks. Myelosuppression nadir at 10-14 days with recovery by 21-28 days. |
VIEKIRA XR (dasabuvir, ombitasvir, paritaprevir, ritonavir) extended-release tablets: 1 tablet (dasabuvir 250 mg, ombitasvir 12.5 mg, paritaprevir 75 mg, ritonavir 50 mg) orally once daily with a meal.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for any degree of renal impairment, including end-stage renal disease (ESRD) on hemodialysis. |
| Liver impairment | Contraindicated in Child-Pugh class B or C hepatic impairment. No dose adjustment for Child-Pugh class A. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended based on age; clinical studies included patients ≥65 years with no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VIEKIRA XR (VIEKIRA XR).
| Breastfeeding | No data on drug excretion in human milk; ribavirin is concentrated in animal milk. M/P ratio unknown; potential for serious adverse reactions in nursing infants, including ribavirin-induced hemolysis. Discontinue breastfeeding or consider alternative therapy. |
| Teratogenic Risk | First trimester: ribavirin component is contraindicated due to teratogenicity; dasabuvir, ombitasvir, paritaprevir, ritonavir show limited human data but animal studies indicate no major malformations. Second and third trimesters: potential risk of fetal hepatotoxicity and impaired growth; ribavirin may cause fetal anemia. Avoid in pregnancy unless benefit outweighs risk; women of childbearing potential must use contraception during and 6 months after therapy. |
■ FDA Black Box Warning
WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV. Test all patients for evidence of current or prior HBV infection before initiating treatment. Monitor HCV/HBV coinfected patients for HBV reactivation during and post-treatment. If HBV reactivation occurs, discontinue VIEKIRA XR and initiate appropriate HBV treatment.
| Serious Effects |
Severe hepatic impairment (Child-Pugh Class C); concomitant use with drugs highly dependent on CYP3A4 (e.g., alfuzosin, amiodarone, ergot derivatives, lovastatin, simvastatin, midazolam oral, pimozide, sildenafil for PAH, triazolam) or strong CYP2C8 inhibitors; hypersensitivity to any component.
| Precautions | Risk of HBV reactivation; hepatic decompensation/failure in patients with cirrhosis; ALT elevations; increased risk of bleeding with warfarin; drug interactions (e.g., CYP3A4 substrates); sulfonamide allergy (cross-reactivity with paritaprevir). |
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| Fetal Monitoring | Monitor hepatic function (ALT, AST, bilirubin) monthly; complete blood count with differential for ribavirin-related anemia; viral load and HCV RNA at treatment end and 12-24 weeks post-therapy. In pregnancy, monitor fetal growth via ultrasound and assess for liver function abnormalities. |
| Fertility Effects | Ribavirin may impair spermatogenesis with reversible oligospermia in males; female fertility effects not specifically reported but ribavirin is teratogenic, requiring contraception during and 6 months after therapy. No known effects from dasabuvir, ombitasvir, paritaprevir, ritonavir on fertility in animal studies. |