VIEKIRA PAK (COPACKAGED)
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIEKIRA PAK (COPACKAGED) (VIEKIRA PAK (COPACKAGED)).
VIEKIRA PAK combines three direct-acting antiviral agents (dasabuvir, ombitasvir, paritaprevir, and ritonavir) that inhibit hepatitis C virus (HCV) nonstructural proteins: ombitasvir inhibits NS5A, paritaprevir inhibits NS3/4A protease, dasabuvir inhibits NS5B RNA polymerase, and ritonavir boosts paritaprevir levels by inhibiting CYP3A4.
| Metabolism | Paritaprevir and ritonavir are metabolized primarily by CYP3A4; ombitasvir is metabolized via amide hydrolysis; dasabuvir is metabolized primarily by CYP2C8. |
| Excretion | Dasabuvir: 94.4% fecal (mostly unchanged), 1.9% renal; Paritaprevir: 88.0% fecal (mostly unchanged), 8.8% renal; Ombitasvir: 90.2% fecal, 1.9% renal; Ritonavir: 86% fecal, 11% renal. |
| Half-life | Dasabuvir: 5.5-7.1h; Paritaprevir: 5.5h; Ombitasvir: 21-25h; Ritonavir: 3-5h. Clinical context: Supports once-daily dosing for ombitasvir, twice-daily for others; half-lives may be prolonged in hepatic impairment. |
| Protein binding | Dasabuvir: >99.9% (albumin, alpha-1-acid glycoprotein); Paritaprevir: 97-98.6% (albumin); Ombitasvir: 99.9% (albumin); Ritonavir: 98-99% (albumin, alpha-1-acid glycoprotein). |
| Volume of Distribution | Dasabuvir: 0.3-0.6 L/kg; Paritaprevir: 0.2-0.3 L/kg; Ombitasvir: 0.6-0.9 L/kg; Ritonavir: 0.6 L/kg. Clinical meaning: Low Vd indicates limited extravascular distribution, consistent with high protein binding. |
| Bioavailability | Oral dasabuvir: 70%; paritaprevir: not reported (enhanced by ritonavir); ombitasvir: 48%; ritonavir: 60-80%. |
| Onset of Action | Oral: Rapid antiviral effect with HCV RNA decline within 24-48 hours; maximal suppression by 2-4 weeks of therapy. |
| Duration of Action | Sustained virologic response (SVR) is measure of cure; drug levels decline over 5-6 half-lives; no residual antiviral effect after discontinuation. |
Two tablets of ombitasvir 12.5 mg / paritaprevir 75 mg / ritonavir 50 mg once daily (morning) plus one tablet of dasabuvir 250 mg twice daily (morning and evening) with food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Contraindicated in severe renal impairment (CrCl <30 mL/min) or ESRD. |
| Liver impairment | Contraindicated in Child-Pugh class B or C hepatic impairment. No dose adjustment for Child-Pugh class A. |
| Pediatric use | Not approved for pediatric patients (safety and efficacy not established). |
| Geriatric use | No specific dose adjustment based on age alone; renal and hepatic function should be assessed due to potential age-related impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VIEKIRA PAK (COPACKAGED) (VIEKIRA PAK (COPACKAGED)).
| Breastfeeding | No human data available. Paritaprevir and ombitasvir are excreted in rat milk; unknown in humans. M/P ratio not determined. Caution advised: consider the benefits of breastfeeding, the risk of infant drug exposure, and the mother's underlying condition (e.g., HCV treatment). |
| Teratogenic Risk | VIEKIRA PAK (ombitasvir, paritaprevir, ritonavir, dasabuvir) is classified as FDA Pregnancy Category B. No teratogenic effects observed in animal studies. Limited human data: no increased risk of major birth defects reported in first trimester exposures. Second and third trimester: no fetal risks identified, but hepatic adverse events (elevated liver enzymes, hyperbilirubinemia) may occur in mother, potentially affecting fetus. |
■ FDA Black Box Warning
WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION. Test all patients for HBV before starting therapy. Monitor during and post-treatment for HBV reactivation and manage appropriately.
| Serious Effects |
Hypersensitivity to any component; moderate to severe hepatic impairment (Child-Pugh B or C); coadministration with strong CYP3A4 inducers or sensitive CYP3A4 substrates with narrow therapeutic index (e.g., alfuzosin, amiodarone, atorvastatin, etc.)
| Precautions | Risk of hepatic decompensation/failure in patients with cirrhosis; ALT elevations; HBV reactivation; drug interactions with CYP3A4 substrates, CYP2C8 substrates, and P-glycoprotein substrates; avoid in moderate to severe hepatic impairment. |
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| Fetal Monitoring | Monitor liver function tests (ALT, AST, bilirubin) at baseline and periodically during therapy. In pregnancy, monitor for signs of hepatic decompensation. Assess HCV RNA at end of treatment and 12-24 weeks post-treatment (sustained virologic response). Monitor for fetal growth and well-being via ultrasound if maternal hepatic impairment develops. |
| Fertility Effects | No studies on male or female fertility in humans. In animal studies, no impairment of fertility or reproductive performance observed. Indirect effects: successful HCV treatment may improve fertility outcomes by reducing hepatic inflammation and improving overall health. |