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. |
| Molecular Weight | Glecaprevir: 838.94 Da; Pibrentasvir: 1133.2 Da; Combination not additive. |
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 | Avoid due to insufficient data; embryo-fetal toxicity observed in animal studies with glecaprevir/pibrentasvir (component). |
| 2nd trimester | May be used if potential benefit outweighs risk; no adequate human studies, but animal studies show no teratogenicity at clinically relevant doses. |
| 3rd trimester | May be used if potential benefit outweighs risk; limited human data suggest no increased risk of adverse fetal outcomes. |
Clinical note
Comprehensive clinical and safety monograph for VIEKIRA PAK (COPACKAGED) (VIEKIRA PAK (COPACKAGED)).
| Placental transfer | Limited data; glecaprevir and pibrentasvir are highly protein bound (>94%) and may cross placenta to a limited extent. Animal studies show detectable fetal levels. |
| Breastfeeding | No human data on transfer into breast milk; however, based on high protein binding and large molecular weight, excretion into breast milk is expected to be low. Use with caution in breastfeeding women. |
■ 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 |
Moderate to severe hepatic impairment (Child-Pugh B or C)Co-administration with atazanavirCo-administration with rifampin
| 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. |
| Food/Dietary | No significant food interactions; take with or without food. However, avoid grapefruit and grapefruit juice due to potential CYP3A4 inhibition. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) - No data in humans, but risk appears low. |
| 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. |
| 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. |
| Clinical Pearls | VIEKIRA PAK (ombitasvir, paritaprevir, ritonavir, and dasabuvir) is indicated for genotype 1 chronic hepatitis C. Note that it is contraindicated in moderate to severe hepatic impairment (Child-Pugh B or C). Monitor for signs of hepatic decompensation, especially in patients with cirrhosis. Also, ritonavir is a strong CYP3A4 inhibitor, so co-administration with drugs metabolized by CYP3A4 can cause serious interactions. |
| Patient Advice | Take VIEKIRA PAK exactly as prescribed with or without food. Do not skip doses. · Complete the full course of therapy even if you feel well. · Inform your doctor immediately if you experience yellowing of the skin or eyes, dark urine, or abdominal pain (signs of liver problems). · Avoid alcohol and over-the-counter medications, especially those containing acetaminophen. · Use effective contraception during treatment and for 30 days after stopping due to potential harm to a fetus. |