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. |
| Molecular Weight | Ombitasvir: 894.0 Da; Paritaprevir: 765.8 Da; Ritonavir: 720.9 Da; Dasabuvir: 592.6 Da |
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 | Insufficient human data; animal studies have shown no evidence of teratogenicity. However, ribavirin component has significant teratogenicity and is contraindicated in pregnancy. |
| 2nd trimester | Limited data; use only if potential benefit justifies risk. Ribavirin is known to cause fetal harm and is contraindicated. |
| 3rd trimester | Limited data; use only if potential benefit justifies risk. Ribavirin is contraindicated due to teratogenicity. |
Clinical note
Comprehensive clinical and safety monograph for VIEKIRA XR (VIEKIRA XR).
| Placental transfer | Limited data on ombitasvir, paritaprevir, ritonavir, and dasabuvir. Ribavirin is known to cross the placenta and accumulate in fetal tissues. |
| Breastfeeding | It is unknown if ombitasvir, paritaprevir, ritonavir, or dasabuvir are excreted in human milk. Ribavirin is excreted in breast milk and accumulates in nursing infants. Due to the potential for adverse effects in nursing infants, breastfeeding is not recommended during 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 |
Hypersensitivity to any componentSevere hepatic impairment (Child-Pugh Class C)Concomitant use with strong CYP3A4 inducers (e.g., rifampin, St. John's wort)Concomitant use with ethinyl estradiol-containing contraceptives (increased risk of ALT elevations)Pregnancy (due to ribavirin 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). |
| Food/Dietary | Administer with a meal to ensure adequate absorption. Grapefruit and grapefruit juice should be avoided due to potential CYP3A4 inhibition. |
Loading safety data…
| Lactation Rating | Avoid - Contraindicated due to ribavirin component. |
| 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. |
| 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. |
| Clinical Pearls | VIEKIRA XR (dasabuvir, ombitasvir, paritaprevir, ritonavir) is indicated for HCV genotype 1b treatment. It must be taken with food to enhance absorption. Avoid use in moderate hepatic impairment (Child-Pugh B or C) due to risk of decompensation. Monitor for ALT elevations, especially in women taking ethinyl estradiol-containing contraceptives; switch to alternative contraception. Note significant drug interactions with CYP3A4 substrates and strong CYP inducers. |
| Patient Advice | Take one tablet (two tablets for VIEKIRA XR) once daily with a meal, at the same time each day. · Do not take with ethinyl estradiol-containing contraceptives; use alternative non-hormonal birth control. · Inform your doctor of all medications, including over-the-counter drugs and supplements, to avoid serious interactions. · Report symptoms of liver problems such as yellowing eyes/skin, dark urine, or abdominal pain immediately. · Avoid grapefruit and grapefruit juice, and do not take St. John's wort while on this medication. |