OLYSIO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OLYSIO (OLYSIO).
OLYSIO (simeprevir) is an HCV NS3/4A protease inhibitor that inhibits viral replication by binding to the active site of the NS3/4A protease, preventing cleavage of the HCV polyprotein.
| Metabolism | Primarily hepatic via CYP3A4. Simeprevir is also a substrate for OATP1B1/3 and P-glycoprotein. |
| Excretion | Primarily hepatic metabolism; 90% of dose eliminated in feces (<1% unchanged), 1% in urine (unchanged). |
| Half-life | Terminal half-life approximately 40 hours (range 27-50 h), supporting once-daily dosing. |
| Protein binding | 99.9% bound to human plasma proteins (primarily albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Apparent Vd approximately 59 L (0.7 L/kg based on 70 kg), indicating extensive tissue distribution. |
| Bioavailability | Absolute bioavailability not determined; absorption is rapid with oral administration; high-fat meal increases Cmax and AUC (by 60% and 28%, respectively). |
| Onset of Action | Time to maximum plasma concentration (Tmax) 2-4 hours post-dose; clinical antiviral effect observed within 24 hours. |
| Duration of Action | Given once daily; steady state achieved by Day 7; antiviral effect persists for the dosing interval. |
150 mg orally once daily with food, in combination with other direct-acting antivirals for 12 weeks.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to severe renal impairment; not dialyzable. |
| Liver impairment | Contraindicated in moderate to severe hepatic impairment (Child-Pugh B or C). Use with caution in mild impairment (Child-Pugh A) with no dose adjustment. |
| Pediatric use | Approved for children 3 years and older: weight-based dosing (≥45 kg: 150 mg; 30 to <45 kg: 100 mg; 15 to <30 mg/kg: 75 mg) once daily with food. |
| Geriatric use | No specific dose adjustment needed; pharmacokinetics similar to younger adults. Monitor for renal function and potential drug interactions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OLYSIO (OLYSIO).
| Breastfeeding | Unknown if simeprevir is excreted in human milk. M/P ratio not available. Because of the potential for adverse reactions in nursing infants, breastfeeding is not recommended during treatment. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. In animal studies, no evidence of teratogenicity at exposures up to 4 times the human exposure. However, increased fetal loss and reduced fetal body weights were observed at maternally toxic doses. Classified as FDA Pregnancy Category C. Risk cannot be ruled out. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Severe hepatic impairment (Child-Pugh class B or C)","Coadministration with potent CYP3A4 inducers (e.g., rifampin, St. John's wort)","Coadministration with drugs that significantly decrease simeprevir exposure and may reduce efficacy","Hypersensitivity to simeprevir or any component"]
| Precautions | ["Risk of hepatitis B virus reactivation in patients co-infected with HCV and HBV","Photosensitivity reactions; avoid sun exposure and use sunscreen","Dyspnea and symptomatic bradycardia when used with sofosbuvir and amiodarone","Hepatic decompensation/failure in patients with cirrhosis","Pancreatitis"] |
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| Fetal Monitoring |
| Monitor hepatic function (ALT, AST, total bilirubin) and renal function. Assess for adverse effects such as rash, photosensitivity, and dyspnea. In pregnancy, monitor for fetal growth and well-being via ultrasound if indicated. |
| Fertility Effects | No human data on fertility. Animal studies showed no impairment of fertility at exposures up to 4 times the human exposure. Reversible effects on male reproductive organs observed in rats at high doses. |