Indications for OLYSIO:
Chronic hepatitis C virus (HCV) genotype 1 infection, in combination with sofosbuvir, or genotype 1 or 4 infection, in combination with peginterferon alfa and ribavirin, without cirrhosis or with compensated cirrhosis.
Limitations of Use:
Efficacy in combination with peginterferon alfa and ribavirin is reduced in patients infected with HCV genotype 1a with an NS3 Q80K polymorphism. Not for patients who have previously failed therapy that included simeprevir or other HCV protease inhibitors.
Test for HBV infection prior to initiation. In combination with peginterferon alfa and ribavirin: screen for presence of virus with NS3 Q80K polymorphism at baseline; consider alternative therapy if Q80K polymorphism is detected. Not for monotherapy. Swallow whole. Take with food. 150mg once daily. Genotype 1: Treatment-naïve or treatment-experienced: (without cirrhosis): treat for 12 weeks (simeprevir + sofosbuvir); (with compensated cirrhosis [Child-Pugh A]): treat for 24 weeks (simeprevir + sofosbuvir). Genotype 1 or 4: Treatment-naive and prior relapsers in HCV mono-infected without cirrhosis or with compensated cirrhosis, or HCV/HIV-1 co-infected without cirrhosis: treat for 12 weeks (simeprevir + peginterferon + ribavirin), followed by additional 12 weeks of peginterferon + ribavirin (total treatment = 24 weeks). Treatment-naive and prior relapsers in HCV/HIV-1 co-infected with compensated cirrhosis, prior non-responders (partial and null) in HCV/HIV-1 co-infected or HCV mono-infected without cirrhosis or with compensated cirrhosis: treat for 12 weeks (simeprevir + peginterferon + ribavirin), followed by additional 36 weeks of peginterferon + ribavirin (total treatment = 48 weeks). Do not reduce simeprevir dose or interrupt therapy; if discontinued, do not reinitiate. Discontinue if HCV-RNA levels indicate futility when used in combination with peginterferon or ribavirin (see full labeling). If peginterferon, ribavirin, or sofosbuvir is permanently discontinued, simeprevir must also be discontinued.
<18yrs: not established.
Peginterferon, ribavirin, sofosbuvir contraindications also apply to combination therapy with simeprevir.
Risk of HBV reactivation in patients coinfected with HCV/HBV. Test all patients for HBV infection by measuring HBsAg and anti-HBc; if positive serologic evidence, monitor for hepatitis flare or HBV reactivation during and at post-treatment follow-up; treat if clinically indicated. Increased risk of symptomatic bradycardia when concomitant with amiodarone and a sofosbuvir-containing regimen, esp. in patients also taking beta-blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Monitor LFTs before and during therapy; discontinue if elevated bilirubin and transaminases, or signs/symptoms of hepatic decompensation develop. Moderate or severe hepatic impairment: not recommended. Avoid sun exposure, tanning devices; consider discontinuing if photosensitivity occurs and monitor. Discontinue if severe rash occurs. Monitor HCV-RNA levels as clinically indicated. Sulfa allergy. East Asian ancestry. Severe renal impairment, ESRD or dialysis. Liver transplant patients. Pregnancy. Nursing mothers.
HCV NS3/4A protease inhibitor.
Concomitant certain immunosuppressants or chemotherapeutic agents: may increase risk of HBV reactivation. Concomitant amiodarone with simeprivir in combination with sofosbuvir: not recommended; if no alternatives, monitor cardiac function (see full labeling). Concomitant moderate or strong CYP3A inducers/inhibitors (eg, anticonvulsants, macrolides, azole antifungals, rifampin, rifabutin, rifapentine, dexamethasone, St. John's wort, cobicistat-containing products, ledipasvir, efavirenz, etravirine, nevirapine, delavirdine, darunavir/ritonavir, ritonavir, other HIV PIs), cisapride, cyclosporine, milk thistle: not recommended. May potentiate antiarrhythmics, digoxin, calcium channel blockers, statins (use lowest dose), PDE-5 inhibitors for PAH, oral midazolam or triazolam; caution. Monitor sirolimus. Monitor INR with warfarin.
Rash, photosensitivity, pruritus, nausea, myalgia, dyspnea, fatigue, headache.
For peginterferon alfa, ribavirin, sofosbuvir specific dosing and safety information, refer to their respective prescribing information.