Indication(s):

Chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin in patients with compensated liver disease, including cirrhosis. Not for use as monotherapy. Screen for presence of virus with NS3Q80K polymorphism at baseline; consider alternative therapy if Q80K polymorphism is present.

Pharmacology:

Simeprevir is an inhibitor of the HCV NS3/4A protease. In a biochemical assay simeprevir inhibited the proteolytic activity of recombinant genotype 1a and 1b HCV NS3/4A proteases, with median Ki values of 0.5 nM and 1.4 nM, respectively.

Clinical Trials:

The efficacy of Olysio in patients with HCV genotype 1 infection was eva luated in three Phase 3 trials—QUEST-1 and QUEST-2 in treatment-naïve patients and PROMISE in patients who have relapsed after prior interferon-based treatment—as well as one Phase 2b ASPIRE study in prior non-responder patients.

Results from a pooled analysis of QUEST-1 and QUEST-2 demonstrated that 80% of treatment-naive patients in the group receiving Olysio achieved sustained virologic response 12 weeks after the end of treatment (SVR12), vs. 50% in the placebo groups. In PROMISE, 79% of prior relapsers in the Olysio group achieved SVR12 vs. 37% in the placebo group. Results from ASPIRE demonstrated that use of Olysio led to SVR24 after the end of treatment in 65% of prior partial-responders and 53% of prior-null responders vs. 9% and 19% of prior partial- and null-responder patients in the placebo groups, respectively.

For more clinical trial data, see full labeling.

Legal Classification:

Rx

Adults:

Swallow whole. Take with food. 150mg once daily. Treat for 12 wks (with peginterferon + ribavirin). Treatment-naive and prior relapsers, including cirrhosis: give additional 12 wks of peginterferon +  ribavirin (total treatment  =  24 wks). Prior non-responders (partial and null), including cirrhosis: give additional 36 wks of peginterferon + ribavirin (total treatment  =  48 wks). Do not reduce simeprevir dose or interrupt therapy; if discontinued, do not reinitiate. Discontinue if HCV-RNA levels indicate futility (see full labeling). If peginterferon or ribavirin is discontinued, simeprevir must also be discontinued.

Children:

<18yrs: not established.

Contraindication(s):

Pregnant women and in men whose partners are pregnant (note: ribavirin is Cat. X). Peginterferon and ribavirin contraindications also apply to combination therapy with simeprevir.

Warnings/Precautions:

Female patients/partners of male patients must have (–) pregnancy test before therapy; use 2 effective forms of contraception during and 6 months after treatment completion; perform routine monthly pregnancy test. Avoid sun exposure, tanning devices; consider discontinuing if photosensitivity or rash occurs. Sulfa allergy. Monitor HCV-RNA levels as clinically indicated. East Asian ancestry. Severe renal impairment, ESRD or dialysis. Moderate or severe hepatic impairment. Liver transplant patients. Other HCV genotypes. Pregnancy (Cat. C). Nursing mothe