OLYSIO Rx
Pharmacological Class:
Hepatitis C virus (HCV) NS3/4A protease inhibitor.
Active Ingredient(s):
Simeprevir 150mg; caps.
Company
Janssen Therapeutics
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 mothers: not recommended.
Interaction(s)
Concomitant moderate or strong CYP3A inducers/inhibitors: not recommended. Avoid use with macrolides, azole antifungals, milk thistle, cobicistat-containing products, delavirdine, darunavir, ritonavir, other HIV PIs. May be antagonized by anticonvulsants, rifabutin, rifampin, rifapentine, dexamethasone, efavirenz, etravirine, nevirapine, St. John's wort; avoid. May potentiate cisapride (avoid), antiarrhythmics (caution), digoxin, calcium channel blockers, statins (use lowest dose), PDE-5 inhibitors for PAH, oral midazolam or triazolam. Monitor warfarin, immunosuppressants.
Adverse Reaction(s)
Rash, photosensitivity, pruritus, nausea, myalgia, dyspnea.
Notes:
For peginterferon alfa and ribavirin specific dosing and safety information, refer to their respective prescribing information.
How Supplied:
Caps—7, 28
LAST UPDATED:
1/31/2014
