- ACRONYMS AND DEFINITIONS
- DRUGS IN CLASS
- Hepatitis C treatment
- MECHANISM OF ACTION
- Simeprevir is a HCV NS3/4A protease inhibitor
- HCV NS3/4A protease cleaves HCV-encoded polyprotein into the individual proteins NS3, NS4A, NS4B, NS5A, and NS5B. These proteins form a complex that is necessary for viral replication.
- FDA-APPROVED INDICATIONS
- Treatment of HCV genotype 1 in combination with sofosbuvir - no cirrhosis or Child-Pugh A
- Simeprevir is also approved to treat HCV genotype 1 and 4 in combination ribavirin and PegIFN. Regimens containing PegIFN are no longer recommended.
- HCV genotype 1
- In trials, simeprevir + sofosbuvir was > 90% effective in eradicating HCV genotype 1 in patients with no cirrhosis or Child-Pugh A
- NS3 Q80K polymorphism
- A genetic variant in the Hepatitis C virus causes it to be less responsive to simeprevir + PegIFN + Rib therapy
- The genetic variant is called the Q80K polymorphism. Most labs offer a test that will detect the presence of Q80K polymorphism.
- In simeprevir trials with pegylated interferon and ribavirin, the Q80K polymorphism was present in 30% of patients with Genotype 1a and 0.5% of patients with Genotype 1b. Response rates were lower in these patients.
- Q80K polymorphism does not appear to have a significant effect on simeprevir + sofosbuvir therapy
- SIDE EFFECTS
- The table below is presented in the simeprevir PI. It shows the incidence of side effects observed in trials where simeprevir was prescribed in combination with pegylated interferon and ribavirin
- In the COSMOS trial where simeprevir was prescribed with sofosbuvir, only rash (13%), itching (9%), and photosensitivity (7%) were reported in greater than one patient in groups treated with simeprevir + sofosbuvir only
|Side Effect||Simeprevir + PegIFN + RBV
||Placebo + PegIFN + RBV|
(shortness of breath)
|Elevated alkaline phosphatase
(> 1.25 to ≤ X 2.5 ULN)
(> 1.1 to ≤ 1.5 X ULN)
(> 1.5 to ≤ 2.5 X ULN)
(> 2.5 to ≤ 5 X ULN)
- In phase 3 trials, photosensitivity (sensitivity to the sun) was reported in about 5% of patients taking simeprevir. Patients in these trials were instructed to wear sunscreen which may have lowered the observed incidence.
- Photosensitivity reactions include burning, redness, skin oozing, rash, blistering, and swelling
- Sunscreen and limiting skin exposure (ex. long sleeves) can help prevent the reaction
- Simeprevir may cause a rash
- Rash is more common when used with ribavirin and/or pegylated interferon
- Severe rashes have been reported
- Patients with mild-to-moderate rash should be watched closely for the development of mucosal signs (e.g., oral lesions, conjunctivitis) or systemic symptoms
- If severe rash occurs, simeprevir should be discontinued
- None known
- Kidney disease
- No dose adjustment is necessary in mild, moderate, or severe kidney disease
- Liver disease
- Child-Pugh A: No dose adjustment necessary
- Child-Pugh B/C: DO NOT USE
- Sulfa allergy
- The molecular structure of simeprevir contains a sulfonamide moiety. Patients with a sulfa allergy may have a reaction to simeprevir.
- In studies from the PI, 16 patients reported a history of sulfa allergy, and none had a reaction to simeprevir
- East Asian ancestry
- In studies from the PI, patients of East Asian ancestry had higher blood levels of simeprevir (mean plasma exposure 3.4-fold higher than average population)
- Despite this, no dose adjustment is required based on race
- Hepatitis B coinfection
- In October 2016, the FDA placed a boxed warning on all new hepatitis C drugs about the possible reactivation of hepatitis B infection in coinfected patients who are taking direct-acting antiviral hepatitis C drugs
- At the time of the warning, the FDA had identified 24 cases of hepatitis B reactivation in patients taking these drugs. Reactivation occurred in patients who were HBsAg positive and in those who were HBsAg negative and anti-HBc positive (see hepatitis B serology for more).
- The FDA recommends that providers check all patients for hepatitis B coinfection (HBsAg and anti-HBc) before starting therapy and that they monitor patients for reactivation during and after therapy
- See AASLD guidelines for HBV coinfected patients for more
- MONITORING THERAPY
- DRUG INTERACTIONS
- NOTE: The drug interactions presented here are NOT A COMPREHENSIVE LIST of all known interactions. Other interactions exist. The interactions below are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- Numerous medications and drug classes
- Simeprevir is a CYP3A4 sensitive substrate and inhibitor. It is also a p-glycoprotein and OATP1B1/3 inhibitor. Because of this, it has the potential for a long list of drug interactions.
- See the simeprevir PI for a list of potential drug interactions
- METABOLISM AND ELIMINATION
- NOTE: Drugs can be metabolized by more than one enzyme. Drugs may be metabolized by an enzyme and inhibit/induce the enzyme at the same time. Drug transporters (ex. p-glycoprotein) can play a role in drug metabolism. Not all drug interactions are clinically significant. Consult your physician or pharmacist if you are taking medications together and are concerned about a possible interaction.
- Simeprevir (Olysio®)
HIGH ALERT INTERACTIONS
- LONG TERM SAFETY
- Simeprevir was FDA-approved in 2013
- There is no long-term safety data for the medication
- Dosage form:
- 150 mg capsule
- 150 mg once daily
- Take with food. Food increases absorption.
- Treatment regimens:
- HCV Genotype 1 (in combination with sofosbuvir)
- Treatment-naïve and treatment-experienced✝ patients without cirrhosis: Sofosbuvir 400 mg once daily + simeprevir 150 mg once daily for 12 weeks
- Treatment-naïve and treatment-experienced✝ patients with Child-Pugh A: Sofosbuvir 400 mg once daily + simeprevir 150 mg once daily for 24 weeks
- ✝Prior treatment with interferon-based therapies
- Possible generic:
- NOTE: Drug companies typically file multiple patents on their drugs in order to protect them from competition. The patent expiration listed here is the date that the earliest patent on the drug expires (accounting for pediatric exclusivity). Because drug companies use numerous techniques to extend the life of their patents, it does not necessarily mean a generic will become available around this date.
|Simeprevir (Olysio®)||MAY 2025|
- PI = Manufacturer's Package Insert
- 1 - Simeprevir PI
- 2 - AASLD website