simeprevir

Simeprevir is a direct-acting antiviral agent used in the treatment of chronic hepatitis C virus (HCV) infection. It is an oral inhibitor of the NS3/4A protease, an enzyme required for processing the HCV polyprotein. By blocking protease activity, simeprevir disrupts viral replication.

Therapeutic use and regimens vary by regulatory approval, but simeprevir has been prescribed for adults with chronic HCV genotype 1 infection in combination with other antiviral agents. Historically it was used with pegylated interferon and ribavirin; in more recent regimens it has been combined with sofosbuvir in interferon-free therapies, depending on the approved indications in a given country. Its activity beyond genotype 1 is limited and treatment decisions rely on local guidelines and approvals.

Pharmacology and interactions: simeprevir is predominantly metabolized by the cytochrome P450 3A (CYP3A) system. Because of this, many drug interactions can alter its exposure. Strong CYP3A inhibitors or inducers, such as certain antifungals or anticonvulsants, can significantly affect levels of simeprevir and require avoidance or dose adjustments. Coadministration with certain statins (for example, simvastatin or high-dose atorvastatin) can increase statin exposure and may necessitate dose modification.

Adverse effects commonly observed with simeprevir include headache, fatigue, nausea, rash, and photosensitivity. Rash or hypersensitivity reactions can be severe in rare cases, and liver-related adverse events require monitoring, especially in patients with underlying liver disease. Simeprevir is generally not used in patients with decompensated cirrhosis or in certain other hepatic conditions, and pregnancy considerations apply as with many antivirals.

Development and approval: simeprevir was developed by Janssen Pharmaceuticals and approved for use in HCV infection in the early 2010s, with subsequent adaptation to interferon-free regimens in combination therapy.