Simeprevir
Mechanism :
Simeprevir is an inhibitor of HCV NS3/4A protease, a protease that is essential for viral replication. It is considered a direct-acting antiviral treatment for HCV, also called a specifically targeted antiviral therapy for HCV (STAT-C).
Indication :
- Treatment of genotype 1 chronic hepatitis C in combination with sofosbuvir or with peginterferon alfa and ribavirin.
Contraindications :
Hypersensitivity to simeprevir or any component of the formulation.
Dosing :
Safety and efficacy not established in pediatric population
Adults:
150 mg/day PO with
sofosbuvir for 12 weeks. In patients with compensated cirrhosis give for 24 weeks.
Genotype 1 and 4 infection with peginterferon alfa and
ribavirin:
Adults:
150 mg PO once daily with peginterferon alfa and
ribavirin, for an initial 12 weeks of treatment. After the initial 3-drug regimen, give an additional 12 weeks of only peginterferon alfa and
ribavirin (24 weeks for total course). In patients with compensated cirrhosis, give 36 weeks of only peginterferon alfa and
ribavirin (48 weeks for total course).
Adverse Effect :
Rash, photosensitivity, pruritus, nausea, myalgia, hyperbilirubinemia, dyspnea, elevated alkaline phosphatase.
Interaction :
Aminolevulinic Acid: Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid.
Cyclosporine: Simeprevir may increase the serum concentration.
CYP3A4 Inducers: May decrease the serum concentration of Simeprevir.
CYP3A4 Inhibitors: May increase the serum concentration of Simeprevir.
Digoxin: Simeprevir may increase the serum concentration of Digoxin.
Dexamethasone: May decrease the serum concentration of Simeprevir.
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Phosphodiesterase 5 Inhibitors: Simeprevir may increase the serum concentration of Phosphodiesterase 5 Inhibitors.
Warfarin: Simeprevir may enhance the anticoagulant effect of Warfarin.
Hepatic Dose :
Mild hepatic impairment: Dose reduction is not necessary.
Moderate to severe impairment: Avoid using simeprevir.
On treatment with simeprevir and peginterferon alpha, ribavirin or sofosbuvir, there are reports of hepatic decompensation and failure, therefore monitor patients with advanced or decompensated cirrhosis closely and those who have an increase in bilirubin greater than 2.5 times the upper limit of normal. Stop treatment if liver transaminase levels also increase or there are signs of hepatic decompensation.
Patients with concurrent hepatitis B can develop reactivation on simeprevir, leading to fulminant hepatitis, failure and death. Start treatment for hepatitis B if required.