Generic Name

Simeprevir

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Classification

FDA Approved Indications

• Treatment of chronic hepatitis C (HCV) genotype 1 infection in combination with peginterferon alfa and ribavirin

Mechanism of Action

Simeprevir inhibits the NS3/4A protease enzyme critical for HCV replication, thereby decreasing viral load.

Dosage and Administration

Adult: 150 mg orally once daily with food for 12-24 weeks, in combination with peginterferon alfa and ribavirin.

Pediatric: Not approved for pediatric use.

Geriatric: No specific dosage adjustments; monitor renal and hepatic function.

Renal Impairment: No dose adjustment needed for mild to moderate impairment; caution in severe impairment.

Hepatic Impairment: Use with caution in patients with decompensated cirrhosis; dose adjustments not established.

Pharmacokinetics

Absorption: Rapidly absorbed; food increases absorption.

Distribution: Widely distributed; high plasma protein binding (~99%).

Metabolism: Primarily metabolized by CYP3A4/5 enzymes.

Excretion: Primarily fecal excretion; minimal renal excretion.

Half Life: 15.8 ± 8.4 hours

Contraindications

• Use with strong inducers of CYP3A4/5 (e.g., rifampin, carbamazepine, phenytoin)

Precautions

• Use with caution in patients with hepatic impairment
• Monitor for rash and hypersensitivity reactions
• Assess for drug interactions, especially with CYP3A4 substrates

Adverse Reactions - Common

• Fatigue (Common)
• Pruritus (Common)
• Rash (Common)
• Headache (Common)

Adverse Reactions - Serious

• Interstitial lung disease (Rare)
• Photosensitivity reactions (Rare)
• Hepatotoxicity (Rare)

Drug-Drug Interactions

• CYP3A4 inducers or inhibitors (e.g., rifampin, ketoconazole)
• Protease inhibitors (e.g., telaprevir, boceprevir)
• CYP3A4 substrates with a narrow therapeutic index

Drug-Food Interactions

• High-fat meals can increase absorption

Drug-Herb Interactions

• St. John's Wort (induces CYP3A4)

Nursing Implications

Patient/Family Teaching

• Take medication with food to enhance absorption.
• Report any rash, difficulty breathing, or signs of liver problems immediately.
• Use caution with sun exposure; photosensitivity reactions may occur.
• Inform about potential drug interactions with other medications and supplements.

Special Considerations

Black Box Warnings:

• Risk of hepatotoxicity; monitor hepatic function closely.

Genetic Factors: None established.

Lab Test Interference: May affect bilirubin levels.

Overdose Management

Signs/Symptoms: Nausea, vomiting, dizziness, or abnormal liver function tests.

Treatment: Supportive care; consider activated charcoal if ingestion is recent; monitor hepatic function.

Storage and Handling

Storage: Store at room temperature, away from moisture and light.

Stability: Stable up to the expiration date on the packaging when stored properly.