Generic Name

Simvastatin

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Classification

FDA Approved Indications

• Hyperlipidemia
• Prevention of cardiovascular disease

Mechanism of Action

Simvastatin inhibits HMG-CoA reductase, the enzyme responsible for cholesterol synthesis in the liver, leading to decreased LDL cholesterol and modest increases in HDL cholesterol.

Dosage and Administration

Adult: Initially, 10-20 mg once daily in the evening; may adjust up to 40 mg/day. Max 80 mg/day.

Pediatric: Not indicated for children under 10 years; safety and efficacy not established.

Geriatric: Start at lower end of dosing range; monitor for adverse effects.

Renal Impairment: Use with caution; dose adjustments may be necessary.

Hepatic Impairment: Contraindicated in active liver disease; caution in patients with liver enzyme elevations.

Pharmacokinetics

Absorption: Well absorbed orally, but extensive first-pass metabolism.

Distribution: Widely distributed; crosses blood-brain barrier.

Metabolism: Primarily hepatic via CYP3A4 enzyme.

Excretion: Fecal and renal, mainly as metabolites.

Half Life: Approximately 2-3 hours, but activity duration is longer due to active metabolites.

Contraindications

• Active liver disease
• Pregnancy and lactation
• Known hypersensitivity

Precautions

• Monitor liver function tests
• Use with caution in patients on other hepatotoxic or CYP3A4-interacting drugs

Adverse Reactions - Common

• Muscle pain or weakness (Common)
• Gastrointestinal discomfort (Uncommon)

Adverse Reactions - Serious

• Rhabdomyolysis (Rare)
• Hepatotoxicity (Rare)
• Allergic reactions (Uncommon)

Drug-Drug Interactions

• Drugs affecting CYP3A4 (e.g., erythromycin, ketoconazole, grapefruit juice)
• Fibrates (e.g., gemfibrozil)
• Other lipid-lowering agents

Drug-Food Interactions

• Grapefruit and grapefruit juice can increase plasma levels and risk of adverse effects.

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Take medication as prescribed, preferably in the evening.
• Report unexplained muscle pain, tenderness, or weakness.
• Limit grapefruit juice intake.
• Maintain a low-fat, low-cholesterol diet.

Special Considerations

Black Box Warnings:

• Myopathy and rhabdomyolysis risk, especially in certain populations or with drug interactions.

Genetic Factors: Genetic variations can influence metabolism and risk for adverse effects (e.g., SLCO1B1 polymorphism).

Lab Test Interference: Can slightly increase serum transaminases and creatine kinase levels.

Overdose Management

Signs/Symptoms: Muscle pain, weakness, elevated liver enzymes.

Treatment: Supportive care; no specific antidote. Discontinue medication and provide symptomatic treatment.

Storage and Handling

Storage: Store at room temperature, 20-25°C (68-77°F).

Stability: Stable for recommended shelf life when stored properly.