Drug Guide
Ezetimibe and Simvastatin
Classification
Therapeutic: Cholesterol-lowering agent
Pharmacological: HMG-CoA reductase inhibitor and cholesterol absorption inhibitor combination
FDA Approved Indications
- Hyperlipidemia
- Mixed dyslipidemia to reduce LDL cholesterol, total cholesterol, and apolipoprotein B, and to increase HDL cholesterol
Mechanism of Action
Ezetimibe inhibits intestinal absorption of cholesterol and phytosterols by targeting the NPC1L1 transporter. Simvastatin inhibits HMG-CoA reductase, an enzyme involved in endogenous cholesterol synthesis, leading to decreased cholesterol levels.
Dosage and Administration
Adult: Typically, 10/20 mg once daily in the evening or as directed by a healthcare provider.
Pediatric: Not approved for use in children.
Geriatric: No specific dose adjustments necessary; monitor liver function and renal function accordingly.
Renal Impairment: Use with caution; consider dose adjustments based on renal function.
Hepatic Impairment: Contraindicated in active liver disease or unexplained persistent elevation of serum transaminases.
Pharmacokinetics
Absorption: Ezetimibe is well absorbed; simvastatin is absorbed with approximately 30% bioavailability due to extensive first-pass metabolism.
Distribution: Ezetimibe is extensively plasma protein-bound; simvastatin is highly protein-bound (>95%).
Metabolism: Ezetimibe is glucuronidated; simvastatin is extensively metabolized in the liver by CYP3A4.
Excretion: Ezetimibe: feces (~78%), urine (~13%). Simvastatin: mainly feces (~60%), some urine.
Half Life: Ezetimibe's active metabolites: 22 hours; simvastatin: 2 hours (parent drug), but effects last longer due to active metabolites.
Contraindications
- Active liver disease, unexplained persistent elevations of serum transaminases.
- Hypersensitivity to ezetimibe or simvastatin.
Precautions
- Use with caution in patients with renally impaired or hepatic impairment.
- Monitor liver function during therapy.
- Pregnancy Category X; use is contraindicated in pregnancy. Breastfeeding: not recommended.
Adverse Reactions - Common
- Myalgia (Common)
- Diarrhea (Common)
- Elevated liver enzymes (Common)
Adverse Reactions - Serious
- Rhabdomyolysis (Rare)
- Hepatotoxicity (Rare)
Drug-Drug Interactions
- Levels of simvastatin may increase with CYP3A4 inhibitors (e.g., ketoconazole, erythromycin).
- Fibrates may increase risk of myopathy.
- Warfarin: potential increased bleeding risk.
Drug-Food Interactions
- Grapefruit juice may increase simvastatin levels.
Drug-Herb Interactions
- St. John's Wort may reduce efficacy.
Nursing Implications
Assessment: Monitor lipid panels, liver function tests, and muscle symptoms.
Diagnoses:
- Risk for impaired kidney function related to rhabdomyolysis.
- Risk for hepatic injury.
Implementation: Administer as prescribed, preferably in the evening. Educate on potential side effects.
Evaluation: Assess lipid levels, liver enzymes, and patient reports of muscle pain regularly.
Patient/Family Teaching
- Take medication as directed, preferably in the evening.
- Report unexplained muscle pain, tenderness, or weakness.
- Avoid heavy alcohol use and grapefruit juice.
- Inform healthcare provider of all medications and supplements.
Special Considerations
Black Box Warnings:
- Potential for severe myopathy including rhabdomyolysis, especially when used with certain other drugs.
- Pregnancy category X; contraindicated in pregnancy.
Genetic Factors: Genetic variability in CYP3A4 activity may affect drug levels.
Lab Test Interference: May cause elevations in liver enzymes and CK levels.
Overdose Management
Signs/Symptoms: Muscle pain, weakness, nausea, vomiting, abdominal pain.
Treatment: Supportive care, symptomatic treatment. No specific antidote; consider activated charcoal if ingestion is recent, and seek emergency medical attention.
Storage and Handling
Storage: Store at room temperature away from moisture, heat, and light.
Stability: Stable until expiration date when stored properly.