BLACK BOX WARNING
- simvastatin 80 mg: increased risk of myopathy — do not initiate at 80 mg
simvastatin
Brand: Zocor
⚠ BBW Prototype: atorvastatin
Drug Class: statin
Drug Family: antilipemic
Subclass: HMG-CoA reductase inhibitor (semisynthetic)
Organ Systems: cardiovascular
Mechanism of Action
Prodrug (simvastatin acid as active metabolite); inhibits HMG-CoA reductase; extensively metabolized by CYP3A4; numerous significant drug interactions limit its use.
HMG-CoA reductase
Indications
- hyperlipidemia
- secondary prevention of CV events
- heterozygous familial hypercholesterolemia
Contraindications
- active liver disease
- pregnancy
- strong CYP3A4 inhibitors
- simvastatin 80 mg dose (myopathy risk)
Adverse Effects
Common
- myalgia
- GI upset
- headache
Serious
- rhabdomyolysis (especially at 80 mg or with CYP3A4 inhibitors)
- hepatotoxicity
Pharmacokinetics (ADME)
| Absorption | ~5% oral bioavailability (extensive first-pass) |
| Distribution | large Vd |
| Metabolism | extensive hepatic CYP3A4 (prodrug) |
| Excretion | fecal 60%, renal 13% |
| Half-life | 2-3 hours (simvastatin acid) |
| Onset | evening (take at bedtime) |
| Peak | 1.3-2.4 hours |
| Duration | 24 hours |
| Protein Binding | 95-98% |
| Vd | large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| strong CYP3A4 inhibitors | markedly increased simvastatin; rhabdomyolysis — avoid or cap at 10 mg | major |
| amiodarone | CYP3A4 inhibition — cap simvastatin at 20 mg | major |
| amlodipine | increases simvastatin exposure — cap at 20 mg | major |
| verapamil/diltiazem | CYP3A4 inhibition — cap at 10 mg | major |
Nursing Considerations
- Take at bedtime (mimics peak cholesterol synthesis at night)
- 80 mg dose NEVER initiated as new therapy — too high myopathy risk
- FDA warning: multiple drug interaction caps (20 mg with amlodipine, amiodarone, etc.)
- Do NOT take with grapefruit juice
Clinical Pearls
- Most drug interaction limitations of all statins — largely replaced by atorvastatin/rosuvastatin
- 4S trial: simvastatin 20-40 mg reduced mortality and MI in secondary prevention
- 80 mg dose: FDA requires dose cap with many drugs; generally avoided
Safety Profile
Pregnancy contraindicated
Lactation contraindicated
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.