BLACK BOX WARNING
- myopathy and rhabdomyolysis — risk increased with certain drug combinations
atorvastatin
Brand: Lipitor
⚠ BBW Prototype Drug
Drug Class: statin
Drug Family: antilipemic
Subclass: HMG-CoA reductase inhibitor (synthetic)
Organ Systems: cardiovascular
Mechanism of Action
Competitive inhibitor of HMG-CoA reductase (rate-limiting enzyme of cholesterol synthesis in liver); reduces intracellular cholesterol synthesis, upregulates LDL receptors, increases clearance of LDL; pleiotropic anti-inflammatory effects.
HMG-CoA reductase
Indications
- hyperlipidemia (primary prevention + secondary prevention)
- atherosclerotic cardiovascular disease (ASCVD)
- heterozygous familial hypercholesterolemia
- hypertriglyceridemia (adjunct)
Contraindications
- active liver disease
- pregnancy
- breastfeeding
- unexplained persistent elevation of serum transaminases
Adverse Effects
Common
- myalgia
- headache
- GI upset
- transaminase elevation
Serious
- rhabdomyolysis
- myopathy
- hepatotoxicity (rare)
- new-onset diabetes
Pharmacokinetics (ADME)
| Absorption | 12% oral bioavailability (first-pass); food reduces Cmax but not AUC |
| Distribution | large Vd; distributed to liver |
| Metabolism | extensive hepatic CYP3A4 to active ortho- and para-hydroxy metabolites |
| Excretion | biliary/fecal (>98%) |
| Half-life | 14 hours (parent); 20-30h with active metabolites |
| Onset | 6-12 hours (but administered at any time of day) |
| Peak | 1-2 hours |
| Duration | 24 hours |
| Protein Binding | ≥98% |
| Vd | 381 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| strong CYP3A4 inhibitors (clarithromycin, itraconazole, HIV protease inhibitors) | markedly increases atorvastatin exposure; rhabdomyolysis risk | major |
| gemfibrozil | increases statin levels via OATP1B1 inhibition and CYP2C8 inhibition; rhabdomyolysis | major |
| cyclosporine | OATP1B1 inhibition markedly increases atorvastatin; avoid | major |
| amiodarone | increases atorvastatin levels | moderate |
Nursing Considerations
- Can be taken at any time (unlike simvastatin/pravastatin which should be at bedtime)
- Explain that muscle pain (myalgia) can be statin-related — report immediately
- CK monitoring only if symptomatic (routine monitoring not needed)
- Rhabdomyolysis rare but serious — dark urine is warning sign
- Hold during major surgery or illness associated with renal failure
Clinical Pearls
- Most prescribed drug in the US
- Active metabolites extend effective duration — can be dosed at any time
- PROVE-IT TIMI 22: high-intensity atorvastatin 80 mg reduced CV events vs pravastatin 40 mg in ACS
- High-intensity statin: ≥50% LDL reduction — atorvastatin 40-80 mg, rosuvastatin 20-40 mg
Safety Profile
Pregnancy contraindicated
Lactation contraindicated
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.