What are the contraindications for statin (HMG-CoA reductase inhibitor) therapy?

Statin Contraindications

The only absolute contraindication to statin therapy is active or chronic liver disease (specifically decompensated cirrhosis or acute liver failure), and pregnancy. 1, 2

Absolute Contraindications

Active or Chronic Liver Disease

• Decompensated cirrhosis and acute liver failure are the only true hepatic contraindications. 2
• Compensated cirrhosis, NAFLD, NASH, and chronic stable liver disease are NOT contraindications—statins are safe and potentially beneficial in these conditions. 2
• Chronic transaminase elevations from hepatitis B, hepatitis C, or fatty liver do not preclude statin use and may actually improve with treatment. 1, 2

Pregnancy and Lactation

• All statins are contraindicated in pregnant women. 1
• Stop statins 1-2 months before attempting pregnancy when pregnancy is planned. 1
• When pregnancy is unplanned, stop statins immediately upon discovery and do not restart until after pregnancy and breastfeeding are completed. 1
• The contraindication stems from a 2004 FDA case series showing 20 malformations including 5 severe CNS defects and 5 unilateral limb deficiencies with lipophilic statins, though subsequent cohort studies have not confirmed increased teratogenic risk. 1, 3
• Meta-analyses show increased risk of spontaneous abortion (OR 1.36) but no increased risk of stillbirth or induced abortion. 4

Hypersensitivity

• History of hypersensitivity to the specific statin medication. 1

Relative Contraindications (Use with Extreme Caution)

Drug Interactions with High Myopathy Risk

Contraindicated or strongly discouraged combinations: 1

• Cyclosporine (potent CYP3A4 and P-glycoprotein inhibitor)
• Gemfibrozil (particularly dangerous—avoid this combination entirely)
• Macrolide antibiotics (erythromycin, clarithromycin)
• Azole antifungals (itraconazole, ketoconazole)
• HIV protease inhibitors (especially ritonavir-boosted regimens)
• Cytochrome P-450 3A4 inhibitors

Note: Simvastatin and lovastatin are absolutely contraindicated with potent CYP3A inhibitors; atorvastatin has less potent interactions but still requires caution. 5

High-Risk Clinical Scenarios for Myopathy

Exercise extreme caution or temporarily withhold statins in: 1

• Advanced age (especially >80 years), particularly in women
• Small body frame and frailty
• Multisystem disease (chronic renal insufficiency, especially with diabetes)
• Perioperative periods (withhold during hospitalization for major surgery)
• Multiple concurrent medications
• Moderate-to-severe hepatic impairment (for ezetimibe combination therapy) 1

Common Pitfalls to Avoid

Do NOT withhold statins for: 2

• Mildly elevated baseline transaminases (up to 3× upper limit of normal)
• Compensated cirrhosis from any cause
• NAFLD or NASH (cardiovascular disease is the leading cause of death in these patients, not liver disease)
• Chronic hepatitis B or C with stable transaminases

Do NOT routinely monitor: 2

• Liver enzymes during ongoing statin therapy (FDA concluded in 2012 this does not prevent rare adverse effects)
• CK levels in asymptomatic patients (not recommended by ATP III) 1

Only measure transaminases if: 2

• Signs or symptoms of hepatotoxicity develop (jaundice, fatigue, severe abdominal pain)
• Baseline assessment before starting therapy

For muscle symptoms: 1

• If CK >10× ULN with symptoms: discontinue immediately
• If CK 3-10× ULN at baseline or asymptomatic: can treat with careful monitoring
• If symptomatic with CK <10× ULN: follow weekly until resolved or worsening