Can nifedipine (calcium channel blocker) cause muscle aches when paired with a statin (HMG-CoA reductase inhibitor)?

Nifedipine and Statin Combination: Risk of Muscle Aches

Yes, nifedipine can increase the risk of muscle aches when paired with statins, particularly through drug interactions that affect statin metabolism and transport mechanisms. 1

Mechanism of Interaction

• Nifedipine can interact with statins through inhibition of cytochrome P450 (CYP450) enzymes, particularly the 3A4 isozyme, which is responsible for metabolizing several statins including atorvastatin, lovastatin, and simvastatin 1
• This interaction can lead to increased statin concentrations in the blood, potentially increasing the risk of muscle-related adverse effects 1
• Additionally, nifedipine may compete with statins for membrane transporters such as P-glycoprotein (P-gp), further increasing statin bioavailability and risk of myopathy 2

Clinical Evidence

• The USAGE study demonstrated that concomitant use of CYP450 inhibitors (like nifedipine) was associated with 42% increased odds of new or worsening muscle pain in statin users (OR = 1.42; P < .001) 1
• Medications that inhibit both OATP1B1 and P-gp transporters were associated with 80% increased odds (OR = 1.80; P = .030) of patients stopping statin therapy due to muscle pain 1
• Even without drug interactions, statins alone can cause muscle symptoms in approximately 5-10% of patients 3

Risk Factors for Statin-Nifedipine Muscle Symptoms

• Advanced age (especially >80 years), with women at higher risk than men 2
• Small body frame and frailty 2
• Multisystem disease (e.g., chronic renal insufficiency, especially due to diabetes) 2
• Multiple medications (polypharmacy) 2
• Perioperative periods 2

Management Approach

If muscle symptoms develop while on statin-nifedipine combination:

1. Discontinue the statin temporarily until symptoms can be evaluated 2
2. Evaluate for other conditions that might increase muscle symptom risk (e.g., hypothyroidism, reduced renal/hepatic function, rheumatologic disorders, vitamin D deficiency) 2, 3
3. Measure creatine kinase (CK) levels to assess for muscle damage 3
4. If symptoms resolve after statin discontinuation, consider:
   • Restarting with a lower dose of the same statin 2
   • Switching to a different statin with less potential for interaction 2, 3
   • Using a statin less dependent on CYP3A4 metabolism (e.g., rosuvastatin, pravastatin, fluvastatin) 2

Specific Statin Considerations with Nifedipine

• Higher risk combinations: Atorvastatin, lovastatin, and simvastatin with nifedipine (due to CYP3A4 metabolism) 2, 1
• Lower risk combinations: Rosuvastatin, fluvastatin, pravastatin, and pitavastatin with nifedipine (less dependent on CYP3A4) 2

Important Clinical Considerations

• Muscle symptoms are often subjective and may be difficult to attribute directly to the medication combination 4
• A recent meta-analysis found that only about 1 in 15 reports of muscle pain in patients taking statins were actually attributable to the statin itself 5
• The risk is highest during the first year of therapy, with a 7% relative increase in muscle pain or weakness compared to placebo 5
• Higher intensity statin regimens have greater risk of muscle symptoms (RR 1.08) compared to moderate-intensity regimens (RR 1.03) 5

Monitoring Recommendations

• Instruct patients to report muscle discomfort, weakness, or brown urine immediately 2
• Monitor for muscle symptoms at 6-12 weeks after starting therapy and at each follow-up visit 2
• Obtain CK measurements when patients report muscle soreness, tenderness, or pain 2
• Consider the timing of symptoms in relation to exercise, as statin-related myopathy typically persists beyond normal post-exercise recovery period 3

Remember that while the risk of muscle symptoms with statin-nifedipine combination exists, the cardiovascular benefits of appropriate statin therapy generally outweigh these risks for most patients 5.