Is it safe to prescribe Flexeril (cyclobenzaprine) to a patient with back pain who is currently taking statins (HMG-CoA reductase inhibitors)?

Can You Give Flexeril with Statins to a Patient with Back Pain?

Yes, you can safely prescribe Flexeril (cyclobenzaprine) to a patient taking statins who has back pain, as there is no documented pharmacokinetic or pharmacodynamic interaction between these medications. 1, 2

Key Safety Considerations

No Direct Drug Interaction

• Cyclobenzaprine is metabolized primarily by CYP3A4, CYP1A2, and to a lesser extent CYP2D6, while statins have varying metabolic pathways (simvastatin, lovastatin, and atorvastatin via CYP3A4; others through different routes). 2, 3
• The ACC/AHA guidelines list relative contraindications for statin use including cyclosporine, gemfibrozil, niacin, macrolide antibiotics, azole antifungals, and cytochrome P-450 inhibitors—cyclobenzaprine is notably absent from this list. 1
• The FDA label for cyclobenzaprine does not list statins as interacting medications and specifically notes that concomitant administration with NSAIDs (naproxen, aspirin, diflunisal) was well tolerated. 2

Critical Diagnostic Distinction Required

Before prescribing cyclobenzaprine, you must first determine whether the back pain is actually statin-induced myopathy or unrelated musculoskeletal pain. This distinction is essential because:

• The American College of Cardiology recommends obtaining a creatine kinase (CK) level immediately when a patient on statin therapy reports muscle soreness, tenderness, or pain, comparing it to baseline measurements. 4
• If CK is >10 times the upper limit of normal with muscle symptoms, discontinue the statin immediately—this represents significant myopathy requiring cessation, not symptomatic treatment with muscle relaxants. 4
• For CK elevations between 3-10 times ULN with muscle symptoms, follow CK levels weekly and monitor symptoms closely rather than simply masking symptoms with cyclobenzaprine. 4

When Cyclobenzaprine Is Appropriate

If the back pain is mechanical/musculoskeletal in origin (normal or minimally elevated CK, localized pain pattern, no diffuse muscle weakness), cyclobenzaprine can be safely prescribed alongside statins. 2, 5

• Cyclobenzaprine is indicated for acute musculoskeletal conditions with muscle spasm, local pain and tenderness, and limitation of motion. 2
• The combination does not increase myopathy risk beyond the baseline statin risk, as cyclobenzaprine does not inhibit statin metabolism or increase statin plasma concentrations. 1, 2

Monitoring and Precautions

• The American College of Cardiology recommends evaluating muscle symptoms and CK before starting statin therapy, at 6-12 weeks after initiation, and at each follow-up visit. 1
• Obtain TSH levels in any patient presenting with muscle symptoms on statin therapy, as hypothyroidism predisposes to myopathy and can exacerbate statin-related muscle injury. 4
• Cyclobenzaprine may enhance the effects of alcohol, barbiturates, and other CNS depressants, so counsel patients accordingly. 2
• In elderly patients, initiate cyclobenzaprine at 5 mg and titrate slowly upward due to increased plasma concentrations (approximately 1.7-fold higher AUC). 2

Common Pitfall to Avoid

Do not use cyclobenzaprine to mask evolving statin-induced myopathy. If a patient on statins develops new muscle pain:

1. Obtain CK level immediately and compare to baseline 4
2. If CK is significantly elevated (>3× ULN) or symptoms are progressive/diffuse, address the statin first 4
3. Only prescribe cyclobenzaprine if the pain is clearly mechanical and CK is normal or minimally elevated 4, 2

Risk Factors Requiring Extra Vigilance

The American College of Cardiology identifies factors that increase statin myopathy risk, which should heighten your suspicion that muscle pain may be statin-related rather than mechanical: 1, 6, 7

• Advanced age (>80 years) 6, 7
• Small body frame and frailty 7
• Chronic renal insufficiency 7
• Concomitant use of CYP3A4 inhibitors (macrolide antibiotics, azole antifungals, calcium channel blockers) 1, 6
• Hypothyroidism 4
• Female gender 4
• Higher statin doses 4