Can topical minoxidil cause creatine kinase (CK) elevations or myositis?

Topical Minoxidil and CK Elevations/Myositis

Topical minoxidil is not associated with creatine kinase (CK) elevations or myositis based on available clinical evidence.

Understanding Topical Minoxidil

Topical minoxidil is FDA-approved for androgenetic alopecia in men and women, available in 2% and 5% formulations 1. The medication works through multiple pathways including vasodilation, anti-inflammatory effects, and modulation of hair follicle growth cycles.

Key pharmacokinetic considerations:

• Only approximately 1.4% of topical minoxidil is absorbed systemically through the skin 1
• Minoxidil is a prodrug that requires conversion to minoxidil sulfate (the active form) by follicular sulfotransferase 1
• This limited systemic absorption explains the lack of association with muscle-related adverse effects

Myositis and CK Elevations: Causes and Presentation

Myositis is characterized by:

• Muscle weakness (primarily proximal)
• Elevated muscle enzymes (CK, aldolase)
• Inflammatory changes on diagnostic testing 2

The most common medication-associated causes of myositis include:

• Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 inhibitors 2, 3
• Statins
• Certain antibiotics

When evaluating for medication-induced myositis, key diagnostic findings include:

• Markedly elevated CK levels (median 2650 IU/L, range 335-20,270 IU/L) 2
• Elevated inflammatory markers (ESR, CRP)
• Muscle weakness, primarily in proximal extremities 2

Evidence Regarding Topical Minoxidil Safety

Multiple clinical studies on topical minoxidil have not reported CK elevations or myositis:

• A 48-week randomized controlled trial comparing 5% and 2% topical minoxidil in 381 women reported no systemic adverse effects 4
• Studies comparing different concentrations (including 10% vs 5%) of topical minoxidil did not report muscle-related adverse events 5
• The most common side effects reported with topical minoxidil are local reactions such as:
  • Pruritus
  • Local irritation
  • Hypertrichosis 4

Differential Diagnosis for CK Elevations

If a patient using topical minoxidil presents with CK elevations or muscle symptoms, consider alternative causes:

1. Immune checkpoint inhibitor therapy (if applicable)

   • PD-1/PD-L1 inhibitors are more commonly associated with myositis than CTLA-4 inhibitors 2
   • ICI-related myositis can be severe with higher mortality rates (20%) 2

2. Other medications known to cause myositis

   • Statins
   • Certain antibiotics
   • Colchicine

3. Strenuous exercise or muscle trauma

   • Can cause transient CK elevations without true myositis

Monitoring and Management

For patients on topical minoxidil:

• Routine monitoring of CK levels is not indicated
• If muscle symptoms develop, evaluate for other causes

If myositis is suspected from another cause:

• Check CK, aldolase, transaminases (AST, ALT), and LDH 6
• Consider inflammatory markers (ESR, CRP) 6
• Evaluate for cardiac involvement with troponin testing 6
• Consider EMG, MRI, or muscle biopsy in unclear cases 6

Conclusion

Topical minoxidil has minimal systemic absorption and has not been associated with CK elevations or myositis in clinical studies. If a patient using topical minoxidil develops muscle symptoms or CK elevations, clinicians should investigate other potential causes rather than attributing these findings to minoxidil use.