What are the potential side effects of daptomycin and how are they managed?

Daptomycin Side Effects and Management

Daptomycin's most significant side effects include myopathy/rhabdomyolysis, eosinophilic pneumonia, and drug reaction with eosinophilia and systemic symptoms (DRESS), requiring regular monitoring of creatine phosphokinase (CPK) levels and prompt discontinuation if these adverse effects occur. 1, 2

Common Side Effects

Frequency ≥2% in adults with complicated skin infections:

• Diarrhea
• Headache
• Dizziness
• Rash
• Abnormal liver function tests
• Elevated creatine phosphokinase (CPK)
• Urinary tract infections
• Hypotension
• Dyspnea 2

Frequency ≥5% in adults with S. aureus bacteremia/endocarditis:

• Sepsis
• Bacteremia
• Abdominal pain
• Chest pain
• Edema
• Pharyngolaryngeal pain
• Pruritus
• Increased sweating
• Insomnia
• Elevated CPK
• Hypertension 2

Serious Adverse Effects

1. Myopathy and Rhabdomyolysis

• Mechanism: Direct skeletal muscle cell membrane injury via calcium-dependent binding, similar to its antibacterial mechanism 1
• Risk factors:
  • Higher doses (≥6 mg/kg/day)
  • Renal impairment
  • Concurrent medications affecting muscle function 1
• Monitoring:
  • Baseline CPK measurement before starting therapy
  • Weekly CPK monitoring during treatment
  • More frequent monitoring for high-risk patients 1
• Management:
  • Discontinue daptomycin if significant CPK elevation occurs or if myopathy develops
  • Consider alternative antibiotics 2

2. Eosinophilic Pneumonia

• Presentation: Fever, shortness of breath, nonproductive cough, bilateral interstitial infiltrates, peripheral eosinophilia 3
• Timing: Can occur after variable exposure to daptomycin (days to weeks) 4
• Management:
  • Immediate discontinuation of daptomycin
  • Initiation of systemic corticosteroids (e.g., methylprednisolone 40-60 mg every 6 hours)
  • Dramatic clinical improvement typically occurs within 72 hours of corticosteroid initiation 4

3. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

• Management: Discontinue daptomycin and institute appropriate treatment 2

4. Tubulointerstitial Nephritis (TIN)

• Management: Discontinue daptomycin and institute appropriate treatment 2

5. Peripheral Neuropathy

• Monitoring: Assess for neuropathic symptoms
• Management: Consider discontinuation if neuropathy develops 2

Risk Factors for Adverse Effects

A recent study identified common determinants for daptomycin-induced eosinophilic pneumonia and myotoxicity 5:

• Daptomycin AUC24h > 939 mg/h/L (HR 3.1,95% CI 1.48-6.5)
• C-reactive protein > 21.6 mg/L (HR 9.8,95% CI 3.94-24.5)
• Serum protein < 72 g/L (HR 2.4,95% CI 1.02-5.65)

Monitoring Recommendations

1. Before starting therapy:

   • Baseline CPK measurement
   • Complete blood count
   • Renal function
   • Liver enzymes 1

2. During therapy:

   • Weekly monitoring of CPK, CBC, renal function, and liver enzymes
   • More frequent CPK monitoring for patients with:
     • Renal impairment
     • Concurrent medications affecting muscle function
     • Higher doses of daptomycin (8-12 mg/kg daily) 1

3. Clinical monitoring:

   • Muscle pain or weakness, particularly in distal extremities
   • Respiratory symptoms (cough, dyspnea, fever)
   • Rash or other hypersensitivity reactions 2

Special Considerations

• Pulmonary infections: Daptomycin is inhibited by pulmonary surfactant and is contraindicated for pneumonia acquired via aspiration 6
• Pediatric patients: Different dosing regimens based on age; avoid use in patients younger than 12 months due to potential nervous system and/or muscular system effects 2
• High-dose therapy: Despite concerns, some studies suggest no significantly increased risk of CK elevation with high-dose daptomycin (8-12 mg/kg daily) compared to standard dosing, though monitoring remains essential 1

Management of Specific Side Effects

1. For myopathy/elevated CPK:

   • Discontinue daptomycin
   • Consider alternative antibiotics like linezolid, quinupristin-dalfopristin, or telavancin for MRSA infections 6

2. For eosinophilic pneumonia:

   • Discontinue daptomycin
   • Initiate systemic corticosteroids
   • Provide respiratory support as needed 4

3. For hypersensitivity reactions:

   • Discontinue daptomycin immediately
   • Provide supportive care 2

Regular monitoring and prompt recognition of adverse effects are essential for safe use of daptomycin, particularly when using higher doses or treating patients with risk factors for toxicity.