Daptomycin Side Effects
The most common side effects of daptomycin include elevated creatine phosphokinase (CPK), muscle pain or weakness, rhabdomyolysis, and eosinophilic pneumonia, with CPK elevation requiring regular monitoring during treatment. 1
Major Side Effects
Musculoskeletal Effects
- Elevated creatine phosphokinase (CPK) levels - occurs more frequently at higher doses (≥6 mg/kg/day) compared to lower doses (4 mg/kg/day) 1
- Myopathy and muscle pain/weakness - can occur even without significant CPK elevation 2
- Rhabdomyolysis - rare but serious complication requiring immediate discontinuation 3
- Weekly CPK monitoring is recommended for all patients, with more frequent monitoring for those with renal insufficiency or on concurrent statin therapy 1
Respiratory Effects
- Eosinophilic pneumonia - multiple case reports have been documented 1, 3
- Should not be used for non-hematogenous pneumonia as daptomycin is inactivated by pulmonary surfactant 1, 4
Other Significant Side Effects
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) 5
- Tubulointerstitial Nephritis (TIN) 5
- Peripheral neuropathy 5
- Clostridioides difficile-associated diarrhea 5
Common Side Effects in Adults
For Complicated Skin and Skin Structure Infections (≥2% incidence)
- Diarrhea, headache, dizziness, rash 5
- Abnormal liver function tests 5
- Urinary tract infections, hypotension, dyspnea 5
For S. aureus Bacteremia/Endocarditis (≥5% incidence)
- Sepsis, bacteremia, abdominal pain, chest pain 5
- Edema, pharyngolaryngeal pain, pruritus 5
- Increased sweating, insomnia, hypertension 5
Common Side Effects in Pediatric Patients
- Diarrhea, vomiting, abdominal pain 5
- Pruritus, pyrexia, headache 5
- Elevated CPK (particularly in S. aureus bacteremia patients) 5
Risk Factors for CPK Elevation
- Concomitant use of hydrophobic statins significantly increases risk 6
- Higher baseline CPK values predispose to further elevation 6
- Renal insufficiency increases risk of muscle toxicity 1
- Higher doses (>6 mg/kg/day) are associated with greater risk 1
Monitoring Recommendations
- Weekly CPK monitoring for all patients 1
- More frequent monitoring for patients with:
- Monitor for symptoms of muscle pain or weakness regardless of CPK levels 2
- Consider discontinuation if:
Management of Side Effects
- For asymptomatic CPK elevation, a "daptomycin holiday" may be considered - temporarily withholding the drug until CPK levels trend downward before resuming therapy 7
- For symptomatic myopathy, eosinophilic pneumonia, or severe CPK elevation, discontinuation is typically required 1, 3
- CPK levels usually normalize within one week of discontinuation 7
Special Populations
- Patients with severe renal dysfunction (CrCl <30 mL/min) may receive high-dose daptomycin with careful monitoring, as significant CPK elevation appears infrequent in this population 8
- Daptomycin is pregnancy category B 1
- Should be avoided in pediatric patients younger than 12 months due to potential nervous system and/or muscular system effects 5