Daptomycin adverse reactions
The following adverse reactions are described, or described in greater detail, in other sections:
-Anaphylaxis/hypersensitivity reactions
-Myopathy and rhabdomyolysis
-Eosinophilic pneumonia
-Peripheral neuropathy
-Increased International Normalized Ratio (INR)/prolonged prothrombin time
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

# Clinical Trials Experience
Clinical trials enrolled 1,864 patients treated with CUBICIN and 1,416 treated with comparator.
Complicated Skin and Skin Structure Infection Trials
In Phase 3 complicated skin and skin structure infection (cSSSI) trials, CUBICIN was discontinued in 15/534 (2.8%) patients due to an adverse reaction, while comparator was discontinued in 17/558 (3.0%) patients.
The rates of the most common adverse reactions, organized by body system, observed in cSSSI (4 mg/kg CUBICIN) patients are displayed in Table 4
Drug-related adverse reactions (possibly or probably drug-related) that occurred in <1% of patients receiving CUBICIN in the cSSSI trials are as follows:
Body as a Whole: fatigue, weakness, rigors, flushing, hypersensitivity
Blood/Lymphatic System: leukocytosis, thrombocytopenia, thrombocytosis, eosinophilia, increased International Normalized Ratio (INR)
Cardiovascular System: supraventricular arrhythmia
Dermatologic System: eczema
Digestive System: abdominal distension, stomatitis, jaundice, increased serum lactate dehydrogenase
Metabolic/Nutritional System: hypomagnesemia, increased serum bicarbonate, electrolyte disturbance
Musculoskeletal System: myalgia, muscle cramps, muscle weakness, arthralgia
Nervous System: vertigo, mental status change, paresthesia
Special Senses: taste disturbance, eye irritation

# S. aureus Bacteremia/Endocarditis Trial
In the S. aureus bacteremia/endocarditis trial, CUBICIN was discontinued in 20/120 (16.7%) patients due to an adverse reaction, while comparator was discontinued in 21/116 (18.1%) patients.
Serious Gram-negative infections (including bloodstream infections) were reported in 10/120 (8.3%) CUBICIN-treated patients and 0/115 comparator-treated patients.  Comparator-treated patients received dual therapy that included initial gentamicin for 4 days.  Infections were reported during treatment and during early and late follow-up.  Gram-negative infections included cholangitis, alcoholic pancreatitis, sternal osteomyelitis/mediastinitis, bowel infarction, recurrent Crohn's disease, recurrent line sepsis, and recurrent urosepsis caused by a number of different Gram-negative bacteria.
The rates of the most common adverse reactions, organized by System Organ Class (SOC), observed in S. aureus bacteremia/endocarditis (6 mg/kg CUBICIN) patients are displayed in Table 5.
The following reactions, not included above, were reported as possibly or probably drug-related in the CUBICIN-treated group:
Blood and Lymphatic System Disorders: eosinophilia, lymphadenopathy, thrombocythemia, thrombocytopenia
Cardiac Disorders: atrial fibrillation, atrial flutter, cardiac arrest
Ear and Labyrinth Disorders: tinnitus
Eye Disorders: vision blurred
Gastrointestinal Disorders: dry mouth, epigastric discomfort, gingival pain, hypoesthesia oral
Infections and Infestations: candidal infection NOS, vaginal candidiasis, fungemia, oral candidiasis, urinary tract infection fungal
Investigations: blood phosphorous increased, blood alkaline phosphatase increased, INR increased, liver function test abnormal, alanine aminotransferase increased, aspartate aminotransferase increased, prothrombin time prolonged
Metabolism and Nutrition Disorders: appetite decreased NOS
Musculoskeletal and Connective Tissue Disorders: myalgia
Nervous System Disorders: dyskinesia, paresthesia
Psychiatric Disorders: hallucination NOS
Renal and Urinary Disorders: proteinuria, renal impairment NOS
Skin and Subcutaneous Tissue Disorders: pruritus generalized, rash vesicular

# Other Trials
In Phase 3 trials of community-acquired pneumonia (CAP), the death rate and rates of serious cardiorespiratory adverse events were higher in CUBICIN-treated patients than in comparator-treated patients.  These differences were due to lack of therapeutic effectiveness of CUBICIN in the treatment of CAP in patients experiencing these adverse events .

# Laboratory Changes
Complicated Skin and Skin Structure Infection Trials
In Phase 3 cSSSI trials of CUBICIN at a dose of 4 mg/kg, elevations in CPK were reported as clinical adverse events in 15/534 (2.8%) CUBICIN-treated patients, compared with 10/558 (1.8%) comparator-treated patients.  Of the 534 patients treated with CUBICIN, 1 (0.2%) had symptoms of muscle pain or weakness associated with CPK elevations to greater than 4 times the upper limit of normal (ULN).  The symptoms resolved within 3 days and CPK returned to normal within 7 to 10 days after treatment was discontinued .  Table 6 summarizes the CPK shifts from Baseline through End of Therapy in the cSSSI trials.
S. aureus Bacteremia/Endocarditis Trial
In the S. aureus bacteremia/endocarditis trial, at a dose of 6 mg/kg, 11/120 (9.2%) CUBICIN-treated patients, including two patients with baseline CPK levels >500 U/L, had CPK elevations to levels >500 U/L, compared with 1/116 (0.9%) comparator-treated patients.  Of the 11 CUBICIN-treated patients, 4 had prior or concomitant treatment with an HMG-CoA reductase inhibitor.  Three of these 11 CUBICIN-treated patients discontinued therapy due to CPK elevation, while the one comparator-treated patient did not discontinue therapy .

# Post-Marketing Experience
The following adverse reactions have been identified during postapproval use of CUBICIN.  Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or establish a causal relationship to drug exposure.
Immune System Disorders: anaphylaxis; hypersensitivity reactions, including angioedema, drug rash with eosinophilia and systemic symptoms (DRESS), pruritus, hives, shortness of breath, difficulty swallowing, truncal erythema, and pulmonary eosinophilia 
Infections and Infestations: Clostridium difficileassociated diarrhea 
Musculoskeletal Disorders: myoglobin increased; rhabdomyolysis (some reports involved patients treated concurrently with CUBICIN and HMG-CoA reductase inhibitors) 
Respiratory, Thoracic, and Mediastinal Disorders: cough, eosinophilic pneumonia 
Nervous System Disorders: peripheral neuropathy 
Skin and Subcutaneous Tissue Disorders: serious skin reactions, including Stevens-Johnson syndrome and vesiculobullous rash (with or without mucous membrane involvement)
Gastrointestinal Disorders: nausea, vomiting