DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Cubicin (Daptomycin) - Side Effects and Adverse Reactions



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.  The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Clinical studies sponsored by Cubist enrolled 1,667 patients treated with CUBICIN and 1,319 treated with comparator.  Most adverse events reported in Cubist-sponsored Phase 1, 2, and 3 clinical studies were described as mild or moderate in intensity.  In Phase 3 cSSSI trials, CUBICIN was discontinued in 15/534 (2.8%) patients due to an adverse event, while comparator was discontinued in 17/558 (3.0%) patients.  In the S. aureus bacteremia/endocarditis trial, CUBICIN was discontinued in 20/120 (16.7%) patients due to an adverse event, while comparator was discontinued in 21/116 (18.1%) patients.

Gram-Negative Infections

In the S. aureus bacteremia/endocarditis trial, serious Gram-negative infections and nonserious Gram-negative bloodstream infections were reported in 10/120 (8.3%) CUBICIN-treated and 0/115 comparator-treated patients.  Comparator patients received dual therapy that included initial gentamicin for 4 days.  Events 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 organisms.  One patient with sternal osteomyelitis following mitral valve repair developed S. aureus endocarditis with a 2 cm mitral vegetation and had a course complicated with bowel infarction, polymicrobial bacteremia, and death.

Other Adverse Reactions

The rates of most common adverse events, organized by body system, observed in cSSSI patients are displayed in Table 5.

Table 5. Incidence (%) of Adverse Events that Occurred in ≥2% of Patients in Either CUBICIN or Comparator Treatment Groups in Phase 3 cSSSI Studies
Adverse EventCUBICIN 4 mg/kgComparatorComparators were vancomycin (1 g IV q12h) and anti-staphylococcal semi-synthetic penicillins (i.e., nafcillin, oxacillin, cloxacillin, flucloxacillin; 4 to 12 g/day IV in divided doses).
Gastrointestinal disorders
General disorders
    Injection site reactions5.8%7.7%
Nervous system disorders
Skin/subcutaneous disorders
Diagnostic investigations
    Abnormal liver function tests3.0%1.6%
    Elevated CPK2.8%1.8%
    Fungal infections2.6%3.2%
    Urinary tract infections2.4%0.5%
Vascular disorders
Renal/urinary disorders
    Renal failure2.2%2.7%
Blood/lymphatic disorders
Respiratory disorders
Musculoskeletal disorders
    Limb pain1.5%2.0%

Additional adverse events that occurred in 1 to 2% of patients in either CUBICIN (4 mg/kg) or comparator treatment groups in the cSSSI studies are as follows: edema, cellulitis, hypoglycemia, elevated alkaline phosphatase, cough, back pain, abdominal pain, hypokalemia, hyperglycemia, decreased appetite, anxiety, chest pain, sore throat, cardiac failure, confusion, and Candida infections.  These events occurred at rates ranging from 0.2 to 1.7% in CUBICIN-treated patients and at rates of 0.4 to 1.8% in comparator-treated patients.

Additional drug-related adverse events (possibly or probably related) that occurred in <1% of patients receiving CUBICIN in the cSSSI trials are as follows:

Body as a Whole: fatigue, weakness, rigors, discomfort, jitteriness, 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, flatulence, stomatitis, jaundice, increased serum lactate dehydrogenase
Metabolic/Nutritional System: hypomagnesemia, increased serum bicarbonate, electrolyte disturbance
Musculoskeletal System: myalgia, muscle cramps, muscle weakness, osteomyelitis
Nervous System: vertigo, mental status change, paraesthesia
Special Senses: taste disturbance, eye irritation

The rates of most common adverse events, organized by System Organ Class (SOC), observed in S. aureus bacteremia/endocarditis (6 mg/kg CUBICIN) patients are displayed in Table 6.

Table 6. Incidence (%) of Adverse Events that Occurred in ≥5% of Patients in Either CUBICIN or Comparator Treatment Groups in the S. aureus Bacteremia/Endocarditis Study
Adverse EventCUBICIN 6 mg/kgComparatorComparator: vancomycin (1 g IV q12h) or anti-staphylococcal semi-synthetic penicillin (i.e., nafcillin, oxacillin, cloxacillin, flucloxacillin; 2 g IV q4h), each with initial low-dose gentamicin.
n (%)n (%)
Infections and infestations 65 (54.2%) 56 (48.3%)
    Urinary tract infection NOS8 (6.7%)11 (9.5%)
    Osteomyelitis NOS7 (5.8%)7 (6.0%)
    Sepsis NOS6 (5.0%)3 (2.6%)
    Bacteraemia6 (5.0%)0 (0%)
    Pneumonia NOS4 (3.3%)9 (7.8%)
Gastrointestinal disorders 60 (50.0%) 68 (58.6%)
    Diarrhoea NOS14 (11.7%)21 (18.1%)
    Vomiting NOS14 (11.7%)15 (12.9%)
    Constipation13 (10.8%)14 (12.1%)
    Nausea12 (10.0%)23 (19.8%)
    Abdominal pain NOS7 (5.8%)4 (3.4%)
    Dyspepsia5 (4.2%)8 (6.9%)
    Loose stools5 (4.2%)6 (5.2%)
    Gastrointestinal haemorrhage NOS2 (1.7%)6 (5.2%)
General disorders and administration site conditions 53 (44.2%) 69 (59.5%)
    Oedema peripheral8 (6.7%)16 (13.8%)
    Pyrexia8 (6.7%)10 (8.6%)
    Chest pain8 (6.7%)7 (6.0%)
    Oedema NOS8 (6.7%)5 (4.3%)
    Asthenia6 (5.0%)6 (5.2%)
    Injection site erythema3 (2.5%)7 (6.0%)
Respiratory, thoracic and mediastinal disorders 38 (31.7%) 43 (37.1%)
    Pharyngolaryngeal pain10 (8.3%)2 (1.7%)
    Pleural effusion7 (5.8%)8 (6.9%)
    Cough4 (3.3%)7 (6.0%)
    Dyspnoea4 (3.3%)6 (5.2%)
Skin and subcutaneous tissue disorders 36 (30.0%) 40 (34.5%)
    Rash NOS8 (6.7%)10 (8.6%)
    Pruritus7 (5.8%)6 (5.2%)
    Erythema6 (5.0%)6 (5.2%)
    Sweating increased6 (5.0%)0 (0%)
Musculoskeletal and connective tissue disorders 35 (29.2%) 42 (36.2%)
    Pain in extremity11 (9.2%)11 (9.5%)
    Back pain8 (6.7%)10 (8.6%)
    Arthralgia4 (3.3%)13 (11.2%)
Psychiatric disorders 35 (29.2%) 28 (24.1%)
    Insomnia11 (9.2%)8 (6.9%)
    Anxiety6 (5.0%)6 (5.2%)
Nervous system disorders 32 (26.7%) 32 (27.6%)
    Headache8 (6.7%)12 (10.3%)
    Dizziness7 (5.8%)7 (6.0%)
Investigations 30 (25.0%) 33 (28.4%)
    Blood creatine phosphokinase increased8 (6.7%)1 (<1.0%)
Blood and lymphatic system disorders 29 (24.2%) 24 (20.7%)
    Anaemia NOS15 (12.5%)18 (15.5%)
Metabolism and nutrition disorders 26 (21.7%) 38 (32.8%)
    Hypokalaemia11 (9.2%)15 (12.9%)
    Hyperkalaemia6 (5.0%)10 (8.6%)
Vascular disorders 21 (17.5%) 20 (17.2%)
    Hypertension NOS7 (5.8%)3 (2.6%)
    Hypotension NOS6 (5.0%)9 (7.8%)
Renal and urinary disorders 18 (15.0%) 26 (22.4%)
    Renal failure NOS4 (3.3%)11 (9.5%)
    Renal failure acute4 (3.3%)7 (6.0%)

The following events, not included above, were reported as possibly or probably drug-related in the CUBICIN-treated group:

Blood and Lymphatic System Disorders: eosinophilia (1.7%), lymphadenopathy (<1%), thrombocythaemia (<1%), thrombocytopenia (<1%)
Cardiac Disorders: atrial fibrillation (<1%), atrial flutter (<1%), cardiac arrest (<1%)
Ear and Labyrinth Disorders: tinnitus (<1%)
Eye Disorders: vision blurred (<1%)
Gastrointestinal Disorders: dry mouth (<1%), epigastric discomfort (<1%), gingival pain (<1%), hypoaesthesia oral (<1%)
Infections and Infestations: candidal infection NOS (1.7%), vaginal candidiasis (1.7%), fungaemia (<1%), oral candidiasis (<1%), urinary tract infection fungal (<1%)
Investigations: blood phosphorous increased (2.5%), blood alkaline phosphatase increased (1.7%), INR increased (1.7%), liver function test abnormal (1.7%), alanine aminotransferase increased (<1%), aspartate aminotransferase increased (<1%), prothrombin time prolonged (<1%)
Metabolism and Nutrition Disorders: appetite decreased NOS (<1%)
Musculoskeletal and Connective Tissue Disorders: myalgia (<1%)
Nervous System Disorders: dyskinesia (<1%), paraesthesia (<1%)
Psychiatric Disorders: hallucination NOS (<1%)
Renal and Urinary Disorders: proteinuria (<1%), renal impairment NOS (<1%)
Skin and Subcutaneous Tissue Disorders: heat rash (<1%), pruritus generalized (<1%), rash vesicular (<1%)

In Phase 3 studies 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 (see INDICATIONS AND USAGE).

Laboratory Changes

In Phase 3 comparator-controlled cSSSI and CAP studies, there was no clinically or statistically significant difference (p<0.05) in the incidence of CPK elevations between patients treated with CUBICIN and those treated with comparator.  CPK elevations in both groups were generally related to medical conditions—for example, skin and skin structure infection, surgical procedures, or intramuscular injections—and were not associated with muscle symptoms.

In the Phase 3 cSSSI studies, 0.2% of patients treated with CUBICIN had symptoms of muscle pain or weakness associated with CPK elevations to greater than 4X ULN.  The symptoms resolved within 3 days and CPK returned to normal within 7 to 10 days after discontinuing treatment (see PRECAUTIONS, Skeletal Muscle).   Table 7 summarizes the CPK shifts from Baseline through End of Therapy in the cSSSI trials.

Table 7. Incidence (%) of Creatine Phosphokinase (CPK) Elevations from Baseline while on Therapy in Either CUBICIN or Comparator Treatment Groups in Phase 3 cSSSI Studies
ChangeAll PatientsPatients with Normal CPK at Baseline
Note: Elevations in CPK observed in patients treated with CUBICIN or comparator were not clinically or statistically significantly different.
No Increase90.7%39091.1%41891.2%34191.1%357
Maximum Value >1X ULNULN (Upper Limit of Normal) is defined as 200 U/L.9.3%408.9%418.8%338.9%35
                             >2X ULN4.9%214.8%223.7%143.1%12
                             >4X ULN1.4%61.5%71.1%41.0%4
                             >5X ULN1.4%60.4%21.1%40.0%0
                             >10X ULN0.5%20.2%10.2%10.0%0

In the S. aureus bacteremia/endocarditis study, a total of 11 CUBICIN-treated patients (9.2%) had treatment-emergent elevations in CPK to >500 U/L, including 4 patients with elevations >10X ULN.  Three of these 11 patients had CPK levels return to the normal range during continued CUBICIN treatment, 6 had values return to the normal range during follow-up, 1 had values returning toward baseline at the last assessment, and 1 did not have follow-up values reported.  Three patients discontinued CUBICIN due to CPK elevation.

There was more renal dysfunction in comparator-treated patients than in CUBICIN-treated patients.  The incidence of decreased renal function, defined as the proportion of patients with a creatinine clearance level <50 mL/min if baseline clearance was ≥50 mL/min or with a decrease of ≥10 mL/min if baseline clearance was <50 mL/min, is shown in Table 8.

Table 8. Incidence of Decreased Renal Function Based on Creatinine Clearance Levels
Study IntervalCUBICIN 6 mg/kgComparatorComparator: vancomycin (1 g IV q12h) or anti-staphylococcal semi-synthetic penicillin (i.e., nafcillin, oxacillin, cloxacillin, flucloxacillin; 2 g IV q4h), each with initial low-dose gentamicin.
n/N (%)n/N (%)
Days 2 to 42/96 (2.1%)6/90 (6.7%)
Days 2 to 76/115 (5.2%)16/113 (14.2%)
Day 2 to End of Study13/118 (11.0%)30/114 (26.3%)

Post-Marketing Experience

The following adverse reactions have been reported with CUBICIN in worldwide post-marketing experience.  Because these events are reported voluntarily from a population of unknown size, estimates of frequency cannot be made and causal relationship cannot be precisely established.

Immune System Disorders: anaphylaxis; hypersensitivity reactions, including pruritus, hives, shortness of breath, difficulty swallowing, truncal erythema, and pulmonary eosinophilia
Musculoskeletal Disorders: myoglobin increased; rhabdomyolysis (some reports involved patients treated concurrently with CUBICIN and HMG-CoA reductase inhibitors)
Nervous System Disorders: peripheral neuropathy
Skin and Subcutaneous Tissue Disorders: vesiculobullous rash with or without mucous membrane involvement


Below is a sample of reports where side effects / adverse reactions may be related to Cubicin. The information is not vetted and should not be considered as verified clinical evidence.

Possible Cubicin side effects / adverse reactions in 63 year old male

Reported by a pharmacist from United States on 2011-10-05

Patient: 63 year old male weighing 76.0 kg (167.2 pounds)

Reactions: Eosinophilic Pneumonia

Adverse event resulted in: hospitalization

Suspect drug(s):

Other drugs received by patient: Claritin; Ascorbic Acid; Ultram; Miralax; Enoxaparin; Cholecalciferol; Kenalog 0.1 % EX Cream

Possible Cubicin side effects / adverse reactions in 43 year old female

Reported by a physician from Romania on 2011-10-06

Patient: 43 year old female

Reactions: Systemic Lupus Erythematosus, Angina Unstable

Adverse event resulted in: death, life threatening event

Suspect drug(s):

Possible Cubicin side effects / adverse reactions in 80 year old male

Reported by a consumer/non-health professional from United States on 2011-10-11

Patient: 80 year old male weighing 81.6 kg (179.6 pounds)

Reactions: Eosinophilic Pneumonia

Adverse event resulted in: life threatening event, hospitalization, disablity

Suspect drug(s):

See index of all Cubicin side effect reports >>

Drug label data at the top of this Page last updated: 2008-07-30

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017