Cubicin Side Effects

Generic name: daptomycin

Note: This document contains side effect information about daptomycin. Some of the dosage forms listed on this page may not apply to the brand name Cubicin.

Some side effects of Cubicin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to daptomycin: intravenous powder for injection

Get emergency medical help if you have any of these signs of an allergic reaction while taking daptomycin (the active ingredient contained in Cubicin) hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

• new or worsening cough, fever, trouble breathing;

• pain or burning when you urinate;

• diarrhea that is watery or bloody;

• white patches or sores in your mouth or throat;

• vaginal itching or discharge;

• urinating less than usual or not at all;

• muscle pain or weakness with fever or flu symptoms and dark colored urine;

• pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;

• high potassium (slow heart rate, weak pulse, muscle weakness, tingly feeling); or

• low potassium (confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling).

Less serious side effects of daptomycin may include:

• constipation, nausea, diarrhea, vomiting;

• headache;

• swelling;

• back pain, pain in your arms or legs;

• anxiety, sleep problems (insomnia);

• mild itching or skin rash;

• increased sweating; or

• redness, discomfort, or irritation where the injection was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to daptomycin: intravenous powder for injection

General

Most adverse events reported in clinical trials were mild to moderate in intensity. In phase 3 complicated skin and skin structure infection trials, daptomycin (the active ingredient contained in Cubicin) was discontinued in 2.8% of patients due to a side effect, while comparator was discontinued in 3% of patients. In the Staphylococcus aureus bacteremia/endocarditis trial, daptomycin was discontinued in 16.7% of patients due to a side effect, while comparator was discontinued in 18.1% of patients.

Gastrointestinal

Gastrointestinal side effects have included gastrointestinal disorders (unspecified; 50%), diarrhea (up to 11.7%), vomiting (up to 11.7%), constipation (up to 10.8%), nausea (up to 10%), abdominal pain (up to 5.8%), dyspepsia (up to 4.2%), loose stools (4.2%), gastrointestinal hemorrhage (1.7%), abnormal bowel sounds, and aphthous stomatitis. Abdominal distention, flatulence, stomatitis, dry mouth, epigastric discomfort, gingival pain, oral candidiasis, and oral hypoesthesia have been reported in less than 1% of patients. Clostridium difficile associated diarrhea, nausea, and vomiting have been reported during postmarketing experience.

Other

Other side effects have included infections and infestations (unspecified; 54.2%), general disorders and administration site conditions (unspecified; 44.2%), investigations (unspecified; 25%), peripheral edema (6.7%), chest pain (up to 6.7%), sepsis (5%), pneumonia (3.3%), fungal infections (2.6%), edema (up to 6.7%), Candida infections (up to 1.7%), fever (1.9%), chapped lips, adenoviral upper respiratory infection, and upper respiratory tract infection (not otherwise specified). Fatigue, weakness, rigors, discomfort, jitteriness, flushing, fungemia, and taste disturbance have been reported in less than 1% of patients. Injury, poisoning, and procedural complications (unspecified), bacteremia, and laboratory abnormalities (unspecified) have been reported. Serious Gram-negative infections and nonserious Gram-negative bloodstream infections have also been reported.

Serious and nonserious Gram-negative infections were reported in 8.3% (10/120) of daptomycin-treated patients in the Staphylococcus aureus bacteremia/endocarditis trial compared to 0/120 in comparator-treated patients. Gram-negative infections included cholangitis, alcoholic pancreatitis, sternal osteomyelitis/mediastinitis, bowel infarction, recurrent Crohn's disease, recurrent line sepsis, and recurrent urosepsis.

One patient developed S aureus endocarditis with a 2 cm mitral vegetation, bowel infarction, and polymicrobial bacteremia that ultimately lead to death following mitral valve repair complicated by sternal osteomyelitis.

Respiratory

Symptoms of eosinophilic pneumonia have included fever, dyspnea with hypoxic respiratory insufficiency, diffuse pulmonary infiltrates, cough, shortness of breath, and difficulty breathing. Eosinophilic pneumonia may lead to progressive respiratory failure and is potentially fatal if not quickly recognized and appropriately managed.

Respiratory side effects have included respiratory, thoracic, and mediastinal disorders (unspecified; 31.7%), pharyngolaryngeal pain (8.3%), pleural effusions (5.8%), dyspnea (up to 3.3%), cough (up to 3.3%), and sore throat (up to 1.7%). Cough and eosinophilic pneumonia have been reported during postmarketing experience.

Dermatologic

Dermatologic side effects have included skin and subcutaneous tissue disorders (unspecified; 30%), rash (up to 6.7%), pruritus (up to 5.8%), increased sweating (5%), erythema (5%), cellulitis (up to 1.7 %), and papular rash. Eczema, heat rash, generalized pruritus, and vesicular rash have been reported in less than 1% of patients. Serious skin reactions, including Stevens-Johnson syndrome and vesiculobullous rash (with or without mucous membrane involvement) have been reported during postmarketing experience.

Musculoskeletal

A 45-year-old female with refractory acute myeloid leukemia was admitted to the blood and marrow transplant unit for a second attempt to induce remission with myeloablative chemotherapy of high-dose cytarabine. Two months prior, the patient's first course of induction therapy was complicated by neutropenic fever and vancomycin- resistant Enterococcus faecium (VRE) bacteremia that was treated with linezolid for 14 days. The patient was also receiving aztreonam, levofloxacin, acyclovir, amphotericin B lipid complex, and azithromycin. Once her clinical status stabilized, she was transferred from the intensive care unit (ICU) back to the blood and marrow transplant unit. After receiving 8 of 12 scheduled doses of cytarabine, the patient required readmission to the medical ICU due to a decrease in mental status, supraventricular tachycardia, and hypotension. Cultures of blood and urine samples at the time of her transfer showed VRE with intermediate resistance to linezolid. The patient, who was neutropenic at this time, was started on intravenous daptomycin (the active ingredient contained in Cubicin) 550 mg (6 mg/kg) every 24 hours.

The patient's baseline creatine phosphokinase (CPK) was 108 units/L and serum creatinine level was 0.8 mg/dL. Over the following 7 days, the patient's CPK level gradually increased, and on day 10 of daptomycin treatment, her CPK level was 996 units/L, blood urea nitrogen level (BUN) was 73 mg/dL, and serum creatinine level was 1.9 mg/dL. To evaluate for rhabdomyolysis, urine myoglobin was measured and reported at 30,890 ng/mL. Rhabdomyolysis was diagnosed based on increased CPK and urine myoglobin level in a patient with acute renal failure.

Daptomycin was discontinued and the patient was started on treatment for rhabdomyolysis. Despite aggressive hydration and diuresis, CPK and urine myoglobin levels continued to increase up to 5350 units/L and 47,166 ng/mL, respectively. Over 2 weeks, the patient's CPK and urine myoglobin levels slowly resolved. The final CPK and urine myoglobin levels measured were 3395 units/L and 451 ng/mL, respectively.

In another case, a 53-year-old African-American female with a history of hypertension, diabetes mellitus, and peripheral vascular disease was admitted to the hospital and an MRI revealed L5-S1 discitis and osteomyelitis. After an 8-week course of empirical antibiotic therapy with vancomycin and levofloxacin an open biopsy was performed. Specimens from the biopsy cultured positive for Torulopsis glabrata, VRE, and methicillin-resistant Staphylococcus aureus (MRSA) and the patient was started on daptomycin 360 mg (6 mg/kg) intravenously as a single daily dose and voriconazole 250 mg twice daily.

Ten days after the start of daptomycin therapy, the patient developed generalized muscular weakness that progressed to the point she was unable to get out of bed. The patient then developed nonoliguric acute renal failure with a serum creatinine of 27 mg/mL up from baseline of 9 mg/mL. A CPK level drawn was elevated to 21,243 units/L and was associated with elevated levels aspartate aminotransferase (AST) 375 units/L, alanine aminotransferase (ALT) 219 units/L, and lactate dehydrogenase (LDH) 666 units/L. Urinalysis was positive for hemoglobin, myoglobin, and red blood cells which conferred a diagnosis of acute renal failure secondary to daptomycin-induced rhabdomyolysis.

After daptomycin was discontinued and intravenous fluid was administered to alkalinize the urine, renal function, CPK, and liver function tests returned to baseline as well as dissipation of muscular weakness. Myoglobin, hemoglobin, and the red blood cells disappeared from urine as well.

In another similar case, a 52-year-old male with a history hepatitis C, intravenous drug abuse, idiopathic thrombocytopenia, and hyperlipidemia was admitted to the hospital and an MRI revealed findings compatible with L3-L4 discitis and osteomyelitis. He was started on vancomycin but it was discontinued after a rash developed. Daptomycin was started at 500 mg (6.5 mg/kg) intravenous as a single daily dose. The patient was also on simvastatin; however, it was discontinued prior to initiation of daptomycin therapy. After nine days into the course of daptomycin therapy, the patient developed generalized muscle weakness progressing to the point where he was unable to get out of bed. The patient's CPK rose to 20,771 units/L from a baseline of 102 units/L. AST 239 units/L and ALT 40 units/L were elevated from baseline and alkaline phosphatase was elevated to 118 units/L.

Daptomycin was discontinued and the patient was admitted to the intensive care unit for close monitoring and hydration. The patient slowly improved and recovered all muscle strength and within two weeks his enzymes returned to baseline.

Musculoskeletal side effects have included musculoskeletal and connective tissue disorders (unspecified; 29.2%), pain in extremity (9.2%), elevated creatine phosphokinase (CPK; up to 6.7%), back pain (up to 6.7%), arthralgia (up to 3.3%), limb pain (1.5%), and muscle twitching. Myalgia, myositis, muscle cramps, muscle weakness, and osteomyelitis have been reported in less than 1% of patients. In clinical studies, 0.2% of patients had symptoms of muscle pain or weakness associated with CPK elevations to greater than 4 times ULN. After discontinuation of daptomycin, CPK returned to normal within 7 to 10 days and symptoms resolved within 3 days. Myopathy with minor increases in creatine kinase has also been reported. Case reports of rhabdomyolysis with secondary acute renal failure and other reports of severe myopathy and possible hepatotoxicity were recorded with use of daptomycin therapy. Increased myoglobin and rhabdomyolysis (some cases involved patients treated concurrently with daptomycin and HMG-CoA reductase inhibitors) have been reported during postmarketing experience.

Psychiatric

Psychiatric side effects have included psychiatric disorders (unspecified; 29.2%) and anxiety (up to 5%).

Nervous system

Nervous system side effects have included nervous system disorders (unspecified; 26.7%), peripheral nervous system events (such as paresthesias, dysesthesias, and peripheral neuropathies; 9.2%), insomnia (up to 9.2%), headache (up to 6.7%), dizziness (up to 5.8%), and confusion (up to 1.7%). Vertigo, mental status change, hallucination, tinnitus, dyskinesia, and paresthesia have been reported in less than 1% of patients. Peripheral neuropathy has been reported during postmarketing experience.

Hematologic

Hematologic side effects have included blood and lymphatic system disorders (unspecified; 24.2%), anemia (up to 12.5%), eosinophilia (up to 1.7%), and increased INR (up to 1.7%). Leukocytosis, lymphadenopathy, thrombocythemia, thrombocytopenia, thrombocytosis, and prolonged prothrombin time have been reported in less than 1% of patients.

Metabolic

Metabolic side effects have included metabolism and nutrition disorders (unspecified; 21.7%), hypokalemia (up to 9.2%), hyperkalemia (up to 5%), increased blood phosphorous (2.5%), decreased appetite (up to 1.7%), and hypoglycemia (up to 1.7%). Hypomagnesemia, increased serum bicarbonate, and electrolyte disturbance have been reported in less than 1% of patients.

Cardiovascular

Cardiovascular side effects have included vascular disorders (unspecified; 17.5%), hypertension (up to 5.8%), hypotension (up to 5%), cardiac failure (up to 1.7%), and cardiac disorders (unspecified). Supraventricular arrhythmia, atrial fibrillation, atrial flutter, and cardiac arrest have been reported in less than 1% of patients.

Renal

Renal side effects have included renal and urinary disorders (unspecified; 15%), worsening creatinine clearance/decreased renal function (up to 11%), renal failure (up to 3.3%), acute renal failure (3.3%), and renal impairment (unspecified; less than 1%). Renal impairment (interstitial nephritis, toxic nephropathy, acute prerenal failure, acute or chronic renal failure, renal impairment, and renal tubular necrosis) has been reported.

Genitourinary

Genitourinary side effects have included urinary tract infections (up to 6.7%), vaginal candidiasis (1.7%), fungal urinary tract infection (less than 1%), proteinuria (less than 1%), vaginal discharge, and asymptomatic foamy urine.

Local

Local side effects have included injection site reactions (up to 5.8%), injection site erythema (2.5%), and injection site phlebitis.

Hepatic

Hepatic side effects have included abnormal liver function tests (up to 3%) and elevated alkaline phosphatase (up to 1.7%). Jaundice, increased lactate dehydrogenase, increased alanine aminotransferase, and increased aspartate aminotransferase have been reported in less than 1% of patients. Hepatobiliary disorder (unspecified) has been reported in at least 1 patient.

Hypersensitivity

Hypersensitivity side effects have included hypersensitivity (unspecified) in less than 1% of patients. Anaphylaxis and hypersensitivity reactions (including pruritus, hives, shortness of breath, difficulty swallowing, truncal erythema, and pulmonary eosinophilia) have been reported during postmarketing experience.

Other

In phase 3 trials of community-acquired pneumonia, daptomycin (the active ingredient contained in Cubicin) was associated with a higher death rate and rate of serious cardiorespiratory adverse events than comparator drugs, due to lack of clinical efficacy.

Ocular

Ocular side effects have included eye irritation and blurred vision in less than 1% of patients.

Oncologic

Oncologic side effects have included benign and malignant neoplasms (unspecified).

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