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Cubicin RF Side Effects

Generic name: daptomycin

Medically reviewed by Last updated on Jun 16, 2023.

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

Applies to daptomycin: intravenous powder for solution.

Serious side effects of Cubicin RF

Along with its needed effects, daptomycin (the active ingredient contained in Cubicin RF) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking daptomycin:

More common

Less common


Incidence not known

Other side effects of Cubicin RF

Some side effects of daptomycin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Less common


For Healthcare Professionals

Applies to daptomycin: intravenous powder for injection, intravenous solution.


In phase 3 complicated skin and skin structure infection trials, this drug 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, this drug was discontinued in 16.7% of patients due to a side effect, while comparator was discontinued in 18.1% of patients.

In phase 3 community-acquired pneumonia trials, the death rate and rates of serious cardiorespiratory side effects were higher with this drug than comparator due to lack of therapeutic efficacy.[Ref]


Common (1% to 10%): Elevated creatine phosphokinase (CPK), limb pain

Uncommon (0.1% to 1%): Myalgia, muscle cramps, myositis, increased myoglobin, muscle weakness, muscle pain, arthralgia, muscle pain/weakness symptoms associated with CPK elevations to greater than 4 times the upper limit of normal (4 x ULN)

Frequency not reported: Pain in extremity, back pain, osteomyelitis, muscle twitching, myopathy (with minor increases in CPK), rhabdomyolysis (with secondary acute renal failure), severe myopathy (with possible hepatotoxicity)

Postmarketing reports: Rhabdomyolysis (some cases involved coadministration with HMG-CoA reductase inhibitors)[Ref]

In clinical studies, 0.2% of patients had symptoms of muscle pain or weakness associated with CPK elevations to greater than 4 x ULN. After discontinuation of this drug, CPK returned to normal within 7 to 10 days and symptoms resolved within 3 days.

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 IV daptomycin 550 mg (6 mg/kg) every 24 hours. The patient's baseline 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 therapy, her CPK level was 996 units/L, 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 S aureus (MRSA) and the patient was started on daptomycin 360 mg (6 mg/kg) IV as a single daily dose and voriconazole 250 mg twice daily. Ten days after starting this drug, 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: AST 375 units/L, ALT 219 units/L, and LDH 666 units/L. Urinalysis was positive for hemoglobin, myoglobin, and RBCs which conferred a diagnosis of acute renal failure secondary to drug-induced rhabdomyolysis. After this drug was discontinued and IV 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 RBCs disappeared from urine as well.

In another similar case, a 52-year-old male with a history hepatitis C, IV 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) IV as a single daily dose. The patient was also on simvastatin; however, it was discontinued prior to starting this drug. After 9 days of 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. This drug was discontinued and the patient was admitted to the ICU for close monitoring and hydration. The patient slowly improved and recovered all muscle strength and within 2 weeks his enzymes returned to baseline.

Increased myoglobin has also been reported during postmarketing experience.[Ref]


Common (1% to 10%): Insomnia, anxiety

Uncommon (0.1% to 1%): Mental status change

Frequency not reported: Hallucination, confusion[Ref]


Common (1% to 10%): Pyrexia, asthenia, serious gram-negative infections (including bloodstream infections, cholangitis, alcoholic pancreatitis, sternal osteomyelitis/mediastinitis, bowel infarction, recurrent Crohn's disease, recurrent line sepsis, recurrent urosepsis), chest pain, edema, sepsis, bacteremia, fungal infections, candidal infection

Uncommon (0.1% to 1%): Fatigue, weakness, rigors, flushing, taste disturbance, fungemia, pain, chills

Frequency not reported: Discomfort, jitteriness, pneumonia, chapped lips, peripheral edema

Postmarketing reports: Infusion reactions (including tachycardia, wheezing, pyrexia, rigors, systemic flushing, vertigo, syncope, metallic taste)[Ref]

Serious gram-negative infections (including bloodstream infections) were reported in 10/120 daptomycin-treated patients in the S aureus bacteremia/endocarditis trial compared to 0/115 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.

Pyrexia has also been reported during postmarketing experience.[Ref]


Common (1% to 10%): Pharyngolaryngeal pain, dyspnea

Frequency not reported: Pleural effusions, sore throat, adenoviral upper respiratory infection, upper respiratory tract infection (not otherwise specified), dyspnea with hypoxic respiratory insufficiency, diffuse pulmonary infiltrates

Postmarketing reports: Cough, eosinophilic pneumonia, organizing pneumonia[Ref]

Symptoms of eosinophilic pneumonia have included fever, dyspnea with hypoxic respiratory insufficiency, diffuse pulmonary infiltrates, cough, shortness of breath, and difficulty breathing.[Ref]


Common (1% to 10%): Abdominal pain, diarrhea, gastrointestinal and abdominal pain, nausea, vomiting, constipation, flatulence, bloating and distension

Uncommon (0.1% to 1%): Abdominal distention, stomatitis, dyspepsia, glossitis

Frequency not reported: Dry mouth, epigastric discomfort, gingival pain, oral candidiasis, oral hypoesthesia, loose stools, gastrointestinal hemorrhage, abnormal bowel sounds, aphthous stomatitis

Postmarketing reports: Clostridium difficile-associated diarrhea[Ref]

Nausea and vomiting have also been reported during postmarketing experience.[Ref]


Common (1% to 10%): Pruritus, increased sweating, rash

Uncommon (0.1% to 1%): Eczema, urticaria

Frequency not reported: Heat rash, generalized pruritus, vesicular rash, erythema, cellulitis, papular rash

Postmarketing reports: Serious skin reactions (including Stevens-Johnson syndrome, vesiculobullous rash [with or without mucous membrane involvement]), acute generalized exanthematous pustulosis[Ref]


Common (1% to 10%): Hypertension, hypotension

Uncommon (0.1% to 1%): Supraventricular arrhythmia, supraventricular tachycardia, extrasystole

Frequency not reported: Atrial fibrillation, atrial flutter, cardiac arrest, cardiac failure, cardiac disorders (unspecified)[Ref]

Nervous system

Common (1% to 10%): Headache, dizziness

Uncommon (0.1% to 1%): Vertigo, paresthesia, taste disorder, tremor

Frequency not reported: Peripheral nervous system events (such as paresthesias, dysesthesias, peripheral neuropathies), tinnitus, dyskinesia

Postmarketing reports: Peripheral neuropathy[Ref]


Common (1% to 10%): Abnormal liver function tests (increased ALT, increased AST, increased alkaline phosphatase)

Rare (less than 0.1%): Jaundice

Frequency not reported: Hepatobiliary disorder[Ref]


Common (1% to 10%): Urinary tract infections

Uncommon (0.1% to 1%): Vaginitis

Frequency not reported: Vaginal candidiasis, fungal urinary tract infection, proteinuria, vaginal discharge, asymptomatic foamy urine[Ref]


Anemia and thrombocytopenia have also been reported during postmarketing experience.[Ref]

Common (1% to 10%): Anemia

Uncommon (0.1% to 1%): Leukocytosis, thrombocytopenia, thrombocytosis, eosinophilia, increased INR, thrombocythemia

Rare (less than 0.1%): Prolonged prothrombin time

Frequency not reported: Lymphadenopathy

Postmarketing reports: Decreased platelet count[Ref]


Common (1% to 10%): Infusion site reactions

Frequency not reported: Injection site reactions, injection site erythema, injection site phlebitis[Ref]


Uncommon (0.1% to 1%): Hypomagnesemia, increased serum bicarbonate, electrolyte imbalance/disturbance, decreased appetite, hyperglycemia, increased serum lactate dehydrogenase (LDH)

Frequency not reported: Increased blood phosphorous, elevated alkaline phosphatase, hypoglycemia, hypokalemia, hyperkalemia[Ref]


Uncommon (0.1% to 1%): Hypersensitivity

Postmarketing reports: Anaphylaxis, hypersensitivity reactions (including angioedema, drug rash with eosinophilia and systemic symptoms [DRESS], pruritus, hives, shortness of breath, difficulty swallowing, truncal erythema, pulmonary eosinophilia, vesiculobullous rash with mucous membrane involvement, sensation of oropharyngeal swelling)[Ref]


Uncommon (0.1% to 1%): Eye irritation

Frequency not reported: Blurred vision

Postmarketing reports: Visual disturbances[Ref]


Uncommon (0.1% to 1%): Renal impairment (including renal failure, renal insufficiency), increased serum creatinine

Frequency not reported: Renal impairment (including interstitial nephritis, toxic nephropathy, acute prerenal failure, acute or chronic renal failure, renal impairment, renal tubular necrosis), worsening CrCl/decreased renal function

Postmarketing reports: Acute kidney injury[Ref]

Renal insufficiency and renal failure have also been reported during postmarketing experience.[Ref]


Frequency not reported: Benign and malignant neoplasms (unspecified)[Ref]


1. (2003) "Product Information. Cubicin (daptomycin)." Cubist Pharmaceuticals Inc

2. Cerner Multum, Inc. "UK Summary of Product Characteristics."

3. Cerner Multum, Inc. "Australian Product Information."

4. Raghavan M, Linden PK (2004) "Newer treatment options for skin and soft tissue infections." Drugs, 64, p. 1621-42

5. Veligandla SR, Louie KR, Malesker MA, Smith PW (2004) "Muscle pain associated with daptomycin." Ann Pharmacother, 38, p. 1860-2

6. Echevarria K, Datta P, Cadena J, Lewis JS 2nd (2005) "Severe myopathy and possible hepatotoxicity related to daptomycin." J Antimicrob Chemother, 55, p. 599-600

7. Kazory A, Dibadj K, Weiner ID (2006) "Rhabdomyolysis and acute renal failure in a patient treated with daptomycin." J Antimicrob Chemother

8. Papadopoulos S, Ball AM, Liewer SE, Martin CA, Winstead PS, Murphy BS (2006) "Rhabdomyolysis during therapy with daptomycin." Clin Infect Dis, 42, e108-10

9. Akins RL, Haase MR, Levy EN (2006) "Pharmacokinetics of daptomycin in a critically ill adolescent with vancomycin-resistant enterococcal endocarditis." Pharmacotherapy, 26, p. 694-8

10. Grayson ML (2006) "The treatment triangle for staphylococcal infections." N Engl J Med, 355, p. 724-7

11. Fowler VG Jr, Boucher HW, Corey GR, et al. (2006) "Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus." N Engl J Med, 355, p. 653-65

12. Deryke CA, Sutherland C, Zhang B, Nicolau DP, Kuti JL (2006) "Serum Bactericidal Activities of High-Dose Daptomycin with and without Coadministration of Gentamicin against Isolates of Staphylococcus aureus and Enterococcus species." Antimicrob Agents Chemother, 50, p. 3529-34

13. Cobb E, Kimbrough RC, Nugent KM, Phy MP (2007) "Organizing pneumonia and pulmonary eosinophilic infiltration associated with daptomycin." Ann Pharmacother, 41, p. 696-701

14. Abraham G, Finkelberg D, Spooner LM (2008) "Daptomycin-induced acute renal and hepatic toxicity without rhabdomyolysis (May)." Ann Pharmacother, 42, p. 719-21

15. Hawkey PM (2008) "Pre-clinical experience with daptomycin." J Antimicrob Chemother, 62 Suppl 3, iii7-14

16. Doan TL, Depetrillo J, Singer C (2010) "Daptomycin-induced eosinophilia without pulmonary involvement." Am J Health Syst Pharm, 67, p. 2107-9

17. Lal Y, Assimacopoulos AP (2010) "Two cases of daptomycin-induced eosinophilic pneumonia and chronic pneumonitis." Clin Infect Dis, 50, p. 737-40

18. Miller BA, Gray A, Leblanc TW, Sexton DJ, Martin AR, Slama TG (2010) "Acute eosinophilic pneumonia secondary to daptomycin: a report of three cases." Clin Infect Dis, 50, e63-8

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.