Is daptomycin FDA-approved, and what does the research show?

What is daptomycin?

Daptomycin kills bacteria; it is an antibiotic, and its label's class for it is "lipopeptide antibacterial" ¹. A lipopeptide is a short chain of amino acids with a fatty tail attached, and daptomycin's chain closes into a ring, so the label calls it a cyclic lipopeptide ¹. Peptide lists carry it for that ring, not for any action like a hormone's. Its molecular weight is about 1,621 ¹.

It is neither a hormone nor a signaling peptide, and no use on its label concerns weight, muscle, recovery or aging ¹. Its uses are serious infections caused by Gram-positive bacteria, the group that includes the staphylococci, or staph bacteria ¹. Gram-positive bacteria take up the violet dye in the laboratory stain that names them. FDA approved it in 2003 as Cubist Pharmaceuticals' Cubicin, whose prescribing information is now Merck's ⁴, ⁸. Drugs@FDA, the public register FDA keeps of approved drugs, also lists it under the names Daptomycin, Daptomycin in 0.9% Sodium Chloride and Dapzura RT, the last of them discontinued ⁶.

Is daptomycin FDA-approved?

Yes. Daptomycin is approved by FDA as a prescription antibiotic, with "Initial U.S. Approval: 2003" on its label ¹. FDA approved Cubist Pharmaceuticals' Cubicin, new drug application (NDA) 021572, on September 12, 2003, for complicated skin and skin structure infections ⁴, ². A supplement to the application, approved May 25, 2006, added Staphylococcus aureus bloodstream infections ⁴, ³. Two supplements approved in 2017 extended both uses to children aged 1 to 17 ⁴, ⁹, ¹⁰.

The current label approves it "for the treatment of" three groups of infections ¹. The first is "complicated skin and skin structure infections (cSSSI)," the label's term for serious infections of the skin and the tissue beneath it ¹. It covers adults and children aged 1 to 17, and susceptible Gram-positive bacteria including MRSA ¹.

The second is Staphylococcus aureus bloodstream infections, called bacteremia, in adults, "including adult patients with right-sided infective endocarditis" ¹. Bacteremia is bacteria growing in the blood, and infective endocarditis is an infection on the heart's valves or its inner lining; right-sided means the valves on the heart's right side. The third is Staphylococcus aureus bacteremia in children aged 1 to 17 ¹.

The label also sets Limitations of Use. Daptomycin "is not indicated for the treatment of pneumonia" ¹. It "is not indicated for the treatment of left-sided infective endocarditis due to S. aureus" ¹. The bloodstream-infection trial "included limited data from patients with left-sided infective endocarditis; outcomes in these patients were poor" ¹.

It "has not been studied in patients with prosthetic valve endocarditis" ¹. And it "is not recommended in pediatric patients younger than 1 year of age," because of effects on muscles and nerves seen in newborn dogs ¹.

The Cubicin brand itself has been discontinued. Drugs@FDA lists all three products under NDA 021572, Cubicin 250 and 500 mg and Cubicin RF 500 mg, as "Discontinued" as of November 9, 2026, the date of its data ⁴. The company told FDA in 2021 and 2022 that it was discontinuing two of them; the 250 mg vial was already listed as discontinued ⁵. In August 2023 FDA determined that they "were not withdrawn from sale for reasons of safety or effectiveness" ⁵. That determination lets FDA go on approving generic versions ⁵.

Drugs@FDA holds 33 daptomycin applications, 25 of them for generics, and 27 of them have a product marketed by prescription as of November 9, 2026, the date of its data ⁶. The label is Sagent Pharmaceuticals', for its daptomycin for injection, NDA 208385, approved September 12, 2017 and revised in August 2026 ¹, ⁶. The route to any of them is a clinician's prescription, and the label's words are "for intravenous use" ¹.

See the FDA status of every peptide, updated weekly.

How does daptomycin work?

Daptomycin "binds to bacterial cell membranes and causes a rapid depolarization of membrane potential," the label says ¹. A bacterium holds an electrical charge across its membrane, and losing it "causes inhibition of DNA, RNA, and protein synthesis, which results in bacterial cell death" ¹. The label describes "rapid, concentration-dependent bactericidal activity against Gram-positive bacteria in vitro," that is, it kills bacteria in the test tube, faster at higher concentrations ¹.

Daptomycin is active "both in vitro and in clinical infections" against Staphylococcus aureus including MRSA and three species of streptococci (strep bacteria) ¹. It is also active against Enterococcus faecalis, a gut bacterium, where vancomycin still kills it ¹. For other bacteria, including vancomycin-resistant enterococci, the label gives test-tube data only and says their clinical significance is unknown ¹. The mechanism of resistance "is not fully understood," and "there are no known transferable elements that confer resistance to daptomycin" ¹.

The label counts 7 patients in the bloodstream trial with non-susceptible Staphylococcus aureus, without saying which arm ¹. The drug leaves the body mainly through the kidneys ¹.

What does the research show?

Daptomycin's evidence level is "Approved for a use": FDA approval, held since 2003, rests on the trials the label describes ¹, ⁴. Each approval rested on a comparison with older antibiotics ¹.

Studied in people for skin infections: two randomized trials enrolled adults with complicated skin and skin structure infections and compared daptomycin with vancomycin or a penicillin that acts on staph ¹. They were investigator-blinded, meaning the doctors judging the outcome did not know the treatment ¹. Across the two, 534 adults received daptomycin and 558 the comparator ¹. The first ran mainly in the United States and South Africa ¹. Clinical success among all treated patients, the label's intent-to-treat population, was 62.5 percent (165 of 264) on daptomycin and 60.9 percent (162 of 266) on the comparator ¹.

In the second, run outside the United States, it was 80.4 percent (217 of 270) against 80.5 percent (235 of 292) ¹. Across both trials, against MRSA in microbiologically evaluable patients, success was 21 of 28 on daptomycin and 25 of 36 on the comparator ¹. FDA's 2003 approval rested on this use ².

Studied in people for bloodstream infection: the trial behind the 2006 indication was a randomized trial published in August 2006 ⁷. It was open-label and ran at 48 centers in the United States and Europe ⁷, ¹. Open-label means patients and doctors knew which treatment was given ¹¹. Cubist Pharmaceuticals, which held the Cubicin approval, sponsored it, and it ran from March 2002 to February 2005 ¹¹, ⁴.

It enrolled 246 adults, aged 18 or over, with Staphylococcus aureus bacteremia, with or without endocarditis ⁷, ¹. Of these, 124 were assigned to daptomycin and 122 to standard therapy, which was initial low-dose gentamicin, another antibiotic, plus either a penicillin that acts on staph or vancomycin ⁷. A treatment-blinded committee judged each patient's outcome ¹.

The trial's main measure, its primary end point, was treatment success 42 days after the end of therapy ⁷. In the modified intention-to-treat analysis, 53 of 120 on daptomycin (44.2 percent) and 48 of 115 on standard therapy (41.7 percent) succeeded ⁷. The absolute difference was 2.4 percent, with a 95 percent confidence interval, the range the true difference most likely lies in, from minus 10.2 to 15.1 percent ⁷.

That met the trial's prespecified test of noninferiority ⁷. Noninferiority means daptomycin was shown to be no worse than standard therapy by more than a set margin, not that it was better. Success rates were similar in the subgroups the paper defined: complicated bacteremia (infection that persisted or spread beyond the blood), right-sided endocarditis and MRSA ⁷.

The trial reported its failures and harms by arm. Microbiologic failure, the germ persisting or returning, occurred in 19 patients on daptomycin and 11 on standard therapy, a difference that was not statistically significant ⁷. In 6 of those 19, by the paper's count, the bacteria became less susceptible to daptomycin ⁷. Clinically significant kidney dysfunction occurred in 11.0 percent of the daptomycin arm and 26.3 percent of the standard-therapy arm ⁷.

Adverse events that ended treatment and counted as failure numbered 8 on daptomycin and 17 on standard therapy, also short of statistical significance ⁷. During the trial, 18 of 120 patients on daptomycin died and 19 of the 116 the label counts on the comparator ¹. Among the 18 patients with left-sided endocarditis, success was 1 of 9 on daptomycin and 2 of 9 on the comparator, the finding behind the label's limitation ¹.

Studied in children: two randomized trials, each designed first to measure safety, compared daptomycin with standard antibiotics in children aged 1 to 17 ¹. In the skin-infection trial, 389 children were treated, 257 on daptomycin and 132 on a comparator ¹. Clinical success at the test-of-cure visit, the follow-up visit that checks whether the infection has cleared, was 88 percent (227 of 257) against 86 percent (114 of 132) ¹. In the bacteremia trial, 73 children had proven Staphylococcus aureus bacteremia, and success was 88 percent (45 of 51) on daptomycin against 77 percent (17 of 22) on the comparator ¹. These trials underlie the 2017 label changes ⁹, ¹⁰.

What failed: in phase 3 trials, the large trials run for approval, of community-acquired pneumonia (CAP), "the death rate and rates of serious cardiorespiratory adverse events were higher in daptomycin-treated patients than in comparator-treated patients" ¹. The label attributes those differences to "lack of therapeutic effectiveness of daptomycin in the treatment of CAP," and the drug is not indicated for pneumonia ¹. The label states that long-term animal studies of cancer risk have not been conducted ¹.

What are the side effects?

The label names the most common adverse reactions by trial population ¹. In adults with skin infections, nine reactions were reported by 2 percent or more on daptomycin ¹. They were diarrhea, headache, dizziness, rash, abnormal liver function tests, elevated creatine phosphokinase (CPK, a muscle enzyme), urinary tract infections, low blood pressure and shortness of breath ¹.

In adults with bloodstream infection, eleven were reported by 5 percent or more ¹. They were sepsis, the body's dangerous response to infection, bacteremia, abdominal pain, chest pain, swelling, sore throat, itching, increased sweating, insomnia, elevated CPK and high blood pressure ¹. In children with skin infections the most common were diarrhea, vomiting, abdominal pain, itching, fever, elevated CPK and headache; in children with bacteremia, vomiting and elevated CPK ¹. Across the adult trials, 1,864 patients took daptomycin and 1,416 a comparator ¹.

CPK leaks from damaged muscle into the blood, and the label's first warning concerns muscle damage ¹. "Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values to greater than 10 times the upper limit of normal (ULN), has been reported with the use of daptomycin" ¹. "Rhabdomyolysis, with or without acute renal failure, has been reported"; rhabdomyolysis is the breakdown of muscle tissue ¹. The label has prescribers monitor CPK regularly, watch for muscle pain or weakness, and consider suspending statins, the cholesterol drugs it calls HMG-CoA reductase inhibitors ¹. In the bloodstream trial, CPK rose above 500 units per liter in 11 of 120 patients (9.2 percent) on daptomycin and 1 of 116 (0.9 percent) on the comparator ¹.

The label's next warnings concern the lungs and the immune system. "Eosinophilic pneumonia has been reported in patients receiving daptomycin"; patients "developed fever, dyspnea with hypoxic respiratory insufficiency, and diffuse pulmonary infiltrates," that is, fever, breathlessness with low oxygen and shadowing across the lungs on imaging, generally 2 to 4 weeks after starting ¹. It is lung inflammation driven by eosinophils, a type of white blood cell, and patients improved when the drug was stopped and steroids were given ¹.

"Anaphylaxis/hypersensitivity reactions have been reported with the use of antibacterial agents, including daptomycin for injection, and may be life-threatening" ¹. Anaphylaxis is a severe whole-body allergic reaction. DRESS (drug reaction with eosinophilia and systemic symptoms), a severe drug rash with fever and organ involvement, "has been reported in post-marketing experience," that is, in reports since the drug went on sale, "with daptomycin" ¹. So has tubulointerstitial nephritis, an inflammation of the kidney ¹.

Peripheral neuropathy, nerve damage felt as tingling or numbness, has been reported since approval ¹. The label's warning repeats its limitation for infants under 12 months ¹. Diarrhea caused by the gut bacterium Clostridioides difficile "may range in severity from mild diarrhea to fatal colitis" ¹.

For a bloodstream infection that persists or returns, the label tells prescribers to repeat blood cultures and test the germ's susceptibility ¹. Efficacy was lower in adults whose kidneys worked poorly at the start of treatment ¹. With certain laboratory reagents the drug falsely prolongs the prothrombin time, a clotting test ¹.

Post-marketing reports add serious skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, two severe blistering reactions, acute kidney injury, high potassium, low platelets and visual disturbances ¹. The label carries no boxed warning, FDA's strongest warning, printed in a box ¹. Its one contraindication, the case in which it must not be given, is "known hypersensitivity," meaning a known allergy, "to daptomycin" ¹. On pregnancy, "limited published data on use of daptomycin in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage" ¹. Clinical success was lower, and adverse events more common, in patients aged 65 or older ¹.

In sport

Daptomycin does not appear on WADA's 2026 Prohibited List ¹². WADA, the World Anti-Doping Agency, publishes the list that tested athletes are held to. Besides substances, the list prohibits methods, and M2.2 limits intravenous infusions and injections of any substance, this one included ¹². M2.2 prohibits "Intravenous infusions and/or injections of more than a total of 100 mL per 12-hour period except for those legitimately received in the course of hospital treatments, surgical procedures or clinical diagnostic investigations" ¹².

What JumpstartMD offers

JumpstartMD does not prescribe daptomycin. Our peptide library covers it so you have the facts on its FDA status and the evidence, current as of November 10, 2026.

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Compounded medications are not FDA-approved, and FDA does not review their safety, effectiveness, or quality before they are marketed. A licensed clinician decides after an evaluation whether a peptide is appropriate for you, and not every patient will qualify.