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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
DAPTOMYCIN (NDA-209949)
(DAPTOMYCIN)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
04/30/2025 (SUPPL-14)
6 Adverse Reactions
6.2 Postmarketing ExperienceAdditions and/or revisions underlined:
…
Metabolic and Nutritional Disorders: hyperkalemia
…
10/06/2023 (SUPPL-11)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
Allergic Reactions
Advise patients that allergic reactions, including serious skin, kidney, lung, or other organ reactions, could occur and that these serious reactions require immediate treatment. Patients should report any previous allergic reactions to daptomycin [see Warnings and Precautions (5.1, 5.4, 5.5)].
Muscle Pain or Weakness (Myopathy and Rhabdomyolysis, Peripheral Neuropathy)
Advise patients to report muscle pain or weakness, especially in the forearms and lower legs, as well as tingling or numbness [see Warnings and Precautions (5.2, 5.6)].
…
C. difficile-Associated Diarrhea (CDAD)
Advise patients that diarrhea is a common problem caused by antibacterials, including daptomycin for injection, that usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, including Daptomycin for Injection, patients can develop watery and bloody stools (with or without stomach cramps and fever), even as late as 2 or more months after having received the last dose of the antibacterial. If this occurs, patients should contact their physician as soon as possible [see Warnings and Precautions (5.8)].
…
05/05/2021 (SUPPL-6)
5 Warnings and Precautions
5.10 Decreased Efficacy in Patients with Moderate Baseline Renal Impairment(Additions and/or revisions underlined)
Limited data are available from the two Phase 3 complicated skin and skin structure infection (cSSSI) trials regarding clinical efficacy of daptomycin for injection treatment in adult patients with creatinine clearance (CLCR) <50 mL/min; only 31/534 (6%) patients treated with daptomycin for injection in the intent-to-treat (ITT) population had a baseline CLCR <50 mL/min. Table 4 shows the number of adult patients by renal function and treatment group who were clinical successes in the Phase 3 cSSSI trials.
Table 4: Clinical Success Rates by Renal Function and Treatment Group in Phase 3 cSSSI Trials in Adult Patients (Population: ITT)
…
In a subgroup analysis of the ITT population in the Phase 3 S. aureus bacteremia/endocarditis trial, clinical success rates, as determined by a treatment-blinded Adjudication Committee [see Clinical Studies (14.2)], in the daptomycin for injection-treated adult patients were lower in patients with baseline CLCR <50 mL/min (see Table 5). A decrease of the magnitude shown in Table 5 was not observed in comparator-treated patients.
Table 5: Adjudication Committee Clinical Success Rates at Test of Cure by Baseline Creatinine Clearance and Treatment Subgroup in the S. aureus Bacteremia/Endocarditis Trial in Adult Patients (Population: ITT)
…
(Subsection title revised)
(Subsection title revised; Additions and/or revisions underlined)
Prescribing Daptomycin for Injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
(Newly added subsection)
DRESS has been reported in post-marketing experience with daptomycin for injection [see Adverse Reactions (6.2)]. Patients who develop skin rash, fever, peripheral eosinophilia, and systemic organ (for example, hepatic, renal, pulmonary) impairment while receiving Daptomycin for Injection should undergo medical evaluation. If DRESS is suspected, discontinue Daptomycin for Injection promptly and institute appropriate treatment.
(Newly added subsection)
TIN has been reported in post-marketing experience with daptomycin for injection [see Adverse Reactions (6.2)]. Patients who develop new or worsening renal impairment while receiving Daptomycin for Injection should undergo medical evaluation. If TIN is suspected, discontinue Daptomycin for Injection promptly and institute appropriate treatment.
(Subsection title revised; Additions and/or revisions underlined)
Clostridioides difficile–associated diarrhea (CDAD) has been reported with the use of nearly all systemic antibacterial agents, including daptomycin for injection, and may range in severity from mild diarrhea to fatal colitis [see Adverse Reactions (6.2)]. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile.
C. difficile produces toxins A and B, which contribute to the development of CDAD.
Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, since these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
6 Adverse Reactions
(Addition of the following to the bulleted line listing)
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.4)]
Tubulointerstitial Nephritis (TIN) [see Warnings and Precautions (5.5)]
(Extensive revisions/additions; please refer to label)
(Additions and/or revisions underlined)
The following adverse reactions have been identified during post-approval use of daptomycin for injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and lymphatic system disorders: anemia, thrombocytopenia
General and administration site conditions: pyrexia
Immune System Disorders: anaphylaxis; hypersensitivity reactions, including angioedema, pruritus, hives, shortness of breath, difficulty swallowing, truncal erythema, and pulmonary eosinophilia [see Contraindications (4), Warnings and Precautions (5.1)]
Infections and Infestations: Clostridioides difficile–associated diarrhea [see Warnings and Precautions (5.8)] Laboratory Investigations: platelet count decreased
Musculoskeletal Disorders: myoglobin increased; rhabdomyolysis (some reports involved patients treated concurrently with Daptomycin for Injection and HMG-CoA reductase inhibitors) [see Warnings and Precautions (5.2), Drug Interactions (7.1), and Clinical Pharmacology (12.3)]
Respiratory, Thoracic, and Mediastinal Disorders: cough, eosinophilic pneumonia, organizing pneumonia [see Warnings and Precautions (5.3)]
Nervous System Disorders: peripheral neuropathy [see Warnings and Precautions (5.6)]
Skin and Subcutaneous Tissue Disorders: serious skin reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), vesiculobullous rash (with or without mucous membrane involvement, including Stevens-Johnson syndrome [SJS] or toxic epidermal necrolysis [TEN]), acute generalized exanthematous pustulosis [see Warnings and Precautions (5.4)]
Gastrointestinal Disorders: nausea, vomiting
Renal and urinary disorders: acute kidney injury, renal insufficiency, renal failure and tubulointerstitial nephritis (TIN) [see Warnings and Precautions (5.5)]
Special Senses: visual disturbances
8 Use in Specific Populations
8.4 Pediatric Use(Additions and/or revisions underlined)
The safety and effectiveness of daptomycin for injection in the treatment of cSSSI and S. aureus bloodstream infections (bacteremia) have been established in the age groups 1 to 17 years of age. Use of daptomycin for injection in these age groups is supported by evidence from adequate and well-controlled studies in adults, with additional data from pharmacokinetic studies in pediatric patients, and from safety, efficacy and PK studies in pediatric patients with cSSSI and S. aureus bloodstream infections [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1, 14.2)].
Safety and effectiveness of Daptomycin for Injection in pediatric patients below the age of one year have not been established. Avoid use of Daptomycin for Injection in pediatric patients younger than one year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs [see Warnings and Precautions (5.7) and Nonclinical Toxicology (13.2)].
Daptomycin for Injection is not indicated in pediatric patients with renal impairment because dosage has not been established in these patients.
Daptomycin for Injection has not been studied in pediatric patients with other bacterial infections.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION(Additions and/or revisions underlined)
Allergic Reactions
Advise patients that allergic reactions, including serious allergic reactions, could occur and that serious reactions require immediate treatment. Patients should report any previous allergic reactions to daptomycin [see Warnings and Precautions (5.1, 5.4, 5.5)].
Muscle Pain or Weakness
Advise patients to report muscle pain or weakness, especially in the forearms and lower legs, as well as tingling or numbness [see Warnings and Precautions (5.2, 5.6)].
Cough, Breathlessness or Fever
Advise patients to report any symptoms of cough, breathlessness, or fever [see Warnings and Precautions (5.3)].
Diarrhea
Advise patients that diarrhea is a common problem caused by antibacterials, including daptomycin for injection, that usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, including Daptomycin for Injection, patients can develop watery and bloody stools (with or without stomach cramps and fever), even as late as 2 or more months after having received the last dose of the antibacterial. If this occurs, patients should contact their physician as soon as possible [see Warnings and Precautions (5.8)].
Antibacterial Resistance Patients should be counseled that antibacterial drugs, including Daptomycin for Injection, should be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Daptomycin for Injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Daptomycin for Injection or other antibacterial drugs in the future.
05/05/2021 (SUPPL-7)
5 Warnings and Precautions
5.10 Decreased Efficacy in Patients with Moderate Baseline Renal Impairment(Additions and/or revisions underlined)
Limited data are available from the two Phase 3 complicated skin and skin structure infection (cSSSI) trials regarding clinical efficacy of daptomycin for injection treatment in adult patients with creatinine clearance (CLCR) <50 mL/min; only 31/534 (6%) patients treated with daptomycin for injection in the intent-to-treat (ITT) population had a baseline CLCR <50 mL/min. Table 4 shows the number of adult patients by renal function and treatment group who were clinical successes in the Phase 3 cSSSI trials.
Table 4: Clinical Success Rates by Renal Function and Treatment Group in Phase 3 cSSSI Trials in Adult Patients (Population: ITT)
…
In a subgroup analysis of the ITT population in the Phase 3 S. aureus bacteremia/endocarditis trial, clinical success rates, as determined by a treatment-blinded Adjudication Committee [see Clinical Studies (14.2)], in the daptomycin for injection-treated adult patients were lower in patients with baseline CLCR <50 mL/min (see Table 5). A decrease of the magnitude shown in Table 5 was not observed in comparator-treated patients.
Table 5: Adjudication Committee Clinical Success Rates at Test of Cure by Baseline Creatinine Clearance and Treatment Subgroup in the S. aureus Bacteremia/Endocarditis Trial in Adult Patients (Population: ITT)
…
(Subsection title revised)
(Subsection title revised; Additions and/or revisions underlined)
Prescribing Daptomycin for Injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
(Newly added subsection)
DRESS has been reported in post-marketing experience with daptomycin for injection [see Adverse Reactions (6.2)]. Patients who develop skin rash, fever, peripheral eosinophilia, and systemic organ (for example, hepatic, renal, pulmonary) impairment while receiving Daptomycin for Injection should undergo medical evaluation. If DRESS is suspected, discontinue Daptomycin for Injection promptly and institute appropriate treatment.
(Newly added subsection)
TIN has been reported in post-marketing experience with daptomycin for injection [see Adverse Reactions (6.2)]. Patients who develop new or worsening renal impairment while receiving Daptomycin for Injection should undergo medical evaluation. If TIN is suspected, discontinue Daptomycin for Injection promptly and institute appropriate treatment.
(Subsection title revised; Additions and/or revisions underlined)
Clostridioides difficile–associated diarrhea (CDAD) has been reported with the use of nearly all systemic antibacterial agents, including daptomycin for injection, and may range in severity from mild diarrhea to fatal colitis [see Adverse Reactions (6.2)]. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile.
C. difficile produces toxins A and B, which contribute to the development of CDAD.
Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, since these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
6 Adverse Reactions
(Addition of the following to the bulleted line listing)
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.4)]
Tubulointerstitial Nephritis (TIN) [see Warnings and Precautions (5.5)]
(Extensive revisions/additions; please refer to label)
(Additions and/or revisions underlined)
The following adverse reactions have been identified during post-approval use of daptomycin for injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and lymphatic system disorders: anemia, thrombocytopenia
General and administration site conditions: pyrexia
Immune System Disorders: anaphylaxis; hypersensitivity reactions, including angioedema, pruritus, hives, shortness of breath, difficulty swallowing, truncal erythema, and pulmonary eosinophilia [see Contraindications (4), Warnings and Precautions (5.1)]
Infections and Infestations: Clostridioides difficile–associated diarrhea [see Warnings and Precautions (5.8)] Laboratory Investigations: platelet count decreased
Musculoskeletal Disorders: myoglobin increased; rhabdomyolysis (some reports involved patients treated concurrently with Daptomycin for Injection and HMG-CoA reductase inhibitors) [see Warnings and Precautions (5.2), Drug Interactions (7.1), and Clinical Pharmacology (12.3)]
Respiratory, Thoracic, and Mediastinal Disorders: cough, eosinophilic pneumonia, organizing pneumonia [see Warnings and Precautions (5.3)]
Nervous System Disorders: peripheral neuropathy [see Warnings and Precautions (5.6)]
Skin and Subcutaneous Tissue Disorders: serious skin reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), vesiculobullous rash (with or without mucous membrane involvement, including Stevens-Johnson syndrome [SJS] or toxic epidermal necrolysis [TEN]), acute generalized exanthematous pustulosis [see Warnings and Precautions (5.4)]
Gastrointestinal Disorders: nausea, vomiting
Renal and urinary disorders: acute kidney injury, renal insufficiency, renal failure and tubulointerstitial nephritis (TIN) [see Warnings and Precautions (5.5)]
Special Senses: visual disturbances
8 Use in Specific Populations
8.4 Pediatric Use(Additions and/or revisions underlined)
The safety and effectiveness of daptomycin for injection in the treatment of cSSSI and S. aureus bloodstream infections (bacteremia) have been established in the age groups 1 to 17 years of age. Use of daptomycin for injection in these age groups is supported by evidence from adequate and well-controlled studies in adults, with additional data from pharmacokinetic studies in pediatric patients, and from safety, efficacy and PK studies in pediatric patients with cSSSI and S. aureus bloodstream infections [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1, 14.2)].
Safety and effectiveness of Daptomycin for Injection in pediatric patients below the age of one year have not been established. Avoid use of Daptomycin for Injection in pediatric patients younger than one year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs [see Warnings and Precautions (5.7) and Nonclinical Toxicology (13.2)].
Daptomycin for Injection is not indicated in pediatric patients with renal impairment because dosage has not been established in these patients.
Daptomycin for Injection has not been studied in pediatric patients with other bacterial infections.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION(Additions and/or revisions underlined)
Allergic Reactions
Advise patients that allergic reactions, including serious allergic reactions, could occur and that serious reactions require immediate treatment. Patients should report any previous allergic reactions to daptomycin [see Warnings and Precautions (5.1, 5.4, 5.5)].
Muscle Pain or Weakness
Advise patients to report muscle pain or weakness, especially in the forearms and lower legs, as well as tingling or numbness [see Warnings and Precautions (5.2, 5.6)].
Cough, Breathlessness or Fever
Advise patients to report any symptoms of cough, breathlessness, or fever [see Warnings and Precautions (5.3)].
Diarrhea
Advise patients that diarrhea is a common problem caused by antibacterials, including daptomycin for injection, that usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, including Daptomycin for Injection, patients can develop watery and bloody stools (with or without stomach cramps and fever), even as late as 2 or more months after having received the last dose of the antibacterial. If this occurs, patients should contact their physician as soon as possible [see Warnings and Precautions (5.8)].
Antibacterial Resistance Patients should be counseled that antibacterial drugs, including Daptomycin for Injection, should be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Daptomycin for Injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Daptomycin for Injection or other antibacterial drugs in the future.
09/18/2019 (SUPPL-3)
6 Adverse Reactions
6.2 Postmarketing Experience(additions underlined)
…
Blood and lymphatic system disorders: anemia, thrombocytopenia
…
Laboratory Investigations: platelel count decreased
…
8 Use in Specific Populations
8.4 Pediatric Use(additions underlined)
…
Daptomycin for injection has not been studied in pediatric patients with other bacterial infections.