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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.
CUBICIN (NDA-021572)
(DAPTOMYCIN)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
10/26/2021 (SUPPL-65)
5 Warnings and Precautions
5.11 Increased International Normalized Ratio (INR)/Prothrombin Time(Subsection title revised)
(Subsection title revised; Additions and/or revisions underlined)
Prescribing CUBICIN 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.
6 Adverse Reactions
6.2 Postmarketing Experience(Additions and/or revisions underlined)
The following adverse reactions have been identified during post-approval use of CUBICIN. 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) and 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 CUBICIN 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] and toxic epidermal necrolysis [TEN]), and 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
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)].
Cough, Breathlessness or Fever (Eosinophilic Pneumonia)
Advise patients to report any symptoms of cough, breathlessness, or fever [see Warnings and Precautions (5.3)].
C. difficile-Associated Diarrhea (CDAD)
Advise patients that diarrhea is a common problem caused by antibacterials including CUBICIN, that usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, including CUBICIN, 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 CUBICIN, should be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When CUBICIN 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 administered 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 CUBICIN or other antibacterial drugs in the future.
10/26/2021 (SUPPL-66)
5 Warnings and Precautions
5.11 Increased International Normalized Ratio (INR)/Prothrombin Time(Subsection title revised)
(Subsection title revised; Additions and/or revisions underlined)
Prescribing CUBICIN RF 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.
6 Adverse Reactions
6.2 Postmarketing Experience(Additions and/or revisions underlined)
The following adverse reactions have been identified during post-approval use of CUBICIN. 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) and 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 CUBICIN 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] and toxic epidermal necrolysis [TEN]), and 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
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)].
Cough, Breathlessness or Fever (Eosinophilic Pneumonia)
Advise patients to report any symptoms of cough, breathlessness, or fever [see Warnings and Precautions (5.3)].
C. difficile-Associated Diarrhea (CDAD)
Advise patients that diarrhea is a common problem caused by antibacterials, including CUBICIN RF, that usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, including CUBICIN RF, 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 CUBICIN RF, should be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When CUBICIN RF 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 administered 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 CUBICIN RF or other antibacterial drugs in the future.
08/26/2020 (SUPPL-63)
5 Warnings and Precautions
5.4 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)(Newly added section)
DRESS has been reported in post-marketing experience with CUBICIN [see Adverse Reactions (6.2)]. Patients who develop skin rash, fever, peripheral eosinophilia, and systemic organ (for example, hepatic, renal, pulmonary) impairment while receiving CUBICIN should undergo medical evaluation. If DRESS is suspected, discontinue CUBICIN promptly and institute appropriate treatment.
(Newly added information)
TIN has been reported in post-marketing experience with CUBICIN [see Adverse Reactions (6.2)]. Patients who develop new or worsening renal impairment while receiving CUBICIN should undergo medical evaluation. If TIN is suspected, discontinue CUBICIN promptly and institute appropriate treatment.
(Section 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 CUBICIN, and may range in severity from mild diarrhea to fatal colitis [see Adverse Reactions (6.2)].
6 Adverse Reactions
(Newly added information)
Drug reaction with eosinophilia and systemic symptoms [see Warnings and Precautions (5.4)]
Tubulointerstitial nephritis [see Warnings and Precautions (5.5.)]
(Additions and/or revisions underlined)
Infections and Infestations: Clostridioides difficile–associated diarrhea [see Warnings and Precautions (5.8)]
Skin and Subcutaneous Tissue Disorders: serious skin reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome and vesiculobullous rash (with or without mucous membrane involvement), acute generalized exanthematous pustulosis [see Warnings and Precautions (5.4)]
Renal and urinary disorders: acute kidney injury, renal insufficiency, renal failure, and tubulointerstitial nephritis (TIN) [see Warnings and Precautions (5.5)]
12/03/2018 (SUPPL-61)
6 Adverse Reactions
6.2 Post-Marketing Experience(additions underlined)
...
Blood and lymphatic system disorders: anemia, thrombocytopenia
…
Laboratory Investigations: platelet count decreased
…
09/01/2017 (SUPPL-57)
6 Adverse Reactions
6.1 Clinical Trials ExperienceClinical Trial Experience in Pediatric Patients
Addition of the following:
S. aureus Bacteremia Trial in Pediatric Patients
The safety of CUBICIN was evaluated in one clinical trial (in S. aureus bacteremia), which treated 55 pediatric patients with intravenous CUBICIN and 26 patients with comparator agents. Patients were given age-dependent doses once daily for a treatment period of up to 42 days (mean duration of IV treatment was 12 days). The doses by age group were as follows: 12 mg/kg for 1 to less than 6 years, 9 mg/kg for 7 to 11 years and 7 mg/kg for 12 to 17 years of age. Patients treated with CUBICIN were (69%) male and (31%) female. No patients 1 to less than 2 years of age were enrolled.
Additions and/or revisions underlined:
Adverse Reactions Leading to Discontinuation
In the bacteremia study, CUBICIN was discontinued in 3/55 (5.5%) patients due to an adverse reaction, while comparator was discontinued in 2/26 (7.7%) patients.
Most Common Adverse Reactions
The rates of the most common adverse reactions, organized by body system, observed in these pediatric patients with bacteremia are displayed in Table 10.
Table 10: Incidence of Adverse Reactions that Occurred in greater than or equal to 5% of Pediatric Patients in the CUBICIN Treatment-Arm and Greater Than or Equal to the Comparator Treatment-Arm in the Pediatric Bacteremia Trial Newly added table; please refer to label for full information.
*Comparators included intravenous therapy with either vancomycin, cefazolin, or an anti-staphylococcal semi-synthetic penicillin (nafcillin, oxacillin or cloxacillin)
8 Use in Specific Populations
8.4 Pediatric UseAdditions and/or revisions underlined:
The safety and effectiveness of CUBICIN 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 CUBICIN 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 infection ….
06/09/2017 (SUPPL-59)
5 Warnings and Precautions
5.3 Eosinophilic Pneumonia(Additions and/or revisions are underlined)
Eosinophilic pneumonia has been reported in patients receiving CUBICIN. In reported cases associated with CUBICIN, patients developed fever, dyspnea with hypoxic respiratory insufficiency, and diffuse pulmonary infiltrates or organizing pneumonia.
(Additions and/or revisions are underlined)
Limited data are available from the two Phase 3 complicated skin and skin structure infection (cSSSI) trials regarding clinical efficacy of CUBICIN treatment in adult patients with creatinine clearance (CLCR) less than 50 mL/min; only 31/534 (6%) patients treated with CUBICIN in the intent-to-treat (ITT) population had a baseline CLCR less than 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.
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 CUBICIN-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.
6 Adverse Reactions
6.1 Clinical Trials Experience(Additions and/or revisions to Table numbering are underlined)
The rates of the most common adverse reactions, organized by body system, observed in adult patients with cSSSI (receiving 4 mg/kg CUBICIN) are displayed in Table 6.
S. aureus Bacteremia/Endocarditis Trial in Adults
The rates of the most common adverse reactions, organized by System Organ Class (SOC), observed in adult patients with S. aureus bacteremia/endocarditis (receiving 6 mg/kg CUBICIN) are displayed in Table 7.
Laboratory Changes in Adults
…Table 8 summarizes the CPK shifts from Baseline through End of Therapy in the cSSSI adult trials.
Most Common Adverse Reactions
The rates of the most common adverse reactions, organized by body system, observed in these pediatric patients with cSSSI are displayed in Table 9.
(Additions and/or revisions are underlined)
Respiratory, Thoracic, and Mediastinal Disorders: cough, eosinophilic pneumonia, organizing pneumonia
8 Use in Specific Populations
8.4 Pediatric Use(Additions and/or revisions are underlined)
The safety and effectiveness of CUBICIN RF in the treatment of cSSSI has been established in the age groups 1 to 17 years of age. Use of CUBICIN RF in these age groups is supported by evidence from adequate and well-controlled studies with CUBICIN …
03/29/2017 (SUPPL-55)
5 Warnings and Precautions
Additions and/or revisions underlined:
5.2 Myopathy and Rhabdomyolysis
… In adult patients with renal impairment, both renal function and CPK should be monitored more frequently than once weekly.
In Phase 1 studies and Phase 2 clinical trials in adults, CPK elevations …
5.4 Peripheral Neuropathy
… Therefore, physicians should be alert to signs and symptoms of peripheral neuropathy in patients receiving CUBICIN. Monitor for neuropathy and consider discontinuation.
5.8 Decreased Efficacy in Patients with Moderate Baseline Renal Impairment
Limited data are available from the two Phase 3 complicated skin and skin structure infection (cSSSI) trials regarding clinical efficacy of CUBICIN treatment in adult patients with creatinine clearance (CLCR) <50 mL/min; only 31/534 (6%) patients treated with CUBICIN in the intent-to-treat (ITT) population had a baseline CLCR <50 mL/min. Table 3 shows the number of adult patients by renal function and treatment group who were clinical successes in the Phase 3 cSSSI trials.
Table 3: Clinical Success Rates by Renal Function and Treatment Group in Phase 3 cSSSI Trials in Adult Patients (Population: ITT)
… Adjudication Committee, in the CUBICIN-treated adult patients were lower in patients with baseline CLCR less than 50 mL/min (see Table 4) ...
Table 4: 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)
Consider these data when selecting antibacterial therapy for use in adult patients with baseline moderate to severe renal impairment.
5.10 Non-Susceptible Microorganisms
The use of antibacterials may promote the overgrowth of non-susceptible microorganisms. If these infections occur during therapy …
6 Adverse Reactions
Additions and/or revisions underlined:
6.1 Clinical Trials Experience
Clinical Trial Experience in Adult Patients
Clinical trials enrolled 1,864 adult patients
Complicated Skin and Skin Structure Infection Trials in Adults
In Phase 3 complicated skin and skin structure infection (cSSSI) trials in adult patients, CUBICIN was discontinued …
The rates of the most common adverse reactions, organized by body system, observed in adult patients with cSSSI (receiving 4 mg/kg CUBICIN) patients are displayed in Table 5.
Table 5: Incidence of Adverse Reactions that Occurred in greater than or equal to 2% of Adult Patients in the CUBICIN Treatment Group and greater than or equal to the Comparator Treatment Group in Phase 3 cSSSI Trials
Drug-related adverse reactions (possibly or probably drug-related) that occurred in less than 1% of adult patients receiving …
S. aureus Bacteremia/Endocarditis Trial in Adults
In the S. aureus bacteremia/endocarditis trial involving adult patients, CUBICIN was discontinued …
The rates of the most common adverse reactions, organized by System Organ Class (SOC), observed in adult patients with S. aureus bacteremia/endocarditis (receiving 6 mg/kg CUBICIN) are displayed in Table 6.
Table 6: Incidence of Adverse Reactions that Occurred in greater than or equal to 5% of Adult Patients in the CUBICIN Treatment Group and greater than or equal to the Comparator Treatment Group in the S. aureus Bacteremia/Endocarditis Trial
Other Trials in Adults
In Phase 3 trials of community-acquired pneumonia (CAP) in adult patients, the death rate …
Laboratory Changes in Adults
Complicated Skin and Skin Structure Infection Trials in Adults
In Phase 3 cSSSI trials of adult patients receiving CUBICIN at a dose … within 7 to 10 days after treatment was discontinued. Table 7 summarizes the CPK shifts from Baseline through End of Therapy in the cSSSI adult trials.
Table 7: Incidence of CPK Elevations from Baseline during Therapy in Either the CUBICIN Treatment Group or the Comparator Treatment Group in Phase 3 cSSSI Adult Trials
S. aureus Bacteremia/Endocarditis Trial in Adults
In the S. aureus bacteremia/endocarditis trial in adult patients, at a dose …
Addition of the following:
Clinical Trial Experience in Pediatric Patients
Complicated Skin and Skin Structure Infection Trial in Pediatric Patients
The safety of CUBICIN was evaluated in one clinical trial (in cSSSI), which included 256 pediatric patients (1 to 17 years of age) treated with intravenous CUBICIN and 133 patients treated with comparator agents. Patients were given age- dependent doses once daily for a treatment period of up to 14 days (median treatment period was 3 days). The doses given by age group were as follows: 10mg/kg for 1 to less than 2 years, 9 mg/kg for 2 to 6 years, 7mg/kg for 7 to 11 years and 5 mg/kg for 12 to 17 years of age. Patients treated with CUBICIN were (51%) male, (49%) female and (46 %) Caucasian and (32 %) Asian.
Adverse Reactions Leading to Discontinuation
In the cSSSI study, CUBICIN was discontinued in 7/256 (2.7%) patients due to an adverse reaction, while comparator was discontinued in 7/133 (5.3%) patients.
Most Common Adverse Reactions
The rates of the most common adverse reactions, organized by body system, observed in these pediatric patients with cSSSI are displayed in Table 8.
Table 8: Adverse Reactions that Occurred in greater than or equal to 2% of Pediatric Patients in the CUBICIN Treatment-Arm and Greater Than or Equal to the Comparator Treatment-Arm in the cSSSI Pediatric Trial
The safety profile in the clinical trial of cSSSI pediatric patients was similar to that observed in the cSSSI adult patients.
7 Drug Interactions
7.1 HMG-CoA Reductase InhibitorsAdditions and/or revisions underlined:
In healthy adult subjects, concomitant administration of CUBICIN and simvastatin had no effect …
However, inhibitors of HMG-CoA reductase may cause myopathy, which is manifested as muscle pain or weakness associated with elevated levels of creatine phosphokinase (CPK). In the adult Phase 3 S. aureus bacteremia/endocarditis …
8 Use in Specific Populations
8.1 PregnancyPLLR conversion, as below:
Risk Summary
Limited published data on use of CUBICIN in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies performed in rats and rabbits daptomycin was administered intravenously during organogenesis at doses 2 and 4-times, respectively, the recommended 6 mg/kg human dose (on a body surface area basis). No evidence of adverse developmental outcomes was observed.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data
Animal Data
In pregnant rats, daptomycin was administered intravenously at doses of 5, 20, or 75 mg/kg/day during the gestation days 6 to 18. Maternal body weight gain was decreased at 75 mg/kg/day.
No embryo/fetal effects were noted at the highest dose of 75 mg/kg/day, a dose approximately 2-fold higher than in humans at the recommended maximum dose of 6mg/kg (based on body surface area).
In pregnant rabbits, daptomycin was administered intravenously at doses of 5, 20, or 75 mg/kg/day during the gestation days 6 to 15. Maternal body weight gain and food consumption were decreased at 75 mg/kg/day. No embryo/fetal effects were noted at the highest dose of 75 mg/kg/day, a dose approximately 4-fold higher than in humans at the maximum recommended dose of 6mg/kg (based on body surface area).
In a combined fertility and pre/postnatal development study, daptomycin was administered intravenously to female rats at doses of 2, 25, 75 mg/kg/day from 14-days pre-mating through lactation/postpartum day 20). No effects on pre/postnatal development were observed up to the highest dose of 75 mg/kg/day, a dose approximately 2-fold higher than the maximum recommended human dose of 6 mg/kg (based on body surface area)1.
PLLR conversion; as below:
Risk Summary
published data report that daptomycin is present in human milk at infant 150 mL/kg/ddoses of 0.1% of the maternal dose [see Data]2,3,4. There is no information on the effects of daptomycin on the breastfed infant or the effects of daptomycin on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CUBICIN and any potential adverse effects on the breastfed infant from CUBICIN or from the underlying maternal condition.
Additions and/or revisions underlined:
The safety and effectiveness of CUBICIN in the treatment of cSSSI has been established in the age groups 1 to 17 years of age. Use of CUBICIN 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 additional data from a safety, efficacy and PK study in pediatric patients 1 to 17 years of age with cSSSI. Safety and effectiveness in pediatric patients below the age of one year have not been established. Avoid use of CUBICIN 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.
CUBICIN is not indicated in pediatric patients with renal impairment because dosage has not been established in these patients.
The safety and efficacy of CUBICIN has not been established in pediatric patients (below 18 years of age) with Staphylococcus aureus bloodstream infections (bacteremia). The safety and efficacy of CUBICIN has also not been established in pediatric patients with cSSSI associated with bloodstream infections. CUBICIN has also not been studied in pediatric patients with other bacterial infections.
Addition of the word adult before patients, clinical trials, and subjects throughout subsection.
Addition of the word adult prior to patients throughout this subsection.
Additions and/or revisions underlined:
The dosage regimen for CUBICIN in pediatric patients with renal impairment has not been established.
07/07/2016 (SUPPL-53)
6 Adverse Reactions
Post-Marketing ExperienceAddition of the following adverse reactions:
- Blood and lymphatic system disorders: anemia
- General and administration site conditions: pyrexia
- Renal and urinary disorders: acute kidney injury, renal insufficiency, and renal failure
- Skin and Subcutaneous Tissue Disorders: acute generalized exanthematous pustulosis