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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.
CEFAZOLIN IN PLASTIC CONTAINER (NDA-207131)
(CEFAZOLIN SODIUM)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
05/31/2024 (SUPPL-10)
4 Contraindications
4.1 Hypersensitivity to Cefazolin or the Cephalosporin Class of Antibacterial Drugs, Penicillins, or Other Beta-lactams
Additions and/or revisions underlined:
Cefazolin in Dextrose Injection is contraindicated in patients who have a history of immediate hypersensitivity reactions (e.g., anaphylaxis, serious skin reactions) to cefazolin or the cephalosporin class of antibacterial drugs, penicillins, or other beta-lactams [see Warnings and Precautions (5.1)].
5 Warnings and Precautions
5.1 Hypersensitivity Reactions to Cefazolin, Cephalosporins, Penicillins, or Other Beta-lactams
Additions
and/or revisions underlined:
Serious
and occasionally fatal hypersensitivity (anaphylactic) reactions have been
reported in patients receiving beta-lactam antibacterial drugs. Before therapy
with Cefazolin in Dextrose Injection is instituted, careful inquiry
should be made to determine whether the patient has had previous immediate
hypersensitivity reactions to cefazolin, cephalosporins, penicillins, or carbapenems.
Exercise caution if this product is to be given to penicillin-sensitive
patients because cross-hypersensitivity among beta- lactam antibacterial drugs
has been clearly documented and may occur in up to 10% of patients with a
history of penicillin allergy. If an allergic reaction to Cefazolin in
Dextrose Injection occurs, discontinue the drug.
5.2 Seizures in Patients with Renal Impairment
Additions and/or revisions underlined:
Seizures may occur with the administration of Cefazolin in Dextrose Injection, particularly in patientswith renal impairment when the dosage is not reduced appropriately. Discontinue Cefazolin in Dextrose Injection if seizures occur or make appropriate dosage adjustments in patients with renal impairment [see Dosage and Administration (2.4)]. Anticonvulsant therapy should be continued in patients with known seizure disorders.
5.5 Prothrombin Activity
Additions and/or revisions underlined:
Cefazolin in Dextrose Injection may be associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated.
5.6 Risk of Development of Drug-resistant Bacteria
Additions and/or revisions underlined:
Prescribing Cefazolin in Dextrose Injection in the absence of 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.
As with other antimicrobials, prolonged use of Cefazolin in Dextrose Injection may result in overgrowth of nonsusceptible microorganisms. Repeated evaluation of the patient's condition is essential. Should superinfection occur during therapy, appropriate measures should be taken.
5.7 Drug/Laboratory Test Interactions
Additions and/or revisions underlined:
Urinary Glucose
The administration of Cefazolin in Dextrose Injection may result in a false-positive reaction with glucose in the urine when using glucose tests based on Benedict’s copper reduction reaction that determine the amount of reducing substances like glucose in the urine. It is recommended that glucose tests based on enzymatic glucose oxidase be used.
…
5.8 Patients with Overt or Known Subclinical Diabetes Mellitus or Carbohydrate Intolerance
Additions and/or revisions underlined:
As with other dextrose-containing solutions, Cefazolin in Dextrose Injection should be prescribed with caution in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.
6 Adverse Reactions
Additions and/or revisions underlined:
- Hypersensitivity Reactions to Cefazolin, Cephalosporins, Penicillins, or Other Beta-lactams [see Warnings and Precautions (5.1)]
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
Two studies (Study 1: NCT 3231228 and Study 2: NCT 01904357) were conducted to assess the safety and pharmacokinetics of a single 30-minute infusion of either 1 gram or 2 grams (based on weight) of cefazolin for injection and dextrose injection for perioperative prophylaxis in pediatric patients.
Study 1 was a multicenter, open-label, non-comparative, parallel group study to evaluate the safety and pharmacokinetics of a single 30-minute infusion of either 1 gram or 2 grams (based on weight) of cefazolin for injection and dextrose injection for perioperative prophylaxis in 61 pediatric patients 10 to 17 years of age. Thirty- three subjects with a weight of at least 25 kg but less than 60 kg received a single dose of 1 gram of cefazolin for injection and dextrose injection and 28 subjects with a weight of at least 60 kg received a single dose of 2 grams of cefazolin for injection and dextrose injection.
…
Study 2 was a multicenter, non-comparative study that evaluated the safety and pharmacokinetics of a single 30- minute infusion of either 1 gram or 2 grams (based on weight) of cefazolin for injection and dextrose injection for perioperative prophylaxis in 12 pediatric patients 10 to 12 years of age. Subjects weighing at least 25 kg to less than 50 kg received a single dose of 1 gram of cefazolin for injection and dextrose injection and subjects weighing at least 50 kg to less than 85 kg received a single dose of 2 grams of cefazolin for injection and dextrose injection.
7 Drug Interactions
Additions and/or revisions underlined:
The renal excretion of cefazolin is inhibited by probenecid. Co-administration of probenecid with Cefazolin in Dextrose Injection is not recommended.
8 Use in Specific Populations
8.2 Lactation
Additions and/or revisions underlined:
Risk Summary
Data from published literature report that cefazolin is present in human milk, but is not expected to accumulate in a breastfed infant. There are no data on the effects of cefazolin on the breastfed child or on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Cefazolin in Dextrose Injection and any potential adverse effects on the breastfed child from Cefazolin in Dextrose Injection or from the mother’s underlying condition.
8.4 Pediatric Use
Additions and/or revisions underlined:
Cefazolin in Dextrose Injection is indicated for the treatment of respiratory tract infections, urinary tract infections, skin and skin structure infections, biliary tract infections, bone and joint infections, genital infections, septicemia, and endocarditis in pediatric patients for whom appropriate dosing with this formulation can be achieved and for perioperative prophylaxis in pediatric patients aged 10 to 17 years old [see Indications and Usage (1.1 to 1.8)].
Safety and effectiveness of Cefazolin in Dextrose Injection in premature infants and neonates have not been established and is not recommended for use in this age group of pediatric patients. Dosing for cefazolin in pediatric patients younger than one month old has not been established.
Because of the limitations of the available strengths and administration requirements (i.e., administration of fractional doses is not recommended) of Cefazolin in Dextrose Injection, and to avoid unintentional overdose, this product is not recommended for use if a dose of Cefazolin in Dextrose Injection that does not equal 1 gram or 2 grams is required and an alternative formulation of cefazolin should be considered [see Dosage and Administration (2.2, 2,3, 2.4 and 2.5)].
The safety and effectiveness of cefazolin for injection and dextrose injection for perioperative prophylaxis have been established in pediatric patients aged 10 to 17 years old. Use of cefazolin for injection and dextrose injection in these age groups is supported by evidence from adults with additional safety and pharmacokinetic data in pediatric patients aged 10 to 17 years old.
Safety and pharmacokinetics were evaluated in two multicenter, non-comparative studies (Study 1 and Study 2). These studies were conducted to assess the safety and pharmacokinetics of a single 30-minute infusion of either 1 gram or 2 grams (based on weight) of cefazolin for injection and dextrose injection for perioperative prophylaxis in pediatric patients. Study 1 evaluated the safety and pharmacokinetics of 1 g of cefazolin for injection and dextrose injection in pediatric patients aged 10 to 17 years old scheduled for surgery with a weight of at least 25 kg but less than 60 kg and 2 g in pediatric patients with a weight of at least 60 kg. Study 2 evaluated 1 g of another cefazolin injection product in pediatric patients aged 10 to 12 years old scheduled for surgery with a weight of at least 25 kg but less than 50 kg and 2 g in pediatric patients with a weight of at least 50 kg to less than 85 kg [see Dosage and Administration (2.3), Adverse Reactions (6.1) and Clinical Pharmacology (12.3)].
The safety and effectiveness of Cefazolin in Dextrose Injection for perioperative prophylaxis have not been established in pediatric patients younger than 10 years old.
8.6 Patients with Renal Impairment
Additions and/or revisions underlined:
When Cefazolin in Dextrose Injection is administered to adult and pediatric patients with low urinary output because of impaired renal function (creatinine clearance less than 55 mL/min and 70 mL/min for adults and pediatric patients, respectively), lower daily dosage is required [see Dosage and Administration (2.4) and Warnings and Precautions (5.2)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
Serious Allergic Reactions
Advise patients that allergic reactions, including serious allergic reactions could occur and that serious reactions require immediate treatment and discontinuation of Cefazolin in Dextrose Injection. Patients should report to their health care provider any previous allergic reactions to cefazolin, cephalosporins, penicillins, or other similar antibacterials.
Seizures
Advise patients that seizures could occur with Cefazolin in Dextrose Injection. Instruct patients to inform a healthcare provider at once of any signs and symptoms of seizures, for immediate treatment, dosage adjustment, or discontinuation of Cefazolin in Dextrose Injection.
…
Antibacterial Resistance
Patients should be counseled that antibacterial drugs, including Cefazolin in Dextrose Injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold).
When Cefazolin in Dextrose 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 Cefazolin in Dextrose Injection or other antibacterial drugs in the future.
02/01/2024 (SUPPL-9)
5 Warnings and Precautions
5.5 Prothrombin ActivityNewly added subsection:
Cefazolin Injection may be associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated.
6 Adverse Reactions
6.1 Clinical Trials ExperienceNewly added information:
Adverse Reactions in Pediatric Patients for Perioperative Prophylaxis
Two studies (Study 1: NCT 3231228 and Study 2: NCT 01904357) were conducted to assess the safety and pharmacokinetics of a single 30-minute infusion of either 1 gram or 2 grams (based on weight) of cefazolin for injection for perioperative prophylaxis in pediatric patients.
Study 1 was a multicenter, open-label, non-comparative, parallel group study to evaluate the safety and pharmacokinetics of a single 30-minute infusion of either 1 gram or 2 grams (based on weight) of cefazolin for injection for perioperative prophylaxis in 61 pediatric patients 10 to 17 years of age. Thirty-three subjects with a weight of at least 25 kg but less than 60 kg received a single dose of 1 gram of cefazolin and 28 subjects with a weight of at least 60 kg received a single dose of 2 grams of cefazolin. The mean age of the safety population was 14 years and ranged from 10 to 17 years. There were no adverse reactions leading to study discontinuation or deaths reported during the study. The most frequently reported adverse reactions were nausea (14.8%), infusion site pain (6.6%), and headache (4.9%).
Study 2 was a multicenter, non-comparative study that evaluated the safety and pharmacokinetics of a single 30- minute infusion of either 1 gram or 2 grams (based on weight) of cefazolin for injection for perioperative prophylaxis in 12 pediatric patients 10 to 12 years of age. Subjects weighing at least 25 kg to less than 50 kg received a single dose of 1 gram of cefazolin for injection and subjects weighing at least 50 kg to less than 85 kg received a single dose of 2 grams of cefazolin for injection. The safety findings in Study 2 in pediatric patients aged 10 to 12 years old were similar to those observed in adult patients and the pediatric patients aged 10 to 17 years old in Study 1.
8 Use in Specific Populations
8.4 Pediatric UseNewly added information:
The safety and effectiveness of Cefazolin Injection for perioperative prophylaxis have been established in pediatric patients aged 10 to 17 years old. Use of Cefazolin Injection in these age groups is supported by evidence from adults with additional safety and pharmacokinetic data in pediatric patients aged 10 to 17 years old. Safety and pharmacokinetics were evaluated in two multicenter, non-comparative studies (Study 1 and Study 2). These studies were conducted to assess the safety and pharmacokinetics of a single 30-minute infusion of either 1 gram or 2 grams (based on weight) of Cefazolin Injection for perioperative prophylaxis in pediatric patients. Study 1 evaluated the safety and pharmacokinetics of 1 g of cefazolin for injection in pediatric patients aged 10 to 17 years old scheduled for surgery with a weight of at least 25 kg but less than 60 kg and, 2 g in pediatric patients with a weight of at least 60 kg. Study 2 evaluated 1 g of cefazolin for injection in pediatric patients aged 10 to 12 years old scheduled for surgery with a weight of at least 25 kg but less than 50 kg and, 2 g in pediatric patients with a weight of at least 50 kg to less than 85 kg [see Dosage and Administration (2.3), Adverse Reactions (6.1) and Clinical Pharmacology (12.3)].
09/20/2021 (SUPPL-8)
6 Adverse Reactions
6.2 Postmarketing Experience(Additions and/or revisions underlined)
The following adverse reactions have been identified during post approval use of cefazolin. 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.
Immune system disorders: Serum sickness-like reaction
Renal and urinary disorders: Acute tubulointerstitial nephritis (ATIN)
Skin and subcutaneous tissue disorders: Acute generalized exanthematous pustulosis (AGEP)
02/01/2021 (SUPPL-6)
5 Warnings and Precautions
5.1 Hypersensitivity Reactions to Cefazolin, Cephalosporins, Penicillins, or Other Beta-lactams(Additions and/or revisions underlined)
Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibacterial drugs has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy.
(Newly added section)
Seizures may occur with the administration of cefazolin injection, particularly in patients with renal impairment when the dosage is not reduced appropriately. Discontinue cefazolin injection if seizures occur or make appropriate dosage adjustments in patients with renal impairment [see Dosage and Administration (2.4)]. Anticonvulsant therapy should be continued in patients with known seizure disorders.
(Additions and/or revisions underlined)
Urinary Glucose
The administration of cefazolin may result in a false-positive reaction with glucose in the urine when using glucose tests based on Benedict’s copper reduction reaction that determine the amount of reducing substances like glucose in the urine.
(Additions and/or revisions underlined)
As with other dextrose-containing solutions, cefazolin injection should be prescribed with caution in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.
6 Adverse Reactions
(Additions and/or revisions underlined)
The following serious adverse reactions to cefazolin injection are described below and elsewhere in the labeling:
Hypersensitivity reactions [see Warnings and Precautions (5.1)]
Seizures in Patients with Renal Impairment [see Warnings and Precautions (5.2)]
Clostridioides difficile-associated diarrhea [see Warnings and Precautions (5.3)]
(Additions and/or revisions underlined)
The following adverse reactions were reported from clinical trials:
Gastrointestinal: Diarrhea, oral candidiasis (oral thrush),
Hepatic: Transient rise in SGOT, SGPT, and alkaline phosphatase levels has been observed. Reports of hepatitis have been received.
Renal: Reports of increased BUN and creatinine levels, as well as renal failure, have been received.
Local Reactions: Instances of phlebitis have been reported at site of injection. Some induration has occurred.
Other Reactions: Pruritus (including genital, vulvar and anal pruritus, genital moniliasis, and vaginitis). Dizziness, fainting, lightheadedness, confusion, weakness, tiredness, hypotension, somnolence and headache.
Additional pediatric use information is approved for B. Braun Medical Inc.'s CEFAZOLIN FOR INJECTION AND DEXTROSE INJECTION. However, due to B. Braun Medical Inc.'s marketing exclusivity rights, this drug product is not labeled with that information.
(Newly added section)
The following adverse reactions have been identified during post approval use of cefazolin. 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.
Immune system disorders: Serum sickness-like reaction
Renal and urinary disorders: Acute tubulointerstitial nephritis (ATIN)
8 Use in Specific Populations
8.1 Pregnancy(PLLR conversion. Please refer to label for complete information.)
(PLLR conversion. Please refer to label for complete information.)
(Additions and/or revisions underlined)
Cefazolin injection is indicated for the treatment of respiratory tract infections, urinary tract infections, skin and skin structure infections, biliary tract infections, bone and joint infections, genital infections, septicemia, and endocarditis in pediatric patients for whom appropriate dosing with this formulation can be achieved [see Indications and Usage (1.1 to 1.8)].
Safety and effectiveness of cefazolin injection in prematureinfants and neonates have not been established and is not recommended for use in this age group of pediatric patients. Dosing for cefazolin in pediatric patients younger than one month old has not been established.
Because of the limitations of the available strengths and administration requirements (i.e., administration of fractional doses is not recommended) of cefazolin injection, and to avoid unintentional overdose, this product is not recommended for use if a dose of cefazolin injection that does not equal 1 gram or 2 grams is required and an alternative formulation of cefazolin should be considered [see Dosage and Administration (2.2, 2,3, 2.4 and 2.5)].
The safety and effectiveness of cefazolin injection for perioperative prophylaxis have not been established in pediatric patients younger than 10 years old.
Additional pediatric use information is approved for B. Braun Medical Inc.'s CEFAZOLIN FOR INJECTION AND DEXTROSE INJECTION. However, due to B. Braun Medical Inc.'s marketing exclusivity rights, this drug product is not labeled with that information.
(Additions and/or revisions underlined)
When cefazolin injection is administered to adult and pediatric patients with low urinary output because of impaired renal function (creatinine clearance less than 55 mL/min and 70 mL/min for adults and pediatric patients, respectively), lower daily dosage is required [see Dosage and Administration (2.4) and Warnings and Precautions (5.2)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION(Additions and/or revisions underlined)
Serious Allergic Reactions
Advise patients that allergic reactions, including serious allergic reactions could occur and that serious reactions require immediate treatment and discontinuation of cefazolin injection. Patients should report to their health care provider any previous allergic reactions to cefazolin, cephalosporins, penicillins, or other similar antibacterials.
Seizures
Advise patients that seizures could occur with cefazolin injection. Instruct patients to inform a healthcare provider at once of any signs and symptoms of seizures, for immediate treatment, dosage adjustment, or discontinuation of cefazolin injection.
Diarrhea
Advise patients that diarrhea is a common problem caused by antibacterials, which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterials. If this occurs, patients should contact a physician as soon as possible.
Antibacterial Resistance
Patients should be counseled that antibacterial drugs, including cefazolin injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cefazolin 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 cefazolin injection or other antibacterial drugs in the future.