CEFTRIAXONE AND DEXTROSE (Page 4 of 8)

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following reactions occurred in less than or equal to 6% of the patients:

  • Local reactions—pain, induration, tenderness, and phlebitis after IV administration.
  • Hypersensitivity—rash, pruritus, fever or chills.
  • Hematologic—eosinophilia, thrombocytosis, leucopenia, anemia, hemolytic anemia, neutropenia, lymphopenia, thrombocytopenia, and prolongation of the prothrombin time.
  • Gastrointestinal—diarrhea, nausea or vomiting, and dysgeusia. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [see Warnings and Precautions (5.4)].
  • Hepatic—elevations of SGOT, SGPT, alkaline phosphatase, bilirubin.
  • Renal—elevations of the BUN, creatinine, and the presence of casts in the urine.
  • Central nervous system—headache or dizziness.
  • Genitourinary—moniliasis or vaginitis.
  • Miscellaneous—diaphoresis and flushing.
  • Ceftriaxone-calcium precipitates—Cases of fatal reactions with ceftriaxone-calcium precipitates in lung and kidneys in neonates have been described. In some cases the infusion lines and times of administration of ceftriaxone and calcium-containing solutions differed [see Warnings and Precautions (5.2) and Drug Interactions (7.2)].
  • Other observed adverse reactions—abdominal pain, agranulocytosis, allergic pneumonitis, anaphylaxis, basophilia, biliary lithiasis, bronchospasm, colitis, dyspepsia, epistaxis, flatulence, gallbladder sludge, glycosuria, hematuria, jaundice, leukocytosis, lymphocytosis, monocytosis, nephrolithiasis, palpitations, a decrease in the prothrombin time, renal precipitations, seizures, and serum sickness.

6.2 Postmarketing Experience

The following adverse reactions have been reported during postapproval use of ceftriaxone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to readily estimate their frequency or establish a causal relationship to drug exposure.

  • Gastrointestinal—stomatitis and glossitis.
  • Genitourinary—oliguria, ureteric obstruction, post-renal acute renal failure.
  • Hepatic—hepatitis.
  • Dermatologic—severe cutaneous adverse reactions (erythema multiforme, Stevens-Johnson syndrome or Lyell’s syndrome/toxic epidermal necrolysis), exanthema, allergic dermatitis, urticaria, and edema.
  • Immunologic—Anaphylaxis (anaphylactic shock, transient leucopenia, neutropenia, agranulocytosis and thrombocytopenia).
  • Neurologic – Encephalopathy, seizures, myoclonus, and non-convulsive status epilepticus [see Warnings and Precautions (5.3)].

6.3 Cephalosporin-class Adverse Reactions

In addition to the adverse reactions listed above that have been observed in patients treated with ceftriaxone, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibacterials:

  • Adverse Reactions: Allergic reactions, drug fever, serum sickness-like reaction, renal dysfunction, toxic nephropathy, reversible hyperactivity, hypertonia, hepatic dysfunction including hepatitis, cholestasis, aplastic anemia, hemorrhage, and superinfection.
  • Altered Laboratory Tests: Positive direct Coombs’ test, false-positive test for urinary glucose, and elevated lactic acid dehydrogenase (LDH).

7 DRUG INTERACTIONS

7.1 Vancomycin, Amsacrine, Aminoglycosides, and Fluconazole

Vancomycin, amsacrine, aminoglycosides, and fluconazole are physically incompatible with ceftriaxone in admixtures [see Dosage and Administration (2.3)].

7.2 Calcium-containing Products

Precipitation of ceftriaxone-calcium can occur when Ceftriaxone for Injection and Dextrose Injection is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone for Injection and Dextrose Injection must not be administered simultaneously with calcium-containing IV solutions. Ceftriaxone for Injection and Dextrose Injection and calcium-containing solutions may be administered sequentially. [see Warnings and Precautions (5.2)]

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Available data from published prospective cohort studies, case series, and case reports over several decades with cephalosporin use, including Ceftriaxone, in pregnant women have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Ceftriaxone crosses the placenta.

In animal reproduction studies, no adverse developmental effects were observed when ceftriaxone was administered to pregnant rats at doses up to approximately 2.8 times the clinical dose of 2 g/day (see Data).

The estimated 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% to 4% and 15% to 20%, respectively.

Data

Human Data

Published literature shows that ceftriaxone crosses the placenta. While available studies cannot definitively establish the absence of risk, published data from case-control studies and case reports over several decades have not identified an association with cephalosporin use during pregnancy and major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Available studies have methodologic limitations, including small sample size, retrospective data collection, and inconsistent comparator groups.

Animal Data

Reproductive studies have been performed in mice, rats, and primates at intravenous doses of 625, 586, and 84 mg/kg/day, respectively, without evidence of embryotoxicity, fetotoxicity, or teratogenicity. These doses are approximately 1.5, 2.8, and 0.8 times the clinical dose of 2 g/day based on body surface area comparisons. Ceftriaxone was tested in a Segment III (pre-postnatal) study in rats at intravenous doses of up to 586 mg/kg/day (approximately 2.8 times the clinical dose of 2 g/day based on body surface area comparison). No adverse effects were noted on various reproductive parameters during gestation and lactation, including postnatal growth, functional behavior, and reproductive ability of the offspring.

8.2 Lactation

Risk Summary

Data from published literature report that ceftriaxone is present in human milk. There are no data on the effects of Ceftriaxone 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 Ceftriaxone for Injection and Dextrose Injection and any potential adverse effects on the breastfed child from Ceftriaxone for Injection and Dextrose Injection or from the mother’s underlying condition.

8.4 Pediatric Use

Ceftriaxone for Injection and Dextrose Injection in the DUPLEX® Container is designed to deliver a 1 g or 2 g dose of ceftriaxone. To prevent unintentional overdose, this product should not be used in pediatric patients who require less than the full 1 g or 2 g adult dose of ceftriaxone.

8.5 Geriatric Use

Of the total number of subjects in clinical studies of ceftriaxone sodium, 32% were 60 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Ceftriaxone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

The pharmacokinetics of ceftriaxone were only minimally altered in geriatric patients compared to healthy adult subjects and dosage adjustments are not necessary for geriatric patients with ceftriaxone dosages up to 2 grams per day, provided there is no severe renal and hepatic impairment. [see Clinical Pharmacology (12)]

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