Ceftriaxone (Page 4 of 7)
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.
- Neurologic-Encephalopathy, seizures, myoclonus, and non-convulsive status epilepti us [see Warnings and Precautions (5.3)]
- Gastrointestinal – stomatitis and glossitis
- Genitourinary – oliguria
- Dermatologic – exanthema, allergic dermatitis, urticaria, edema
Cases of severe cutaneous adverse reactions (erythema multiforme, Stevens-Johnson syndrome or Lyell’s syndrome/toxic epidermal necrolysis) have been reported.
Anaphylaxis (including anaphylactic shock, transient leukopenia, neutropenia, agranulocytosis and thrombocytopenia) has been reported.
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 cholestasis, aplastic anemia, hemorrhage, and superinfection.
- Altered Laboratory Tests: Positive direct Coombs’ test, false-positive test for urinary glucose, and elevated 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 is mixed with calcium-containing solutions in the same intravenous administration line. Ceftriaxone for Injection, USP must not be administered simultaneously with calcium-containing intravenous solutions. Ceftriaxone for Injection and calcium-containing solutions can be administered sequentially [see Warnings and Precautions (5.2)]
8 USE IN SPECIFIC POPULATIONS
Pregnancy Category B.
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 recommended clinical dose of 2 grams/day based on body surface area comparisons.
There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
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 (mg/m2 comparison) the recommended daily dose of 2 grams/day. No adverse effects were noted on various reproductive parameters during gestation and lactation, including postnatal growth, functional behavior, and reproductive ability of the offspring.
8.3 Nursing Mothers
Ceftriaxone is excreted in human breast milk. Caution should be exercised when Ceftriaxone for Injection is administered to a nursing woman.
8.4 Pediatric Use
Ceftriaxone for Injection USP, Pharmacy Bulk Package bag, SmartPak® should not be used in pediatric patients who require less than the 1 gram dose of ceftriaxone. To prevent unintentional overdose, this product should not be used in pediatric patients who require less than the adult 1 gram 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 [see Clinical Pharmacology (12)].
Ceftriaxone overdosage has been reported in patients with severe renal impairment. Reactions have included neurological outcomes, including encephalopathy, seizures, myoclonus, and non -convulsive status epilepticus. In the event of overdosage discontinue Ceftriaxone for Injection therapy and provide general supportive treatment [see Dosage and Administration (2.1) and Warnings and Precautions (5.3) ].
In the case of overdosage, drug concentration would not be reduced by hemodialysis or peritoneal dialysis. There is no specific antidote. Treatment of overdosage should be symptomatic.
Ceftriaxone for Injection, USP, Pharmacy Bulk Package bag SmartPak® should be used only in patients who require a 1 gram dose and not any fraction thereof.
Ceftriaxone for Injection USP, Pharmacy Bulk Package bag SmartPak® should not be used in patients who require less than the 1 gram dose of ceftriaxone.
Ceftriaxone for Injection, USP, is a sterile, semisynthetic, broad-spectrum cephalosporin antibacterial for intravenous administration. Ceftriaxone sodium is (6R ,7R)-7-[2-(2-Amino-4-thiazolyl)glyoxylamido]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-as -triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 72 -(Z)-(O-methyloxime), disodium salt, sesquaterhydrate.
The chemical formula of ceftriaxone sodium is C18 H16 N8 Na2 O7 S3 •3.5H2 O. It has a calculated molecular weight of 661.60 and the following structural formula:
Ceftriaxone sodium is a white to yellowish-orange crystalline powder, which is readily soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol. The p H of a 1% aqueous solution is approximately 6.7. The color of ceftriaxone sodium solutions ranges from light yellow to amber, depending on the length of storage and concentration. Each Pharmacy Bulk Package contains approximately 83 mg (3.6 mEq) of sodium per 1 gram of ceftriaxone activity. Ceftriaxone for Injection, USP is supplied in 100 grams SmartPak® Pharmacy Bulk Packages bags equivalent. Each SmartPak® Pharmacy Bulk Package bag contains ceftriaxone sodium, USP equivalent to 100 grams of ceftriaxone.
BEFORE ADMINISTRATION, THIS PHARMACY BULK PACKAGE REQUIRES RECONSTITUTION USING STERILE WATER FOR INJECTION, USP TO A CONCENTRATION OF 100 mg per mL AND FURTHER DILUTION IN 50 mL OF A COMPATIBLE SOLUTION AND INFUSED INTRAVENOUSLY OVER 30 MINUTES.
THIS PRODUCT IS NOT INTENDED TO BE USED IN PEDIATRIC PATIENTS AND RENALLY IMPAIRED PATIENTS WHO REQUIRE LESS THAN A 1 GRAM DOSE.
A Pharmacy Bulk Package is a container of a sterile preparation for parenteral use that contains many single doses. The contents are intended for use in a pharmacy admixture service and are restricted to the preparation of admixtures for intravenous infusion.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Ceftriaxone is an antibacterial drug. [see Microbiology (12.4)]
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