Cefamandole warnings and precautions

Cefamandole
MANDOL® FDA Package Insert
Description
Clinical Pharmacology
Microbiology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Overdosage
Dosage and Administration
How Supplied

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Warnings and Preacuations

Warnings

BEFORE THERAPY WITH MANDOL (cefamandole) IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. THIS PRODUCT SHOULD BE GIVEN CAUTIOUSLY TO PENICILLIN-SENSITIVE PATIENTS. ANTIBIOTICS SHOULD BE ADMINISTERED WITH CAUTION TO ANY PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PARTICULARLY TO DRUGS. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE EPINEPHRINE AND OTHER EMERGENCY MEASURES.

In neonates, accumulation of other cephalosporin-class antibiotics (with resulting prolongation of drug half-life) has been reported.

Pseudomembranous colitis has been reported with virtually all broad-spectrum antibiotics (including macrolides, semisynthetic penicillins, and cephalosporins); therefore, it is important to consider its diagnosis in patients who develop diarrhea in association with the use of antibiotics. Such colitis may range in severity from mild to life threatening.

Treatment with broad-spectrum antibiotics alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of antibiotic-associated colitis.

Mild cases of pseudomembranous colitis usually respond to drug discontinuance alone. In moderate to severe cases, management should include sigmoidoscopy, appropriate bacteriologic studies, and fluid, electrolyte, and protein supplementation. When the colitis does not improve after the drug has been discontinued, or when it is severe, oral vancomycin is the drug of choice for antibiotic-associated pseudomembranous colitis produced by C. difficile. Other causes of colitis should be ruled out.

Precautions

General Although Mandol (cefamandole) rarely produces alteration in kidney function, evaluation of renal status is recommended, especially in seriously ill patients receiving maximum doses.

Prolonged use of Mandol (cefamandole) may result in the overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Nephrotoxicity has been reported following concomitant administration of aminoglycoside antibiotics and cephalosporins.

A false-positive reaction for glucose in the urine may occur with Benedict's or Fehling's solution or with Clinitest® tablets. There may be a false-positive test for proteinuria with acid and denaturization-precipitation tests.

As with other broad-spectrum antibiotics, hypoprothrombinemia, with or without bleeding, has been reported rarely, but it has been promptly reversed by administration of vitamin K. Such episodes usually have occurred in elderly, debilitated, or otherwise compromised patients with deficient stores of vitamin K. Treatment of such individuals with antibiotics possessing significant gram-negative and/or anaerobic activity is thought to alter the number and/or type of intestinal bacterial flora, with consequent reduction in synthesis of vitamin K. Prophylactic administration of vitamin K may be indicated in such patients, especially when intestinal sterilization and surgical procedures are performed.

In a few patients receiving Mandol (cefamandole) , nausea, vomiting, and vasomotor instability with hypotension and peripheral vasodilatation occurred following the ingestion of ethanol.

Cefamandol (cefamandole) inhibits the enzyme acetaldehyde dehydrogenase in laboratory animals. This causes accumulation of acetaldehyde when ethanol is administered concomitantly.

Broad-spectrum antibiotics should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Certain (beta)-lactam antibiotics containing the N-methylthiotetrazole side chain have been reported to cause delayed maturity of the testicular germinal epithelium when given to neonatal rats during initial spermatogenic development (6 to 36 days of age). In animals that were treated from 6 to 36 days of age with 1,000 mg/kg/day of cefamandol (cefamandole) (approximately 5 times the maximum clinical dose), the delayed maturity was pronounced and was associated with decreased testicular weights and a reduced number of germinal cells in the leading waves of spermatogenic development. The effect was slight in rats given 50 or 100 mg/kg/day. Some animals that were given 1,000 mg/kg/day during days 6 to 36 were infertile after becoming sexually mature. No adverse effects have been observed in rats exposed in utero, in neonatal rats (4 days of age or younger) treated prior to the initiation of spermatogenesis, or in older rats (more than 36 days of age) after exposure for up to 6 months. The significance to humans of these findings in rats is unknown because of differences in the time of initiation of spermatogenesis, rate of spermatogenic development, and duration of puberty.

Pregnancy Category: B

Reproduction studies have been performed in rats given doses of 500 or 1,000 mg/kg/day and have revealed no evidence of impaired fertility or harm to the fetus due to Mandol (cefamandole) . There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Caution should be exercised when Mandol (cefamandole) is administered to a nursing woman.

Usage in Infants

Mandol (cefamandole) has been effectively used in this age group, but all laboratory parameters have not been extensively studied in infants between 1 and 6 months of age; safety of this product has not been established in premature infants and term neonates under 1 month of age. Therefore, if Mandol (cefamandole) is administered to infants, the physician should determine whether the potential benefits outweigh the possible risks involved.

References

Adapted from the FDA Package Insert.