WARNINGS
BEFORE THERAPY WITH LORABID IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO LORACARBEF, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG β-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN ALLERGIC REACTION TO LORABID OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE THE USE OF EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.
Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.
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.”
After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of drug alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug effective against C. difficile -associated colitis.
PRECAUTIONS
General —In patients with known or suspected renal impairment (see DOSAGE AND ADMINISTRATION), careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy. The total daily dose of loracarbef should be reduced in these patients because high and/or prolonged plasma antibiotic concentrations can occur in such individuals administered the usual doses. Loracarbef, like cephalosporins, should be given with caution to patients receiving concurrent treatment with potent diuretics because these diuretics are suspected of adversely affecting renal function.
As with other broad-spectrum antimicrobials, prolonged use of loracarbef 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.
Loracarbef, as with other broad-spectrum antimicrobials, should be prescribed with caution in individuals with a history of colitis.
Information for Patients —Lorabid should be taken either at least 1 hour prior to eating or at least 2 hours after eating a meal.
Drug Interactions—
Probenecid: As with other β-lactam antibiotics, renal excretion of loracarbef is inhibited by probenecid and resulted in an approximate 80% increase in the AUC for loracarbef (see CLINICAL PHARMACOLOGY).
Carcinogenesis, Mutagenesis, Impairment of Fertility —Although lifetime studies in animals have not been performed to evaluate carcinogenic potential, no mutagenic potential was found for loracarbef in standard tests of genotoxicity, which included bacterial mutation tests and in vitro and in vivo mammalian systems. In rats, fertility and reproductive performance were not affected by loracarbef at doses up to 33 times the maximum human exposure in mg/kg (10 times the exposure based on mg/m2).
Usage in Pregnancy — Pregnancy Category B —Reproduction studies have been performed in mice, rats, and rabbits at doses up to 33 times the maximum human exposure in mg/kg (4, 10, and 4 times the exposure, respectively, based on mg/m2) and have revealed no evidence of impaired fertility or harm to the fetus due to loracarbef. 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.
Labor and Delivery —Lorabid has not been studied for use during labor and delivery. Treatment should be given only if clearly needed.
Nursing Mothers —It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Lorabid is administered to a nursing woman.
Pediatric Use —The safety and efficacy of Lorabid have been established for pediatric patients aged six months to twelve years for acute maxillary sinusitis based upon its approval in adults. Use of Lorabid in pediatric patients is supported by pharmacokinetic and safety data in adults and children, and by clinical and microbiologic data from adequate and well-controlled studies of the treatment of acute maxillary sinusitis in adults and of acute otitis media with effusion in children. It is also supported by post-marketing adverse events surveillance. (See CLINICAL PHARMACOLOGY, INDICATIONS AND USAGE, ADVERSE REACTIONS, DOSAGE AND ADMINISTRATION, and CLINICAL STUDIES sections).
Geriatric Use —Healthy geriatric volunteers (≥65 years old) with normal renal function who received a single 400-mg dose of loracarbef had no significant differences in AUC or clearance when compared to healthy adult volunteers 20 to 40 years of age (see CLINICAL PHARMACOLOGY). Of 3541 adult patients in controlled clinical studies of loracarbef, 705 (19.9%) were 65 years of age or older. In these controlled clinical studies, when geriatric patients received the usual recommended adult doses, clinical efficacy and safety were comparable to results in non-geriatric patients.
Loracarbef is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because significant numbers of elderly patients have decreased renal function, care should be taken in dose selection and evaluation of renal function in this population is recommended (see DOSAGE AND ADMINISTRATION).
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