Lorbef

Loracarbef is contraindicated in patients with known allergy to loracarbef or cephalosporin-class antibiotics.

WARNINGS

BEFORE THERAPY WITH LORACARBEF 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 b-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 LORACARBEF 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 the Patient: Loracarbef should be taken either at least 1 hour prior to eating or at least 2 hours after eating a meal.

Carcinogenesis, Mutagenesis, and Impairment of Fertility: Although life-time 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).

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: Loracarbef 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 loracarbef is administered to a nursing woman.

Pediatric Use: The safety and efficacy of Lorbef (loracarbef) have been established for children aged six months to twelve years for acute maxillary sinusitis based upon its approval in adults. Use of Lorbef (loracarbef) 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).

Geriatric Use: Healthy geriatric volunteers (³65 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. In clinical studies, when geriatric patients received the usual recommended adult doses, clinical efficacy and safety were comparable to results in nongeriatric adult patients. Because significant numbers of elderly patients have decreased renal function, evaluation of renal function in this population is recommended (see DOSAGE AND ADMINISTRATION.)

The nature of adverse reactions to loracarbef are similar to those observed with orally administered b-lactam antimicrobials. The majority of adverse reactions observed in clinical trials were of a mild and transient nature; 1.5% of patients discontinued therapy because of drug-related adverse reactions. No one reaction requiring discontinuation accounted for >0.03% of the total patient population; however, of those reactions resulting in discontinuation, gastrointestinal events (diarrhea and abdominal pain) and skin rashes predominated.

All Patients

The following adverse events, irrespective of relationship to drug, have been reported following the use of loracarbef in clinical trials. Incidence rates (combined for all dosing regimens and dosage forms) were less than 1% for the total patient population, except as otherwise noted:

Gastrointestinal: The most commonly observed adverse reactions were related to the gastrointestinal system. The incidence of gastrointestinal adverse reactions increased in patients treated with higher doses. Individual event rates included diarrhea, 4.1%; nausea, 1.9%; vomiting 1.4%; abdominal pain, 1.4%; and anorexia.

Hypersensitivity: Hypersensitivity reactions including, skin rashes (1.2%), urticaria, pruritus, and erythema multiforme.

Central Nervous System: Headache (2.9%), somnolence, nervousness, insomnia, and dizziness.

Hemic and Lymphatic Systems: Transient thrombocytopenia, leukopenia, and eosinophilia.

Hepatic: Transient elevations in AST (SGOT), ALT (SGPT), and alkaline phosphatase.

Renal: Transient elevations in BUN and creatinine.

Cardiovascular System: Vasodilatation.

Genitourinary: Vaginitis (1.3%), vaginal moniliasis (1.1%).

As with other b-lactam antibiotics, the following potentially severe adverse experiences have been reported rarely with loracarbef in worldwide post-marketing surveillance: anaphylaxis, hepatic dysfunction including cholestasis, prolongation of the prothrombin time with clinical bleeding in patients taking anticoagulants, and Stevens-Johnson syndrome.

Pediatric Patients

The incidences of several adverse events, irrespective of relationship to drug, following treatment with loracarbef were significantly different in the pediatric population and the adult population as follows (TABLE 12):

b-Lactam Antimicrobial Class Labeling

The following adverse reactions and altered laboratory test results have been reported in patients treated with b-lactam antibiotics:

Adverse Reactions: Allergic reactions, aplastic anemia, hemolytic anemia, hemorrhage, agranulocytosis, toxic epidermal necrolysis, renal dysfunction, toxic nephropathy. As with other b-lactam antibiotics, serum sickness-like reactions have been reported rarely with loracarbef.

Several b-lactam antibiotics have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures associated with drug therapy should occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

Altered Laboratory Tests: Increased prothrombin time, positive direct Coombs' test, elevated LDH, pancytopenia, and neutropenia.

Signs and Symptoms: The toxic symptoms following an overdose of b-lactams may include nausea, vomiting, epigastric distress, and diarrhea.

Loracarbef is eliminated primarily by the kidneys. Forced diuresis, peritoneal dialysis, hemodialysis, or hemoperfusion have not been established as beneficial for an overdose of loracarbef. Hemodialysis has been shown to be effective in hastening the elimination of loracarbef from plasma in patients with chronic renal failure.