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.
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.
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):
|TABLE 12 |
|Event ||Pediatric ||Adult |
| Diarrhea ||5.8% ||3.6% |
| Headache ||0.9% ||3.2% |
| Rhinitis ||6.3% ||1.6% |
| Nausea ||0.0% ||2.5% |
| Rash ||2.9% ||0.7% |
| Vomiting ||3.3% ||0.5% |
| Somnolence ||2.1% ||0.4% |
| Anorexia ||2.3% ||0.3% |
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.
Probenecid: As with other b-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).