Cefaclor

Cefaclor is indicated in the treatment of the following infections when caused by susceptible strains of the designated microorganisms: Otitis media caused by Streptococcus pneumoniae, Haemophilus influenzae, staphylococci, and Streptococcus pyogenes Note: β-lactamase-negative, ampicillin-resistant (BLNAR) strains of Haemophilus influenzae should be considered resistant to cefaclor despite apparent in vitro susceptibility of some BLNAR strains. Lower respiratory tract infections, including pneumonia, caused by Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus pyogenes Note: β-lactamase-negative, ampicillin-resistant (BLNAR) strains of Haemophilus influenzae should be considered resistant to cefaclor despite apparent in vitro susceptibility of some BLNAR strains. Pharyngitis and Tonsillitis, caused by Streptococcus pyogenes Note: Penicillin is the usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. Cefaclor is generally effective in the eradication of streptococci from the nasopharynx; however, substantial data establishing the efficacy of cefaclor in the subsequent prevention of rheumatic fever are not available at present. Urinary tract infections, including pyelonephritis and cystitis, caused by Escherichia coli, Proteus mirabilis, Klebsiella spp ., and coagulase-negative staphylococci Skin and skin structure infections caused by Staphylococcus aureus and Streptococcus pyogenes Appropriate culture and susceptibility studies should be performed to determine susceptibility of the causative organism to cefaclor. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefaclor Capsule and other antibacterial drugs, Cefaclor Capsule should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Cefaclor is contraindicated in patients with known allergy to the cephalosporin group of antibiotics.

BEFORE THERAPY WITH CEFACLOR IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFACLOR, 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 CEFACLOR OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED. Antibiotics, including cefaclor, should be administered cautiously to any patient who has demonstrated some form of allergy, particularly to drugs. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including cefaclor, and has ranged in severity 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 antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one 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 drug discontinuation 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.

General Prescribing cefaclor in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Prolonged use of cefaclor 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. Positive direct Coombs' tests have been reported during treatment with the cephalosporin antibiotics. It should be recognized that a positive Coombs' test may be due to the drug, e.g., in hematologic studies or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side or in Coombs' testing of newborns whose mothers have received cephalosporin antibiotics before parturition. Cefaclor should be administered with caution in the presence of markedly impaired renal function. Since the half-life of cefaclor in anuria is 2.3 to 2.8 hours, dosage adjustments for patients with moderate or severe renal impairment are usually not required. Clinical experience with cefaclor under such conditions is limited; therefore, careful clinical observation and laboratory studies should be made. As with other β-lactam antibiotics, the renal excretion of cefaclor is inhibited by probenecid. Antibiotics, including cephalosporins, should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis. Information for Patients Patients should be counseled that antibacterial drugs including cefaclor should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cefaclor is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by cefaclor or other antibacterial drugs in the future. Drug/Laboratory Test Interactions Patients receiving cefaclor may show a false-positive reaction for glucose in the urine with tests that use Benedict's and Fehling's solutions and also with Clinitest ® tablets. There have been reports of increased anticoagulant effect when cefaclor and oral anticoagulants were administered concomitantly. Carcinogenesis, Mutagenesis, Impairment of Fertility Studies have not been performed to determine potential for carcinogenicity, mutagenicity, or impairment of fertility. Pregnancy ─ Teratogenic Effects ─ Pregnancy Category B Reproduction studies have been performed in mice and rats at doses up to 12 times the human dose and in ferrets given 3 times the maximum human dose and have revealed no harm to the fetus due to cefaclor. 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 The effect of cefaclor on labor and delivery is unknown. Nursing Mothers Small amounts of cefaclor have been detected in mother's milk following administration of single 500-mg doses. Average levels were 0.18, 0.20, 0.21, and 0.16 mcg/mL at 2, 3, 4, and 5 hours respectively. Trace amounts were detected at 1 hour. The effect on nursing infants is not known. Caution should be exercised when cefaclor is administered to a nursing woman. Pediatric Use Safety and effectiveness of this product for use in infants less than 1 month of age have not been established. Geriatric Use Of the 3703 patients in clinical studies of cefaclor, 594 (16.0%) were 65 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. 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. This drug is known to be substantially excreted by the kidney (see CLINICAL PHARMACOLOGY ), and the risk of toxic 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 in monitor renal function (see DOSAGE AND ADMINISTRATION ).

Adverse effects considered to be related to therapy with cefaclor are listed below: Hypersensitivity reactions have been reported in about 1.5% of patients and include morbilliform eruptions (1 in 100). Pruritus, urticaria, and positive Coombs' tests each occur in less than 1 in 200 patients. Cases of serum-sickness-like reactions have been reported with the use of cefaclor. These are characterized by findings of erythema multiforme, rashes, and other skin manifestations accompanied by arthritis/arthralgia, with or without fever, and differ from classic serum sickness in that there is infrequently associated lymphadenopathy and proteinuria, no circulating immune complexes, and no evidence to date of sequelae of the reaction. Occasionally, solitary symptoms may occur, but do not represent a serum-sickness-like reaction. While further investigation is ongoing, serum-sickness-like reactions appear to be due to hypersensitivity and more often occur during or following a second (or subsequent) course of therapy with cefaclor. Such reactions have been reported more frequently in pediatric patients than in adults with an overall occurrence ranging from 1 in 200 (0.5%) in one focused trial to 2 in 8,346 (0.024%) in overall clinical trials (with an incidence in pediatric patients in clinical trials of 0.055%) to 1 in 38,000 (0.003%) in spontaneous event reports. Signs and symptoms usually occur a few days after initiation of therapy and subside within a few days after cessation of therapy; occasionally these reactions have resulted in hospitalization, usually of short duration (median hospitalization = 2 to 3 days, based on postmarketing surveillance studies). In those requiring hospitalization, the symptoms have ranged from mild to severe at the time of admission with more of the severe reactions occurring in pediatric patients. Antihistamines and glucocorticoids appear to enhance resolution of the signs and symptoms. No serious sequelae have been reported. More severe hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and anaphylaxis have been reported rarely. Anaphylactoid events may be manifested by solitary symptoms, including angioedema, asthenia, edema (including face and limbs), dyspnea, paresthesias, syncope, hypotension, or vasodilatation. Anaphylaxis may be more common in patients with a history of penicillin allergy. Rarely, hypersensitivity symptoms may persist for several months. Gastrointestinal symptoms occur in about 2.5% of patients and include diarrhea (1 in 70). Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. (see WARNINGS ). Nausea and vomiting have been reported rarely. As with some penicillins and some other cephalosporins, transient hepatitis and cholestatic jaundice have been reported rarely. Other effects considered related to therapy included eosinophilia (1 in 50 patients), genital pruritus, moniliasis or vaginitis (about 1 in 50 patients), and, rarely, thrombocytopenia or reversible interstitial nephritis. Causal Relationship Uncertain – CNS ─ Rarely, reversible hyperactivity, agitation, nervousness, insomnia, confusion, hypertonia, dizziness, hallucinations, and somnolence have been reported. Transitory abnormalities in clinical laboratory test results have been reported. Although they were of uncertain etiology, they are listed below to serve as alerting information for the physician. Hepatic ─ Slight elevations of AST, ALT, or alkaline phosphatase values (1 in 40). Hematopoietic ─ As has also been reported with other β-lactam antibiotics, transient lymphocytosis, leukopenia, and, rarely, hemolytic anemia, aplastic anemia, agranulocytosis, and reversible neutropenia of possible clinical significance. There have been rare reports of increased prothrombin time with or without clinical bleeding in patients receiving cefaclor and Coumadin ® concomitantly. Renal ─ Slight elevations in BUN or serum creatinine (less than 1 in 500) or abnormal urinalysis (less than 1 in 200). Cephalosporin-class Adverse Reactions In addition to the adverse reactions listed above that have been observed in patients treated with cefaclor, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics: fever, abdominal pain, superinfection, renal dysfunction, toxic nephropathy, hemorrhage, false positive test for urinary glucose, elevated bilirubin, elevated LDH, and pancytopenia. Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated (see DOSAGE AND ADMINISTRATION and OVERDOSAGE sections).

─ Teratogenic Effects ─ Pregnancy Category B Reproduction studies have been performed in mice and rats at doses up to 12 times the human dose and in ferrets given 3 times the maximum human dose and have revealed no harm to the fetus due to cefaclor. 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.

Small amounts of cefaclor have been detected in mother's milk following administration of single 500-mg doses. Average levels were 0.18, 0.20, 0.21, and 0.16 mcg/mL at 2, 3, 4, and 5 hours respectively. Trace amounts were detected at 1 hour. The effect on nursing infants is not known. Caution should be exercised when cefaclor is administered to a nursing woman.

Safety and effectiveness of this product for use in infants less than 1 month of age have not been established.

Of the 3703 patients in clinical studies of cefaclor, 594 (16.0%) were 65 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. 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. This drug is known to be substantially excreted by the kidney (see CLINICAL PHARMACOLOGY ), and the risk of toxic 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 in monitor renal function (see DOSAGE AND ADMINISTRATION ).