Cefaclor Extended Release Tablets: Package Insert / Prescribing Info

Pharmacokinetics

The cefaclor extended-release tablet formulation of cefaclor is pharmacokinetically different from the cefaclor immediate-release capsule formulation of cefaclor. (See TABLE 1.) No direct comparisons with the suspension formulation of cefaclor have been conducted; therefore, there are no data with which to compare the pharmacokinetic properties of the extended-release tablet formulation and the suspension formulation. Until further data are available, the pharmacokinetic equivalence of the extended-release tablet and the suspension formulations should NOT be assumed.

Special Populations

Microbiology

Mechanism of Action

As with other cephalosporins, the bactericidal action of cefaclor results from inhibition of cell-wall synthesis.

Mechanism of Resistance

Resistance to cefaclor is primarily through hydrolysis of ß-lactamases alteration of penicillin-binding proteins (PBPs) and decreased permeability. Pseudomonas spp., Acinetobacter calcoaceticus and most isolates of Enterococci (Enterococcus faecalis, group D streptococci), Enterobacter spp., indole-positive Proteus, Morganella morganii (formerly Proteus morganii), Providencia rettgeri (formerly Proteus rettgeri) and Serratia spp. are resistant to cefaclor. Cefaclor is inactive against methicillin-resistant staphylococci, ß-lactamase-negative, ampicillin-resistant isolates of H. influenzae should be considered resistant to cefaclor despite apparent in vitro susceptibility to this agent.

List of Microorganisms

Cefaclor has been shown to be active against most isolates of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Gram-positive Bacteria

Staphylococcus aureus (methicillin susceptible only)

Streptococcus pneumoniae

Streptococcus pyogenes

Gram-negative Bacteria

Haemophilus influenzae (excluding β-lactamase-negative, ampicillin-resistant isolates)

Moraxella catarrhalis

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit in vitro minimum inhibitory concentrations (MICs) less than or equal to the susceptible breakpoint for cefaclor against isolates of similar genus or organism group. However, the efficacy of cefaclor in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled trials.

Gram-positive Bacteria

Staphylococcus epidermidis (methicillin susceptible only)

Gram-negative Bacteria

Haemophilus parainfluenzae

Klebsiella pneumoniae

Anaerobic Bacteria

Peptococcus niger

Peptostreptococci

Propionibacterium acnes

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

General

Prescribing cefaclor extended-release tablets USP 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.

Superinfection (overgrowth by non-susceptible organisms) should always be considered a possibility in a patient being treated with a broad spectrum antimicrobial. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Information for Patients

Patients should be counseled that antibacterial drugs including cefaclor extended-release tablets USP should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cefaclor extended-release tablets USP are 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 extended-release tablets USP or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Drug Interactions

Laboratory Test Interactions

Administration of cefaclor extended-release tablets may result in a false-positive reaction for glucose in the urine. This phenomenon has been seen in patients taking cephalosporin antibiotics when the test is performed using Benedict's and Fehling's solutions and also with Clinitest® tablets.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies in animals have not been performed to evaluate the carcinogenic or mutagenic potential for cefaclor. Reproduction studies have revealed no evidence of impaired fertility.

Usage in Pregnancy

Labor and Delivery

Cefaclor extended-release tablets have not been studied for use during labor and delivery. Treatment should be given only if clearly needed.

Nursing Mothers

No studies in lactating women have been performed with cefaclor extended-release tablets. Small amounts of cefaclor (≤ 0.21 mcg/mL) have been detected in human milk following administration of single 500 mg doses of cefaclor extended-release tablets. The effect on nursing infants is not known. Caution should be exercised when cefaclor extended-release tablets are administered to a nursing woman.

Pediatric Use

Safety and effectiveness of cefaclor extended-release tablets in pediatric patients less than 16 years of age have not been established.

Geriatric Use

Of the 3272 patients in clinical studies of cefaclor extended-release tablets, 608 (18.2%) were 65 and older. No overall differences in safety or effectiveness were observed between these and younger patients. 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 to monitor renal function (see DOSAGE AND ADMINISTRATION).

Clinical Trials

There were 3272 patients treated with multiple doses of cefaclor extended-release tablets in controlled clinical trials and an additional 211 subjects in pharmacology studies. There were no deaths in these trials thought to be related to toxicity from cefaclor extended-release tablets. Treatment was discontinued in 1.7% of patients due to adverse events thought to be possibly or probably drug-related.

The following adverse clinical and laboratory events were reported during the cefaclor extended-release tablets clinical trials conducted in North America at doses of 375 mg or 500 mg BID; however, relatedness of the adverse events to the drug was not assigned by clinical investigators during the trials (see TABLES 4 and 5).

Adverse reactions occurring during the clinical trials with cefaclor extended-release tablets with an incidence of less than 1% but greater than 0.1% included the following (listed alphabetically):

Accidental injury, anorexia, anxiety, arthralgia, asthma, bronchitis, chest pain, chills, congestive heart failure, conjunctivitis, constipation, dizziness, dysmenorrhea, dyspepsia, dysuria, ear pain, edema, fever, flatulence, flu syndrome, gastritis, infection, insomnia, leukorrhea, lung disorder, maculopapular rash, malaise, menstrual disorder, myalgia, nausea and vomiting, neck pain, nervousness, nocturia, otitis media, pain, palpitation, peripheral edema, rash, respiratory disorder, sinusitis, somnolence, surgical procedure, sweating, tremor, urticaria, vomiting.

NOTE: One case of serum-sickness-like reaction was reported among the 3272 adult patients treated with cefaclor extended-release tablets during the controlled clinical trials. These reactions have also been reported with the use of cefaclor in other oral formulations and are seen more frequently in pediatric patients than in adults. These reactions are characterized by findings of erythema multiforme, rash, 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. 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 with overall occurrence ranging from 1 in 200 (0.5%) in one focused trial; to 2 in 8346 (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 patients 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.

In Postmarketing Experience

In addition to the events reported during clinical trials with cefaclor extended-release tablets, the following adverse experiences are among those that have been reported during worldwide postmarketing surveillance: allergic reaction, anaphylactoid reaction, angioedema, face edema, hypotension, Stevens-Johnson syndrome, syncope, paresthesia, vasodilatation and vertigo.

Other Adverse Reactions Associated With Other Formulations of Cefaclor

In addition to the above, the following other adverse reactions and altered laboratory tests have been associated with cefaclor in other oral formulations:

Cephalosporin-Class Reactions

In addition to the adverse reactions listed above, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics:

ACUTE BACTERIAL EXACERBATIONS OF CHRONIC BRONCHITIS

In adequate and well-controlled clinical trials of cefaclor extended-release tablets in the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB), only 4 evaluable patients with ABECB had infections caused by ß-lactamase-producing H. influenzae. Four patients do not provide adequate data upon which to judge clinical efficacy of cefaclor extended-release tablets against ß-lactamase-producing H. influenzae.

UNCOMPLICATED SKIN AND SKIN STRUCTURE INFECTIONS

Cefaclor extended-release tablets (375 mg Q12H) (n = 115) were compared to cefaclor immediate-release capsules (250 mg TID) (n = 106) for the treatment of patients with uncomplicated skin and skin structure infections, including cellulitis, pyoderma, abscess and impetigo. Patients were treated for 7 to 10 days and were evaluated for clinical resolution and bacterial eradication approximately one week after completing therapy. To be evaluable, all patients had to have a recognized pathogen isolated from the skin infection just prior to the initiation of therapy. The results of this randomized, double-blinded, U.S. trial demonstrated:

1. overall clinical cure rates were 72% (83 of 115 patients) and 75% (80 of 106 patients), respectively, for cefaclor extended-release tablets and cefaclor immediate-release capsules [95% CI around the 3% difference = -16% to +9%],
2. overall bacteriologic eradication rates against Staphylococcus aureus were comparable (see TABLE 6).

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Teva Pharmaceuticals USA, Inc.

North Wales, PA 19454

Rev. N 7/2019