Cefaclor (Cefaclor) , USP, the active ingredient in Cefaclor (Cefaclor) extended-release tablets USP, is a semisynthetic cephalosporin antibiotic for oral administration. Cefaclor (Cefaclor) , USP, is chemically designated as 3-chloro-7-D-(2-phenylglycinamido)-3-cephem-4-carboxylic acid monohydrate. The Cefaclor (Cefaclor) extended-release tablets formulation of Cefaclor (Cefaclor) differs pharmacokinetically from the immediate-release formulation of Cefaclor (Cefaclor) .

Each Cefaclor (Cefaclor) extended-release tablet contains Cefaclor (Cefaclor) monohydrate equivalent to 500 mg (1.36 mmol) anhydrous Cefaclor (Cefaclor) . In addition, each extended-release tablet contains the following inactive ingredients: FD&C Blue #2 - indigo carmine lake, hypromellose, magnesium stearate, mannitol, polyethylene glycol, povidone and titanium dioxide.

The Cefaclor (Cefaclor) extended-release tablet formulation of Cefaclor (Cefaclor) is pharmacokinetically different from the Cefaclor (Cefaclor) immediate-release capsule formulation of Cefaclor (Cefaclor) . (See TABLE 1.) No direct comparisons with the suspension formulation of Cefaclor (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.

Absorption and Metabolism

The extent of absorption (AUC) and the maximum plasma concentration (Cmax) of Cefaclor (Cefaclor) from Cefaclor (Cefaclor) extended-release tablets are greater when the extended-release tablet is taken with food.

[NOTE: The extent of absorption (AUC) of Cefaclor (Cefaclor) from Cefaclor (Cefaclor) immediate-release capsules is unaffected by food intake; however, when Cefaclor (Cefaclor) immediate-release capsules are taken with food, the C is decreased.]

There is no evidence of metabolism of Cefaclor (Cefaclor) in humans.

Comparative Serum Pharmacokinetics

Serum pharmacokinetic parameters for Cefaclor (Cefaclor) extended-release tablets and Cefaclor (Cefaclor) immediate-release capsules are shown in the table below.

No drug accumulation was noted when Cefaclor (Cefaclor) extended-release tablets were given twice daily.

The plasma half-life in healthy subjects is independent of dosage form and averages approximately 1 hour.

Food Effect on Pharmacokinetics

When Cefaclor (Cefaclor) extended-release tablets are taken with food, the AUC is 10% lower while the C is 12% lower and occurs 1 hour later compared to Cefaclor (Cefaclor) immediate-release capsules. In contrast, when Cefaclor (Cefaclor) extended-release tablets are taken without food, the AUC is 23% lower while the C is 67% lower and occurs 0.6 hours later, using an equivalent milligram dose of Cefaclor (Cefaclor) immediate-release capsules as a reference.

Renal Insufficiency

In patients with reduced renal function, the serum half-life of Cefaclor (Cefaclor) is slightly prolonged. In those with complete absence of renal function, the plasma half-life of the intact molecule is 2.3 to 2.8 hours. Excretion pathways in patients with markedly impaired renal function have not been determined. Hemodialysis shortens the half-life by 25% to 30%.

Geriatric Patients

In elderly subjects (over age 65) with normal serum creatinine values, higher peak plasma concentrations and AUCs have been observed. This is considered to be primarily a result of an age-related decrement in renal function, and has no apparent clinical significance. Therefore, dosage adjustment is not necessary in elderly subjects with normal serum creatinine values.

Cefaclor (Cefaclor) has activity against a broad range of gram-positive and gram-negative bacteria. The bactericidal action of Cefaclor (Cefaclor) results from inhibition of cell-wall synthesis. Cefaclor (Cefaclor) is stable in the presence of some bacterial ß-lactamases; consequently, some ß-lactamase-producing organisms may be susceptible to Cefaclor (Cefaclor) .

Cefaclor (Cefaclor) extended-release tablets have been shown to be active against most strains of the following microorganisms both and in clinical infections as described in the section.

Gram-positive aerobes:

Gram-negative aerobes:

The following data are available, . Cefaclor (Cefaclor) exhibits minimum inhibitory concentrations (MICs) of 8 mcg/mL or less (systemic susceptibility breakpoint) against most (≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of Cefaclor (Cefaclor) extended-release tablets in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.

Gram-positive aerobes:

Gram-negative aerobes:

Anaerobic bacteria:

Dilution Techniques

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method1 (broth, agar, or microdilution) or equivalent with standardized inoculum concentrations and standardized amounts of Cefaclor (Cefaclor) powder. The MIC values should be interpreted according to the following criteria:

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in blood reaches the concentrations usually achievable. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard Cefaclor (Cefaclor) powder should provide the following MIC values:

Diffusion Techniques Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30 mcg Cefaclor (Cefaclor) to test the susceptibility of microorganisms to Cefaclor (Cefaclor) .

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30 mcg Cefaclor (Cefaclor) disk should be interpreted according to the following criteria:

When testing* , the following interpretive criteria should be used:

*Disk susceptibility tests performed using Haemophilus Test Medium (HTM)

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for Cefaclor (Cefaclor) .

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30 mcg Cefaclor (Cefaclor) disk should provide the following zone diameters in these laboratory test quality control strains:

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefaclor (Cefaclor) extended-release tablets USP and other antibacterial drugs, Cefaclor (Cefaclor) extended-release tablets USP 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 (Cefaclor) extended-release tablets are contraindicated in patients with known hypersensitivity to Cefaclor (Cefaclor) and other cephalosporins.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of and surgical evaluation should be instituted as clinically indicated.

Prescribing Cefaclor (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.

There were 3272 patients treated with multiple doses of Cefaclor (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 (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 (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 2 and 3).

Adverse reactions occurring during the clinical trials with Cefaclor (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.

In addition to the events reported during clinical trials with Cefaclor (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.

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

Clinical

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, edema (including face and limbs), paresthesias, syncope, or vasodilatation. Anaphylaxis may be more common in patients with a history of penicillin allergy. Rarely, hypersensitivity symptoms may persist for several months.

Symptoms of pseudomembranous colitis may appear either during or after antibiotic treatment. (See .)

Laboratory

Abnormal urinalysis, eosinophilia, leukopenia, neutropenia, transient elevations in AST, and transient thrombocytopenia have been reported.

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

Clinical

Confusion, erythema multiforme, genital pruritus, hepatic dysfunction including cholestasis, hemolytic anemia, reversible hyperactivity, hypertonia, and reversible interstitial nephritis.

Laboratory

Positive direct Coombs’ test.

The toxic symptoms following an overdose of Cefaclor (Cefaclor) may include nausea, vomiting, epigastric distress, and diarrhea. The severity of the epigastric distress and the diarrhea are dose-related.

Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage. Consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed.

Although Cefaclor (Cefaclor) is considered dialyzable, neither forced diuresis, peritoneal dialysis, hemodialysis, nor charcoal hemoperfusion have been demonstrated to be beneficial in an overdose of Cefaclor (Cefaclor) .

The absorption of Cefaclor (Cefaclor) extended-release tablets is enhanced when it is administered with food. (See .) Therefore, . The extended-release tablets should not be cut, crushed, or chewed.

See for information about patients for whom Cefaclor (Cefaclor) extended-release tablets are indicated.

Adults (age 16 years and older):

Elderly patients with normal renal function do not require dosage adjustments.

Cefaclor (Cefaclor) extended-release tablets USP, 500 mg (based on the anhydrous), are available as film-coated, oval-shaped, unscored, dark blue tablets, debossed with “93” on one side and “1087” on the other side. They are available in bottles of 100 (NDC 49884-080-01).

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

In adequate and well-controlled clinical trials of Cefaclor (Cefaclor) extended-release tablets in the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB) and secondary bacterial infections of acute bronchitis (SBIAB), only 4 evaluable patients with ABECB and no evaluable patients with SBIAB had infections caused by ß-lactamase-producing . Four patients do not provide adequate data upon which to judge clinical efficacy of Cefaclor (Cefaclor) extended-release tablets against ß-lactamase-producing .

Cefaclor (Cefaclor) extended-release tablets (375 mg Q12H) (n = 115) were compared to Cefaclor (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:

Manufactured By:

Sellersville, PA 18960

Manufactured For:

Spring Valley, NY 10977