Cefaclor

Cefaclor is indicated for the treatment of infections caused by sensitive microorganisms. These are infections of the respiratory tract which include pneumonia, bronchitis (including deteriorations in chronic bronchitis), tonsillitis, pharyngitis and the management of sinusitis.

Cefaclor is also effective in otitis media. It is active in acute and chronic urinary tract infections including cystitis and pyelonephritis and also in infections of the skin and soft tissues. Cefaclor may also be used in the eradication of nasopharyngeal streptococci but resulting prevention of rheumatic fever and/or bacterial endocarditis has not been proven.

The following microorganisms are susceptible in vitro to cefaclor: - Alpha and beta-haemolytic streptococci - Staphylococci (including coagulase-negative, coagulase-positive and penicillinase- producing strains) - Strep. pneumoniae - Strep.

pyogenes (group A beta-haemolytic streptococci) - Branhamella catarrhalis - E. ccli - Proteus mirabilis - Klebsiella spp. , Morganella morganii, Proteus vulgaris and Providencia rettgeri. Methicillin-resistant staphylococci and most strains of enterococci including Strep.

faecalis are resistant to cefaclor.

Posology Adults and the elderly:

The usual dosage is 250mg every eight hours, may be doubled to 500mg every eight hours for more severe infections or those caused by less susceptible organisms. Doses of 4g per day have been administered safely to normal subjects for 28 days, but the total daily dosage should not exceed this amount.

Cefaclor may be administered in the presence of impaired renal function. 4).

Patients undergoing haemodialysis:

Haemodialysis shortens serum half-life by 25-30%. In patients undergoing regular haemodialysis, a loading dose of 250mg-1g administered prior to dialysis and a therapeutic dose of 250-500mg every six to eight hours maintained during interdialytic periods is recommended.

Paediatric population The usual recommended daily dosage for children is 20mg/kg/day in divided doses every eight hours, as indicated. For bronchitis and pneumonia, the dosage is 20mg/kg/day in divided doses administered 3 times daily.

For otitis media and pharyngitis, the total daily dosage may be divided and administered every twelve hours. Safety and efficacy have not been established for use in infants aged less than one month. 0mg In more serious infections, otitis media, sinusitis and infections caused by less susceptible organisms, 40mg/kg/day in divided doses is recommended, up to a daily maximum of 1g.

In infections caused by beta-haemolytic streptococci, treatment should be continued for at least 10 days. Method of administration Cefaclor is administered orally.

Gastro-intestinal:

The most frequent side-effect has been diarrhoea. It is rarely severe enough to warrant cessation of therapy. Colitis, including rare instances of pseudomembranous colitis, has been reported. Nausea and vomiting have also occurred.

Hypersensitivity:

Allergic reactions such as morbilliform eruptions, pruritus and urticaria have been observed. These reactions usually subside upon discontinuation of therapy. Serum sickness-like reactions (erythema multiforme minor, rashes or other skin manifestations accompanied by arthritis/arthralgia, with or without fever) have been reported.

Lymphadenopathy and proteinuria are infrequent, there are no circulating immune complexes and no evidence of sequelae. Occasionally, solitary symptoms may occur, but do not represent a serum sickness-like reaction. Serum sickness-like reactions are apparently due to hypersensitivity and have usually occurred during or following a second (or subsequent) course of therapy with cefaclor.

Such reactions have been reported more frequently in children than in adults. Signs and symptoms usually occur a few days after initiation of therapy and usually subside within a few days of cessation of therapy. Antihistamines and corticosteroids appear to enhance resolution of the syndrome.

No serious sequelae have been reported. There are rare reports of erythema multiforme major (Stevens-Johnson syndrome), toxic epidermal necrolysis, and anaphylaxis. Anaphylaxis may be more common in patients with a history of penicillin allergy.

Anaphylactoid events may present as solitary symptoms, including angioedema, asthenia, oedema (including face and limbs), dyspnoea, paraesthesias, syncope, or vasodilatation. Rarely, hypersensitivity symptoms may persist for several months.

Haematological:

Eosinophilia, positive Coombs’ tests and, rarely, thrombocytopenia. 5).

Hepatic:

Transient hepatitis and cholestatic jaundice have been reported rarely, slight elevations in AST, ALT or alkaline phosphatase values.

Renal:

Reversible interstitial nephritis has occurred rarely, also slight elevations in blood urea or serum creatinine or abnormal urinalysis.

Central Nervous System:

Reversible hyperactivity, agitation, nervousness, insomnia, confusion, hypertonia, dizziness, hallucinations and somnolence have been reported rarely.

Miscellaneous:

Genital pruritus, vaginitis and vaginal moniliasis. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continues monitoring of the benefit/risk balance of the medicinal product.

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1. Hypersensitivity to other cephalosporins.

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefaclor extended-release tablets USP and other antibacterial drugs, 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.

The safety and effectiveness of cefaclor extended-release tablets in treating some of the indications and pathogens for which other formulations of cefaclor are approved have NOT been established. When administered at the recommended dosages and durations of therapy, cefaclor extended-release tablets are indicated for the treatment of patients with the following mild to moderate infections when caused by susceptible strains of the designated organisms.

) Acute bacterial exacerbations of chronic bronchitis due to Haemophilus influenzae (excluding ß-lactamase-negative, ampicillin-resistant isolates), Moraxella catarrhalis, or Streptococcus pneumoniae .

NOTE:

In view of the insufficient numbers of isolates of ß-lactamase-producing isolates of Haemophilus influenzae that were obtained from clinical trials with cefaclor extended-release tablets for patients with acute bacterial exacerbations of chronic bronchitis, it was not possible to adequately evaluate the effectiveness of cefaclor extended-release tablets for bronchitis known, suspected, or considered potentially to be caused by ß-lactamase-producing H.

influenzae . Pharyngitis and tonsillitis due to Streptococcus pyogenes .

NOTE:

Only penicillin by the intramuscular route of administration has been shown to be effective in the prophylaxis of rheumatic fever. Cefaclor extended-release tablets are generally effective in the eradication of S. pyogenes from the oropharynx; however, data establishing the efficacy of cefaclor extended-release tablets for the prophylaxis of subsequent rheumatic fever are not available.

Uncomplicated skin and skin and structure infections due to Staphylococcus aureus (methicillin-susceptible only).

NOTE:

In view of the insufficient numbers of isolates of Streptococcus pyogenes that were obtained from clinical trials with cefaclor extended-release tablets for patients with uncomplicated skin and skin structure infections, it was not possible to adequately evaluate the effectiveness of cefaclor extended-release tablets for skin infections known, suspected, or considered potentially to be caused by S.

pyogenes .

DOSAGE AND ADMINISTRATION

The absorption of cefaclor extended-release tablets is enhanced when it is administered with food. , at least within one hour of eating) . The extended-release tablets should not be cut, crushed, or chewed. See INDICATIONS AND USAGE for information about patients for whom cefaclor extended-release tablets are indicated.

NOTE: 500 mg BID of cefaclor extended-release tablets is clinically equivalent to 250 mg TID of cefaclor immediate-release as a capsule in those indications listed in the INDICATIONS AND USAGE section of this label. 500 mg BID of cefaclor extended-release tablets is NOT equivalent to 500 mg TID of other cefaclor formulations.

Adults (age 16 years and older):

Type of Infection (as qualified in the INDICATIONS AND USAGE section of this labeling) Total Daily Dose Dose and Frequency Duration Acute Bacterial Exacerbations of Chronic Bronchitis due to H. influenzae (non-ß-lactamase-producing strains only).

) 1000 mg 500 mg q 12 hours 7 days Pharyngitis and/or tonsillitis due to S. pyogenes 750 mg 375 mg q 12 hours 10 days Uncomplicated Skin and Skin Structure Infections due to S. ) 750 mg 375 mg q 12 hours 7 to 10 days Elderly patients with normal renal function do not require dosage adjustments.

ADVERSE REACTIONS

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.

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 ).

4% Vaginitis n = 934 for these events (subset of female participants). 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. 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. 4% 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: 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. ) Laboratory Abnormal urinalysis, eosinophilia, leukopenia, neutropenia, transient elevations in AST, and transient thrombocytopenia have been reported.

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

Laboratory Positive direct Coombs’ test.

CONTRAINDICATIONS

Cefaclor extended-release tablets are contraindicated in patients with known hypersensitivity to cefaclor and other cephalosporins.