COMPOSITION: Each tablet contains cefaclor monohydrate equivalent to 500 mg Cefaclor.
PHARMACOLOGICAL CLASSIFICATION: A 20.1.1 Broad and medium spectrum antibiotics.
PHARMACOLOGICAL ACTION: Cefaclor is bactericidal and has a broad range of antimicrobial activity against certain Gram-positive and Gram-negative micro-organisms. MICROBIOLOGY: In-vitro tests demonstrate that the bactericidal activity of Cephalosporins results from inhibition of cell wall synthesis.
Cefaclor is active in-vitro against the following organisms:
(Note: in-vitro sensitivity does not necessarily imply in-vivo efficacy.)
Strains of staphylococci including coagulase positive, coagulase negative and penicillinase producing strains, are moderately sensitive.
Streptococcus pyrogenes (Group A ß-haemolytic streptococci).
Haemophilis influenzae, including ampicillin-resistant strains.
Moraxella (Branhamella) catarrhalis. Note: Cefaclor has no activity against Pseudomonas species, enterococci (E. faecalis), Enterobacter sp., indole-positive Proteus and Serratia.
Some strains of staphylococci are resistant to Cefaclor. HUMAN PHARMACOLOGY: Cefaclor is absorbed from the gastro-intestinal tract with oral doses of 250 and 500 mg producing peak plasma concentrations of about 6 and 13 µg per mL respectively at 0,5 to 1 hour. The presence of food in the gut may delay the absorption of cefaclor, but will not affect the total amount of cefaclor absorbed. A plasma half-life of 0,5 to 1 hour has been reported; this may be slightly prolonged in renal failure. About 25% is bound to plasma proteins.
Cefaclor appears to be widely distributed in the body; it crosses the placenta and is excreted in low concentrations in breast milk. It is rapidly excreted by the kidneys; approximately 60% of a dose appears unchanged in the urine within 8 hours, the greater part within 2 hours.
Peak concentrations of cefaclor are achieved in the urine within 8 hours of a dose; peak concentrations of 600 and 900 µg per mL have been reported after doses of 250 and 500 mg respectively.
Probenecid delays excretion.
Some cefaclor is removed by haemodialysis.
INDICATIONS: Cefaclor is indicated in the treatment of the following infections due to susceptible micro-organisms:
Pneumonia, bronchitis, acute exacerbations of chronic bronchitis, streptococcal pharyngitis and tonsillitis.
Skin and soft tissue infections.
Urinary tract infections, including pyelonephritis and cystitis. Note: Appropriate culture and susceptibility studies should be performed to determine susceptibility of the causative organism to cefaclor.
CONTRA-INDICATIONS: Cefaclor is contra-indicated in patients with known hypersensitivity to the cephalosporin group of antibiotics. Cefaclor should not be used in critically ill patients because parenteral antibiotic therapy is more appropriate in these patients.
Safety and efficacy of cefaclor for use in children less than 1 month of age have not been established. The safety of the use of cefaclor during pregnancy has not been established. Cephalosporins are considered to be unsafe for use in patients with acute porphyria.
WARNINGS: Cefaclor should not be given to patients who are hypersensitive to it or to other cephalosporins. About 10% of penicillin-sensitive patients may also be allergic to cephalosporins, great care should therefore be taken before cefaclor is given to such patients. Care is also necessary in patients with known histories of allergy.
If any allergic reaction occurs, the medication should be discontinued and the patient treated with appropriate agents, eg, adrenaline, corticosteroids, aminophylline and antihistamines.
Efficacy of cefaclor in the prophylaxis of rheumatic fever has not been established.
DOSAGE AND DIRECTIONS FOR USE: The adult dosage is 250 mg every eight hours.
For more severe infections, such as pneumonia, or those caused by less susceptible organisms, the dosage may be doubled.
In the treatment of ß-haemolytic streptococcal infections, a therapeutic dosage of cefaclor should be administered for at least 10 days.
Dosage recommendations in the presence of impaired renal function:
Creatinine clearance (mL/min/1,73 m²)
24 hour dose
40 to 10
50% of usual 24 hour dose
25% of usual 24 hour dose
SIDE EFFECTS AND SPECIAL PRECAUTIONS: The most common adverse effects experienced are gastro-intestinal disturbances, eg, nausea, vomiting and diarrhoea, and hypersensitivity reactions including skin rash, urticaria, eosinophilia, fever, reactions resembling serum-sickness and anaphylaxis.
Serum sickness like reactions (erythema multiforme, rashes or skin manifestations accompanied by arthritis, arthralgia and frequently fever) have been reported.
These reactions are apparently due to hypersensitivity and usually occur after or during a second course of cefaclor therapy.
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 subside within a few days after cessation of therapy. Antihistamines and corticosteroids may enhance the resolution of the syndrome.
Pseudomembranous colitis has been reported.
It is important to consider the diagnosis of pseudomembranous colitis in patients who develop diarrhoea. Such colitis may be life-threatening.
Appropriate measures should be taken and include immediate discontinuation of treatment with cefaclor.
Neutropenia and thrombocytopenia have less frequently been reported.
Agranulocytosis has been associated less frequently with some cephalosporins.
Since cefaclor is eliminated primarily by the kidneys, it should be administered with caution to older patients or those with pre-existing renal impairment, or with the concomitant administration of nephrotoxic medicine such as aminoglycoside antibiotics. Acute interstitial nephritis is also a possibility as a manifestation of hypersensitivity.
Transient increases in liver enzyme values have been reported.
Positive direct Coombs' tests have been reported and these can interfere with blood cross-matching. The urine of patients being treated with cefaclor may give false-positive reactions for glucose using copper-reduction reactions.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT: The symptoms of overdosage are in general toxic gastro-intestinal adverse effects, with the severity of symptoms being dose related.
Treatment of overdosage would be symptomatic and supportive.
CEC 500 tablets are film-coated, ochre yellow, oblong and biconvex with facet and score notches on both sides.
CEC 500 tablets are supplied in PP securitainers containing 15 tablets.
STORAGE INSTRUCTIONS: Store below 30°C.
KEEP OUT OF REACH OF CHILDREN
REGISTRATION NUMBERS: 30/20.1.1/0114
NAME AND ADDRESS OF THE APPLICANT: HEXAL PHARMA (SA) (PTY) LTD
10 FANGIO ROAD
DATE OF PUBLICATION OF THIS PACKAGE INSERT: February 1997.