INFORMATION FOR HEALTH PROFESSIONALS
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Capsule 250 mg: Purple/white size 2 gelatine capsule imprinted with "CEFACLOR 250' on both the cap and body of the capsule.
Oral suspension 125 mg/5 ml: White to off-white granular powder which upon reconstitution with water forms a red strawberry flavoured suspension with a sweet taste.
In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell-wall synthesis.
Cefaclor is usually active against the following organisms in vitro and in clinical infections:
Staphylococci, including penicillinase-producing, coagulase-positive and coagulase-negative strains, Streptococcus pyogenes (Group A beta-haemolytic streptococci); Streptococcus pneumoniae; Escherichia coli; Proteus mirabilis; Klebsiella sp.: Haemophilus influenzae, including post beta-lactamase-producing ampicillin-resistant strains; Neisseria gonorrhoeae (penicillinase-producing and non-penicillinase-producing strains), Propionibacteria acnes and Bacteroides sp. (excluding Bacteroides fragilis); Moraxella (Branhamella) catarrhalis, Citrobacter diversus; Corynebacterium; Peptococcus sp.; Peptostreptococcus sp.
Note: Pseudomonas sp., Acinetobacter calcoaceticus, and most strains of enterococci (S. faecalis, Group D streptococci), Enterobacter sp., indole-positive Proteus, and Serratia sp. are resistant to cefaclor. When tested by in vitro methods, staphylococci exhibit cross-resistance between cefaclor and methicillin-type antibiotics.
Cefaclor is well absorbed after oral administration, whether taken with food or while fasting; however, when it is taken with food, the peak concentration achieved is 50-75 % of that observed when the medicine is administered to fasting subjects and generally appears from 45 to 60 minutes later. The presence of food in the gastrointestinal tract does not alter the total amount of cefaclor absorbed. Following doses of 250 mg, 500 mg, and 1 g, to fasting subjects average peak serum levels of approximately 7, l3, and 23 μg/ ml, respectively, were obtained at 30 to 60 minutes.
About 25 % of cefaclor is bound to plasma proteins. Cefaclor is widely distributed in the body with bactericidal concentrations achieved in middle ear fluid, sinus drainage and bronchial secretions. The drug crosses the placenta and is excreted in very low concentrations in breast milk.
Approximately 60-85 % of the medicine is excreted unchanged in the urine within 8 hours, the greater portion being excreted within the first 2 hours. During this 8-hour period, peak urine concentrations following the 250 mg, 500 mg and 1 g doses were approximately 600, 900 and 1900 μg/ml, respectively.
The serum half-life in normal subjects is 0.6 to 0.9 hour. In patients with reduced renal function, the serum half-life of cefaclor is slightly prolonged. In those with complete absence of renal function, the biologic 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. Haemodialysis shortens the half-life by 25-30 %.
Cefaclor is indicated in the treatment of the following infections when caused by susceptible strains of the designated micro-organisms:
Lower respiratory infections, including pneumonia caused by S. pneumoniae, H. influenzae (including both ampicillin-sensitive and ampicillin-resistant strains), and S. pyogenes (Group A beta- haemolytic streptococci), M.catarrhalis, acute bronchitis, and acute exacerbations of chronic bronchitis.
Upper respiratory infections, including pharyngitis and tonsillitis caused by S. pyogenes (Group A beta-haemolytic streptococci) and M. catarrhalis.
Note: Penicillin is the usual medicine of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. Amoxicillin has been recommended by The American Heart Association as the standard regimen for the prophylaxis of bacterial endocarditis for dental, oral, and upper respiratory tract procedures, with Penicillin V a rational and acceptable alternative in the prophylaxis against α-haemolytic streptococcal bacteriaemia in this setting. 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 or bacterial endocarditis are not available at present.
Otitis media caused by S. pneumoniae, H. influenzae (including both ampicillin-sensitive and ampicillin-resistant strains) staphylococci, and S. pyogenes (Group A beta-haemolytic streptococci), and M. catarrhalis.
Skin and soft-tissue infections caused by Staphylococcus aureus (including β-lactamase producing strains), S. pyogenes (Group A beta-haemolytic streptococci) and Staphylococcus epidermidis (including β-lactamase producing strains).
Urinary tract infections, including pyelonephritis and cystitis caused by E. coli, P, mirabilis, Klebsiella sp., and coagulase-negative staphylococci.
Note: Cefaclor has been found to be effective in both acute and chronic urinary tract infectious; sinusitis; gonococcal urethritis.
Bacteriological studies to determine the causative organism and its susceptibility to cefaclor should be performed. Therapy may be started while awaiting the results of these studies. Once these results become available, antimicrobial therapy should be adjusted accordingly.
Cefaclor is administered orally.
Adults: The usual adult dosage is 250 mg every 8 to 12 hours. For bronchitis and pneumonia, the dosage is 250 mg administered 3 times daily. A dosage of 250 mg administered 3 times daily for l0 days is recommended for sinusitis. For more severe infections, such as pneumonia, or those caused by less susceptible organisms doses may be doubled. For mild to moderate infections of the urinary tract, skin and soft tissues, and upper respiratory tract, a dosage of 250 mg administered 2 times daily may be sufficient. Doses of 4 g/day have been administered safely to normal subjects for 28 days, but the total daily dosage should not exceed this amount.
For the treatment of acute gonococcal urethritis in males and females, a single dose of 3 g combined with probenecid 1 g, is given.
Children: The usual recommended daily dosage for children with mild to moderate infections is 20 mg/kg/day in divided doses every 8 to 12 hours.
For bronchitis and pneumonia, the dosage is 20 mg/kg/day in divided doses administered 3 times daily.
In more serious infections, otitis media, and infections caused by less susceptible organisms, the recommended dosage is 40 mg/kg/day in divided doses every 8 to 12 hours, with a maximum dosage of 1 gram.
| Cefaclor for Oral Suspension 125 mg/5 ml | |
|---|---|
| Under 1 year (9 kg) | 2.5 ml tid |
| 1-5 years (9-18 kg) | 5.0 ml tid |
Cefaclor may be administered in the presence of impaired renal function. Under
such a condition, the dosage usually is unchanged (see Precautions).
In the treatment of beta-haemolytic streptococcal inflections, a therapeutic dosage of cefaclor should be administered for at least 10 days.
Directions for preparing the oral suspension: Add 70 ml of water to the dry powder and shake to disperse. To help with dispersion, the water may be added in two portions shaking between each addition.
Cefaclor is contraindicated in patients with known allergy to the cephalosporin group of antibiotics.
Warnings: In penicillinase resistant patients, cephalosporin antibiotics should be administered with caution. There is clinical and laboratory evidence of partial cross-allergenicity of the penicillins and the cephalosporins and there are instances in which patients have had reactions, including anaphylaxis, to both medicine classes. Antibiotics, including cefaclor, should be administered cautiously to any patient who has demonstrated some form of allergy, particularly to medicines.
Pseudomembranous colitis has been reported with virtually all broad-spectrum antibiotics (including macrolides, semisynthetic penicillins, and cephalosporins): therefore it is important to consider its diagnosis in patients who develop diarrhoea in association with the use of antibiotics. Such colitis may range in severity from mild to life-threatening. Mild cases of pseudomembranous colitis usually respond to medicine discontinuance alone. In moderate to severe cases, appropriate measures should be taken.
Precautions: If an allergic reaction to cefaclor occurs, the medicine should be discontinued and if necessary, the patient should be treated with appropriate agents e.g. pressor amines, antihistamines or corticosteroids. Prolonged use of cefaclor may result in the overgrowth of susceptible 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. In haematologic 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, it should be recognised that a positive Coombs' test may be due to the medicine.
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 a result of administration of cefaclor, a false-positive reaction for glucose in the urine may occur with Benedict's or Fehling's solution or with CLINITEST Tablets but not with TESTAPE (urine sugar analysis paper, Lilly).
Broad-spectrum antibiotics should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.
Use in Pregnancy: [(Category B1) Prescribing medicines in Pregnancy 4th edition] Reproduction studies have been performed in mice and rats at doses up to l 2 times the human dose and in ferrets given 3 times the maximum human dose and have revealed no evidence of impaired fertility or harm to the foetus 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 medicine should be used during pregnancy only if clearly needed.
Use in Lactation: 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 μg/ml at 2, 3, 4 and 5 hours, respectively. Trace amounts were detected at l hour. The effect on nursing infants is not known. Caution should be exercised when cefaclor is administered to nursing woman.
Use in Neonates: Safety and effectiveness of cefaclor for use in infants less than 1 month of age have not been established.
Carcinogenesis, mutagenesis, and impairment of fertility: Studies in animals have not been performed to evaluate the carcinogenic or mutagenic potential for cefaclor. Reproduction studies of other cefaclor products have revealed no evidence of impaired fertility.
Cefaclor is presumed to be safe or unlikely to produce an effect on the ability to drive or use machinery.
Gastrointestinal: Symptoms occur in about 2.5 % of patients and include diarrhoea (1 in 70). Symptoms of pseudomembranous colitis may appear either during or after antibiotic treatment. Nausea and vomiting have been reported rarely.
As with some penicillins and some other cephalosporins, transient hepatitis and cholestatic jaundice have been reported rarely. 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. Angioedema has been reported rarely.
Cases of serum-sickness-like reactions have been reported with the use of cefaclor. These are characterised by findings of erythema mulliforme, 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. 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 children than in adults with an 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 children in clinical trials of 0.055 %) to 1 in 38000 (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 hospitalisation, usually of short duration (median hospitalisation = 2 to 3 days, based on post-marketing surveillance studies). In those requiring hospitalisation, the symptoms have ranged from mild to severe at the time of admission with more of the severe reactions occurring in children.
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, Anaphylaxis may be more common in patients with a history of penicillin allergy.
Other: Effects considered related to therapy included eosinophilia (1 in 50 patients). genital pruritus or vaginitis (less than 1 in l00 patients), and rarely, thrombocytopenia or reversible interstitial nephritis.
Causal Relationship Uncertain:
CNS: Rarely, reversible hyperactivity, 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 SGOT, SGPT, or alkaline phosphatase values (1 in 40).
Haematopoietic: As has also been reported with other β-lactam antibiotics, transient lymphocytosis, leukopenia, and rarely, haemolytic anaemia 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).
As a result of administration of cefaclor a false positive reaction for glucose in the urine may occur with Benedict's or Fehling's Solution or with CLINITEST Tablets.
Clinical Features: The toxic symptoms following an overdose of cefaclor may include nausea, vomiting, epigastric distress, and diarrhoea. The severity of the epigastric distress and the diarrhoea are dose related. If other symptoms are present, it is probable that they are secondary to an underlying disease state, an allergic reaction. or the effects of other intoxication.
Management: In managing overdosage consider the possibility of multiple agent overdoses, medicine interaction, and unusual kinetics in your patient. Unless 5 times the normal dose of cefaclor has been ingested, gastrointestinal decontamination will not be necessary. Protect the patients airway and support ventilation and perfusion. Meticulously monitor and maintain. within acceptable limits, the patients vital signs. blood gases, serum electrolytes, etc.
Absorption of medicines 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 medicines that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal. Forced diuresis, peritoneal dialysis, haemodialysis, or charcoal haemoperfusion have not been established as beneficial for an overdose of cefaclor.
Capsules: Store below 25 °C protected from light and moisture. Shelf life: 2 years.
Oral suspension: store below 25 °C in well closed containers protected from light and moisture. Shelf life: 2 years. Once reconstituted the suspension should be stored between 2 and 8 °C and used within 14 days.
Directions for preparing the oral suspension: Add 70 ml of water to the dry powder and shake to disperse. To help with dispersion, the water may be added in two portions shaking between each addition.
Prescription Medicine
Ranbaxy-Cefaclor capsules: 100 capsules packed in HDPE bottles.
Ranbaxy-Cefaclor oral suspension 125 mg/5 ml: bottles of powder for 100 ml suspension.
Cefaclor is 3-chloro-7-d-(2-phenylglycinamido)-3-cephem-4-carboxylic acid and is available commercially as the monohydrate. The formula and molecular weight of the monohydrate form is C15H14ClN3O4S H2O and 385.8 respectively.
Ranbaxy-Cefaclor capsules contain maize starch, colloidal silicon dioxide, croscarmellose sodium and magnesium stearate. Capsule shell: gelatine, Ponceau 4R, Carmoisine, Brilliant blue, titanium dioxide, methyl paraben and propyl paraben.
Ranbaxy-Cefaclor oral suspension contain xanthan gum, sodium benzoate, sucrose, colloidal silicon dioxide, FD & C Red No 40 (allura red AC), strawberry flavour, sodium citrate, citric acid and simethicone.
Douglas Pharmaceuticals Ltd
P O Box 45 027
Auckland 8
New Zealand
Phone: (09) 835 0660
Fax: (09) 835 0665
23 June 2004