Ceclor/Ceclor MR

Ceclor/Ceclor MR

cefaclor

Manufacturer:

A. Menarini

Distributor:

Zuellig
/
Agencia Lei Va Hong

Marketer:

A. Menarini
Full Prescribing Info
Contents
Cefaclor monohydrate.
Description
Ceclor: Each capsule contains cefaclor monohydrate equivalent to 250 mg (0.68 mmol) cefaclor.
After mixing, each 5 mL of cefaclor for oral suspension will contain cefaclor monohydrate equivalent to 125 mg (0.34 mmol) or 250 mg (0.68 mmol) cefaclor.
Cefaclor, USP, is a semisynthetic cephalosporin antibiotic for oral administration. It is chemically designated as 3-chloro-7-D-(2-phenylglycinamido)-3-cephem-4-carboxylic acid monohydrate.
Ceclor MR: Each extended-release tablet contains cefaclor monohydrate equivalent to 375 mg (0.972 mmol) cefaclor.
Ceclor MR, is a pharmaceutically-modified form of the orally active cephalosporin, cefaclor. It is a semisynthetic cephalosporin antibiotic for oral administration. The active ingredient is chemically designated as 3-chloro-7-D-(2-phenylglycinamido)-3-cephem-4-carboxylic acid monohydrate and known as Cefaclor, USP. Ceclor MR differs from cefaclor in its rate of dissolution, producing a lower peak serum concentration, but retaining sustained measurable serum concentrations, which provides the advantage of twice daily dosing.
Action
Ceclor: Pharmacology: Cefaclor is well absorbed after oral administration to fasting subjects. Total absorption is the same whether the drug is given with or without food; however, when it is taken with food, the peak concentration achieved is 50% to 75% of that observed when the drug is administered to fasting subjects and generally appears from three fourths to 1 hour later. Following administration of 250-mg, 500-mg, and 1-g doses to fasting subjects, average peak serum levels of approximately 7, 13, and 23 mg/L respectively were obtained within 30 to 60 minutes. Approximately 60% to 85% of the drug 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 1,900 mg/L respectively. The serum half-life in normal subjects is approximately 1 hour (range 0.6 to 0.9). In patients with reduced renal function, the serum half-life of 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%.
Microbiology: In vitro tests demonstrate that the bactericidal action of the cephalosporins results from their inhibition of cell-wall synthesis. While in vitro studies have demonstrated the susceptibility of most strains of the following organisms to cefaclor, clinical efficacy for infections other than those included in the Indications/Uses is unknown.
Aerobes, Gram-positive: Staphylococci, including coagulase-positive, coagulase-negative, and penicillinase-producing strains (when tested by in vitro methods), exhibit cross-resistance between cefaclor and methicillin; Streptococcus pneumoniae; Streptococcus pyogenes.
Aerobes, Gram-negative: Citrobacter diversus; Escherichia coli; Haemophilus influenzae, including β-lactamase-producing, ampicillin-resistant strains; Klebsiella spp; Moraxella (Branhamella) catarrhalis; Neisseria gonorrhoeae; Proteus mirabilis.
Anaerobes: Bacteroides spp (excluding Bacteroides fragilis); Peptococcus niger; Peptostreptococcus spp; Propionibacteria acnes.
Note: Methicillin-resistant staphylococci and most strains of enterococci (Enterococcus faecalis [formerly Streptococcus faecalis] and Enterococcus faecium (formerly Streptococcus faecium)] are resistant to cefaclor and other cephalosporins. Cefaclor is not active against most strains of Enterobacter spp, Serratia spp, Morganella morganii, Proteus vulgaris and Providencia rettgeri. It has no activity against Pseudomonas spp or Acinetobacter spp.
Disk Susceptibility Tests: Diffusion techniques: Quantitative methods that require measurement of zone diameters give the most precise estimates of antibiotic susceptibility of bacteria to antimicrobial agents. One such standard procedure has been recommended for use with disks to test susceptibility of organisms to cefaclor, using the 30 µg cefaclor disk. Interpretation involves the correlation of the diameters obtained in the disk test with the minimum inhibitory concentration (MIC) for cefaclor.
Reports from the laboratory giving results of the standard single-disk susceptibility test with a 30 µg cefaclor disk should be interpreted according to the following criteria: See Table 1.

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Although the spectrum of activity of cefaclor is qualitatively similar to that of cephalothin and of the other first-generation cephalosporins, its activity against H. influenzae is considerably greater than that of the first generation cephalosporins. For this reason, a disk containing 30 µg of cefaclor may be used to determine the susceptibility of H. influenzae using the method described by NCCLS. In the testing of H. influenzae (on Mueller-Hinton agar supplemented with hemoglobin and a commercial VX supplement) or other organisms, zone diameter interpretive criteria, are identical to those used for the cephalothin disk: ≥18 mm, susceptible; 15-17 mm, moderately susceptible (intermediate for Haemophilus); and ≤14 mm, resistant. A report of "Susceptible" indicates that the pathogen is likely to be inhibited by generally achievable blood levels. A report of "Intermediate" suggests that the organism would be susceptible if high dosage is used or if the infection is confined to tissue and fluids in which high antibiotic levels are obtained. A report of "Resistant" indicates that achievable concentration of the antibiotic are unlikely to be inhibitory and other therapy should be selected. Standardized procedures require the use of laboratory control organisms. The 30 µg cefaclor disk should give the following zone diameters: See Table 2.

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Dilution techniques: Use a standardized dilution method (broth, agar, microdilution) or equivalent with cefaclor powder. The MIC values obtained should be interpreted according to the following criteria: See Table 3.

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As with standard diffusion techniques, dilution methods require the use of laboratory control organisms. Standard cefaclor powder should provide the following MIC values: See Table 4.

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Ceclor MR: Pharmacology: Ceclor MR is well-absorbed from the gastrointestinal tract after oral administration. Although Ceclor MR can be taken with or without food, total absorption is enhanced with food. When it was given within 1 hour after a meal, the bioavailability of Ceclor MR was greater than 90% using cefaclor as a reference. When taken in the fasting state, the bioavailability of Ceclor MR was 77% that of cefaclor. Compared to cefaclor (fasted state), mean peak plasma concentrations of Ceclor MR (both fed and fasted states) were delayed 40 to 90 minutes and were lower. Concomitant administration of H2 blockers does not affect the rate or extent of absorption. Administration of magnesium- or aluminum hydroxide-containing antacids 1 hour after Ceclor MR had no effect on the rate of absorption but resulted in a 17% decrease in the extent of absorption.
Following administration of 375-mg, 500-mg, and 750-mg tablets to fed subjects, average peak serum concentrations of 4, 8 and 11 μg/mL, respectively, were obtained within 2.5 to 3 hours. No drug accumulation was noted when it was given twice daily.
The plasma half life in healthy subjects is independent of dosage form and averages approximately 1 hour (range 0.6 to 0.9). In elderly subjects (over age 65) with normal serum creatinine values, a higher peak plasma concentration and AUC are effects resulting from mildly diminished renal function and have no apparent clinical significance. Therefore, dosage changes are not necessary in elderly subjects with normal renal function. There is no evidence of metabolism of cefaclor in humans.
Microbiology: The in vitro bactericidal activity of Ceclor MR is due to cefaclor. In vitro tests demonstrate that the bactericidal action of the cephalosporins results from their inhibition of cell-wall synthesis. Cefaclor is stable in the presence of bacterial β-lactamases; consequently, β-lactamase-producing organisms resistant to penicillin and some cephalosporins may be susceptible to cefaclor. Ceclor MR has been shown to be active against most strains of the following organisms both in vitro and in clinical infections (see Indications/Uses).
Gram-positive organisms: Staphylococcus aureus (including β-lactamase-producing strains); Staphylococcus epidermidis (including β-lactamase-producing strains); Staphylococcus saprophyticus; Streptococcus pneumoniae; Streptococcus pyogenes (group A streptococci).
Note: Cefaclor is inactive against methicillin-resistant staphylococcus.
Gram-negative organisms: Haemophilus parainfluenzae; Haemophilus influenzae (including β-lactamase-producing strains); Moraxella (Branhamella) catarrhalis (including β-lactamase-producing strains); Escherichia coli; Klebsiella pneumoniae; Proteus mirabilis.
Cefaclor has been shown to be active in vitro against most strains of the following organisms; however, clinical efficacy has not been established.
Gram-negative organisms: Citrobacter diversus; Neisseria gonorrhoeae.
Anaerobic organisms: Propionibacterium acnes; Bacteroides species (excluding Bacteroides fragilis); Peptococci; Peptostreptococci.
Note: Pseudomonas sp, Acinetobacter calcoaceticus, most strains of enterococci, Enterobacter sp, indole-positive Proteus, and Serratia sp are resistant to cefaclor.
Susceptibility Tests: Diffusion techniques: Quantitative methods that require measurement of zone diameters give an estimate of antibiotic susceptibility. One such procedure is the National Committee for Clinical Laboratory Standards (NCCLS) approved procedure. This method has been recommended for use with disks to test susceptibility to cefaclor. Interpretation involves the correlation of the diameters obtained in the disk test with the minimum inhibitory concentration (MIC) for cefaclor. Reports from the laboratory giving results of the standard single-disk susceptibility test with a 30 μg cefaclor disk should be interpreted according to the following criteria: See Table 1.

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A report of "Susceptible" indicates that the pathogen is likely to be inhibited by generally achievable blood concentrations. A report of "Intermediate" indicates that inhibitory concentrations of the antibiotic may be achieved if high dosage is used or if the infection is confined to tissues and fluids (e.g. urine) in which high antibiotic concentrations are attained. A report of "resistant" indicates that achievable concentration of the antibiotic are unlikely to be inhibitory and other therapy should be selected.
Standardized procedures require the use of laboratory control organisms. The 30 μg cefaclor disk should give the following zone diameters: See Table 2.

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Pathogenesis other than M. catarrhalis and H. influenzae can be tested using the 30-mg cephalothin disk or by a dilution test. Distaclor MR administration was associated with a favourable clinical and bacteriologic response in virtually all cases of infection from M. catarrhalis regardless of zone diameter, thus there is little gained by testing cefaclor against this organism. H. influenzae should be tested with the cefaclor disk on chocolate Mueller Hinton and interpreted by the usual zone diameter criteria depicted previously. Alternatively, H. influenzae may be tested on Haemophilus Test Medium (HTM) using the interpretive criteria recommended by NCCLS listed as follows: See Table 5.

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Dilution Techniques: Broth and agar dilution methods, such as those recommended by the NCCLS may be used to determine the MIC of cefaclor. MIC test results should be interpreted according to the following criteria: See Table 3.

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As with standard diffusion techniques, dilution procedures require the use of laboratory control organisms. Standard cefaclor powder should provide the following MIC values: See Table 4.

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Indications/Uses
Ceclor: Cefaclor is indicated in the treatment of the following infections when caused by susceptible strains of the designated microorganisms: Otitis media caused by S. pneumoniae, H. influenzae, staphylococci, S. pyogenes (group A β-hemolytic streptococci) and M. catarrhalis.
Lower respiratory tract infections, including pneumonia, caused by S. pneumoniae, H. influenzae, S. pyogenes (group A β-hemolytic streptococci) and M. catarrhalis.
Upper respiratory infections, including pharyngitis and tonsillitis, caused by S. pyogenes (group A β-hemolytic streptococci) and M. catarrhalis.
Note: Penicillin is the usual drug 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 β-hemolytic streptococcal bacteremia 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 either rheumatic fever or bacterial endocarditis are not available at present.
Urinary tract infections, including pyelonephritis and cystitis, caused by E. coli, P. mirabilis, Klebsiella spp, and coagulase-negative staphylococci.
Note: Cefaclor has been found to be effective in both acute and chronic urinary tract infections.
Skin and skin structure infections caused by Staphylococcus aureus and S. pyogenes (group A β-hemolytic streptococci).
Sinusitis; Gonococcal urethritis.
Appropriate culture and susceptibility studies should be performed to determine susceptibility of the causative organism to cefaclor.
Ceclor MR: Ceclor MR is indicated in the treatment of the following infections when caused by susceptible strains of the designated microorganisms: Acute bronchitis and acute exacerbations of chronic bronchitis caused by S. pneumoniae, H. influenzae (including β-lactamase-producing strains) and S. aureus.
Pharyngitis and tonsillitis caused by S. pyogenes (group A streptococci). (Penicillin is the usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. Ceclor MR is generally effective in the eradication of streptococci from the oropharynx; however, substantial data establishing the efficacy of Ceclor MR in the subsequent prevention of rheumatic fever are not available.)
Pneumonia caused by S. pneumoniae, H. influenzae (including β-lactamase-producing strains) and M. catarrhalis (including β-lactamase-producing strains).
Sinusitis caused by S. pneumoniae (penicillin susceptible strains only), H. influenzae (including β-lactamase-producing strains) and M. catarrhalis (including β-lactamase-producing strains).
Uncomplicated lower urinary tract infections including cystitis and asymptomatic bacteriuria, caused by E. coli, K. pneumoniae, P. mirabilis and S. saprophyticus.
Skin and skin structure infections caused by S. pyogenes (group A streptococci), S. aureus (including β-lactamase-producing strains) and S. epidermidis (including β-lactamase-producing strains).
Bacteriologic 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.
Dosage/Direction for Use
Ceclor: Cefaclor is administered orally.
Adults: The usual adult dosage is 250 mg every 8 hours. For bronchitis and pneumonia, the dosage is 250 mg administered 3 times daily. A dosage of 250 mg administered 3 times daily for 10 days is recommended for sinusitis. For more severe infections (such as pneumonia) or those caused by less susceptible organisms, doses may be doubled. 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 is 20 mg/kg/day in divided doses every 8 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, 40 mg/kg/day in divided doses are recommended, with a maximum dosage of 1 g/day. (See Table 6.)

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B.I.D. Treatment Option: For the treatment of otitis media and pharyngitis, the total daily dosage may be divided and administered every 12 hours. (See Table 7.)

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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 β-hemolytic streptococcal infections, a therapeutic dosage of cefaclor should be administered for at least 10 days.
Ceclor MR: Ceclor MR may be given orally without regard to meals. However, absorption is enhanced when Ceclor MR is administered with food (see Pharmacology under Actions). The tablets should not be cut, crushed or chewed. The recommended dosage for pharyngitis and tonsillitis, skin and skin structure is 375 mg twice daily. For lower urinary tract infections, the recommended dosage is 375 mg twice daily or 500 mg once daily. The recommended dosage for bronchitis is 375 mg or 500 mg twice daily. For pneumonia and sinusitis, the recommended dosage is 750 mg twice daily. In the treatment of infections caused by S. pyogenes (group A streptococci), a therapeutic dosage of Ceclor MR should be administered for at least 10 days.
Overdosage
Signs and Symptoms: The toxic symptoms following an overdose of cefaclor may include nausea, vomiting, epigastric distress and diarrhea. The severity of the epigastric distress and the diarrhea 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.
Treatment: In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs and unusual drug kinetics in the patient.
Unless 5 times the normal dose of cefaclor has been ingested, gastrointestinal decontamination will not be necessary. Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. 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. Safeguard the patient's airway when employing gastric emptying or charcoal. Forced diuresis, peritoneal dialysis, hemodialysis or charcoal hemoperfusion have not been established as beneficial for an overdose of cefaclor.
Contraindications
Ceclor/Ceclor MR is contraindicated in patients with known hypersensitivity to cefaclor and other cephalosporins.
Warnings
Before therapy with cefaclor is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cefaclor, cephalosporins, penicillins or other drugs. If this product is to be given to penicillin-sensitive patients, caution should be exercised because cross-hypersensitivity, including anaphylaxis, among β-lactam antibiotics has been clearly documented.
If an allergic reaction to cefaclor occurs, the drug should be discontinued, and, if necessary, the patient should be treated with appropriate agents, eg, pressor amines, antihistamines, or corticosteroids.
Antibiotics, including cefaclor, should be administered cautiously to any patient who has demonstrated some form of allergy, particularly to drugs.
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 diarrhea 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 drug discontinuance alone. In moderate to severe cases, appropriate measures should be taken.
Special Precautions
Ceclor: General: Prolonged use of cefaclor may result in the overgrowth of nonsusceptible 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. It should be recognized that a positive Coombs' test may be due to the drug, eg, in hematologic 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.
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.
Antibiotics, including cephalosporins, should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.
Drug/Laboratory Test interactions: Patients receiving cefaclor may show a false-positive reaction for glucose in the urine with tests that use Benedict's and Fehling's solutions and also with Clinitest tablets but not with Tes-Tape (Glucose Enzymatic Test Strip, USP, Lilly). There have been rare reports of increased anticoagulant effect when cefaclor and oral anticoagulants were administered concomitantly (see Adverse Reactions).
As with other β-lactam antibiotics, the renal excretion of cefaclor is inhibited by probenecid.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies have not been performed to determine potential for carcinogenicity or mutagenicity, Reproduction studies have revealed no evidence of impaired fertility.
Use in Pregnancy: Reproduction studies have been performed in mice and rats at doses up to 12 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 fetus 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 drug should be used during pregnancy only if clearly needed.
Use in Labor and Delivery: The effect of cefaclor on labor and delivery is unknown.
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 mg/L at 2, 3, 4, and 5 hours respectively. Trace amounts were detected at 1 hour. The effect on nursing infants is not known.
Caution should be exercised when cefaclor is administered to a nursing woman.
Use in Children: Safety and effectiveness of this product for use in infants less than 1 month of age have not been established.
Ceclor MR: General: The possibility of emergence of resistant organisms which might result in overgrowth should be kept in mind, particularly during prolonged treatment. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Drug Interactions: The extent of absorption of Ceclor MR is diminished if magnesium- or aluminum hydroxide-containing antacids are taken within 1 hour of administration; H2 blockers do not alter either the rate or the extent of absorption of Ceclor MR. As with other β-lactam antibiotics, the renal excretion of cefaclor (and presumably Ceclor MR) is inhibited by probenecid. No other significant drug interactions were noted during clinical trials.
Laboratory Test Interactions: Administration of Ceclor MR 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 but not with Tes-Tape (Glucose Enzymatic Test Strip, USP, Lilly).
Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies in animals have not been performed to evaluate the carcinogenic or mutagenic potential for Ceclor MR. Reproduction studies have revealed no evidence of impaired fertility.
Use in Pregnancy: Reproduction studies have been performed in mice and rats at doses up to 12 times the human dose and in ferrets given 3 times the maximum human dose. These studies 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, Ceclor MR should be used during pregnancy only if clearly needed.
Use in Labor and Delivery: Ceclor MR has not been studied for use during labor and delivery. Treatment should be given only if clearly needed.
Use in Lactation: No studies have been done with Ceclor MR. Small amounts of cefaclor have been detected in mother's milk following administration of single 500-mg dose of cefaclor. Average levels were 0.18, 0.20, 0.21, and 0.16 mg/L at 2, 3, 4, and 5 hours respectively. Trace amounts were detected at 1 hour. The effect on nursing infants is not known. Caution should be exercised when cefaclor is administered to a nursing woman.
Use in Children: Safety and effectiveness in children have not been established.
Use In Pregnancy & Lactation
Ceclor: Usage in Pregnancy: Reproduction studies have been performed in mice and rats at doses up to 12 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 fetus 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 drug should be used during pregnancy only if clearly needed.
Labor and Delivery: The effect of cefaclor on labor and delivery is unknown.
Nursing Mothers: 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 mg/L at 2, 3, 4, and 5 hours respectively. Trace amounts were detected at 1 hour. The effect on nursing infants is not known.
Caution should be exercised when cefaclor is administered to a nursing woman.
Ceclor MR: Usage in Pregnancy: Reproduction studies have been performed in mice and rats at doses up to 12 times the human dose and in ferrets given 3 times the maximum human dose. These studies 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, Ceclor MR should be used during pregnancy only if clearly needed.
Labor and Delivery: Ceclor MR has not been studied for use during labor and delivery. Treatment should be given only if clearly needed.
Nursing Mothers: No studies have been done with Ceclor MR. Small amounts of cefaclor have been detected in mother's milk following administration of single 500-mg dose of cefaclor. Average levels were 0.18, 0.20, 0.21, and 0.16 mg/L at 2, 3, 4, and 5 hours respectively. Trace amounts were detected at 1 hour. The effect on nursing infants is not known. Caution should be exercised when cefaclor is administered to a nursing woman.
Adverse Reactions
Ceclor: Adverse effects considered to be related to therapy with cefaclor are listed as follows: Hypersensitivity 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.
Cases of serum-sickness-like reactions have been reported with the use of cefaclor. These are characterized by findings of erythema multiforme, 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. Occasionally, solitary symptoms may occur, but do not represent a serum-sickness-like 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 8,346 (0.024%) in overall clinical trials (with an incidence in children 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 requiring hospitalization, 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. Anaphylactoid events may be manifested by solitary symptoms including angioedema, asthenia, edema (including face and limbs), dyspnea, 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.
Gastrointestinal symptoms occur in about 2.5% of patients and include diarrhea (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.
Other effects considered related to therapy included eosinophilia (1 in 50 patients), genital pruritus or vaginitis (less than 1 in 100 patients), and, rarely, thrombocytopenia or reversible interstitial nephritis.
Causal Relationship Uncertain: CNS: Rarely, reversible hyperactivity, agitation, 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 as follows to serve as alerting information for the physician.
Hepatic: Slight elevations of AST (SGOT), ALT (SGPT) or alkaline phosphatase values (1 in 40).
Hematopoietic: As has also been reported with other β-lactam antibiotics, transient lymphocytosis, leukopenia and, rarely, hemolytic anemia, aplastic anemia, agranulocytosis 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).
Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced.
If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.
Ceclor MR: The majority of adverse reactions observed in clinical trials of Ceclor MR were mild and transient. Drug-related adverse reactions requiring discontinuation of therapy occurred in 1.7% of patients. The following adverse reactions have been reported following the use of Ceclor MR in clinical trials. Incidence rates were less than 1 in 100 (less than 1%), except as otherwise noted.
Gastrointestinal: Diarrhea (3.4%), nausea (2.5%), vomiting and dyspepsia.
Hypersensitivity: Rash, urticaria, or pruritus occurred in approximately 1.7% of patients. One serum-sickness-like reaction (0.03%) was reported among the 3,272 patients treated with Ceclor MR during the controlled clinical trials.
Cases of serum-sickness-like reactions have been reported with the use of cefaclor. These are characterized by findings of erythema multiforme, rashes, and other skin manifestations accompanies 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. Occasionally, solitary symptoms may occur, but do not represent a serum-sickness-like 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 occurence ranging from 1 in 200 (0.5%) in one focused trial to 2 in 8,346 (0.024%) in overall clinical trials (with an incidence in children 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 requiring hospitalization, 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.
Hematologic and Lymphatic Systems: Eosinophilia.
Genitourinary: Vaginal moniliasis (2.5%) and vaginitis (1.7%).
The following adverse effects have been reported in patients treated with Ceclor MR; causal relationship is uncertain: Central Nervous System: Headache, dizziness and somnolence.
Hepatic: Transient elevations in AST, ALT and alkaline phosphatase.
Renal: Transient increase in BUN or creatinine.
Laboratory Tests: Transient thrombocytopenia, leucopenia, lymphocytosis, neutropenia and abnormal urinalysis.
In addition to adverse reactions listed previously that have been observed in patients taking Ceclor MR, the following adverse reactions and altered laboratory tests have been reported in patients treated with cefaclor: Erythema multiforme, fever, anaphylaxis (may be more common in patients with a history of penicillin allergy), Stevens-Johnson syndrome, positive direct Coombs' test and genital pruritus. Symptoms of pseudomembranous colitis may appear either during or after antibiotic treatment. Anaphylactoid events may be manifested by solitary symptoms, including angioedema, asthenia, edema (including face and limbs), dyspnea, paresthesias, syncope or vasodilation.
Rarely, hypersensitivity symptoms may persist for several months.
The following reactions have been reported rarely in patients treated with cefaclor: Toxic epidermal necrolysis, reversible interstitial nephritis, hepatic dysfunction including cholestasis, increased prothrombin time in patients receiving cefaclor and warfarin concomitantly, reversible hyperactivity, nervousness, insomnia, confusion, hypertonia, aplastic anemia, agranulocytosis and hemolytic anemia.
In addition to the adverse reactions listed previously, the following adverse reactions have been reported in patients treated with β-lactam antibiotics: Colitis, renal dysfunction, and toxic nephropathy.
Several β-lactam antibiotics have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures associated with drug therapy should occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.
Storage
Store below 25°C.
MIMS Class
ATC Classification
J01DC04 - cefaclor ; Belongs to the class of second-generation cephalosporins. Used in the systemic treatment of infections.
Presentation/Packing
Ceclor: Cap 250 mg x 10 x 10's. Susp 125 mg/5 mL x 60 mL. 250 mg/5 mL x 60 mL.
Ceclor MR: Extended-release tab 375 mg x 10's.
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