Cefaclor Information
Cefaclor ()
Cefaclor () Description
Cefaclor () 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. The molecular formula for Cefaclor () is CHClNOS•HO and the molecular weight is 385.82.
Each capsule contains Cefaclor () monohydrate equivalent to 250 mg (0.68 mmol) or 500 mg (1.36 mmol) anhydrous Cefaclor () . The capsules also contain black iron oxide, croscarmellose sodium, FD&C Red No. 3, FD&C Blue No. 2, gelatin, magnesium stearate, corn starch, and titanium dioxide.
The color of the capsule powder is white to off white.
Cefaclor () Clinical 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 mcg/mL 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 mcg/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 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%.
INDICATIONS AND USAGE
Aerobes, Gram-positiveStaphylococci, including coagulase-positive, coagulase-negative, and penicillinase-producing strains (group A β-hemolytic streptococci)
Aerobes, Gram-negative , excluding β-lactamase-negative, ampicillin-resistant strains
The following data are available,
Cefaclor () exhibits minimal inhibitory concentrations (MICs) of 8 mcg/mL against most ( 90%) strains of the following microorganisms; however, the safety and effectiveness of Cefaclor () in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.
Aerobes, Gram-negative
Anaerobes, Gram-positive spp (excluding )
Dilution Techniques
1
*When testing spp. these interpretive standards are applicable only to broth microdilution method using Haemophilus Test Medium (HTM)
A report of “Susceptible” indicates that the pathogen is likely to be inhibited by usually achievable concentrations of the antimicrobial compound in blood. 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 that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that usually achievable concentrations of the antimicrobial compound in the blood are unlikely to be inhibitory and that other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory control microorganisms. Standard Cefaclor () powder should provide the following MIC values:
When testing
*Broth microdilution test performed using Haemophilus Test Medium (HTM)
Diffusion Techniques
2
When Testing Organisms Other Than spp. and Streptococci
When testing *
*Disk susceptibility test performed using Haemophilus Test Medium (HTM)
Interpretation should be as stated above for results using dilution techniques.
As with standard dilution techniques, diffusion methods require the use of laboratory control microorganisms. The 30 mcg Cefaclor () disk should provide the following zone diameters in these laboratory test quality control strains:
When testing *
*Disk susceptibility test performed using Haemophilus Test Medium (HTM)
Cefaclor () Indications And Usage
Cefaclor () is indicated in the treatment of the following infections when caused by susceptible strains of the designated microorganisms:
Appropriate culture and susceptibility studies should be performed to determine susceptibility of the causative organism to Cefaclor () .
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefaclor () and other antibacterial drugs, Cefaclor () 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 () Contraindications
Cefaclor () is contraindicated in patients with known allergy to the cephalosporin group of antibiotics.
Cefaclor () Warnings
Antibiotics, including Cefaclor () , should be administered cautiously to any patient who has demonstrated some form of allergy, particularly to drugs.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowthof clostridia. Studies indicate that a toxin produced by is one primary cause of antibiotic-associated colitis.
After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug effective against
Cefaclor () Precautions
Prescribing Cefaclor () 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.
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, e.g., 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.
As with other β-lactam antibiotics, the renal excretion of Cefaclor () is inhibited by probenecid. Antibiotics, including cephalosporins, should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.
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.
There have been reports of increased anticoagulant effect when Cefaclor () and oral anticoagulants were administered concomitantly.
Of the 3703 patients in clinical studies of Cefaclor () , 594 (16.0%) were 65 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney ( ), and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see ).
Cefaclor () Adverse Reactions
Adverse effects considered to be related to therapy with Cefaclor () are listed below:
Cases of 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 reaction. While further investigation is ongoing, 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 pediatric ptients 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 pediatric patients 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 pediatric patients. 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, hypotension, or vasodilatation. Anaphylaxis may be more common in patients with a history of penicillin allergy.
Rarely, hypersensitivity symptoms may persist for several months.
Onset of pseudomembranous colitis symptoms may occur 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.
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.
There have been rare reports of increased prothrombin time with or without clinical bleeding in patients receiving Cefaclor () and warfarin concomitantly.
Cefaclor () Overdosage
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 () .
Cefaclor () Dosage And Administration
Cefaclor () is administered orally.
Cefaclor () may be administered in the presence of impaired renal function. Under such a condition, the dosage usually is unchanged ( ).
In the treatment of β-hemolytic streptococcal infections, a therapeutic dosage of Cefaclor () should be administered for at least 10 days.
Cefaclor () How Supplied
Capsules:Cefaclor () Capsules, USP 250 mg: opaque purple and white hard gelatin capsules imprinted with "West Ward 985" in bottles of 15 and bottles of 100.Cefaclor () Capsules, USP 500 mg: opaque purple and gray hard gelatin capsules imprinted with "West Ward 986" in bottles of 15 and bottles of 100.
Store bottles at 20° to 25°C (68° to 77° F). [See USP Controlled Room Temperature]
Cefaclor () References
1. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically - Fourth Edition. Approved Standard NCCLS Document M7-A4, Vol. 17, No. 2, NCCLS, Wayne, PA, January 1997.2. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Test - Sixth Edition, Approved Standard NCCLS Document M2-A6, Vol. 17, No. 1, NCCLS, Wayne, PA, January 1997.
West-ward Pharmaceutical Corp.Eatontown, NJ 07724 - USADistributor
Manufactured by:Jazeera Pharmaceutical Industries (JPI)Al- Kharj RoadP.O. Box 106229Riyadh 11666Saudi Arabia
An Affiliate of:Hikma PharmaceuticalsP.O. Box 182400Amman 11118Jordan
Rev.: July 2006
