Cefaclor Capsules 250mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Cefaclor Capsules 250 mg.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule, hard, contains 250 mg of Cefaclor (as cefaclor monohydrate). For excipients see 6.1
3 PHARMACEUTICAL FORM
Capsule, hard.
Hard gelatin size 2, with a white opaque body and a dark blue opaque cap. Printing: “Cefaclor” on the body and “250” on the cap.
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
Cefaclor is indicated for the treatment of the following infections due to susceptible micro-organisms:
Respiratory tract infections, including pneumonia, bronchitis, exacerbations of chronic bronchitis, pharyngitis (see section 4.4) and tonsillitis, and as part of the management of sinusitis.
Otitis media
Skin and soft tissue infections
Urinary tract infections, including pyelonephritis and cystitis
Cefaclor has been found to be effective in both acute and chronic urinary tract infections.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
4.2. Posology and method of administration
For oral administration:
Cefaclor capsules are chiefly recommended for adults. A low dose suspension is available for use in children under 12 years of age.
Adults:
The usual adult dosage is 250 mg every eight hours. For more severe infections or those caused by less susceptible organisms, doses may be doubled. Doses of 4 g per day have been administered safely to normal subjects for 28 days, but the daily dosage should not exceed this amount.
Cefaclor may be administered in the presence of impaired renal function. Under such conditions dosage is usually unchanged (see section 4.4).
Children under 12 years of age:
The usual recommended daily dosage for children is 20 mg/kg/day in divided doses every eight hours. For bronchitis and pneumonia, the dosage is 20 mg/kg/day in divided doses administered three times daily. For otitis media and pharyngitis, the total daily dosage may be administered in two divided doses every 12 hours. Safety and efficacy have not been established for use in infants aged less than one month.
In more serious infections, otitis media, sinusitis and infections caused by less susceptible organisms, 40 mg/kg/day in divided doses is recommended, up to a daily maximum of 1 g.
In the treatment of beta-haemolytic streptococcal infections, therapy should be continued for at least ten days.
The elderly:
As for adults.
Patients undergoing haemodialysis:
Haemodialysis shortens serum half-life by 25-30%. In patients undergoing regular haemodialysis, a loading dose of 250 mg - 1 g administered prior to dialysis and a therapeutic dose of 250 - 500 mg every six to eight hours maintained during interdialytic periods is recommended.
4.3. Contraindications
Hypersensitivity to cefaclor, to any of the cephalosporins or to any of the excipients.
Previous immediate and/or severe hypersensitivity reaction to a penicillin or to any other type of beta-lactam medicinal product.
4.4. Special warnings and precautions for use
Warnings:
Cefaclor is generally effective in the eradication of streptococci from the nasopharynx. However, penicillin remains the active substance of choice for streptococcal pharyngitis due to its proven efficacy in the prevention of rheumatic fever.
Before instituting therapy with cefaclor, every effort should be made to determine whether the patient has had previous hypersensitivity reactions to cefaclor, cephalosporins, penicillins or other active substances. Cefaclor should be given cautiously to penicillin-sensitive patients, because crosshypersensitivity, including anaphylaxis, among beta-lactam antibiotics has been clearly documented.
If an allergic reaction to cefaclor occurs, the medicinal product should be discontinued and the patient treated with the appropriate agents. Pseudomembranous colitis has been reported with virtually all broad-spectrum antibiotics, including macrolides, semi-synthetic penicillins and cephalosporins. It is important, therefore, to consider its diagnosis in patients who develop diarrhoea during or after treatment with antibiotics. Such colitis may range in severity from mild to life-threatening. Cefaclor should be discontinued immediately and appropriate measures taken. Anti-peristaltics are contraindicated.
Precautions:
Cefaclor should be administered with caution in the presence of markedly impaired renal function. Since the half-life of cefaclor in anuric patients is 2.3 to 2.8 hours (compared to 0.6 - 0.9 hours in normal subjects), dosage adjustments for patients with moderate or severe renal impairment are not usually required. Clinical experience with cefaclor under such conditions is limited; therefore, careful clinical observation and laboratory studies should be made.
Broad-spectrum antibiotics should be prescribed with caution in individuals with a history of gastro-intestinal disease, particularly colitis.
Prolonged use of cefaclor may result in the over-growth of non-susceptible organisms. If superinfection occurs during therapy, appropriate measures should be taken.
4.5. Interactions with other medicinal products and other forms of interaction
There have been rare reports of increased prothrombin time, with or without clinical bleeding, in patients receiving cefaclor and oral anticoagulants concomitantly. It is recommended that in such patients, regular monitoring of prothrombin time should be considered, with adjustment of dosage of oral anticoagulants if necessary.
The renal excretion of cefaclor is inhibited by probenecid.
Positive direct Coombs' tests have been reported during treatment with the cephalosporin antibiotics. In haematological studies or in transfusion crossmatching procedures, when anti-globulin 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 cefaclor.
A false-positive reaction for glucose in the urine may occur with Benedict's or Fehling's solutions or with copper sulphate test tablets.
4.6. Pregnancy and lactation
Pregnancy: Animal studies have shown no evidence of impaired fertility or teratogenicity. However, since there are no adequate or well-controlled studies in pregnant women, caution should be exercised when prescribing for the pregnant patient. Cefaclor should be used during pregnancy only if clearly needed.
Lactation: Small amounts of cefaclor have been detected in breast milk following administration of single 500 mg doses. Average levels of about 0.2 micrograms/ml or less were detected up to 5 hours later. Trace amounts were detected at one hour. As the effect on nursing infants is not known, caution should be exercised when cefaclor is administered to a nursing woman.
4.7. Effects on ability to drive and use machines
No effects on ability to drive and use machines have been observed. However, dizziness and somnolence have been reported rarely.
4.8. Undesirable effects
Blood and lymphatic system disorders: Eosinophilia, positive Coombs' tests and, rarely, thrombocytopenia. Transient lymphocytosis, leucopenia and, rarely, haemolytic anaemia, aplasic anaemia, agranulocytosis and reversible neutropenia of possible clinical significance. See section 4.5.
Immune system disorders: Allergic reactions such as morbilliform eruptions, pruritus and urticaria have been observed. These reactions usually subside on 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 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 (incl. anaphylactic shock). Anaphylaxis may be more common in patients with a history of penicillin allergy. Anaphylactoid events may be 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.
Nervous system disorders: Reversible hyperactivity, agitation, nervousness, insomnia, confusion, hypertonia, dizziness, hallucinations and somnolence have been reported rarely.
Gastrointestinal disorders: 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.
Hepatobiliary disorders: Transient hepatitis and cholestatic jaundice have been reported rarely, slight elevations in AST, ALT or alkaline phosphatase values.
Skin and subcutaneous tissue disorders: Genital pruritus
Renal and urinary disorders: Reversible interstitial nephritis has occurred rarely, also slight variations in blood urea or serum creatinine or abnormal urinalysis.
Reproductive system and breast disorders: Vaginitis and vaginal moniliasis.
4.9. Overdose
Overdose: Symptoms of nausea, vomiting, epigastric distress and diarrhoea would be anticipated .
Treatment: Unless 5 times the normal daily dose has been ingested, gastrointestinal decontamination will not be necessary.
General management may consist of supportive therapy.
PHARMACOLOGICAL PROPERTIES
5.
5.1. Pharmacodynamic properties
Pharmacotherapeutic group ATC-classification: J01D A08
Mechanism of action
Cefaclor is a second generation cephalosporin given by mouth. Cephalosporin are usually bactericidal in action. The antibacterial activity results from inhibition of mucopeptide synthesis in the bacterial cell wall.
Minimum inhibitory concentration (MIC)
The MIC is determined using a standardised dilution method, or equivalent, as recommended by the National Committee for Clinical Laboratory Standards (NCCLS).
The MIC values obtained should be interpreted according to the following criteria:
MIC (gg/ml)_Interpretation
<8 Susceptible (S)
16 Intermediate (I)
>32 Resistant (R)
Susceptibility
Susceptible (S): the pathogen is likely to be inhibited by usually achievable concentrations in blood.
Intermediate (I): moderately susceptible to cefaclor in vitro. This category implies possible clinical applicability in body distribution sites where the active substance is physiologically concentrated or in situations where high dosage of active substance can be used.
Resistant (R): usually achievable concentrations in blood are unlikely to be inhibitory, other therapy should be selected
The following table shows the bactericidal spectrum of cefaclor:
|
Susceptibility (S, I, R) |
Existing acquired resistance* | |
|
Commonly susceptible | ||
|
Gram-positive | ||
|
Branhamella catarrhalis |
S |
Y |
|
Corynebacterium diphteriae |
S | |
|
Propionibacterium acnes |
S | |
|
Staphylococcus aureus |
S |
Y |
|
Staphylococcus epidermidis |
S | |
|
S. epidermidis penicillinase producing |
S |
R |
|
Streptococcus agalactiae |
S | |
|
Streptococcus pneumoniae |
S |
Y |
|
Susceptibility (S, I, R) |
Existing acquired resistance* | |
|
Streptococcus pyogenes |
S |
Y |
|
Streptococcus, viridans group |
S | |
|
Gram-negative | ||
|
Citrobacter diversus |
S | |
|
Moraxella catarrhalis |
S | |
|
Neisseria gonorrhoeae |
S | |
|
Neisseria meningitidis |
S | |
|
Pasteurella |
S | |
|
Salmonella typhi |
S | |
|
Shigella sp |
S | |
|
Anaerobes | ||
|
Fusobacterium |
S |
Y |
|
Prevotella |
S |
Y |
|
Species _ for which acquired resistance may represent a problem | ||
|
Gram-negative | ||
|
Escherichia coli |
S-R |
Y |
|
Haemophilus influenza |
S-I |
Y |
|
Haemophilus influenza, penicillinase producing |
I | |
|
Klebsiella sp |
I |
Y |
|
Proteus mirabilis |
S-R |
Y |
|
Salmonella sp |
I | |
|
Anaerobes | ||
|
Clostridium perfringens |
I | |
|
Peptostreptococcus |
I | |
|
Inherently resistant organisms | ||
|
Gram-positive | ||
|
Enterococcus faecalis |
R |
Y |
|
Listeria monocytogenes |
R |
Y |
|
S. aureus methicillin-resistant |
R |
Y |
|
Streptococcus faecalis |
R | |
|
Gram-negative | ||
|
Acinetobacter |
R |
Y |
|
Citrobacter freundii |
R |
Y |
|
Enterobacter aerogenes |
R |
Y |
|
Enterobacter cloacae |
R | |
|
Morganella morganii |
R |
Y |
|
N. gonorrhoeae penicillinase producing |
R |
Y |
|
Proteus indole-positive |
R | |
|
Proteus vulgaris |
R |
Y |
|
Providencia rettgeri |
R | |
|
Providencia stuartii |
R |
Y |
|
Pseudomonas aeruginosa |
R |
Y |
|
Serratia marcescens |
R |
Y |
|
Anaerobes | ||
|
Bacteroides |
R | |
|
Susceptibility (S, I, R) |
Existing acquired resistance* | |
|
Clostridium difficile |
R |
*: the prevalence of resistance may vary geographically and with time with selected species and local information on resistance is desirable, particularly when treating severe infections. This information gives only an approximate guidance on probabilities whether micro-organisms will be susceptible to cefaclor.
The occurrence of cross-resistance to other antimicrobial agents In-vitro there is a crossed resistance between cefaclor and antibiotics of the methicillin type against Staphylococci.
Mechanism of resistance
The resistance of bacteria to cefalosporins may be natural or acquired. It can be due to reduced permeability of the bacterial wall or to changes in cephalosporin binding to penicillin binding proteins. Most frequently the resistance is due to the production of P-lactamases. □-lactamases may be chromosomally encoded or plasmid-borne. Almost all oral cephalosporins are broken down by chromosomal □ -lactamases, whereas they vary widely in their stability to the many different plasmid-borne lactamases (e.g. TEM-1 to TEM-26 and SHV-1 to SHV-6). Cefaclor is highly susceptible to plasmidic □lactamases.
Cefaclor is active against the following organisms in vitro:
Alpha- and beta-haemolytic streptococci
Staphylococci including coagulase-positive, coagulase-negative and penicillinase-producing strains Streptococcus pneumoniae
Streptococcus pyogenes (group A beta-haemolytic streptococci)
Branhamella catarrhalis Escherichia coli Proteus mirabilis Klebsiella species
Haemophilus influenzae, including ampicillin-resistant strains Cefaclor has no activity against Pseudomonas species or Acinetobacter species. Methicillin-resistant staphylococci and most strains of enterococci (e.g. Str. faecalis) are resistant to cefaclor. Cefaclor is not active against most strains of Enterobacter spp, Serratia spp, Morganella morganii, Proteus vulgaris and Providencia rettgeri.
5.2. Pharmacokinetic Properties
Absorption
Cefaclor is well absorbed from the gastro-intestinal tract and doses of 250, 500, and 1000 mg by mouth produce peak plasma concentrations of about 7, 15, and 26mcg per mL, respectively at 0.5 to 1 hour. A plasma half-life of 0.5 to 1 hour has been reported; it may be slightly prolonged in renal failure.
Distribution
Cefaclor appears widely distributed in the body distributed in the body; it crosses the placenta and is excreted in low concentrations in the breast milk. About 25% is bound to plasma proteins.
Elimination
Cefaclor is rapidly excreted by the kidneys, up to 85% of a dose appears unchanged in the urine within 8 hours, the greater part within 2 hours. High concentrations of the cefaclor are achieved in the urine within 8 hours of a dose.
5.3. Preclinical Safety Data
There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary of Product Characteristics.
6. PHARMACEUTICAL PARTICULARS 6.1. List of excipients
Capsule contents:
Sodium starch glycolate (derived from potato) Magnesium stearate (E572)
Capsule shell:
Gelatin
Erythrosine (E127)
Patent blue V (E131)
Titanium dioxide (E171).
Ink composition:
Shellac (E904)
Black iron oxide (E172)
Soy lecithin (E322)
Simethicone based emulsion.
Incompatibilities
6.2.
Not applicable.
6.3. Shelf Life
Bottles: 3 years Blisters: 3 years
6.4. Special precautions for storage
The medicinal product does not require any special storage conditions.
6.5. Nature and contents of container
Cefaclor 250 mg capsules are packed in either HDPE bottles or transparent or white opaque PVC or PVC/PVdC aluminium blisters in the following pack sizes:
Blisters: 7, 8, 10, 12, 14, 15, 16, 20, 21, 24, 28, 49, 50, 98 and 100 capsules Bottles: 7, 8, 10, 12, 14, 15, 16, 20, 21, 24, 28, 49, 50, 98 and 100 capsules
Not all pack sizes may be marketed.
6.6. Instruction for use and handling
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Teva Pharma B.V.
Industrieweg 23, P.O. Box 217 3640 AE Mijdrecht The Netherlands
8. Marketing Authorisation Number
PL 14776/0033
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
15/09/2004
10 DATE OF REVISION OF THE TEXT
22/11/2005