1. Name Of The Medicinal Product
Cefadroxil 500 mg Capsules
2. Qualitative And Quantitative Composition
One capsule contains 500mg of cefadroxil (as monohydrate).
For excipients, see section 6.1
3. Pharmaceutical Form
capsules, hard
Description: white, opaque capsule containing white to slightly yellowish powder
4. Clinical Particulars
4.1 Therapeutic Indications
Treatment of following infections caused by cefadroxil-susceptible organisms, when an oral therapy is indicated:
- streptococcal pharyngitis and tonsillitis
- bronchopneumonia, bacterial pneumonia
- urinary tract infections: pyelonephritis, cystitis
- skin and soft tissue infections: abscesses, furunculosis, impetigo, erysipela, pyoderma, lymphadenitis
Consideration should be given to official local guidance regarding the appropriate use and prescription of antibacterial agents.
Regarding treatment of meningitis, Streptococcus pyogenes infections and prevention of rheumatic fever see section 4.4 ('Special Warnings and Special Precautions for Use')
4.2 Posology And Method Of Administration
The dosage depends on the susceptibility of the pathogens, the severity of the disease and on the clinical status of the patient (renal and hepatic function).
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Children may benefit of increased posology up to 100mg/Kg/day.
Depending on the severity of the infection, adults may require increased posology.
Chronic urinary tract infection may require a prolonged and intensive treatment with continued testing of susceptibility and clinical monitoring.
*Elderly
As cefadroxil is excreted by renal route, the dosage should be adjusted if necessary as described under impaired renal function.
*Dosage in renal insufficiency:
The dosage should be adjusted according to creatinine clearance rates to prevent accumulation of cefadroxil. In patients with creatinine clearance of 50 ml/min or less, the following reduced dosage schedule is recommended as a guideline:
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+Consideration should be given to official local guidelines regarding the appropriate use of antibacterial agents.
*Dosage in hepatic insufficiency:
No adjustment of posology is necessary.
*Dosage for haemodialysis patients:
Haemodialysis eliminates 63% of 1g of cephalosporin after 6 to 8 hours of haemodialysis. Elimination half-life of cephalosporin is about 3 hours during dialysis.
Patients with haemodialysis should receive one additional dose of 500mg – 1000mg at the end of the haemodialysis.
Mode of administration
Bioavailability is not affected by food and cefadroxil may be taken with meals or on an empty stomach. In case of gastro-intestinal disturbances, it may be administered with food.
The capsules are taken unchewed with a liberal quantity of fluid.
Duration of therapy:
Treatment should be applied for 2 to 3 further days after regression of the acute clinical symptoms or evidence of bacterial eradication has been obtained. In infections caused by Streptococcus pyogenes up to 10 days treatment may be considered.
4.3 Contraindications
− History of or suspected hypersensitivity to cephadroxil, to any other cephalosporin or to any of the excipients.
− History of severe reactions to penicillins or to any other beta-lactam dru gs.
4.4 Special Warnings And Precautions For Use
− Cefadroxil does not penetrate in the CSF and is not indicated for the treatment of meningitis (see section 5.2).
− Penicillin is the first drug of choice for the treatment of the Streptococcus pyogenes and for the prevention of rheumatic fever. Data for cefadroxil are not sufficiently substantial for prophylaxis therapy.
− Special caution should be exercised in patients with history of severe allergies or asthma.
− In patients with a history of non severe hypersensitity to penicillins, or other non-cephalosporin beta –lactam drugs, cefadroxil should be used with special caution as cross allergies occur (incidence 5-10%).
− Renal impairment. Caution is necessary in patients with renal impairment; the dosage must be adjusted according to the grade of renal impairment (see § 4.2 "Posology").
− History of gastro-intestinal disturbances. Cefadroxil should be used with caution in patients with a history of gastro-intestinal disturbances particularly colitis.
− Allergic reactions. Treatment must be discontinued at once if allergic reactions occur (urticaria, exanthema, pruritus, fall of blood pressure and increased heart rate, respiratory disturbances, collapse, etc.) and suitable countermeasures should be taken (sympathomimetics, corticosteroids and/or antihistaminics).
− Prolonged use. Particularly on prolonged use frequent checks on the blood count and regular hepatic and renal function tests are advisable. Superinfections with fungi (e.g. candida) can occur on prolonged treatment with cefadroxil.
− In case of severe and persistent diarrhoea, an antibiotic-associated pseudomembranous colitis should be considered. In that case Cefadroxil must be discontinued immediately and a suitable therapy should be started (e.g. oral vancomycin, 250 mg q.i.d.). Antiperistaltics are contraindicated.
− Severe life-threatening infections or those which require higher posology or repetitive administrations per day may benefit of parenteral cephalosporins.
− The result of the Coombs' test can be transiently positive during or after treatment with cefadroxil.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Contraindication of concomitant use
− Cefadroxil should not be combined with bacteriostatic antibiotics (e.g. tetracycline, erythromycin, sulfonamides, chloramphenicol) since an antagonistic effect is possible.
− Treatment with Cefadroxil in combination with aminoglycoside antibiotics, polymyxin B, colistin or high-dose loop diuretics should be avoided since such combinations can potentiate nephrotoxic effects.
Concomitant use not recommended
− Frequent checks on coagulation parameters are necessary during concomitant long term use of anticoagulants or thrombocyte aggregation inhibitors to avoid haemorrhagic complications.
Precautions
− The concomitant administration of probenicid can produce higher and sustained concentrations of cefadroxil in the serum and in the bile.
− The occurence of diarrhoea may impair the resorption of other medicaments and therefore lead to an impairment of their efficacy.
− Forced diuresis leads to a decrease of cefadroxil blood levels.
− Cefadroxil may attenuate the effect of oral contraceptives.
− Cefadroxil binds to cholestyramine which may lead to reduced bioavailability of cefadroxil.
− The result of the direct Coombs' test can be transiently positive during or after treatment with cefadroxil. This also applies to Coombs' tests carried out in newborns whose mother received treatment with cephalosporins before delivery.
− Urinary sugar should be determined enzymatically (e.g. with test strips) during treatment with cefadroxil since reduction tests can furnish falsely elevated values.
4.6 Pregnancy And Lactation
Although animal studies and clinical experience have not shown any evidence of teratogenicity, the safe use during pregnancy has not been established.
Cefadroxil is present in low concentrations in breast milk; sensitization, diarrhoea or colonization of the infants' mucosa with fungi are possible.
The use of cefadroxil during pregnancy and in lactating mothers should therefore be handled very strictly.
4.7 Effects On Ability To Drive And Use Machines
No effect is known so far.
4.8 Undesirable Effects
Adverse drug reactions occur in about 6% to 7%* of treated patients.
Hypersensitivity reactions:
Common (>1/100, < 1/10)
Pruritus, rash, allergic exanthema, urticaria.
Rare (>1/10 000, < 1/1000)
Angioneurotic oedema, drug fever, serum sickness-like reactions, arthralgia, intertitial nephritis.
Very rare (<1/10 000)
Immediate allergic reaction (anaphylactic shock).
Isolated cases of Stevens Johnson syndrome and erythema multiforma have been reported.
Blood disorders:
Rare (>1/10 000, < 1/1000)
Eosinophilia, thrombocytopenia, leucopenia, neutropenia, agranulocytosis: rare cases during prolonged used, which subside upon discontinuation of therapy.
Very rare (<1/10 000)
Isolated cases of haemolytic anaemia of immunologic origin.
Gastrointestinal disorders:
Common (>1/100, < 1/10)
Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, glossitis.
Very rare (<1/10 000)
Isolated cases of pseudomenbranous colitis have been reported.
Liver disorders:
Rare (>1/10 000, < 1/1000)
Minor elevation of serum transaminases (ASAT, ALAT) and alkaline phosphatases.
Cases of cholestase and idiosyncratic hepatic failure have been reported.
CNS disorders
Very rare (<1/10 000)
Headache, dizziness, nervousness, sleeplessness, fatigue.
Other undesirable effects:
Uncommon (>1/1000, <1/100)
Clinical pictures due to a growth of opportunistic organisms (fungi), such as vaginal mycoses, thrush.
*incidence of suspected adverse reactions in an observational post-marketing study in 904 patients.
4.9 Overdose
No clinical reports are as yet available on cefadroxil in this respect. However in view of experience gained with other cephalosporins the following symptoms are possible: nausea, hallucinations, hyperreflexia, extrapyramidal symptoms, clouded consciousness, or even coma and renal functional impairment. First aid after intake of toxic doses: induce vomiting at once or gastric lavage, if necessary haemodialysis. Monitor and if necessary correct the water and electrolyte balance, monitor renal function.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
General properties
ATC-Code: J01AD09
Pharmacotherapeutic group: Beta-lactam antibiotics, cephalosporins.
Cefadroxil is a cephalosporin for oral administration which inhibits bacterial wall synthesis of actively dividing cells by binding to one or more penicillin-binding proteins. The result is formation of a defective cell wall that is osmotically unstable, and bacterial cell lysis.
Breakpoints
The following MIC (Minimal Inhibitory Concentration) breakpoints according to NCCLS (National Committee for Clinical Laboratory Standards) separate susceptible (S) from intermediately susceptible and intermediately susceptible from resistant ( R) organisms:
S
Susceptibility
The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. The information in the table gives only approximate guidance as to whether microorganisms will be susceptible to cefadroxil.
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(a) prevalence of penicillin-resistance in Concerned Member States
Resistance
Cefadroxil may be active against organisms producing some types of beta-lactamase, for example TEM-1, in low to moderate quantities. However, it is inactivated by beta-lactamases that can efficiently hydrolyse cephalosporins, such as many of the extended-spectrum beta-lactamases and chromosomal cephalosporinases, such as AmpC type enzymes.
Cefadroxil cannot be expected to be active against bacteria with penicillin-binding proteins that have reduced affinity for beta-lactam drugs. Resistance may also be mediated by bacterial impermeability or by bacterial drug efflux pumps. More than one of these four means of resistance may be present in the same organism.
In vitro, oral first generation cephalosporins are less active than penicillins G and V on Gram-positive microorganisms and are less active than aminopenicillins on H. influenzae.
5.2 Pharmacokinetic Properties
General characteristics
− After oral administration cefadroxil is practically completely absorbed.
− Simultaneous intake of food has practically no effect on absorption (AUC).
− After oral doses of 500 mg (1 g) peak plasma concentrations of about 16 (30) g/ml are obtained after 1-1.3 hours.
− Between 18 and 20% of cefadroxil is bound to plasma proteins.
− Cefadroxil is not metabolised.
− Cefadroxil is eliminated far more slowly than comparable oral cephalosporins (half life: about 1.4 h to 2.6 h) so that intervals between doses can be prolonged to 12-24 hours.
− Roughly 90% of the substance is eliminated in unchanged form through the kidneys within 24 hours.
− Cefadroxil may be eliminated from the organism through haemodialysis.
− Cephalosporins do not penetrate in the CSF and should not be used for the treatment of meningitis (see section 4.1 – Therapeutic Indications).
Characteristics in patients with highgrade renal functional impairment
Elimination is retarded, so that interval between doses must be prolonged (see Posology).
5.3 Preclinical Safety Data
Pre-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and reproductive toxicology.
6. Pharmaceutical Particulars
6.1 List Of Excipients
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6.2 Incompatibilities
None known
6.3 Shelf Life
3 years
6.4 Special Precautions For Storage
Store in the original container. Keep container in the outer carton.
6.5 Nature And Contents Of Container
single packs of 10, 12, 14, 16, 20, 30, 40, and 100 (100x1) capsules
hospital packs of 100 (10x10) and 1000 (100x10) capsules
in polyvinylchloride/polyvinylidene (PVC/PVDC)-Alu-blister strips
Not all pack sizes may be marketed.
6.6 Special Precautions For Disposal And Other Handling
No special requirements.
7. Marketing Authorisation Holder
Sandoz Ltd
Frimley Business Park,
Frimley,
Camberley,
Surrey,
GU16 7SR.
United Kingdom
8. Marketing Authorisation Number(S)
PL 4416/0433.
9. Date Of First Authorisation/Renewal Of The Authorisation
24 October 2002
10. Date Of Revision Of The Text
11/2010
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