Cefadroxil Mylan
SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
Cefadroxil Mylan 1g film-coated tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains cefadroxil monohydrate 1.049g equivalent to 1g of cefadroxil
For the full list of excipients, see section 6.1
3. PHARMACEUTICAL FORM
Film-coated tablet
White to slightly yellowish, oval, biconvex film-coated tablets with a score line on both sides.
The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Infections caused by microorganisms susceptible to cefadroxil:
Infections of the urinary tract,
Infections of the skin and soft tissues,
Infections of the upper respiratory tract.
Consideration should be given to official local guidance or recommendations regarding the appropriate use and prescription of antibacterial agents.
4.2 Posology and method of administration
Posology
The tablets may be divided to facilitate swallowing but not for administration of a 500 mg dose, when instead capsules or suspension are to be chosen.
Adults and children (>40 kg): Infections of the upper respiratory tract, infections of the skin and soft tissues, and infections of the urinary tract:
Usual dose:
500mg – 1g twice a day
Treatment should be applied 2 to 3 further days after clinical symptoms fade away. In the case of streptococcal infections a minimum of 10 days is recommended.
Paediatric population
This product should notbeusedin children under6years.
Patients with impaired kidneyfunction
Thehalf-lifein plasmais prolonged with impaired kidney function. Therecommended doseis 500 mg, but theinterval between doses should be increased. With acreatinineclearanceof 25-50 ml/min adosemaybegivenevery12 hours, with 10-25 ml/min every24 hours andwith creatinine clearanceof less than10 ml/min one every36 hours.
Method of administration
For oral use.
Cefadroxilshould betaken with food. Thetabletsshould beingestedwith plentyof liquid.
4.3 Contraindications
Hypersensitivity, or suspected hypersensitivity,to the active substance, other cephalosporins or to anyof theexcipients listed in section 6.1.
4.4 Specialwarnings andprecautionsforuse
Special caution is calledforwhen known penicillin allergyis present,as cross-allergymay occur.
Asaconsequenceoftreatment with cephalosporins, in exceptional cases a false positiveCoombs test hasbeen reported.
Duringtreatment with cefadroxil, afalse positive reaction forglucosein theurinemayoccurwhenBenedict´s orFehling´s solutions, copper sulfate orClinitest tablets areusedin thetest, butnot in the enzymetest with Clinistix.
4.5 Interaction with othermedicinal products andotherforms ofinteraction
- Theoccurrenceof diarrhoeamayimpair theabsorption ofothermedicaments and thereforelead toan impairment of their efficacy.
- Forced diuresisleads to adecreaseofcefadroxilblood levels.
- Cefadroxilshould not be combined with bacteriostaticantibiotics (e.gtetracycline, erythromycin, sulfonamides, andchloramphenicol) sincean antagonistic effect is possible.
- Treatment with cefadroxil in combination with aminoglycoside antibiotics,polymyxin B, vancomycin,colistin or high-doseloop diuretics should beavoided sincesuch combinations can potentiatenephrotoxic effects.
- Theconcomitant administration ofprobenecid canproducehigher and sustained concentrations of cefadroxilin theserum and in the bile.
As with othercephalosporins (in high doses)frequent checks oncoagulation parameters arenecessaryduringconcomitant long-term useof anticoagulants or thrombocyte aggregation inhibitors to avoid haemorrhagic complications.
4.6 Fertility, pregnancy andlactation
Pregnancy
Studies inanimals did not reveal anyteratogeniceffect.In theabsenceof teratogeniceffects in animals, amalformativeeffect is not expectedin humans.
To present time, substances causingmalformation in humans havebeen shown to be teratogenic in animals duringwell-conducted studies in two species.
Inclinical practice, analysisof alargenumber ofexposedpregnancies did not appear to revealanymalformativeorfoetotoxic effect specificallyrelated tocefadroxil. However, absenceof risk could beconfirmed byepidemiological studies.
Consequently, cefadroxilcan beprescribed during pregnancy, if necessary.
Breast-feeding
Low levels of cefadroxilareexcreted in breast milk and the ingested quantities arelower than therapeuticdoses. Consequently, breast-feedingis possiblewhen takingthis antibiotic. However, breast-feeding (ortreatment) should bediscontinued if theinfantdevelops diarrhoea, candidosis oraskin eruption.
4.7 Effects on ability to driveandusemachines
No effects havebeen observed.
4.8 Undesirable effects
Theadverseeffects arepresentedaccordingto thefrequencyof thecases,
Verycommon (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); veryrare(<1/10,000);not known (cannot beestimated from the available data).
About 6%of patients takingthe preparation sufferfrom undesirableeffects.
Infections and infestations:
Uncommon: Clinical pictures dueto agrowth ofopportunistic organisms (fungi) such as vaginal mycoses or thrush.
- Blood and lymphatic systemdisorders:
Rare: Eosinophilia, thrombocytopenia, leucopenia, neutropenia, agranulocytosis occurduringprolonged usebut subsideupon discontinuation oftherapy.
Not known: haemolyticanaemia.
- Nervous system disorders:
Veryrare: Headache, dizziness, nervousness, sleeplessness, fatigue.
- Gastrointestinal disorders:
Common: Nausea, vomiting, diarrhoea, dyspepsia,abdominal pain, glossitis.
Not known: pseudomembranous colitis hasbeen reported.
- Hepatobiliary disorders:
Rare: Minor elevation ofserum transaminases (ASAT, ALAT) and alkaline phosphatases.
- Skin and subcutaneous tissue disorders:
Common: Pruritus, rash,allergic exanthema, urticaria.
Rare: Angioneuroticoedema, drugfever, serum sickness-likereactions,
Veryrare:Immediate allergicreaction (anaphylacticshock).
Not known: Stevens Johnson syndromeand erythema multiforme havebeen reported.
- Musculoskeletal and connective tissue disorders
Rare: arthralgia
- Renal and urinary disorders:
Rare: interstitial nephritis
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via [To be completed nationally]
4.9 Overdose
Toxicity:Acute toxicityvaries fordifferent substances butgenerallyspeakingappears low.
Incases of impaired kidneyfunction, parenteral administration ofhigh doses has givenriseto neurological symptoms.
Symptoms:Inexceptional cases, anaphylacticshock mayoccur within 20-40 minutes; a fallin blood pressurewith tachycardiaor bradycardia, breathingdifficulties, nausea, vomiting, exanthema, oedema. Toxic reactions: nausea, vomiting, diarrhoea, electrolyticdisorders, reducedconsciousness,muscular fasciculations, myoclonia,cramps, coma. Haemolytic reactions: kidneyinsufficiency, acidosis. Possiblycoagulopathyand impairment ofalready impaired kidneyfunction.
Treatment: When justified; ventricle emptying,charcoal. Symptomatic treatment. Possibly dialysisin toxic reactions and impaired kidneyfunction.
5. PHARMACOLOGICALPROPERTIES
5.1 Pharmacodynamicproperties
Pharmacotherapeuticgroup: Antibacterials forsystemic use,otherbeta-lactam antibacterials, first generation cephlasporins, ATC code: J01DB05
Mechanism of action
Cefadroxilis a semisynthetic cephalosporin derivativefororal administration which inhibits bacterial wallsynthesisof activelydividing cells bybindingto one ormorepenicillin-binding proteins. Theresultis formation of adefectivecellwallthat is osmoticallyunstable. Cefadroxilexhibits time-dependent bactericidal activity.
Breakpoints
ThefollowingMIC breakpoints aresuggested: Susceptible: <1 mg/lResistant: >16 mg/l
Susceptibility
|
Susceptible |
Betahaemolytic streptocci group A, C, G and B Staphylococcus aureus1 Other staphylococci including S. saprophyticus1 Streptococcus pneumoniae and anaerobic streptococci |
|
Intermediately susceptible |
E. coli2 Klebsiella spp. 2 Proteus mirabilis2 Moxarella catarrhalis3 |
|
Resistant |
Citrobacter spp, Enterobacter spp, Proteus ssp (indol positive) Serratia spp Morganella morganii Campylobacter Haemophilus influenzae Pseudomonas spp including Ps. aeruginosa, Clostridium difficile, Listeria monocytogenes, Legionella, Chlamydia and Mycoplasma spp Enterococci Anaerobic gramnegative rods |
1S. aureus and otherstaphylococci includingbetalactamaseproducingstrains
2E. Coli and Klebsiellaspp., P. mirabilis:Considered susceptible in lowerurinarytract infection
3M. catarrhalis: Betalactamaseproducingstrains, which arein majority,areresistant
All betahaemolyticstreptocci aresusceptible to beta lactam antibiotics andno resistancehas yet been observed. Cefadroxilcannot be used against gram positive rods with plasmid mediated betalactamaseproduction (TEM, SHV)as the substancewillbehydrolysedand inactivated. Thus, resistant isolates of E. coli, Klebsiellaspp, and P. mirabilis maybe encountered.
There can becross-resistancewithin the betalactam antibiotics group(penicillins and cefalosporins).
Penicillin resistant pneumococci and meticillin resistant Staphylococcusaureus areresistant to cefadroxil.
Resistancecan develop duringtreatment in the followingspecies: Enterobacter, Citrobacter, Pseudomonas (predominatelyaeruginosa), Morganellaand Serratia.
5.2 Pharmacokineticproperties
Absorption
Cefadroxilis stablein an acid environment, and isabsorbed justas wellinconjunction with foodas without. Maximal serum concentration (approx. 16 microg/ml afterasingle doseof 500 mgcefadroxil) is attained about 1.5 hours after ingestion.
Distribution
About 20%of cefadroxilisbound to serum proteins.
Elimination
Cefadroxilis excreted via glomerular filtration andtubular secretion. After24 hours, approx. 90%of theactive substancewillhavebeenexcreted in the urine. In people with normally functioningkidneys, thehalf-lifeofcefadroxilin serum is about 1 hour 20minutes.
After asingle doseof 1gofcefadroxil, sufficient concentrationsofcefadroxilarepresentin theurineafter 24 hours to combat the most commonlyoccurringurinal tract pathogens.
5.3 Preclinical safety data
Thereis no preclinical data ofrelevanceforthe safety-judgement beyond what has already
been considered in theSummaryof Product Characteristics.
6. PHARMACEUTICALPARTICULARS
6.1 List ofexcipients
Core:
Silica,colloidal anhydrous, sodium laurilsulfate, magnesiumstearate, macrogol 6000, crospovidone, povidone,talc,cellulose microcrystalline.
Film-coating:
Titanium dioxide (E171),hypromellose, talc.
6.2 Incompatibilities
Not applicable.
6.3 Shelf-life
3years.
6.4 Specialprecautionsforstorage
Keep the containerin theouter carton in order to protect from light.
6.5 Natureandcontents ofcontainer
6, 7, 8, 10, 16, 20 and 100 in securitainers– polypropylenecontainers and polypropylenelids.
6, 7, 8, 10, 16, 20 in blister strips– PVC/PVDC and aluminium foil
100x1 in blister unit dose – PVC/PVDC and aluminiumfoil
Not allpack sizes maybemarketed.
6.6 Specialprecautionsfordisposal andotherhandling
No special instructions.
7. MARKETINGAUTHORISATIONHOLDER
[To be completed nationally]
8. MARKETINGAUTHORISATIONNUMBER(S)
[To be completed nationally]
9. DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION
[To be completed nationally]
10. DATEOFREVISIONOF THETEXT
2016-05-19