Co-Amoxiclav 375mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Co-amoxiclav 375 mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains co-amoxiclav 250/125 (amoxicillin 250 mg (as trihydrate), clavulanic acid 125 mg (as potassium clavulanate)).
3 PHARMACEUTICAL FORM
Tablets
Pale yellow, oblong, biconvex tablets embossed 375 on one side
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Co-amoxiclav 375mg Tablets are indicated for the short-term treatment of infections of the following, when amoxicillin-resistant ^-lactamase producing strains of bacteria are suspected as the cause. Co-amoxiclav 625 mg Tablets can be used when the infections are more severe.
Infections of the lower and upper respiratory tract including otitis media, acute sinusitis, recurrent tonsillitis, acute exacerbations of chronic bronchitis and bronchopneumonia.
Infections of the skin and soft tissues, particularly cellulitis, animal bites and severe dental abscess with spreading cellulitis.
Infections of the genito-urinary tract and abdomen, in particular cystitis (especially when recurrent or complicated or excluding prostatitis), septic abortion, pelvic or puerperal sepsis and intra-abdominal sepsis.
Co-amoxiclav Tablets have a broad spectrum of antibiotic activity. They can be used to treat bacterial infections caused by Gram-negative and Gram-positive microorganisms that are resistant to amoxicillin due to ^-lactamase production. A comprehensive list of sensitive organisms is provided in Section 5.1.
4.2 Posology and method of administration
The tablets should be taken at the start of a meal to minimise gastro-intestinal disturbance. They should be swallowed whole with fluid, and not broken or chewed.
Usual dosages for the treatment of infection
Adults (including the elderly) and children over 12 years: One tablet three times a day, preferably every 8 hours. Treatment should not exceed 14 days without review by a physician. In severe infections the dose may be doubled to two tablets three times a day.
Dosage for the treatment of dental infections (e.g. abscess): One tablet three times a day for five days.
Use in patients with renal impairment:
Mild impairment, (creatinine clearance >30 ml/min): No change in dosage.
Moderate impairment, (creatinine clearance 10-30 ml/min): One tablet to two tablets 12 hourly.
Severe impairment, (creatinine clearance <10 ml/min): Not more than one tablet 12 hourly.
In patients with hepatic impairment:
Use with caution, monitor hepatic function at regular intervals (see Section 4.4).
4.3 Contraindications
Hypersensitivity to penicillins or to ^-lactamase inhibitors or their combinations, or to other ingredients of the preparation.
A previous history of co-amoxiclav or penicillin associated jaundice/hepatic dysfunction.
4.4 Special warnings and precautions for use
Each Co-amoxiclav Tablet 375 mg contains 24.6 mg of potassium.
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported (see Section 4.8).
Hepatic reactions including moderate and asymptomatic rises in AST and/or ALT and alkaline phosphatases, hepatitis and cholestatic jaundice, which may be severe, have been reported. These hepatic reactions have been reported more commonly with co-amoxiclav than with other penicillins. Signs and symptoms usually occur during or shortly after treatment but in some cases may not occur until several weeks after treatment has ended. Hepatic reactions are usually reversible but they may be severe and, very rarely, deaths have been reported. Hepatic reactions have been reported more frequently in males and elderly patients, particularly those over 65 years. The risk increases with duration of treatment longer than 14 days.
Erythematous rashes have been associated with glandular fever in patients receiving amoxicillin.
Prolonged use of antibiotics may result in overgrowth of non-susceptible organisms.
4.5 Interaction with other medicinal products and other forms of interaction
Bacteriostatic drugs such as chloramphenicol, erythromycin, sulfonamides or tetracyclines may interfere with the bacteriocidal effects of penicillins
Co-amoxiclav may interact with anti-coagulants and platelet aggregation inhibitors to prolong bleeding time and prothrombin time. Patients should be monitored carefully for signs of bleeding.
In common with other broad spectrum antibiotics, co-amoxiclav may reduce the efficacy of oral contraceptives and patients should be warned accordingly.
Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions. There are no data on the concomitant use of co-amoxiclav and allopurinol.
Concurrent treatment with probenecid and penicillins results in increased and more prolonged serum concentrations, prolonged elimination half life and an increased risk of toxicity.
4.6 Fertility, Pregnancy and lactation
Reproduction studies in animals (mice and rats) with orally and parenterally administered co-amoxiclav have shown no teratogenic effects. There is limited experience of the use of Co-amoxiclav Tablets in human pregnancy, and, as with all medicines, use should be avoided, especially during the first trimester, unless considered essential by the physician.
Co-amoxiclav Tablets may be taken whilst breast-feeding although there is a risk of sensitisation, associated with the excretion of trace quantities in breast milk. The risks should be balanced against the benefits of treatment.
4.7 Effects on ability to drive and use machines
None known
4.8 Undesirable effects
Side effects are uncommon and mainly of a mild and transitory nature.
The most common side effects are gastro-intestinal disturbances including diarrhoea, indigestion, nausea and vomiting (see Section 42). Headache, oral candidiasis (sore mouth/tongue or white patches in the mouth or on the tongue) and vaginal candidiasis (vaginal itching, soreness or discharge) have been reported. These may require medical intervention if they continue or become bothersome.
Superficial tooth discolouration has been reported rarely. It can usually be removed with brushing.
Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis) has been reported rarely.
Hepatic effects: See Section 4.4.
Hypersensitivity reactions: In common with other ^-lactam antibiotics angioedema and anaphylaxis have been reported. Urticarial and erythematous rashes sometimes occur. Rarely erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis. bullous exfoliative dermatitis, serum sickness-like syndrome and hypersensitivity vasculitis have been reported. Interstitial nephritis can occur rarely. Treatment should be discontinued if one of these disorders occurs.
Haematological effects: As with other ^-lactams transient leucopenia,
thrombocytopenia and haemolytic anaemia have been reported rarely. Prolongation of bleeding time and prothrombin time has also been reported rarely (see Section 4.5).
CNS effects: CNS effects have been seen very rarely. These include reversible hyperactivity, dizziness, headache and convulsions. Convulsions may occur with impaired renal function or in those receiving high doses.
4.9 Overdose
Overdose is unlikely. Symptoms would include gastrointestinal symptoms and disturbance of the fluid and electrolyte balances. They may be treated symptomatically with attention to the water electrolyte balance. Co-amoxiclav may be removed from the circulation by haemodialysis.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic classification: J01C R02 (combinations of penicillins, including P-1actams).
Amoxicillin is active against a wide range of non-P-lactamase producing aerobic and anaerobic Gram-positive and Gram-negative bacteria. Clavulanic acid increases the range by blocking P-lactamase enzymes. The combination product is effective against bacterial infections caused by Gram-negative and Gram-positive micro-organisms that are resistant to amoxicillin due to P-lactamase production.
Clavulanate by itself has little antibacterial activity; however, in association with amoxicillin it produces an antibiotic agent of broad spectrum with wide application in hospital and general practice.
Susceptible organisms include:
Gram-positive aerobes: Bacillus anthracis1, Corynebacterium spp,
Enterococcus faecalis 1 Enterococcus faecium1, Listeria monocytogenes, Nocardia asteroids, Staphylococcus aureus1, Coagulase negative staphylococci1 (including Staphylococcus epidermidis1), Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus spp, Streptococcus viridans.
Gram-positive anaerobes: Clostridium spp, Peptococcus spp,
Peptostreptococcus spp.
Gram-negative aerobes: Bordetella pertussis, Brucella spp, Escherichia coli1, Gardnerella vaginalis, Haemophilus influenzae1, Helicobacter pylori, Klebsiella spp1, Legionella spp, Moraxella catarrhalis 1 (Branhamella catarrhalis), Neisseria gonorrhoeae 1, Neisseria meningitidis 1, Pasteurella multocida, Proteus mirabilis 1 Proteus vulgaris1, Salmonella spp1,’ Shigella spp1, Vibrio cholerae, Yersinia enterocolitica.
Gram-negative anaerobes: Bacteroides spp1 including B.fragilis, Fusobacterium spp.
5.2 Pharmacokinetic properties
The pharmacokinetics of amoxicillin and clavulanic acid are similar. Peak serum levels of both occur about one hour after oral administration. Absorption is optimised at the start of a meal. Both clavulanic acid and amoxicillin have low levels of serum binding; about 70% remains free in the serum.
Doubling the dosage of co-amoxiclav approximately doubles the serum levels achieved.
5.3 Preclinical safety data
Nothing of relevance to the prescriber which does not appear elsewhere in the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Microcrystalline cellulose, quinoline yellow (E104), titanium dioxide (E171). Crospovidone. Povidone K25, colloidal silicon dioxide, stearic acid, polyethylene glycol 6000, methylhydroxypropylcellulose. saccharin sodium, vanilla flavour, magnesium stearate.
6.2 Incompatibilities
None
6.3 Shelf life
Two years when stored in the original packaging.
6.4 Special precautions for storage
Do not store above 25°C. Store in the original package.
Nature and contents of container
6.5
Brown glass bottle with screw cap containing desiccant. Pack size 21 tablets.
6.6 Special precautions for disposal
None
7 MARKETING AUTHORISATION HOLDER
Athlone Pharmaceuticals Limited Ballymurray,
Co. Roscommon Ireland
8 MARKETING AUTHORISATION NUMBER(S)
PL 30464/0153
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
8 May 2002
10 DATE OF REVISION OF THE TEXT
28th February 2013
Some members of these species of bacteria produce P-lactamase, and are insensitive to amoxicillin alone.