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Section 2 - QUALITATIVE AND QUANTITATIVE COMPOSITION, Section 4.1 -Therapeutic indications, Section 4.2 - Posology and method of administration, Section 4.3 - Contraindications, Section 4.4 - Special warnings and precautions for use, Section 4.5 - Interaction with other medicinal products and other forms of interaction, Section 4.6 - Pregnancy and lactation, Section 4.7 - Effects on ability to drive and use machines, Section 4.8 - Undesirable effects, Section 4.9 - Overdose, Section 5.1 - Pharmacodynamic properties, Section 5.2 - Pharmacokinetic properties, Section 5.3 - Preclinical safety data, Section 6.3 - Shelf life, Section 6.4 - Special precautions for storage, Section 6.6 - Special precautions for disposal
(New text marked in red)
6.6 Instructions for Use/Handling
To reconstitute dissolve in 10 ml Water for Injections (final volume 10.5 ml). Reconstituted solutions are normally colourless; however a transient pink colour may appear during reconstitution.
4.4 Special Warnings and Special Precautions for Use
Before initiating therapy with amoxicillin-clavulanate, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens.
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity (see contra indications).
‘Augmentin’ should be used with caution in patients with evidence of hepatic dysfunction and with care in patients with renal dysfunction when dosage should be adjusted (see 4.2 Posology and Method of Administration).
Amoxicillin-clavulanate should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of amoxicillin.
Prolonged use of an anti-infective agent may result in superinfection by microorganisms including candida resistant to that anti-infective.
The presence of clavulanic acid in amoxicillin-clavulanate may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.
Each 1.2g vial of ‘Augmentin’ contains 1.0 mmol of potassium and 3.1 mmol of sodium. If the parenteral administration of high doses is necessary, the sodium content must be taken into account in patients on a sodium restricted diet.
In patients with reduced urine output crystalluria has been observed very rarely, predominantly with parenteral therapy. During administration of high doses of amoxicillin it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria (see Overdosage).
4.5 Interaction with Other Medicaments and Other Forms of Interaction
Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use of probenecid may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.
Prolongation of bleeding time and prothrombin time have been reported in some patients receiving ‘Augmentin’. ‘Augmentin’ should be used with care in patients on anti-coagulation therapy.
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 amoxicillin-clavulanate and allopurinol.
In common with other antibiotics, amoxicillin-clavulanate may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.
Section 4.4
In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the administration of high doses of Amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of Amoxicillin crystalluria (see Overdosage).
Section 4.8 (whole section rearranged & just crystalluria added)
Data from large clinical trials was used to determine the frequency of very common to rare undesirable effects. The frequencies assigned to all other undesirable effects (i.e., those occurring at <1/10,000) were mainly determined using post-marketing data and refer to a reporting rate rather than a true frequency.
The following convention has been used for the classification of frequency :-
very common >1/10
common >1/100 and <1/10
uncommon >1/1000 and <1/100
rare >1/10,000 and <1/1000
very rare <1/10,000.
Infections and infestations
Common Mucocutaneous candidiasis
Blood and lymphatic system disorders
Rare Reversible leucopenia (including neutropenia) and thrombocytopenia
Very rare Reversible agranulocytosis and haemolytic anaemia. Prolongation of bleeding time and prothrombin time (see Section 4.4 Special warnings and special precautions for use)
Immune system disorders
Very Rare Angioneurotic oedema, anaphylaxis, serum sickness-like syndrome, hypersensitivity vasculitis
Nervous system disorders
Uncommon Dizziness, headache
Very Rare Reversible hyperactivity and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.
Gastrointestinal disorders
Very common Diarrhoea
Common Nausea, vomiting
Nausea is more often associated with higher oral dosages. If gastrointestinal reactions are evident, they may be reduced by taking AUGMENTIN at the start of a meal.
Uncommon Indigestion
Very Rare Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis).
Hepatobiliary disorders
Uncommon A moderate rise in AST and/or ALT and Alkaline Phosphatases has been noted in patients treated with beta-lactam class antibiotics, but the significance of these findings is unknown.
Very Rare Hepatitis and cholestatic jaundice. These events have been noted with other penicillins and cephalosporins.
Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment.
Signs and symptoms usually occur during or shortly after treatment but in some cases may not become apparent until several weeks after treatment has ceased. These are usually reversible. Hepatic events may be severe and in extremely rare circumstances, deaths have been reported.
Skin and subcutaneous tissue disorders
Uncommon Skin rash, pruritus, urticaria
Rare Erythema multiforme
Very Rare Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative-dermatitis, acute generalised exanthemous pustulosis (AGEP)
If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued.
Renal and urinary disorders
Very rare Interstitial nephritis, crystalluria (see Overdosage)
Section 4.9
Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see Section 4.4 Special warnings and special precautions for use).
Amoxicillin has been reported to precipitate in bladder catheters after intravenous administration of large doses. A regular check of patency should be maintained.