SYNTOCLAV Film-coated tablet, Powder for oral suspension Ref.[28256] Active ingredients: Amoxicillin Clavulanic acid

In moderate to severe renal impairment dosage adjustment is required.

Caution should be exercised in administration to patients with hepatic impairment or evidence of hepatic dysfunction. In some patients there have been changes in liver function tests, the clinical significance of which is unknown.

There are rare reports of cholestatic jaundice, sometimes severe, usually reversible, the signs and symptoms of which did not appear until several weeks after therapy cessation.

In patients with reduced urine output, crystalluria has been observed very rarely, predominately 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.

Anaphylactoid reactions, which are serious and sometimes fatal, have occurred in patients on penicillin therapy. These reactions are more likely in patients with a history of penicillin sensitivity. The possibility of cross sensitivity in patients known to be hypersensitive to cephalosporins should be considered.

Syntoclav should be administered with extreme caution to patients with asthma, infectious mononucleosis or chronic lymphoid leukaemia due to the increased risk of erythematous rash developing.

There have been reports of prolongation of bleeding time and prothrombin time in some patients on anticoagulant therapy. Caution should be exercised in such patients and the bleeding time monitored.

Prolonged usage of Syntoclav, as with any antibiotic, may result in the overgrowth of non susceptible micro-organisms.

Allopurinol: concurrent use with amoxicillin may increase the possibility of allergic skin reactions.

Anticoagulants: There have been reports of prolongation of the bleeding time and prothrombin time in some patients. Caution should be exercised in administration to patients on anticoagulation therapy.

Oral contraceptives: The efficacy of oral contraceptives may be reduced during Syntoclav therapy. Patients should be cautioned and advised to use additional non hormonal contraception.

Probenecid: Concurrent administration with Syntoclav may result in elevated and prolonged serum levels of amoxicillin due to a decrease in the renal tubular secretion of amoxicillin.

Tetracycline antibiotics: The bactericidal activity of amoxicillin is decreased with concurrent administration of tetracycline antibiotics.

Laboratory tests

Glucose in urine: False positive results may be obtained using test methods relying on copper sulphate reagent.

Pregnancy

Although reproductive studies in rodents gave no evidence of toxicity such studies are not always predictive of behaviour in man. In a single study in women with preterm, premature rupture of the foetal membrane, it was reported that prophylactic treatment with amoxicillin/clavulanic acid may be associated with an increased risk of necrotising enterocolitis in neonates. Use of Syntoclav in pregnancy should be avoided, especially in the first trimester, unless the clinical benefits outweigh the potential unknown risk to the foetus.

Breastfeeding

Small quantities of amoxicillin are excreted in milk. Due to the risk of sensitisation of the infant, caution should be exercised in the administration of Syntoclav during lactation.

There are no known effects on the ability to drive and use machines.

Syntoclav is generally well tolerated and such side effects as occur are usually mild and transitory. The majority of side effects reported in bibliography are of mild and transient action and less than 3% of patients discontinued therapy because of drug related side effects. The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and vomiting.

The ADRs derived from clinical studies and post-marketing surveillance with amoxicillin/clavulanic acid, sorted by MedDRA System Organ Class are listed below.

The following terminologies have been used in order to classify the occurrence of undesirable effects: Very common (>1/10), Common (>1/100 to <1/10), Uncommon (>1/1000to <1/100), Rare (>1/10,000 to<1/1000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).

¹ See section 4.4
² See section 4.4
³ At the site of injection
⁴ Including pseudomembranous colitis and haemorrhagic colitis (see section 4.4)
⁵ A moderate rise in AST and/or ALT has been noted in patients treated with beta-lactam class antibiotics, but the significance of these findings is unknown.
⁶ These events have been noted with other penicillins and cephalosporins (see section 4.4).
⁷ If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued (see section 4.4).
⁸ See section 4.9
⁹ See section 4.4
¹⁰ See sections 4.3 and 4.4

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 the national reporting system.

Not applicable.