SPECIAL WARNINGS AND PRECAUTIONS FOR USE

Before initiating therapy with amoxicillin / clavulanic acid, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other beta-lactam agents.

Convulsions may occur in patients with impaired renal function or in those receiving high doses.

Amoxicillin / clavulanic acid 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. Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions

INTERACTION WITH OTHER MEDICINAL PRODUCTS

Oral anticoagulants

Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction. However, there are cases of increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin. If co-administration is necessary, the prothrombin time or international normalized ratio should be carefully monitored with the addition or withdrawal of amoxicillin. Moreover, adjustments in the dose of oral anticoagulants may be necessary.

Methotrexate

Penicillin may reduce the excretion of methotrexate causing a potential increase in toxicity.

Probenecid

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.

Mycophenolate motetil

In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid (MPA) of approximately 50% has been reported following commencement of oral amoxicillin plus clavulanic acid. The change in pre-dose level may not accurately represent changes in overall MPA exposure. Therefore, a change in the dose of mycophenolate mofetil should not normally be necessary in the absence of clinical evidence of graft dysfunction. However, close clinical monitoring should be performed during the combination and shortly after antibiotic treatment.

FERTILITY, PREGNANCY AND LACTATION

Pregnancy

Limited data on the use of amoxicillin/ clavulanic acid during pregnancy in humans do not indicate an increased risk of congenital malformations.

Use should be avoided during pregnancy, unless considered essential by the physician.

Breastfeeding

Both substances are excreted into breast milk Consequently, diarrhea and fungus infection of the mucous membranes are possible in the breastfed infant, so that breast-feeding might have to be discontinued. The possibility of sensitization should be taken into account. Amoxicillin / clavulanic acid should only be used during breastfeeding after benefit / risk assessment by the physician in charge.

UNDESIRABLE EFFECTS

The most commonly reported adverse drug reactions (ADRs) are diarrhea, nausea and vomiting.

OVERDOSE 

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident.

Amoxicillin crystalluria, in some cases leading to renal failure, has been observed.

Convulsions may occur in patients with impaired renal function or in those receiving high doses.

Amoxicillin has been reported to precipitate in bladder catheters, predominantly after intravenous administration of large doses. A regular check of patency should be maintained.

Treatment of intoxication 

Gastrointestinal symptoms may be treated symptomatically, with attention to the water / electrolyte balance.

Amoxicillin/ clavulanic acid can be removed from the circulation by hemodialysis.