RANCLAV Film-coated tablet Ref.[115275] Active ingredients: Amoxicillin Clavulanic acid

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can result in myocardial infarction (see section 4.8).

Before initiating therapy with RANCLAV 1 g, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins.

These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins.

If a hypersensitivity reaction occurs, RANCLAV 1 g should be discontinued and the appropriate therapy instituted. Serious anaphylactic reactions may require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids and airway management, including intubation may also be required. Since RANCLAV 1 g contains amoxicillin, an aminopenicillin, it is not the treatment of choice in patients presenting with sore throat or pharyngitis because of the possibility that the underlying cause is infectious mononucleosis, in the presence of which, there is a high incidence of morbilliform rash if amoxicillin is used. RANCLAV 1 g should be avoided if infectious mononucleosis is suspected.

RANCLAV 1 g should be given with caution to patients with lymphatic leukaemia since they are especially susceptible to amoxicillin induced skin rashes.

Prolonged may result in overgrowth of non-susceptible organisms. Pseudomembranous enterocolitis has been reported.

The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Aerobacter, Pseudomonas or Candida), the agent should be discontinued and/or appropriate therapy instituted.

Prolongation of prothrombin time has been reported rarely in patients receiving RANCLAV 1 g. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently.

Periodic assessment of organ function, including renal, hepatic and haemopoietic functions, is advisable during prolonged therapy.

Impaired hepatic function

Changes in liver function tests have been observed in some patients receiving RANCLAV 1 g. Transient hepatitis and cholestatic jaundice has been reported. RANCLAV 1 g should be used with caution in patients with evidence of hepatic dysfunction.

Impaired renal function

In patients with moderate or severe renal impairment RANCLAV 1 g dosage should be adjusted (See section 4.2).

RANCLAV 1 g should not be used in patients with a glomerular filtration rate of less than 30 mL/minute. Caution is needed when administering amoxicillin to patients with syphilis as the Jarisch-Herxheimer reaction may occur in these patients. In patients with reduced urine output, crystalluria (including acute renal injury) has been observed very rarely, predominantly with parenteral therapy.

During the administration of high doses of amoxiciliin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria. In patients with bladder catheters, a regular check of patency should be maintained

The sodium content must be taken into account in patients on a sodium-restricted diet if the administration of high doses is necessary.

The use of RANCLAV 1 g may lead to the selection of resistant strains of organisms and sensitivity testing should, therefore, be carried out whenever possible to demonstrate the appropriateness of therapy Drug-induced enterocolitis syndrome (DIES) has been reported mainly in children receiving amoxicillin/clavulanate (see section 4.8). DIES is an allergic reaction with the leading symptom of protracted vomiting (1-4 hours after drug administration) in the absence of allergic skin or respiratory symptoms. Further symptoms could comprise abdominal pain, diarrhoea, hypotension or leucocytosis with neutrophilia. There have been severe cases including progression to shock.

Concomittant use of Probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin but does not affect clavulanic acid excretion. Concurrent use of probencid with RANCLAV 1 g may result in increased and prolonged blood levels of amoxicillin, but not of clavulanic acid.

RANCLAV 1 g may reduce the efficacy of oral contraceptives and patients should be warned accordingly. The concomitant administration of allopurinol and ampicillin substantially increases the incidence of skin rashes in patients receiving both agents as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricaemia present in these patients.

Tetracyclines and other bacteriostatic medicines may interfere with the bactericidal effects of amoxicillin.

Methotrexate

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

Interaction with laboratory tests

It is recommended that when testing for the presence of glucose in urine during RANCLAV 1 g treatment, enzymatic glucose oxidase methods should be used. Due to the high urinary concentrations of amoxicillin, false positive readings are common with chemical methods.

Pregnancy

The safety of RANCLAV 1 g in pregnancy has not been established.

Lactation

Amoxicillin is distributed in breast milk. Although significant problems in humans have not been documented, the use of amoxicillin by nursing mothers may lead to sensitisation, diarrhoea, candidiasis and skin rash in the infant.

Amoxicillin is excreted in breast milk; there are no data on the excretion of clavulanic acid in human milk. Therefore, caution should be exercised when RANCLAV 1 g is administered to a nursing woman.

Fertility

There is no fertility data available.

Patients should be made aware of the symptoms of dizziness or convulsions (when high doses are used), and should be careful when driving, or operating machinery.

a. Summary of the safety profile

The most frequently reported adverse effects are diarrhoea, nausea, vomiting, indigestion, abdominal pain, skin rashes, urticaria and erythema multiforme, vaginitis, abnormal taste, headache, dizziness, tiredness and hot flushes.

The incidence and severity of adverse effects, particularly nausea and diarrhoea, increased with the higher recommended dose and can be minimised by administering RANCLAV 1 g at the start of a meal. In addition, as these symptoms are especially related to the potassium clavulanate component, where these gastro- intestinal symptoms occur and a higher concentration of amoxicillin is required, consideration should be given to administering amoxicillin separately.

b. Tabulated list of adverse reactions

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

Suspected adverse reactions can also be reported directly to the Holder of certificate of registration via email: pharmacovigilance.africasme@sunpharma.com or tel: +27(0) 12 643 2000.

Not applicable.