Actimentin 600 Bd Oral Suspension

ACTIMENTIN 600 BD is indicated for short term treatment of acute bacterial otitis media infections when caused by the following sensitive organisms: Haemophilus influenzae, Streptococcus pneumoniae (penicillin MIC < 4 microgram/ml) and Moraxella catarrhalis.

Posology Duration of therapy should be appropriate to the indication and should not exceed 14 days without review. ACTIMENTIN 600 BD is recommended for dosing at 90/6,4 mg/kg/day in two divided doses at 12 hourly intervals for 10 days, in children aged 3 months and older. There is no experience in paediatric patients weighing > 40 kg or in adults. There are no clinical data in children under 3 months of age.

Body Weight (kg) Volume of ACTIMENTIN 600 BD providing 90/6,4 mg/kg/day

• 8: 3,0 ml twice daily
• 12: 4,5 ml twice daily
• 16: 6,0 ml twice daily
• 20: 7,5 ml twice daily
• 24: 9,0 ml twice daily
• 28: 10,5 ml twice daily
• 32: 12,0 ml twice daily
• 36: 13,5 ml twice daily

ACTIMENTIN 600 BD does not contain the same amount of clavulanic acid (as the potassium salt) as any of the other suspensions containing a combination of amoxicillin and potassium clavulanate. Therefore, these suspensions should not be substituted for ACTIMENTIN 600 BD, as they are not interchangeable.

Special populations Hepatic impairment There are insufficient data on which to base a dosage recommendation. Renal impairment: There are no dosing recommendations for ACTIMENTIN 600 BD in patients with renal impairment. Method of administration ACTIMENTIN 600 BD should be taken immediately before a meal. For instructions on reconstitution of ACTIMENTIN 600 BD before administration, see section 6.6.

ACTIMENTIN 600 BD is contraindicated in:

• patients with hypersensitivity to the active substances (amoxicillin or clavulanate), to any of the penicillins or to any of the excipients of ACTIMENTIN 600 BD listed in section 6.1.
• patients with a history of hypersensitivity, including severe immediate hypersensitivity reaction (e.g. anaphylaxis), to another u03b2-lactams (e.g. cephalosporins, carbapenem or monobactam).
• patients with a previous history of jaundice or hepatic dysfunction associated with amoxicillin/clavulanic acid treatment (see section 4.8).
• children under 3 months of age, as there are no clinical data available for this age group. Safety in children under 2 months of age has not been established.

Prescribers must adhere to the principles of antibiotic stewardship. Serious allergic reactions, including anaphylaxis Before initiating therapy with ACTIMENTIN 600 BD, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, beta-lactam medicines or other allergens (see sections 4.3 and 4.8). Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) angioneurotic oedema have been reported in patients on penicillin therapy, including amoxicillin/clavulanic acid. 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 an allergic reaction occurs, ACTIMENTIN 600 BD must be discontinued, and appropriate alternative therapy instituted. Serious anaphylactic reactions require emergency treatment with epinephrine (adrenaline).

Hepatic dysfunction Use ACTIMENTIN 600 BD with caution in patients with evidence of hepatic dysfunction (see sections 4.3 and 4.8). Changes in liver function tests have been observed in some patients receiving amoxicillin/clavulanic acid. It should be used with care in patients with evidence of severe hepatic dysfunction and hepatic function should be monitored at regular intervals (see section 4.2). Transient hepatitis and cholestatic jaundice have been reported. Hepatic events may be severe and fatal. It has been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been reported less frequently in children. In all populations, 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. It has been reported that such hepatic events most frequently occurred in patients with serious underlying disease or taking concomitant medication known to have the potential for hepatic effects (see section 4.8).

Antibiotic-associated diarrhoea Prolonged use may result in overgrowth of non-susceptible organisms. Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life threatening (see section 4.8). Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of any antibiotics. If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, ACTIMENTIN 600 BD treatment should be discontinued immediately and the patient investigated further. Anti-peristaltic medicines are contraindicated in this situation.

Mononucleosis Since ACTIMENTIN 600 BD 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 rash if amoxicillin is used. ACTIMENTIN 600 BD should be avoided if infectious mononucleosis is suspected.

Prothrombin time Abnormal prolongation of prothrombin time (increased international normalised ratio (INR)) has been reported in patients receiving an amoxicillin/clavulanic acid combination with oral anticoagulants (see sections 4.5 and 4.8).

Crystalluria In patients with reduced urine output, crystalluria has been observed less frequently, predominantly with parenteral therapy. During the administration of high doses or overdosage of amoxicillin, it is advisable to maintain adequate fluid intake and urinary output to reduce the possibility of amoxicillin crystalluria (see section 4.9). In patients with bladder catheters, a regular check of patency should be maintained.

Potential for microbial overgrowth Prolonged use may also result in overgrowth of non-susceptible organisms. 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), ACTIMENTIN 600 BD should be discontinued and / or appropriate therapy instituted.

Sensitivity testing / susceptibility data ACTIMENTIN 600 BD use may lead to resistant strains of organisms and, therefore, sensitivity testing should be carried out whenever possible to demonstrate the appropriateness of therapy. In the case that an infection is proven to be due to amoxicillin-susceptible organisms(s), consideration should be given to switching from ACTIMENTIN 600 BD acid to an amoxicillin only medicine in accordance with official guidance. ACTIMENTIN 600 BD should be used in accordance with local official antibiotic-prescribing guidelines and local susceptibility data. Susceptibility to ACTIMENTIN 600 BD will vary with geography and time. Local susceptibility data should be consulted where available, and microbiological sampling and susceptibility testing performed where necessary.

Convulsions Convulsions may occur in patients with impaired renal function or in those receiving high doses (see section 4.8).

Concomitant allopurinol use Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions (see section 4.5).

Acute generalised exanthemous pustulosis (AGEP) The occurrence of a feverish generalised erythema associated with pustula at treatment initiation may be a symptom of AGEP (see section 4.8). This reaction requires treatment discontinuation and contraindicates any subsequent administration of amoxicillin.

Organ system functions Periodic assessment of organ system functions, including renal, hepatic and haematopoietic function is advisable during prolonged treatment.

Leukaemia ACTIMENTIN 600 BD should be given with caution to patients with lymphatic leukaemia since such patients are especially susceptible to amoxicillin-induced skin rashes.

Interference with laboratory test Urine glucose During treatment with amoxicillin, enzymatic glucose oxidase methods should be used whenever testing for the presence of glucose in urine due to false positive results which may occur with non-enzymatic methods. Coombs test The presence of clavulanic acid in ACTIMENTIN 600 BD may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.

Bio-Rad Laboratories Platelia Aspergillus EIA There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving amoxicillin/clavulanic acid who were subsequently found to be free of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported. Therefore, positive test results in patients taking ACTIMENTIN 600 BD should be interpreted cautiously and confirmed by other diagnostic methods.

Maltodextrin ACTIMENTIN 600 BD contains maltodextrin (glucose) as an ingredient of the flavourant. Patients with rare glucose-galactose malabsorption should not take this medicine.

Probenecid Concurrent use of probenecid with ACTIMENTIN 600 BD is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin but does not affect clavulanic acid excretion. Concomitant use of probenecid with ACTIMENTIN 600 BD may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.

Allopurinol The concurrent administration of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions. It is reported that the concurrent administration of allopurinol and ampicillin could substantially increase the incidence of skin rashes in patients receiving both medicines, 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. There are no data on the combination of amoxicillin and potassium clavulanate used concurrently with allopurinol.

Oral anticoagulants Abnormal prolongation of prothrombin time (increased INR) has been reported in patients receiving amoxicillin-clavulanate with oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently with ACTIMENTIN 600 BD (or during addition or treatment withdrawal). Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation (see sections 4.4 and 4.8).

Oral contraceptives ACTIMENTIN 600 BD may affect the gut flora, leading to lower estrogen re-absorption and, subsequently, reduced efficacy of combined oral contraceptives. Patients should be warned accordingly.

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

Mycophenolate mofetil 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 treatment. 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 normally not be required in the absence of clinical evidence of graft dysfunction. However, close clinical monitoring should be performed with concurrent use and shortly after antibiotic treatment.

Alcohol No information is available about the concurrent use of the amoxicillin/clavulanic acid combination, as contained in ACTIMENTIN 600 BD, and alcohol. However, the ingestion of alcohol whilst being treated with some other u03b2-lactam antibiotics has precipitated a disulfiram-like reaction in some patients. Therefore, the ingestion of alcohol should be avoided during and for several days after treatment with ACTIMENTIN 600 BD.

Pregnancy Use should be avoided during pregnancy, as safety in pregnancy has not been established. Results from a single study in women with preterm, premature rupture of the foetal membrane (pPROM) reported that prophylactic treatment with amoxicillin/clavulanic acid may be associated with an increased risk of necrotising enterocolitis in neonates.

Breastfeeding Both amoxicillin and clavulanic acid are excreted into breast milk (nothing is known of the effects of clavulanic acid on the breastfed infant). Consequently, candidiasis and skin rash are possible in breastfed infants. Mothers on treatment with ACTIMENTIN 600 BD should not breastfeed their infants.

There are no data available from studies on the effects on the ability to drive and use machines. However, undesirable effects may occur (e.g. allergic reactions, dizziness, convulsions), which may influence the ability to drive and use machines (see section 4.8).

Summary of the safety profile The most frequently reported adverse drug reactions (ADRs) are diarrhoea, nausea and vomiting.

Tabulated list of adverse reactions Infections and infestations: Frequent: Mucocutaneous candidiasis (including vaginitis, stomatitis and glossitis). Frequency unknown:* Overgrowth of non-susceptible organisms. Blood and lymphatic system disorders: Less frequent: Reversible leucopenia (including neutropenia) and thrombocytopenia. Frequency unknown:* Reversible agranulocytosis, haemolytic anaemia, prolongation of bleeding time and prothrombin time (see section 4.4). Immune system disorders: Frequency unknown:* Angioneurotic oedema, anaphylaxis, serum sickness-like syndrome and hypersensitivity vasculitis (see sections 4.3 and 4.4). Nervous system disorders: Less frequent: Dizziness and headache. Frequency unknown:* Reversible hyperactivity, aseptic meningitis (2) and convulsions (see section 4.4). Gastrointestinal disorders: Frequent: Diarrhoea, nausea and vomiting. Less frequent: Indigestion and gastritis. Frequency unknown:* Antibiotic-associated colitis (including pseudo-membranous colitis and haemorrhagic colitis u2013 see section 4.4), tooth discolouration and black hairy tongue. Hepato-biliary disorders: Less frequent: Moderate rise in aspartate aminotransferase (AST) and / or elevated alanine aminotransferase (ALT). Frequency Unknown:* Hepatitis and cholestatic jaundice. Skin and subcutaneous tissue disorders: Less frequent: Skin rash, pruritis, urticaria and erythema multiforme. Frequency Unknown:* Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative-dermatitis, acute generalised exanthemous pustulosis (see section 4.4) and drug reaction with eosinophilia and systemic symptoms (DRESS). Renal and urinary disorders: Frequency Unknown:* Interstitial nephritis and crystalluria (see section 4.9).

Nausea is more often associated with higher oral doses. If gastrointestinal reactions are evident, it may be reduced by taking ACTIMENTIN 600 BD at the start of a meal. Superficial tooth discolouration has been reported less frequently in children. Good oral hygiene may help to prevent tooth discolouration and can usually be removed by brushing. 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. If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued (see section 4.4).

*Reported post marketing and therefore, the frequency of occurrence is unknown as it cannot be estimated from available data.

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 asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

Symptoms and signs of overdose Gastrointestinal symptoms (nausea, vomiting and diarrhoea) as well as disturbance of the fluid and electrolyte balances may be evident with overdosage. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see section 4.4). Convulsions may occur in patients with impaired renal function or in those receiving high doses.

Treatment of overdose Gastrointestinal symptoms may be treated symptomatically, with attention to the water / electrolyte balance. ACTIMENTIN 600 BD can be removed from the circulation by haemodialysis.