Amoxycillin Austell 250/500 mg Capsules

AMOXYCILLIN AUSTELL formulations are indicated for the treatment of mild to moderately severe infections caused by susceptible organisms:

• Upper respiratory tract infections such as sinusitis, otitis media, tonsillitis.
• Lower respiratory tract infections such as bronchitis, lobar and bronchopneumonia.
• Gastro-intestinal infections such as typhoid fever.
• Other infections including Borreliosis (Lyme disease).
• In the following infections, Amoxicillin therapy should be initiated only if there is microbiological evidence that the causative organism is sensitive to Amoxicillin: Skin and soft tissue infections. Urinary tract infections: cystitis, urethritis, pyelonephritis, bacteriuria in pregnancy.
• u201cAs part of combination therapy in established Helicobacter pylori infection, associated with duodenal ulceration.u201d
• Prophylaxis of endocarditis.

Posology

The total daily dose as below is administered in divided doses. The most common regimen is 8 hourly.

Oral administration

Treatment should be continued for 48 to 72 hours beyond the time that a clinical response has been obtained. It is recommended that at least 10 days treatment be given for any infection caused by beta-haemolytic streptococci to prevent the occurrence of acute rheumatic fever or glomerulonephritis. The absorption of AMOXYCILLIN AUSTELL is not affected significantly when taken with food.

Adults and children over 40 kg

Total daily dosage of 750 mg to 3 g administered in divided doses. Maximum recommended dose: 6 g/day in divided doses. Respiratory tract infections: 500 mg administered 8 hourly. Lyme disease: 4 g/day in isolated erythema chronicum migrans and 6 g/day in the case of generalized manifestations, both for a minimum of 12 days. Gonorrhoea: 3 g with 1 g probenecid Eradication of Helicobacter pylori: 750 mg u2013 1 g in combination treatment given 12 hourly for the eradication of established H pylori infection associated with duodenal ulceration for seven days.

Children under 40 kg

20-50 mg/kg/day in divided doses. Maximum recommended dose: 150 mg/kg/day in divided doses. Lyme disease: 20-50 mg/kg/day in isolated erythema chronicum migrans and 100 mg/kg/day in the case of generalized manifestations, both for a minimum of 12 days.

Elderly

No adjustment needed: as for adults unless there is evidence of severe renal impairment (see below).

Renal impairment:

Glomerular filtration rate >30 ml/min: No adjustment needed. Glomerular filtration rate 10-30 ml/min: Maximum 500 mg 12 hourly. Glomerular filtration rate <10 ml/min: Maximum 500 mg daily.

In patients receiving peritoneal dialysis: Maximum 500 mg daily.

Method of administration

AMOXYCILLIN AUSTELL is for oral administration.

• Hypersensitivity to the amoxicillin trihydrate, to any of the penicillins or to any of the excipients listed in section 6.1.
• Hypersensitivity to penicillins or to cephalosporins. Cross-sensitivity between penicillins and cephalosporins is well documented.
• History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam medicine (e.g. a cephalosporin, carbapenem or monobactam).
• AMOXYCILLIN AUSTELL should not be given to patients with infectious mononucleosis, since they are especially susceptible to amoxycillin-induced skin rashes, patients with lymphatic leukaemia and patients with hyperuricaemia being treated with allopurinol, may be at increased risk of developing skin rashes.

Hypersensitivity reactions

Before initiating therapy with amoxicillin, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam medicines (see sections 4.3 and 4.8). Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous 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). These reactions are more likely to occur in individuals with a history of penicillin and in atopic individuals. If an allergic reaction occurs, amoxicillin therapy must be discontinued and appropriate alternative therapy instituted.

Drug-induced enterocolitis syndrome (DIES) has been reported mainly in children receiving amoxicillin (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.

Non-susceptible microorganisms

Amoxicillin is not suitable for the treatment of some types of infection unless the pathogen is already documented and known to be susceptible or there is a very high likelihood that the pathogen would be suitable for treatment with amoxicillin (see section 5. 1). This particularly applies when considering the treatment of patients with urinary tract infections and severe infections of the ear, nose and throat.

Convulsions

Convulsions may occur in patients with impaired renal function or in those receiving high doses or in patients with predisposing factors (e.g. history of seizures, treated epilepsy or meningeal disorders (see section 4.8).

Renal impairment

In patients with renal impairment, the dose should be adjusted according to the degree of impairment (see section 4.2).

Skin reactions

The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis (AGEP, see section 4.8). This reaction requires amoxicillin discontinuation and contra-indicates any subsequent administration. Amoxicillin 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.

Jarisch-Herxheimer reaction

The Jarisch-Herxheimer reaction has been seen following amoxicillin treatment of Lyme disease (see section 4.8). It results directly from the bactericidal activity of amoxicillin on the causative bacteria of Lyme disease, the spirochaeta Borrelia burgdorferi. Patients should be reassured that this is a common and usually self-limiting consequence of antibiotic treatment of Lyme disease.

Overgrowth of non-susceptible microorganisms

Prolonged use may occasionally result in overgrowth of non-susceptible organisms. Antibiotic-associated colitis has been reported with nearly all antibacterial medicines 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. Should antibiotic-associated colitis occur, amoxicillin should immediately be discontinued, a medical practitioner consulted and an appropriate therapy initiated. Anti-peristaltic medicinal products are contra-indicated in this situation.

Prolonged therapy

Periodic assessment of organ system functions; including renal, hepatic and haematopoietic function is advisable during prolonged therapy. Elevated liver enzymes and changes in blood counts have been reported (see section 4.8).

Anticoagulants

Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation (see section 4.5 and 4.8).

Crystalluria

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 amoxicillin, 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 (see sections 4.8 and 4.9).

Interference with diagnostic tests

Elevated serum and urinary levels of amoxicillin are likely to affect certain laboratory tests. Due to the high urinary concentrations of amoxicillin, false positive readings are common with chemical methods. It is recommended that when testing for the presence of glucose in urine during amoxicillin treatment, enzymatic glucose oxidase methods should be used. The presence of amoxicillin may distort assay results for oestriol in pregnant women.

Probenecid decreases the renal tubular secretion of AMOXYCILLIN AUSTELL. Concurrent use with AMOXYCILLIN AUSTELL may result in increased and prolonged blood concentrations of AMOXYCILLIN AUSTELL AMOXYCILLIN AUSTELL 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 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.

Tetracyclines and other bacteriostatic drugs may interfere with the bactericidal effects of AMOXYCILLIN AUSTELL.

Interaction with Laboratory tests

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

Oral anticoagulants

Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction. However, in the literature 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 normalised ratio should be carefully monitored with the addition or withdrawal of amoxicillin. Moreover, adjustments in the dose of oral anticoagulants may be necessary (see sections 4.4 and 4.8).

Methotrexate

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

Pregnancy

The safety of AMOXYCILLIN AUSTELL in pregnancy has not been established. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Limited data on the use of amoxicillin during pregnancy in humans do not indicate an increased risk of congenital malformations.

Breastfeeding

AMOXYCILLIN AUSTELL is distributed into breast milk. Although significant problems in humans have not been documented, the use of AMOXYCILLIN AUSTELL by nursing mothers may lead to sensitization, diarrhoea, candidiasis and skin rash in the infant, so that breast-feeding might have to be discontinued.

Fertility

There are no data on the effects of amoxicillin on fertility in humans. Reproductive studies in animals have shown no effects on fertility.

No studies on the effect on the ability to drive and use machines have been performed. 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).

Tabulated list of adverse reactions

The table below shows all adverse drug reactions (ADRs) observed during clinical trials and postmarket spontaneous reports with amoxicillin.

System Organ Class Frequency

Frequent Less Frequent Not known

Infections and infestations -- Mucocutaneous candidiasis --

Blood and lymphatic system disorders -- Reversible leucopenia (including severe neutropenia or agranulocytosis), reversible thrombocytopenia and haemolytic anaemia. Prolongation of bleeding time and prothrombin time (see section 4.4). --

Immune system disorders -- Severe allergic reactions, including angioneurotic oedema, anaphylaxis, serum sickness and hypersensitivity vasculitis (see section 4.4). Jarisch-Herxheimer reaction (see section 4.4).

Nervous system disorders -- Hyperkinesia, dizziness and convulsions (see section 4.4). Headache. Aseptic meningitis

Cardiac disorders -- -- Kounis syndrome

Gastrointestinal disorders *Diarrhoea and nausea Indigestion, abdominal pain *Vomiting Antibiotic associated colitis (including pseudomembraneous colitis and haemorrhagic colitis see section 4.4). Black hairy tongue Drug-induced enterocolitis syndrome

Hepatobiliary disorders -- Hepatitis and cholestatic jaundice. A moderate rise in AST and/or ALT. --

Skin and subcutaneous tissue disorders *Skin rash *Urticaria and pruritus Skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis, acute generalised exanthematous pustulosis (AGEP) (see section 4.4) and drug reaction with eosinophilia and systemic symptoms (DRESS). Linear lgA disease

Renal and urinary disorders -- Interstitial nephritis Crystalluria (including acute renal injury)

Miscellaneous -- Superficial tooth discolouration --

*The incidence of these AEs was derived from clinical studies involving a total of approximately 6,000 adult and paediatric patients taking amoxicillin.

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 HCR via [email protected]

Symptoms and signs of overdose: Gastrointestinal symptoms (such as nausea, vomiting and diarrhoea) and disturbance of the fluid and electrolyte balances may be evident. 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 (see sections 4.4 and 4.8).

Treatment of intoxication

Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance. Amoxicillin can be removed from the circulation by haemodialysis.