Orasil 250 mg and 500 Capsules

ORASIL is indicated for the treatment of mild to moderately severe infections caused by susceptible non-penicillinase-producing organisms:

• Upper Respiratory tract infections such as sinusitis, pharyngitis, epiglottitis and tonsillitis.
• Lower respiratory tract infections such as acute and chronic bronchitis, lobar and bronchopneumonia.
• Otitis media
• Gastrointestinal infections such as typhoid fever and Salmonella
• Uncomplicated gastroenteritis and enteric fever
• Other infections including Borreliosis (Lyme disease).
• Skin and soft tissue infections.
• Urinary tract infections: cystitis, urethritis, pyelonephritis, bacteriuria in pregnancy.
• As part of combination therapy in established Helicobacter pylori infection, associated with duodenal ulceration.
• Prophylaxis of endocarditis.

The total daily dose as below is administered in divided doses. The most common regimen is 8 hourly. The absorption of ORASIL is not affected significantly when taken with food.

Posology

Adults and children over 40 kg: A 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 generalised manifestations, both for a minimum of 12 days.

Eradication of Helicobacter pylori: 750 mg - 1 g in combination treatment given 12 hourly for the eradication of established H. pylori infection associated with duodenal ulceration for seven days.

Special Populations

Paediatric Population

Children under 40 kg: 20 - 50 mg/kg/day in divided doses. Maximum recommended dose: 150 mg/kg/day in divided doses.

Lyme disease: 25 - 50 mg/kg/day in isolated erythema chronicum migrans and 100 mg/kg/day in the case of generalised 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.

Prophylaxis of Endocarditis

Prophylaxis with alternative antibiotics should be considered if the patient has received penicillin within the previous month or is allergic to penicillin. For dental, oral or upper respiratory tract procedures: Prophylaxis for patients undergoing dental extraction, scaling or surgery involving gingival tissues, tonsillectomy, adenoidectomy, bronchoscopy with a rigid bronchoscope and surgical procedures that involve respiratory mucosa.

For patients NOT having a general anaesthetic: Adults: 2 g orally, 1 hour before the procedure. Children: 50 mg/kg, 1 hour before the procedure. Childrenu2019s dose not to exceed the adult dose.

Method of Administration

For oral administration only.

Hypersensitivity to amoxicillin, penicillin, any of the cephalosporins or to any of the excipients (see section 6.1). Amoxicillin as contained in ORASIL is a penicillin and should not be given to patients with a history of hypersensitivity to u03b2-lactam antibiotics (e.g. carbapenem or monobactam). Cross-sensitivity between penicillin and cephalosporin is well documented. Potential cross allergy to other beta-lactams such as cephalosporins should also be taken into account.

Prescribers must adhere to the principles of antibiotic stewardship. Hypersensitivity reactions Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. 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 a cephalosporin. Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can result in myocardial infarction (see section 4.8). Drug-induced enterocolitis syndrome (DIES) has been reported mainly in children receiving amoxicillin, as contained in ORASIL (see section 4.8). DIES is an allergic reaction with the leading symptom of protracted vomiting (1-4 hours after medicine intake) 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. Serious anaphylactic reactions may require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids and airway management, including intubation, may also be required.

Non-susceptible microorganisms Amoxicillin is not suitable for the treatment of some types of infections 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. Amoxicillin, an aminopenicillin, 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 (see sub-header u2018Skin reactionsu2019).

There is insufficient evidence at present to show that ORASIL penetrates into the cerebrospinal fluid in therapeutic quantities and it should, therefore, not be used in the treatment of cerebrospinal infections. The use of ORASIL 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 (see Section 4.6).

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).

Impaired hepatic function: Changes in liver function tests have been observed in some patients receiving amoxicillin such as in ORASIL. It should be used with care in patients with evidence of severe hepatic dysfunction. Transient hepatitis and cholestatic jaundice have been reported.

Skin reactions The occurrence at the treatment initiation of 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 contraindicates 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. Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in patients taking beta-lactam antibiotics. When SCAR is suspected beta-lactam antibiotics should be discontinued.

ORASIL should preferably not be used in patients with lymphatic leukaemia and in patients with hyperuricaemia being treated with allopurinol since they are especially susceptible to amoxicillin induced skin rashes. The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur, the agent should be discontinued and/or appropriate therapy instituted.

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 spirochete Borrelia burgdorferi. Patients should be reassured that this is a common and usually self-limiting consequence of the antibiotic treatment of Lyme disease. Caution is needed when administering amoxicillin to patients with syphilis, as the Jarisch-Herxheimer reaction may occur in these patients.

Overgrowth of non-susceptible microorganisms Prolonged use may occasionally result in overgrowth of non-susceptible organisms. Antibiotic-associated colitis and pseudomembranous colitis have been reported with amoxicillin, 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 or colitis during, or subsequent to, the administration of any antibiotics (this may occur up to several weeks after cessation of ORASIL therapy). Should prolonged or significant diarrhoea, abdominal cramps, or antibiotic-associated colitis occur, amoxicillin should immediately be discontinued, a physician consulted and appropriate therapy initiated. Antiperistaltic 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). The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur, ORASIL should be discontinued and/or appropriate therapy instituted.

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 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. The presence of high urinary concentrations of ORASIL can cause precipitation of the product in urinary catheters. Therefore, in patients with bladder catheters, a regular check of patency should be maintained (see section 4.8 and 4.9).

Use in Lactation Amoxicillin is excreted in the milk. Therefore, caution should be exercised when ORASIL is administered to a nursing woman.

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 also distort assay results for oestriol in pregnant women.

Due to amoxicillinu2019s effect on intestinal flora, the absorption of other medicines may be affected.

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.

Allopurinol

Concurrent administration of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions (see section 4.4).

Digoxin

The absorption of concurrently administered digoxin may be increased during treatment with ORASIL.

Tetracyclines

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

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 warfarin and prescribed a course of amoxicillin. If coadministration 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

Serum methotrexate levels should be closely monitored in patients who receive ORASIL and methotrexate simultaneously. Penicillins may reduce the excretion of methotrexate, probably by competition at the common tubular secretion system, causing a potential increase in toxicity.

Oral Contraceptives

ORASIL may decrease the efficacy of oestrogen-containing oral contraceptives, and patients should be warned accordingly.

Other forms of interactions: Forced diuresis leads to a reduction in blood concentrations by increased elimination of ORASIL. ORASIL may interfere with protein testing when colorimetric methods are used.

Women of childbearing potential / Contraception in males and females Concurrent use of ORASIL and oral contraceptives decreases the efficacy of the oral contraceptive. Patients should be strongly advised to use an alternative or additional method of contraception while taking this medicine (see section 4.5).

Pregnancy

The safety of ORASIL in pregnancy has not been established.

Breastfeeding

Amoxicillin is excreted into breast milk in small quantities with the possible risk of sensitisation. Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breast-feeding might have to be discontinued. ORASIL should therefore be used with caution when administered to lactating women.

Fertility

There is no data available on the effects of ORASIL on fertility.

ORASIL may cause allergic reactions, dizziness, or convulsions which may influence the ability to drive and use machines (see section 4.8). ORASIL may have an effect on the mental and/or physical abilities to perform or execute tasks or activities requiring mental alertness, judgment and/or sound coordination and vision (see section 4.8).

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

Tabulated summary of adverse reactions

Description of selected adverse reactions

1. If gastro-intestinal reactions are evident, they may be reduced by taking ORASIL at the start of a meal.
2. Whenever such reactions occur, treatment should be discontinued.
3. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.
4. The events may be severe and occur predominantly in adult or elderly patients. 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. The hepatic effects are usually reversible. However, in extremely rare circumstances, death has been reported. These have almost always been cases associated with serious underlying disease or concomitant medication.
5. A moderate rise in Aspartate transaminase (AST) or SGOT and/or Alanine transaminase (ALT) or SGPT has been noted in patients treated with amoxicillin, but the significance of these findings is unknown.
6. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly.
7. It can be removed by brushing.
8. Serious and occasional fatal hypersensitivity (anaphylactic) reactions and angioneurotic oedema can occur. In the event of an anaphylactic reaction, immediate treatment with adrenalin, oxygen, corticosteroids and antihistamines should be initiated.
9. Convulsions may occur with impaired renal function or in those receiving high doses.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicine are 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 Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

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. 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 and electrolyte balance. Amoxicillin can be removed from the circulation by haemodialysis.