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Amoxicillin 250mg Capsules

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains Amoxicillin Trihydrate PhEur equivalent to 250 mg amoxicillin.

3 PHARMACEUTICAL FORM

Capsule, hard.

Hard gelatin capsules with a red cap and white body, plain, unprinted.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Treatment of infection: Amoxicillin capsules are indicated for the oral treatment of bacterial infections caused by amoxicillin sensitive organisms. Such indications include infections of the upper and lower respiratory tract, the genito-urinary tract and the gastro-intestinal tract, Helicobacter pylori eradication in peptic (duodenal and gastric) ulcer disease. Specific indications include ear and soft tissue infections and gonorrhoea. In the acute stages of life threatening infections a period of parenteral anti-infective therapy would be essential before initiating oral continuation therapy.

Prophylaxis of endocarditis: Amoxicillin capsules may be used for the prevention of bacteraemia, associated with procedures such as dental extraction, in patients at risk of developing bacterial endocarditis.

Consideration should be given to official local guidance (e.g. national requirements) on the appropriate use of antibacterial agents. Susceptibility of the causative organisms to the treatment should be tested (if possible), although the therapy may be initiated before the results are available.

4.2 Posology and method of administration

For oral administration only

Treatment of infection:

Adults: For less severe infections the usual oral dose is 250 mg three times daily. In more severe conditions the dosage may be doubled. The recommended maximum daily dose is 6 g, in divided doses.

Short course therapy: Simple acute urinary tract infection: two 3 g doses with 10 -12 hours between the doses. Gonorrhoea: a single dose of 3 g.

Prophylaxis of endocarditis: The usual dose is 3 g, 1 hour prior to the procedure which may result in bacteraemia.

Helicobacter eradication in peptic (duodenal and gastric) ulcer disease:

Amoxicillin is recommended twice daily in association with a proton pump inhibitor and antimicrobial agents as detailed below:

[Omeprazole 40mg daily, Amoxicillin 1g BID, Clarithromycin 500mg BID] x 7 days or

[Omeprazole 40mg daily, Amoxicillin 750mg-1g BID, Metronidazole 400mg TID] x 7 days

Elderly: As for adults.

Dosage in impaired renal function:

The dose should be reduced in patients with severe renal function impairment. In patients with a creatinine clearance of less than 30 ml/min an increase in the dosage interval and a reduction in the total daily dose is recommended (see section 4.4).

Glomerular filtration rate >30ml/min: No adjustment necessary Glomerular filtration rate 10-30ml/min: Amoxicillin max. 500mg BID Glomerular filtration rate <10ml/min: Amoxicillin max. 500mg/day

Children’s dosage

Children weighing more than 40 kg should be given the usual adult dosage.

Children weighing < 40 kg

The capsule formulation of Amoxicillin Capsules BP 250mg may not be suitable for children. In such cases a suspension formulation should be used.

The daily dosage for children is 40 - 90 mg/kg/day in two to three divided doses* (not exceeding 3 g/day) depending on the indication, severity of the disease and the susceptibility of the pathogen (see special dosage recommendations below and sections 4.4, 5.1 and 5.2).

*PK/PD data indicate that dosing three times daily is associated with enhanced efficacy, thus twice daily dosing is only recommended when the dose is in the upper range.

Special dosage recommendation

Tonsillitis: 50 mg/kg/day in two divided doses.

Acute otitis media: In areas with high prevalence of pneumococci with reduced susceptibility to penicillins, dosage regimens should be guided by national/local recommendations.

Prophylaxis for endocarditis: 50 mg amoxicillin/kg body weight given as a single dose one hour preceding the surgical procedure.

Dosage in impaired renal function:

Renal impairment in children under 40 kg:

Creatinine clearance ml/min	Dose	Interval between administration
> 30	Usual dose	No adjustment necessary
10 - 30	Usual dose	12 h (corresponding to 2/3 of the dose)
< 10	Usual dose	24 h (corresponding to 1/3 of the dose)

The capsule formulation of Amoxicillin Capsules BP 250mg may not be suitable for children. In such cases a suspension formulation should be used.

4.3 Contraindications

Amoxicillin should not be used in patients with known or suspected hypersensitivity to penicillins, semi-synthetic penicillins or cephalosporins.

4.4 Special warnings and precautions for use

Prolonged use of anti-infective agent may result in superinfection by organisms resistant to that anti-infective.

In patients with renal impairment, the rate of excretion of amoxicillin will be reduced depending on the degree of impairment and it may be necessary to reduce the total daily unit amoxicillin dosage accordingly.

Serious and occasionally fatal hypersensitivity (anaphylactoid) 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 persons 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 severe reactions when treated with cephalosporin. Before initiating therapy with any penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens.

Erythematous (mornilliform) rashes have been associated with glandular fever in patients receiving amoxicillin.

If allergic reaction occurs, amoxicillin should be discontinued and appropriate therapy should be instituted and discontinuance of amoxicillin therapy considered.

Serious anaphylactoid reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including intubation, should be administered as indicated.

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.

Precaution should be taken in premature children and during the neonatal period: renal, hepatic and haematological functions should be monitored.

4.5 Interaction with other medicinal products and other forms of interaction

When administered concurrently, the following drugs may interact with amoxicillin:

Oral Contraceptives:

In common with other broad spectrum antibiotics, amoxicillin may reduce the efficacy of oral contraceptives and patients should be warned accordingly.

Bacteriostatic antibiotics:

Chloramphenicol, erythromycins, sulfonamides or tetracyclines may interfere with the bactericidal effects of penicillins. This has been demonstrated in vitro; however, the clinical significance of this interaction is not well documented.

Probenecid:

Probenecid may decrease renal tubular secretion of amoxicillin resulting in increased blood levels and/or amoxicillin toxicity.

Drug/Laboratory Test Interactions:

After treatment with amoxicillin, a false-positive reaction for glucose in the urine may occur with copper sulphate tests (Benedict’s solution, fehling’s solution, or Clinitest tablets) but not with enzyme based tests.

Allopurinol

Concurrent administration of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions.

Methotrexate

Excretion of methotrexate is reduced by penicillins; increased risk of toxicity.

Oral typhoid vaccine

The oral typhoid vaccine is inactivated by antibacterials

Sulfinpyrazone

Excretion of penicillins is reduced by sulfinpyrazone.

Anticoagulants

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

Muscle relaxants:

Piperacillin (and possibly other penicillins) enhance the effects of non-depolarising muscle relaxants and suxamethonium.

Antibacterials:

Absorption of phenoxymethylpenicillin (and possibly other penicillins) reduced by neomycin.

4.6 Pregnancy and lactation

Animal studies with amoxicillin have shown no teratogenic effects. Amoxicillin has been in extensive clinical use and its suitability in human pregnancy has been well documented in clinical studies. The product should only be used during pregnancy where potential benefits outweigh the potential risks associated with treatment.

Amoxicillin may be administered during the period of lactation. With the exception of the risk of sensitisation associated with the excretion of trace quantities of amoxicillin in breast milk, there are no known detrimental effects for the breast-fed infant.

4.7 Effects on ability to drive and use machines

None stated.

4.8 Undesirable effects

The following convention has been utilised for the classification of undesirable effects:-

Very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000,<1/100), rare (>1/10,000, <1/1000), very rare (<1/10,000)

The majority of side effects listed below are not unique to amoxicillin and may occur when using other pencillins.

Unless otherwise stated, the frequency of adverse events has been derived from more than 30 years of post-marketing reports.

Infections and Infestations

Very rare: Mucocutaneous candidiasis

Blood and lymphatic system disorders:

Very rare: As with other beta-lactam antibiotics, reversible leucopenia

(including severe neutropenia and agranulocytosis), reversible thrombocytopenia and haemolytic anaemia have been reported.

Prolongation of bleeding time and prothrombin time have also been reported (see section 4.5 Interaction with other medicinal products and other forms of interaction).

Immune System disorders

Hypersensitivity reactions:

As with other antibiotics, severe allergic reactions including angioneurotic oedema, and anaphylaxis (see section 4.4 Special Warnings and Precautions for Use) serum sickness and hypersensitivity vasculitis have been reported rarely.

If hypersensitivity reaction occurs, the treatment should be discontinued. (See also skin and subcutaneous tissue disorders)

Nervous system disorders:

Hyperkinesia, dizziness and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.

Very rare:

Gastrointestinal disorders:

Clinical Trial Data

*Common: Nausea, indigestion and diarrhoea

*Uncommon: Vomiting

Post-marketing data

Very rare Antibiotic associated colitis including pseudomembranous colitis and haemorrhagic colitis have been reported

Black hairy tongue.

Superficial tooth discolouration has been reported in children. This may respond to brushing.

Hepato-biliary disorders:

Very rare: Hepatitis and cholestatic jaundice. A moderate rise in AST and/or

ALT, but the significance of this is unclear.

Skin and subcutaneous tissue disorders

Patients with infectious mononucleosis frequently develop rashes with ampicillin therapy. A similar tendency may be apparent with amoxicillin.

Clinical Trial Data *Common: Skin rash,

*Uncommon: Pruritus and urticaria.

Post Marketing Data

Very rare: Skin reactions such as erythema multiforme and Stevens-Johnson

syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis and acute generalised exanthematous pustulosis (AGEP).(See also Immune System Disorders)

Renal and Urinary Tract disorders:

Very rare: Interstitial nephritis

Very rare: Crystalluria (See section 4.9 Overdose) can occur

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

4.9 Overdose

Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and should be treated symptomatically with attention to the water/electrolyte balance. Amoxicillin crystalluria, in some cases leading to renal failure has been observed (see section 4.4 Special warnings and precautions for use).

Amoxicillin may be removed from the circulation by haemodialysis

5.1 Pharmacodynamic properties

Amoxicillin is a broad spectrum semi-synthetic penicillin. It is bactericidal against a wide range of gram-positive and gram-negative microorganisms. It has been reported that amoxicillin predominantly inhibits side wall synthesis in susceptible bacteria.

5.2 Pharmacokinetic properties

Amoxicillin trihydrate is resistant to inactivation by the acid of gastric secretions and is rapidly absorbed when given by mouth. It is more completely absorbed than ampicillin and is reported to produce peak antibiotic plasma concentrations that are up to 2‘A times as high as from the same dose of ampicillin. Peak plasma amoxicillin concentrations of about 5pg per ml have been observed 1 to 2 hours after a dose of 250mg with detectable amounts present for up to 8 hours. Doubling the dose can produce double the concentrations. The presence of food in the stomach does not appear to diminish absorption significantly.

In preterm infants with gestational age 26-33 weeks, the total body clearance after intravenous dosing of amoxicillin, day 3 of life, ranged between 0.75 -2ml/min, very similar to the inulin clearance (GFR) in this population. Following oral administration, the absorption pattern and the bioavailability of amoxicillin in small children may be different to that of adults. Consequently, due to the decreased CL, the exposure is expected to be elevated in this group of patients, although this increase in exposure may in part be diminished be decreased bioavailability when given orally.

5.3 Preclinical safety data

No information submitted.

6.1 List of excipients

Sodium laurilsulfate, magnesium stearate.

Capsule shell:

Red/white shell: Titanium dioxide (E171), red iron oxide (E172), erythrosine (E127), gelatin.

Red/ivory shell: Titanium dioxide (E171), yellow iron oxide (E172), erythrosine (E127), indigo carmine (E132), gelatin.

6.2 Incompatibilities

None stated.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Store below 25°C in a dry place.

Protect from light.

6.5 Nature and contents of container

Polypropylene tubes with low density polyethylene caps.

Pack sizes: 21, 100, 250, 500 and 1000 capsules.

Blister strips consisting of 250 pm clear PVC and 20 pm hard temper aluminium foil, contained in a carton.

Pack sizes: 15, 21 and 28 capsules.

6.6 Special precautions for disposal

Not applicable.

7 MARKETING AUTHORISATION HOLDER

ATHLONE PHARMACEUTICALS LIMITED

BALLYMURRAY

ROSCOMMON

COUNTY ROSCOMMON

IRELAND

8 MARKETING AUTHORISATION NUMBER(S)

PL 30464/0013

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

30 September 1985 / 29 August 1997

10 DATE OF REVISION OF THE TEXT

12/06/2013

11 DOSIMETRY (IF APPLICABLE)

INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS (IF APPLICABLE)