PHENOXYMETHYLPENICILLIN 250 MG FILM-COATED TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Phenoxymethyl­penicillin, 250mg, Film-coated Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains phenoxymethyl­penicillin 250 mg (as phenoxymethyl­penicillin potassium).

For a full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Film-coated tablet

White, circular, biconvex film coated tablets with break line on one side and ‘I 04’ on the other.

The tablet can be divided into equal halves.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Phenoxymethyl­penicillin is indicated in the treatment or prophylaxis of mild to moderately severe infections caused by penicillin sensitive organisms, i.e. those microorganisms whose susceptibility to phenoxymethyl­penicillin is within the range of serum levels attained.

Phenoxymethyl­penicillin is indicated for the treatment of the following infections (See Section 5.1)

Streptococcal infections:

Pharyngitis

Scarlet fever

Skin and soft tissue infections (e.g. erysipelas)

Pneumococcal infections:

Pneumonia

Otitis media

Vincent's gin­givitis and pharyngitis

Phenoxymethyl­penicillin is also indicated for (see Section 5.1):

Prophylaxis of rheumatic fever and/or chorea

Prophylaxis of pneumococcal infection (e.g. in asplenia and in patients with sickle cell disease)

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology and method of administration

Phenoxymethyl­penicillin 250 mg is approximately equivalent to 400,000 units.

Each tablet should be swallowed whole with water, at least 30 minutes before food, as ingestion of phenoxymethyl­penicillin with meals slightly reduces the absorption of the drug.

The usual dosage recommendations are as follows:

Adults:              250–500 mg every six hours.

Children 1–5 years: 125 mg every six hours

6–12 years: 250 mg every six hours

Prophylactic Use

Prophylaxis of rheumatic fever/ chorea: 250 mg twice daily on a continuing basis

Prophylaxis of pneumococcal infection (e.g. in asplenia and in sickle cell disease):

Adults and children over 12 years: 500mg every 12 hours.

Children 6–12 years: 250mg every 12 hours.

Children below 5 years: 125mg every 12 hours.

Children with difficulty in swallowing or in children younger than 5 years of age, tablets are not usually administered. The more appropriate formulation for this age group should be used.

Elderly

The dosage is as for adults. The dosage should be reduced if renal function is markedly impaired.

Renal impairment

The dosage should be reduced if renal function is markedly impaired.

Hepatic impairment

Dosage adjustment may be necessary in patients with impaired liver function when they also have renal failure. In this situation the liver may be a major excretion route

4.3 Contraindi­cations

A history of a previous hypersensitivity reaction to any penicillin is a contraindication.

Attention should be paid to possible cross-sensitivity with other beta-lactam antibiotics e.g. cephalosporins. Severe acute infections should not be treated with phenoxymethyl­penicillin.

4.4 Special warnings and precautions for use

Phenoxymethyl­penicillin should be given with caution to patients with a history of allergy, especially to other drugs. Phenoxymethyl­penicillin should also be given cautiously to cephalosporin-sensitive patients, as there is some evidence of partial cross-allergenicity between the cephalosporins and penicillins. Patients have had severe reactions (including anaphylaxis) to both drugs. If the patient experiences an allergic reaction phenoxymethyl­penicillin should be discontinued and treatment with the appropriate agents initiated. (e.g. adrenaline and other pressor amines, antihistamines and other corticosteroids).

Particular caution should be exercised in prescribing phenoxymethyl­penicillin to patients with an allergic diathesis or with bronchial asthma

Oral Penicillins are not indicated in patients with severe illness or with a gastrointestinal disease that causes persistent nausea, vomiting gastric dilation, cardiospasm, intestinal hypermotility or diarrhoea because absorption may be reduced. Occasionally, patients do not absorb therapeutic amounts of orally administered penicillin.

Streptococcal infections should be treated for a minimum of 10 days and post-therapy cultures should be performed to confirm the eradication of the organisms.

In patients undergoing long-term phenoxymethyl­penicillin treatment the complete and differential blood count, as well as the liver and kidney function, should be monitored.

During long-term treatment attention should also be paid to the potential overgrowth of resistant organisms including Pseudomonas or Candida. If super-infection occurs, appropriate measures should be taken.

Caution should be used when treating patients with a history of antibiotic-associated colitis.

Each tablet contains 28 mg of potassium, which may be harmful to people on low potassium diets and may cause stomach upset, diarrhoea and hyperkalaemia. High doses should be used with caution in patients receiving potassium-containing drugs or potassium sparing-diuretics.

In renal impairment the safe dosage may be lower than usually recommended.

During treatment with phenoxymethyl­penicillin non-enzymatic glucose tests may be falsepositive.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

As penicillins like phenoxymethyl­penicillin are only active against proliferating microorganisms, phenoxymethyl­penicillin should not be combined with bacteriostatic antibiotics such as tetracycline, erythromycin, chloramphenicol and sulphonamides.

Concomitant use of uricosuric drugs (e.g. probenecid and sulfinpyrazone) reduces the excretion of phenoxymethyl­penicillin resulting in increased plasma levels and thus prolongs its action.

Combined use of phenoxymethyl­penicillin and oral anticoagulants (e.g. warfarin) may prolong prothrombin time.

Phenoxymethyl­penicillin may reduce the excretion of methotrexate causing an increased risk of toxicity.

During treatment with phenoxymethyl­penicillin non-enzymatic urinary glucose tests may be false-positive.

Neomycin reduces the absorption of phenoxymethyl­penicillin.

Guar gum may slow the speed of absorption of Phenoxymethyl­penicillin.

Coumarin – common experience in anticoagulant clinics is that INR can be altered by a course of broad-spectrum penicillins such as ampicillin, although studies have failed to demonstrate an interaction with coumarins.

Phenindione – common experience in anticoagulant clinics is that INR can be altered by a course of broad-spectrum penicillins such as ampicillin, although studies have failed to demonstrate an interaction with phenindione.

Thyphoid Vaccines – antibacterials inactive oral typhoid vaccine.

4.6 Fertility, pregnancy and lactation

Pregnancy.

Animal studies with phenoxymethyl­penicillin potassium have shown no teratogenic effects.

Phenoxymethyl­penicillin potassium has been in extensive clinical use and suitability in human pregnancy has been well documented in clinical trials. However, as with other drugs, caution should be exercised when prescribing to pregnant patients.

Lactation

Breast feeding is not contraindicated with phenoxymethyl­penicillin potassium. Trace quantities of phenoxymethyl­penicillin potassium can be detected in breast milk. While adverse effects are apparently rare, two potential problems exist for nursing infant:- modification of bowel flora

– direct effects on the infant such as allergy/sensi­tisation

Caution should therefore be exercised when prescribing for the nursing mother.

4.7 Effects on ability to drive and use machines

There are no effects on ability to drive or to operate machinery.

4.8 Undesirable effects

Hypersensitivity

Potential allergic reactions include urticaria, angioneurotic oedema, erythema multiforme, exfoliative dermatitis, fever, joint pain, serum sickness-like reactions, haemolytic anaemia, interstitial nephritis or anaphylactic shock (which could be fatal) with collapse and anaphylactoid reactions (asthma, purpura, gastrointestinal symptoms). Although these are less common, and take a milder course, in oral treatment than during parenteral penicillin treatment, it should be remembered that all degrees of hypersensitivity, including fatal anaphylaxis, have been observed with oral penicillin.

Gastro-intestinal tract

Phenoxymethyl­penicillin potassium is generally well tolerated. Occasionally soft stools occur and they do not require the interruption of the treatment.

Nausea, diarrhoea, vomiting, stomatitis and glossitis are sometimes seen.

Sustained severe diarrhoea should prompt suspicion of pseudomembranous colitis. As this condition may be life-threatening phenoxymethyl­penicillin should be withdrawn immediately and treatment guided by bacteriologic studies with appropriate antibiotherapy (i.e. vancomycin).

Blood

Eosinophilia, haemolytic anaemia, leukopenia, thrombocytopenia and agranulocytosis are extremely rare. Other possible effects on the blood composition include: neutropenia, haemolytic anaemia and coagulation disorders.

Central nervous system

Central nervous system toxicity, including convulsions, has been reported, especially following high doses or in severe renal impairment. Paraesthesia has been reported with prolonged use.

As with other broad-spectrum antibiotics prolonged use may result in the overgrowth of non-susceptible organisms, e.g. candida. This may present a vulvo-vaginitis.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme (www.mhra.gov.uk/yellowcard) or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

A large overdose may cause nausea, vomiting and diarrhoea. Rarely major motor seizures may occur. There is no known antidote. Symptomatic and supportive therapy is recommended.

Phenoxymethyl­penicillin may be removed by haemodialysis.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Mechanism of action

Phenoxymethyl­penicillin is a broad-spectrum beta-lactam antibiotic with bactericidal action against Gram-positive bacteria and Gram-negative cocci. Its antimicrobial action is similar to that of benzyl penicillin. Phenoxymethyl­penicillin is usually active against the following organisms:

Gram-positive aerobes and anaerobes including

Bacillus anthracis

Clostridium perfringens

Clostridium tetani

Corynebacterium diphtheriae

Erysipelothrix rhusiopathiae

Listeria monocytogenes

Peptostreptococcus spp.

Streptococcus agalactiae (Group B)

Streptococcus pneumoniae

Streptococcus pyogenes (Group A)

Gram-negative including

Neisseria meningitidis

Neisseria gonorrhoeae

Phenoxymethyl­penicillin is inactivated by penicillinase and other beta-lactamases.

Phenoxymethyl­penicillin binds to penicillin-binding proteins located on the inner membrane of the bacterial cell wall.

Phenoxymethyl­penicillin binds to and inactivates these proteins resulting in weakening of the bacterial cell wall and lysis.

5.2 Pharmacokinetic properties

Absorption

Phenoxymethyl­penicillin is stable under acidic conditions so it can be administered by oral route.

Phenoxymethyl­penicillin is rapidly, but incompletely absorbed after oral administration and the absorption level is around 60%. The simultaneous administration of food slightly decreases the peak plasma concentration of phenoxymethyl­penicillin, but does not appear to affect the extent of absorption. Peak plasma concentrations are reached in about 45 minutes. The peak plasma concentration increases approximately in proportion with increased doses. Peak serum concentrations of 3–6 jig per ml have been seen following dosage of 250 mg to 500 mg by mouth.

Distribution

Phenoxymethyl­penicillin is widely distributed round the body tissues and fluids (volume of distribution about 0.2 1 kg-1 of body weight) and more readily penetrates inflamed tissues. It also diffuses across the placenta into foetal circulation and small amounts appear in the milk of nursing mothers. Eighty per cent is reported to be protein bound.

Biotransformation

Phenoxymethyl­penicillin is partially metabolised to inactive penicilloic acid by hydrolysis of the lactam ring. This metabolism occurs in the liver.

Elimination

The plasma half-life of phenoxymethyl­penicillin is about 45 minutes which may increase to four hours in renal failure.

Excretion is by tubular secretion into urine. About 40% of the dose is eliminated in the urine either as under unchanged or as penicilloic acid in the first 10 hours after oral administration. Small excretion occurs in bile.

Impaired absorption is seen in patients with coeliac disease.

5.3 Preclinical safety data

No data of clinical relevance

6.1

Calcium Hydrogen Phosphate Dihydrate

Maize Starch

Microcrystalline Cellulose E460

Magnesium Stearate E572

Basic Butylated Methacrylate

Macrogol 6000

Sodium Laurilsulfate E487

Stearic Acid E570

Titanium Dioxide E171

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Do not store above 25° C.

6.5 Nature and contents of container

Al /PVC blister. Pack sizes of 14, 28, 42, 56, 70, 140 tablets are available

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and handling

No special requirements

7 MARKETING AUTHORISATION HOLDER

Morningside Healthcare Ltd

Unit C, Harcourt Way

Leicester, LE19 1WP, UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 20117/0121

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

01/02/2011