PHENOXYMETHYLPENICILLIN 250 MG / 5ML POWDER FOR ORAL SOLUTION - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Phenoxymethyl­penicillin 250mg/5ml Powder for Oral Solution

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 5ml of Oral Solution contains 250mg of Phenoxymethyl­penicillin as Phenoxymethyl­penicillin Potassium.

Excipient(s) with known effect:

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Powder for oral solution

White to off white granular powder, free from agglomerates or caking.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Phenoxymethyl­penicillin and phenoxymethyl­penicillin potassium are indicated in the treatment of mild to moderately severe infections associated with micro-organisms whose susceptibility to penicillin is within the range of serum levels attained with the dosage form.

Phenoxymethyl­penicillin is indicated for the treatment of the following infections (see section 4.4 and 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 inpatients 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

Posology

For oral administration only.

The dosage and frequency of Phenoxymethyl­penicillin depends on the severity and localisation of the infection and expected pathogens.

Phenoxymethyl­penicillin Solution should be taken at least 30 minutes before or 2 hours after food, as ingestion of Phenoxymethyl­penicillin with meals slightly reduces the absorption of the drug.

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

The usual dosage recommendations are as follows:

Prophylactic Use

Prophylaxis of rheumatic fever/chorea: 250mg 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.

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.

Method of Administration

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

4.3 Contraindications

Phenoxymethyl­penicillin is contraindicated in patients known to be hypersensitive to Penicillin or to any of the excipients listed in section 6.1 and should be used with caution in patients with known histories of allergy.

4.4 Special warnings and precautions for use

Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma. All degrees of hypersensitivity, including fatal anaphylaxis, have been observed with oral penicillin. These reactions are more likely to occur in individuals with a history of sensitivity to penicillins, cephalosporins and other allergens. Enquiries should be made for such a history before therapy is begun. If any allergic reaction occurs, the drug should be discontinued and the patient treated with the usual agents (e.g. adrenaline and other pressor amines, antihistamines and corticosteroids).

Oral therapy should not be relied upon for patients with severe illness, or with nausea, vomiting, gastric dilation, achalasia or intestinal hypermotility.

Occasionally patients do not absorb therapeutic amounts of orally administered penicillin.

Administer with caution in the presence of markedly impaired renal function, as safe dosage may be lower than the usually recommended doses.

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.

Prolonged use of antibiotics may promote the over growth of non-susceptible organisms, including fungi. If super infection occurs, appropriate measures should be taken.

This product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Aminoglycosides: Neomycin is reported to reduce the absorption of phenoxymethyl­penicillin.

Anticoagulants: Penicillins may interfere with anticoagulant control.

Bacteriostatic antibiotics: Certain bacteriostatic antibiotics such as Chloramphenicol, Erythromycin and Tetracyclines have been reported to antagonise the bactericidal activity of penicillins and concomitant use is not recommended.

Guar gum: Reduced absorption of phenoxymethyl­penicillin

Methotrexate: Use of Phenoxymethyl­penicillin while taking methotrexate can cause reduced excretion of methotrexate thereby increasing the risk of toxicity.

Probenecid: Reduced excretion of phenoxymethyl­penicillin by competing with it for renal tubular secretion.

Sulfinpyrazone: Excretion of penicillins reduced by sulfinpyrazone.

Typhoid vaccine (oral): Penicillins may inactivate oral typhoid vaccine if ingested concomitantly.

4.6 Fertility, pregnancy and lactationPregnancy:

There are no or a limited amount of data from the use of Phenoxymethyl­penicillin in pregnant women. As a precautionary measure, it is preferable to avoid the use of Phenoxymethyl­penicillin during pregnancy.

Phenoxymethyl­penicillin metabolites are excreted in human milk to such an extent that effects on breastfed newborns are likely.

4.7 Effects on ability to drive and use machines

None known

4.8 Undesirable effects

The most common reactions to oral penicillin are gastrointestinal effects and hypersensitivity reactions. Although hypersensitivity reactions have been reported much less frequently after oral than after parenteral therapy, it should be remembered that all forms of hypersensitivity, including fatal anaphylaxis have been observed with oral penicillin.

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)

Not known (cannot be estimated from the available data).___________­__________

Reporting 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 at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9

5

5.1

Symptoms: A large oral overdose of penicillin may cause nausea, vomiting, stomach pain, diarrhoea, and rarely, major motor seizures. If other symptoms are present, consider the possibility of an allergic reaction. Hyperkalaemia may result from overdosage, particularly for patients with renal insufficiency.

Management: No specific antidote is known. Symptomatic and supportive therapy is recommended. Activated charcoal with a cathartic, such as sorbitol may hasten drug elimination. Penicillin may be removed by haemodialysis.

General properties

ATC classification Pharmacotherapeutic Group: Beta lactamase sensitive natural penicillins ATC Code: J01C E02.

Mechanism of Action

Phenoxymethyl­penicillin acts through interference with the final stage of synthesis of the bacterial cell wall. The action depends on its ability to bind certain membranebound proteins, (penicillin-binding proteins or PBPs) that are located beneath the cell wall. These proteins are involved in maintaining cell wall structure, in cell wall synthesis and in cell division, and appear to possess transpeptidase and carboxypeptidase activity.

PK/PD relationship

The time above the minimum inhibitory concentration (T>MIC) is considered to be the major determinant of efficacy for phenoxymethyl­penicillin.

Mechanism(s) of Resistance:

Phenoxymethyl­penicillin is inhibited by penicillinase and other betalactamases that are produced by certain micro-organisms. The incidence of beta-lactamase producing organisms is increasing.

Mechanisms of resistance

The two main mechanisms of resistance to phenoxymethyl­penicillin are:

Inactivation by bacterial penicillinases and other betalactamases

Alteration of PBPs, which reduce the affinity of the antibacterial agent for the target.

Impermeability of bacteria or efflux pump mechanisms may cause or contribute to bacterial resistance.

EUCAST clinical MIC breakpoints to separate susceptible (S) pathogens from resistant ® pathogens (version 1.0 22.11.210) are:

The susceptibility of streptococci Groups A, C and G and S. pneumoniae to phenoxymethyl­penicillin is inferred from the susceptibility to benzylpenicillin.

Staphylococci: Most staphylococci are penicillinase-producers. Penicillinase producing strains are resistant. The benzylpenicillin breakpoint (shown) will mostly, but not unequivocally, separate beta-lactamase producers from nonproducers.

Streptococcus pneumoniae: For phenoxymethyl­penicillin, report S. pneumoniae with benzylpenicillin MICs above 0.06 mg/L resistant.

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. Expert advice should be sought as necessary when the local prevalence of resistance is such that the utility of the agent in at least some types of infection is questionable.

Streptococcus A, B, C, G

Species for which acquired resistance may be a problem

Staphylococcus aureus

Streptococcus pneumonia

Staphylococcus epidermidis

5.2 Pharmacokinetic properties

Absorption

Rapidly but incompletely absorbed after oral administration (about 60% of an oral dose is absorbed). Calcium and potassium salts are better absorbed than the free acid. Absorption appears to be reduced in patients with coeliac disease. Absorption appears to be more rapid in fasting than non-fasting subjects.

Blood concentration: after an oral dose of 125mg, peak serum concentrations of 200 to 700ng/ml are attained in 2 hours. After an oral dose of 500mg, peak serum concentrations reach 3 to 5micrograms/ml in 30 to 60 minutes.

Half-life: Biological half-life is about 30 minutes, increased to about 4 hours in severe renal impairment.

Distribution

Widely distributed throughout the body and enters pleural and ascitic fluids and also in cerebrospinal fluid when the meninges are inflamed;

Phenoxymethyl­penicillin crosses the placenta and is secreted in the milk; (protein binding 50 to 80% bound plasma proteins).

Biotransformation: It is metabolised in the liver; several metabolites have been identified, including penicilloic acid.

Elimination: Unchanged drug and metabolites are excreted rapidly in the urine. (20% to 35% of an oral dose is excreted in the urine in 24 hours).

5.3 Preclinical safety data

6   PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sucrose

Saccharin Sodium (E954)

Flavour Orange powder (0473075)

Flavour Refreshing powder (0479539) (Menthol)

6.2 Incompatibilities

None known

6.3 Shelf life

24 Months Unopened, 7 days after reconstitution

6.4 Special precautions for storage

Dry powder: Store below 25oC, Store in the original package.

Reconstituted solution: Store up to 7 days at 20C – 80C in a refrigerator.

6.5 Nature and contents of container

Translucent HDPE round bottle with White Round polypropylene CR Cap liner containing 100 ml of oral Solution on reconstitution.