TRIMETHOPRIM TABLETS 100 MG - summary of medicine characteristics

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 100 mg of trimethoprim.

Excipients with known effect

Each tablet contains 67.5 mg lactose

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablet

White, normal biconvex tablets, engraved Berk 2H7 or 2H7 with a breakline on reverse.

The breakline is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

4 Clinical Particulars

4.1. Therapeutic Indications

Trimethoprim is indicated for the treatment of susceptible infections caused by trimethoprim -sensitive organisms including urinary tract and respiratory tract infections.

Trimethoprim is also indicated for the prevention of recurrent urinary tract infections.

4.2 Posology and method of administration

Posology

Acute infections:

Adults and children over 12 years of age: 200 mg twice daily

Children 6 years to 12 years: 100 mg twice daily

Children under 6 years of age: This dosage form is not suitable for use in children younger than 6 years, a more suitable dosage form (such as a suspension) should be used in this age group.

Elderly: Depending on kidney function, see special dosage schedule.

Treatment should continue for at least one week but not last longer than two weeks. The first dose can be doubled.

Long-term treatment and prophylactic therapy:

Adults and children over 12 years: 100 mg at night

Children under 12 years of age: This dosage form is not suitable for use in children younger than 12 years, a more suitable dosage form (such as a suspension) should be used in this age group.

Elderly: Depending on kidney function, see special dosage schedule.

Dosage advised where there is reduced kidney function:

Monitoring of renal function and serum electrolytes should be considered particularly with longer term use, in patients with impaired renal function.

Trimethoprim should only be initiated and used in dialysis patients under close supervision from specialists in both infectious disease and renal medicine. Trimethoprim is removed by dialysis.

Monitoring trimethoprim plasma concentration may be considered with long term therapy but the value of this in individual cases should first be discussed with specialists in infectious disease and renal medicine.

Method of administration: Oral

4.3 Contraindi­cations

Trimethoprim is contra-indicated in pregnancy, hypersensitivity to trimethoprim or to any of the excipients listed in section 6.1, blood dyscrasias and severe hepatic insufficiency

4.4 Special warnings and precautions for use

In patients with marked impairment of renal function, care should be taken to avoid accumulation and resulting adverse haematological effects. Monitoring of renal function and serum electrolytes should be considered particularly with longer term use.

Trimethoprim should only be initiated and used in dialysis patients under close supervision from specialists in both infectious disease and renal medicine.

Caution should be exercised in the administration of trimethoprim to patients with actual or potential folate deficiency (e.g. the elderly). Administration of a folate supplement should be considered. Although an effect on folic acid metabolism is possible, interference with haematopoiesis rarely occurs at the recommended dose. If any such change occurs, folinic acid should reverse the effect. Elderly people may be more susceptible and a lower dose may be advisable.

Regular haematological tests should be undertaken in patients receiving long term treatment and those predisposed to folate deficiency. Particular care should be exercised in the haematological monitoring of children on long term therapy. The usual caution in prescribing any drug for women of child bearing age should be exercised with trimethoprim.

Trimethoprim should be used under careful medical supervision in neonates.

Elevations in serum potassium have been observed in some patients treated with trimethoprim. Patients at risk for the development of hyperkalaemia include those with renal insufficiency, poorly controlled diabetes mellitus, or those using concomitant potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, renin angiotensin system inhibitors (eg: ACE inhibitors or renin angiotensin receptor blockers), or those patients taking other drugs associated with increases in serum potassium (e.g. heparin). If concomitant use of the above-mentioned agents is deemed appropriate, monitoring of serum potassium is recommended (see section 4.5).

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Sodium

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

4.5 Interaction with other medicinal products and other forms of interaction

Anti-arrhythmics: Trimethoprim increases plasma concentrations of procainamide.

Antimalarials: Increased antifolate effect when trimethoprim is given with pyrimethamine.

Cytotoxics: Increased risk of haematological toxicity when trimethoprim is given with azathioprine or mercaptopurine. Trimethoprim increases the antifolate effect of methotrexate therefore use should be avoided

Rifampicin may increase the elimination and shorten the elimination half-life of trimethoprim. With bone marrow depressants, trimethoprim may increase the potential for bone marrow aplasia.

Digoxin and phenytoin: Trimethoprim may increase the elimination half-life of phenytoin and digoxin therefore patients should be carefully controlled.

Ciclosporin may increase the nephrotoxicity of trimethoprim.

Trimethoprim may potentiate the anticoagulant effect of warfarin.

Concomitant use of drugs that may increase serum potassium levels may lead to a significant increase in serum potassium. Potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, renin-angiotensin system inhibitors (eg: ACE inhibitors or renin angiotensin receptor blockers) and other potassium increasing substances (eg: heparin). Monitoring of potassium should be undertaken as appropriate (see section 4.4).

4.6 Fertility, pregnancy and lactation

Pregnancy

Trimethoprim is contra-indicated in pregnant women.

Breast-feeding

Trimethoprim is excreted in breast milk but is not contra-indicated for short term use in lactating mothers.

4.7. Effects on Ability to Drive and Use Machines

None known.

4.8 Undesirable effects

The frequencies of adverse events are ranked according to the following: very common (> 1/10), common (> 1/100 to < 1/10), uncommon (> 1/1,000 to < 1/100), rare (> 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).

The most frequent adverse effects at usual doses are pruritus and skin rash (in about 3 to 7% of patients) and mild, gastrointestinal disturbances including nausea, vomiting and glossitis. These effects are generally mild and quickly reversible on withdrawal of the drug.

Not Known: Aseptic meningitis has been reported.

Not Known: Isolated cases of megaloblastic anaemia during prolonged therapy with trimethoprim, with higher doses than those recommended, have been reported. These effects are reversible with discontinuation of therapy and administration of calcium folinate.

Not Known: Leucopenia, thrombocytopenia, agranulocyctosis, methaemoglobinaemia

Not Known: Trimethoprim may affect haematopoiesis.

Rare: Anaphylactic reactions, anaphylactoid reactions have been reported.

Hyperkalaemia (particularly in the elderly and in HIV patients)

Nervous system disorders

Rare: Headache

Rare: Nausea, vomiting, gastrointestinal disturbances

Not Known: Glossitis, sore mouth

Not Known: Disturbances in liver enzyme values, cholestatic jaundice

Not Known: Raised serum creatinine and blood urea nitrogen levels. It is not known however, whether this represents inhibition of creatinine tubular secretion or genuine renal dysfunction

Rare: More severe skin sensitivity or allergic reactions such as photosensitivity, angioedema, erythema multiforme, Stevens-Johnson Syndrome and toxic epidermal necrolysis

Not Known: Pruritus, skin rashes, exfoliative dermatitis, urticaria

Not Known: Myalgia

Not Known: Drug fever

Reporting of suspected adverse reactions

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 Overdose

Symptomatic treatment, gastric lavage and forced diuresis can be used. Depression of haematopoiesis by trimethoprim can be counteracted by intramuscular administration of calcium folinate.

Pharmacological Properties

5.1. Pharmaco­dynamic Properties

ATC code:

J01EA01 Sulfonamides And Trimethoprim (Trimethoprim and derivatives)

Trimethoprim inhibits dihydrofolate reductase and thus prevents the synthesis of tetrahydrofolic acid from dihydrofolic acid. It therefore affects the nucleoprotein metabolism of microorganisms.

5.2. Pharmaco­kinetic Properties

Trimethoprim is readily absorbed from the gastro-intestinal tract and peak concentrations in the circulation occur about 3 hours after a dose is taken. About 45% is bound to plasma proteins. Tissue concentrations are reported to be higher than serum concentrations with particularly high concentrations in the kidneys and lungs. Concentrations in the CSF are about half that of those in blood. The half life is about 10–16 hours. 40–50 % of the dose is excreted unchanged in the urine within 24 hours.

5.3. Preclinical Safety Data

Preclinical information has not been included because the safety profile of trimethoprim has been established after many years of clinical use. Please refer to section 4.

Pharmaceutical Particulars

6.1. List of Excipients

The tablet contains:

Lactose Monohydrate

Maize Starch

Microciystalline Cellulose

Sodium Starch Glycollate (Type A)

Polyvidone

Colloidal Anhydrous Silica

Magnesium Stearate

Stearic Acid

6.2. Incompati­bilities

Not applicable.

6.3. Shelf Life

Blisters: 24 months.

Containers/buckets: 36 months.

6.4. Special Precautions for Storage

No special precautions.

6.5. Nature and Contents of Container

HDPE or polypropylene containers with caps or child resistant closures in packs of 28, 100 and 500 tablets.

Polythene container with lid in a pack of 5000 tablets.

Blister strips in packs of 7, 10, 14, 20, 21, 28, 30, 56, 60, 84, 90, 100, 110,

112, 120, 150, 160 and 168 tablets.

6.6.

Instructions for Use/Handling

Not applicabe.

7   MARKETING AUTHORISATION HOLDER

9 Date of the first authorisation or renewal

17/10/2005