Trimethoprim 50mg/5ml Suspension
1.
NAME OF THE MEDICINAL PRODUCT
Trimethoprim 50 mg/5 ml Suspension
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 5 ml contains 50 mg of Trimethoprim Ph.Eur.
For excipients see 6.1.
3. PHARMACEUTICAL FORM
Oral suspension.
A white, opalescent, viscous suspension.
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
Trimethoprim is indicated for the prevention and treatment of urinary tract infections in adults and children, and the treatment of other susceptible infections in adults and children caused by a wide range of trimethoprim sensitive Gm +ve and Gm -ve organisms including Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumoniae, Staphylococcus aureus, E.coli, Enterobacter, Proteus and Streptococcus faecalis.
4.2 Posology and method of administration
For oral administration
Adults & Children over 12 years of age
Treatment of urinary tract infections and all other susceptible infections: 200 mg (20 ml) twice daily.
Long-term prevention of recurrent urinary tract infections: 100 mg (10 ml) at night.
Children 6 weeks to 12 years of age
Treatment of urinary tract infections is based on a dosage of 8 mg/kg body weight daily, subdivided into two equal doses. Suggested regimens are:
50 mg (5 ml) twice daily 100 mg (10 ml) twice daily
6 months - 5 years 6 years - 12 years
Long-term prevention of recurrent urinary tract infection is based on 2 mg/kg body weight daily given as a single dose at night. Suggested regimens are:
6 months - 5 years - 25 mg (2.5 ml) at night
6 years - 12 years - 50 mg (5 ml) at night
Dosage advised where there is reduced kidney function:
|
Creatinine clearance ml/sec |
Plasma creatinine micromol/l |
Dosage advised |
|
Over 0.45 |
Men<250 Women<175 |
Normal |
|
0.25-0.45 |
Men 250-600 Women 175-400 |
Normal for 3 days then half dose |
|
Under 0.25 |
Men>600 Women>400 |
Half the normal dose |
Trimethoprim is removed by dialysis. It should not, however, be administered to dialysis patients unless plasma concentrations can be estimated.
Elderly
Depending on kidney function, see special dosage schedule.
4.3 Contraindications
Trimethoprim is contra-indicated in severe hepatic insufficiency and also in severe renal insufficiency, unless blood trimethoprim concentrations can be monitored regularly. Trimethoprim is contra-indicated in megaloblastic anaemia and other blood dyscrasias. Trimethoprim should not be administered to pregnant women.
Trimethoprim is contra-indicated where there is hypersensitivity to the active ingredient. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
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.
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.
Trimethoprim could cause contraceptive failure in patients who are taking oral contraceptives and have diarrhoea.
4.5 Interaction with other medicinal products and other forms of interaction
Rifampicin may increase the elimination and shorten the elimination half-life of trimethoprim.
Administration of trimethoprim caused an increase in lamivudine exposure. Lamivudine has no effect on the pharmacokinetics of trimethoprim.
Amiodarone - Increased risk of ventricular arrhythmias when trimethoprim is given with amiodarone.
Avoid concomitant use of co-trimoxazole.
Occasional reports suggest that patients receiving pyrimethamine at doses in excess of 25 mg weekly may develop megaloblastic anaemia should co-trimoxazole be prescribed concurrently.
Folate antagonists and anticonvulsants: Trimethoprim may induce folate deficiency in patients predisposed to folate deficiency such as those taking folate antagonists or anticonvulsants.
Bone marrow depressants: Trimethoprim may increase the potential for bone marrow aplasia. Cytotoxics such as azathioprine, mercaptopurine, methotrexate, increase the risk of haematological toxicity when given with trimethoprim.
Phenytoin and Digoxin: Careful monitoring of patients treated with digoxin or phenytoin is advised as trimethoprim may increase plasma concentration of digoxin and phenytoin by increasing their elimination half-life.
Diuretics: In elderly patients concurrently taking diuretics, primarily thiazides, an increased incidence of thrombocytopenia with purpura has been reported. Rare cases of hyponatraemia have been reported in patients treated with trimethoprim and potassium sparing diuretics and/or thiazide diuretics. Hyperkalaemia may be exacerbated by the presence of potassium sparing diuretics, eplerenone and thiazide diuretics.
Ciclosporin: Ciclosporin may increase nephrotoxicity of trimethoprim.
Anticoagulants: The anticoagulatory effect of warfarin and other coumarins may be increased when taken together with trimethoprim.
ACE inhibitors: The likelihood of hyperkalaemia is increased when ACE inhibitors are taken together with trimethoprim.
Procainamide: Trimethoprim increases plasma concentration of procainamide or amantadine.
Oestrogens: Trimethoprim may possibly reduce the contraceptive effect of oestrogens.
Dapsone: Plasma concentrations of trimethoprim and dapsone may increase when taken together.
Repaglinide: Trimethoprim may enhance the effect of repaglinide (see section 4.4).
4.6. Pregnancy and lactation
Trimethoprim is contra-indicated in pregnant women. 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
Trimethoprim would not be expected to affect the ability to drive or operate machinery.
4.8. Undesirable effects
Nausea, vomiting, gastrointestinal upset and headache have been reported. These side effects are rare.
Skin rash, pruritis and urticaria have been reported occasionally. More severe skin sensitivity reactions such as erythema multiforme, Stevens-Johnson syndrome and epidermal necrolysis have been reported rarely.
Photosensitivity, anaphylactic reactions, anaphylactoid reactions and angioedema have been reported rarely.
Disturbances of liver enzyme values and jaundice have been associated with trimethoprim. Isolated cases of aseptic meningitis, myalgia and uveitis have been reported.
There is an increased risk of hyperkalaemia, especially in patients with impaired renal function and in elderly patients. Trimethoprim may affect haemopoiesis (see sections 4.4 and 4.5).
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.
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.
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.
5 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 tetrhydrofolic 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. Pre-clinical safety data
Pre-clinical 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.
6. PHARMACEUTICAL PARTICULARS
6.1. List of excipients
Sorbitol
Agar
Methyl hydroxybenzoate Propyl hydroxybenzoate Polysorbate 80 Saccharin Sodium Purified water
6.2. Incompatibilities
There are no known pharmaceutical incompatibilities.
6.3. Shelf life
36 months unopened.
6.4. Special precautions for storage
Store in the original container. Keep container in the outer carton.
6.5. Nature and contents of container
Amber glass bottles with aluminium pilfer proof screw cap and expanded polyethylene liner. Pack size: 100 ml.
6.6. Instruction for use and handling
Not applicable.
7. MARKETING AUTHORISATION HOLDER
Pinewood Laboratories Limited
Ballymacarbry
Clonmel
Co. Tipperary
Ireland
8. MARKETING AUTHORISATION NUMBER
PL 04917/0065
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
15th July 2005
10 DATE OF REVISION OF THE TEXT
14/09/2016