SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Minotrim 10mg/ml Oral Suspension.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Trimethoprim 10 mg/ml For excipients, see 6.1.

3. PHARMACEUTICAL FORM

Suspension

4.    CLINICAL PARTICULARS

4.1    Therapeutic indications

Treatment of susceptible infections caused by trimethoprim-sensitive organisms including urinary and respiratory tract infections and for prophylaxis of recurrent urinary tract infections.

4.2. Posology and Method of Administration

Acute infections:

Adults and children over 12 years: 200 mg (20 ml) twice daily Children 6 years to 12 years: 100 mg (10 ml) twice daily Children 6 months to 5 years: 50 mg (5 ml) twice daily Children 6 weeks to 5 months: 25 mg (2.5 ml) twice daily.

The approximate dosage in children is 8 mg trimethoprim per kg body weight per day.

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 (10 ml) at night Children 6 years to 12 years: 50 mg (5 ml) at night Children 6 months to 5 years: 25 mg (2.5 ml) at night

The approximate dosage in children is 2 mg trimethoprim per kg body weight per day.

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

Dosage advised where there is reduced kidney function:

Creatinine	Plasma creatinine	Dosage advised
clearance(ml/sec)	(micromol/l)
Over 0.45	Men <250	Normal
	Women <175
0.25-0.45	Men 250-600	Normal for 3 days then
	Women 175-400	half dose
Under 0.25	Men >600	Half the normal dose
	Women >400

Trimethoprim is removed by dialysis. However, it should not be administered to dialysis patients unless plasma concentrations can be estimated regularly.

4.3. Contra-indications

Pregnancy, trimethoprim hypersensitivity, blood dyscrasias, severe renal insufficiency where blood levels cannot be monitored.

4.4 Special warnings and precautions for use

Caution should be exercised in the administration of trimethoprim to patients with actual or potential folate deficiency (e.g. elderly) and administration of 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 is seen, 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 long-term treatment.

In neonates, trimethoprim should be used under careful medical supervision.

In patients with impairment of renal function, care should be taken to avoid accumulation.

Blood glucose should be monitored if used concomitantly with repaglinide (see Section 4.5).

4.5 Interaction with other medicinal products and other forms of interaction

ACE inhibitors: The likelihood of hyperkalaemia is increased when ACE inhibitors are taken together with trimethoprim.

Anticoagulants: The anticoagulatory effect of warfarin and other coumarins may be increased when taken together with trimethoprim.

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.

Ciclosporin: Ciclosporin may increase nephrotoxicity of trimethoprim.

Dapsone: Plasma concentrations of trimethoprim and dapsone may increase when taken together.

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 diuretics, eplerenone and thiazide diuretics.

Folate antagonists and anticonvulsants: Trimethoprim may induce folate deficiency in patients predisposed to folate deficiency such as those taking folate antagonists or anticonvulsants.

Lamivudine: Trimethoprim may increase the plasma concentration of lamivudine.

Oestrogens: Trimethoprim may possibly reduce the contraceptive effect of oestrogens.

Oral Typhoid Vaccine: This is inactivated by concomitant administration of anti-bacterials.

Procainamide: Trimethoprim increases plasma concentration of procainamide.

Pyrimethamine: The anti-folate effect may be increased if there is concomitant administration with trimethoprim.

Repaglinide: Trimethoprim may enhance the effect of repaglinide (see Section

4.4).

4.6. Pregnancy and Lactation

Pregnancy is a contra-indication. Although trimethoprim is excreted in breast milk, lactation is not a contra-indication for short-term trimethoprim therapy.

4.7. Effects on Ability to Drive and Use Machines

None known

4.8    Undesirable effects

Nausea, vomiting, gastrointestinal upset and dermatological reactions such as skin rashes and pruritis have been reported in rare instances. These effects are generally mild and quickly reversible on withdrawal of the drug. Disturbances of liver enzyme values and jaundice have been associated with trimethoprim. Photosensitivity and allergic reactions including angioedema and anaphylaxis have been reported. Rarely, erythema multiforme and toxic epidermal necrolysis have occurred. Aseptic meningitis has been reported. Rare cases of Stevens-Johnson syndrome have been reported following administration of trimethoprim. Isolated cases of myalgia and uveitis have occurred. There is an increased risk of hyperkalaemia, especially in patients with impaired renal function and in elderly patients. Trimethoprim may affect haematopoiesis (see Sections 4.4 and 4.5).

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

Treatment of overdosage: 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

Trimethoprim is an antimicrobial agent. The antimicrobial activity is due to selective inhibition of bacterial dihydrofolate reductase.

Trimethoprim is effective in-vitro against most Gram-positive and Gramnegative aerobic organisms, including enterobacteria - E. coli, Proteus, Klebsiella pneumoniae, Streptococcus faecalis, Streptococcus pneumonia, Haemophilus influenzae, and Staphylococcus aureus.

It is not active against Mycobacterium tuberculosis, Neisseria gonorrhoeae, Pseudomonas aeruginosa, Treponema pallidum, or anaerobic bacteria.

5.2 Pharmacokinetic properties

Absorption and half-life:

Trimethoprim is absorbed rapidly and almost completely following oral administration and maximal plasma concentrations are reached after 1-2 hours. Peak plasma concentrations of about 1 pg per ml have been reported after a single dose of 100mg.

The half-life is about 10 hours in patients with normal renal function but up to 20-50 hours in anuric patients.

Distribution:

Trimethoprim is rapidly and widely distributed to various tissues and fluids, including kidneys, liver, spleen, bronchial secretions, saliva and prostatic tissue and fluid, and the tissue concentrations are generally higher than the plasma concentration.

Excretion:

Trimethoprim is predominantly excreted in the urine in unchanged form. Urinary concentrations are generally well above the MIC of common pathogens for more than 24 hours after the last dose.

5.3. Pre-clinical Safety Data

Not relevant (widely used in clinical practice)

6. PHARMACEUTICAL PARTICULARS 6.1. List of Excipients

Carmellose sodium, Microcrystalline cellulose, carboxymethylcellulose sodium, ammonium glycyrrhizinate, methyl parahydroxybenzoate, sorbitolum, anise oil, purified water.

Incompatibilities

Not applicable.

6.3. Shelf Life

3 years

6.4. Special Precautions for Storage

Store below 25°C.

6.5 Nature and contents of container

Plastic bottle: 25 ml and 100 ml.

6.6. Instructions for Use and Handling

No special requirements.

7. MARKETING AUTHORISATION HOLDER

CHEMIDEX PHARMA LIMITED

CHEMIDEX HOUSE, EGHAM BUSINESS VILLAGE

CRABTREE ROAD

EGHAM

SURREY

TW20 8RB

UNITED KINGDOM

8. MARKETING AUTHORISATION NUMBERS

PL 17736/0087

9.    DATE OF FIRST AUTHORISATION/RENEWAL OF

AUTHORISATION

15^th June 2005

10 DATE OF REVISION OF THE TEXT

29/06/2016