PRODUCT SUMMARY

1. NAME OF THE MEDICINAL PRODUCT TRIMETHOPRIM TABLETS BP 100mg

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 100mg Trimethoprim

3. PHARMACEUTICAL FORM

White uncoated tablets.

Clinical Particulars

4.1    Therapeutic Indications

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

•    Long-term prophylaxis of recurrent urinary tract infections

4.2 Posology and Method of Administration

Posology Acute infections:

Treatment should continue for a period of between three days (e.g. uncomplicated bacterial cystitis in women) and two weeks according to the nature and severity of infection. The first dose can be doubled.

♦    Adults and children over 12 years: 200mg twice daily.

♦    Children 6-12 years: 100mg twice daily.

♦    Children under 6 years of age: Not recommended; a more suitable dosage form should be used in this age group.

♦    Elderly: Dosage is dependent upon kidney function; see special dosage schedule.

Long-term treatment and prophylactic therapy:

♦    Adults and children over 12 years: 100mg at night.

♦    Children 6-12 years: 50mg at night. Where a single daily dose is required, dosage at bedtime may maximise urinary concentrations. The approximate dosage in children is 2mg trimethoprim per kg body weight per day.

♦    Elderly: Dosage is dependent upon kidney function; see special dosage schedule

Advised dosage schedule where there is reduced kidney function:

Creatinine Clearance	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. However, it should not be administered to dialysis patients

unless plasma concentrations can be estimated regularly.

Route of administration For oral administration.

4.3 Contraindications

Hypersensitivity to trimethoprim or any of the excipients; pregnancy; blood dyscrasias, severe renal insufficiency where blood levels cannot be regularly monitored.

4.4 Special Warnings and Precautions for Use

Administer with care to patients with impaired renal function. Regular haematological examination should be performed during long-term therapy.

Caution should be exercised in the administration of trimethoprim to patients with actual or potential folate deficiency (e.g. the elderly) and administration of folate supplement should be considered.

Although an effect on folate 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.

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

4.5 Interactions with other Medicaments and other forms of Interaction

Special care is necessary patients receiving pyrimethamine therapy in addition to trimethoprim.

Bone marrow depressants - trimethoprim may increase the potential for bone marrow aplasia.

Rifampicin may increase the elimination and shorten the elimination half-life of trimethoprim.

Phenytoin and digoxin - the patient should be carefully controlled as trimethoprim may increase the elimination half-life of phenytoin and digoxin. Trimethoprim may potentiate the anticoagulant effect of warfarin Ciclosporin may increase the nephrotoxicity of trimethoprim.

4.6 Pregnancy and Lactation

Trimethoprim should not be given to pregnant women, premature infants or infants during the first few weeks of life.

Although trimethoprim is excreted in breast milk, it is not necessarily contraindicated for short-term therapy during lactation.

4.7 Effects on Ability to Drive and Use Machines

None known.

4.8 Undesirable Effects

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.

Blood and lymphatic system disorders

Leucopenia, megaloblastic anaemia, thrombocytopenia, agranulocyctosis, hyperkalaemia (particularly in the eldery and in HIV patients), methaemoglobinaemia. Trimethoprim therapy may affect haematopoiesis.

Nervous system disorders Aseptic meningitis.

Gastrointestinal disorders

Nausea, vomiting, glossitis, gastrointestinal disturbances, sore mouth. Hepatobiliary disorders

Disturbances in liver enzyme values, cholestatic jaundice.

Renal and Urinary disorders

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.

Skin and subcutaneous tissue disorders

Pruritus, skin rashes, exfoliative dermatitis, urticaria. More severe skin sensitivity or allergic reactions such as photosensitivity, angioedema, erythema multiforme, Stevens Johnson syndrome and epidermal necrolysis have been reported rarely.

Musculoskeletal system disorders Myalgia.

General disorders and administration site conditions Anaphylaxis, drug fever, headache.

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 alkaline diuresis may be used. Depression of haematopoiesis by trimethoprim may be countered with intramuscular calcium folinate.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

Pharmacotherapeutic group: Systemic antibacterial.

ATC Code: J01EA01

Mechanism of action: Trimethoprim is a dihydrofolate reductase inhibitor which affects the nucleoprotein metabolism of micro-organisms by interference in the folic-folinic acid systems.

Trimethoprim is effective in vitro against a wide range of Gram-positive and aerobic Gram-negative organisms, including enterobacteria Escherica coli, Proteus, Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus faecalis, Haemophilus influenzae and Staphylococcus aureus.

It is not effective against Anaerobes, Pseudomonas aeruginosa, Treponema pallidum, Mycobacteria, Nocardia species, Neisseria species and Brucella abortus.

5.2. Pharmacokinetic Properties

Trimethoprim is rapidly and almost completely absorbed from the gastrointestinal tract and peak concentrations in the circulation occur about 1-4 hours after an oral dose. Peak plasma concentrations of about 1pg/ml have been reported after a single dose of 100mg. Approximately 40-70% is bound to plasma proteins. The half life is approximately 8-10 hours. About 40-60% of a dose is excreted unchanged in the urine within 24 hours, together with metabolites; hence, patients with impairment of renal function such as the elderly may require a reduction in dosage due to accumulation. It appears in breast milk.

5.3. Pre-clinical Safety Data

Not applicable.

6. PHARMACEUTICAL PARTICULARS

6.1. List of excipients

Also contains: colloidal silicon dioxide, lactose, macrogol, magnesium stearate, povidone, sodium starch glycollate, stearic acid, E460

6.2. Incompatibilities

None Known

Shelf life

Shelf-life

Three years from the date of manufacture.

Shelf-life after dilution/reconstitution Not applicable.

Shelf-life after first opening Not applicable.

6.4. Special precautions for storage

Store below 25°C in a dry place.

6.5. Nature and contents of container

The product containers are rigid injection moulded polypropylene or injection blow-moulded polyethylene tablet containers with snap-on polyethylene lids; in case any supply difficulties should arise the alternative is amber glass bottles with screw caps.

The product may also be supplied in blister packs in cartons:

a)    Carton: Printed carton manufactured from white folding box board.

b)    Blister pack: (i) 250um white rigid PVC. (ii) Surface printed 20um hard temper aluminium foil with 5-7g/M2 PVC and PVdC compatible heat seal lacquer on the reverse side.

Pack sizes: 7, 14, 28, 30, 50, 56, 60, 84, 90, 100, 112, 120, 168, 180, 250, 500, 1000.

Product may also be supplied in bulk packs, for reassembly purposes only, in polybags contained in tins, skillets or polybuckets filled with suitable cushioning material.

Maximum size of bulk packs: 50,000.

6.6. Special precautions for disposal

Not applicable

7    MARKETING AUTHORISATION HOLDER

Actavis UK Limited (Trading style: Actavis)

Whiddon Valley BARNSTAPLE N Devon EX32 8NS

8.    MARKETING AUTHORISATION NUMBER(S)

PL 0142/0224

9.    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

26 May 1987 May 1992, June 1997

10 DATE OF REVISION OF THE TEXT

07/07/2015