Trimethoprim 200mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Trimethoprim 200mg Tablets.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Trimethoprim 200.00mg
For a full list of all excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet;
White flat beveled edged tablets, engraved with “MT200”.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Treatment of susceptible infections caused by Trimethoprim sensitive organisms including most gram-positive and gram-negative aerobic organisms, including Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumonia, Staphylococcus aureus, Eschersichia coli, Enterobacter, Proteus and Streptococcus faecalis.
Exceptions include anaerobic bacteria. Mycobacterium tuberculosis, Neisseria gonorrhoeae, pseudomonas aeruginosa and Treponema pallidum.
Prophylaxis of recurrent urinary tract infections.
Route of administration: Oral
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
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 |
Dosage advised |
|
(micromol/l) | ||
|
Over 0.45 |
Men <250 |
Normal |
|
Women <175 | ||
|
0.25 - 0.45 |
Men 250-600 Women 175-400 |
Normal for 3 days then half dose |
|
Under 0.25 |
Men >600 |
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 to any other component of the formulation. Severe hepatic insufficiency. Severe renal insufficiency. Megaloblastic anaemia and other blood dyscrasias. Trimethoprim should not be administered to premature infants or children under 4 months of age.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galacactose malabsorption should not take this medicine.
4.4 Special warnings and precautions for use
Trimethoprim should not be administered to pregnant women, premature infants or infants during the first few weeks of life.
Patients with marked impairment of renal function; care should be taken to avoid accumulation and resulting adverse hepatological effects. 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.
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
Women >400
Interaction with other medicinal products 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.
Ciclosporin may increase the nephrotoxicity of trimethoprim.
Trimethoprim may potentiate the anticoagulant effects of warfarin.
4.6 Pregnancy and lactation
Trimethoprim should not be administered to pregnant women. Trimethoprim is not contraindicated for short-term use in lactating mothers, although the drug is excreted in breast milk.
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.
Cases of megaloblastic anaemia during prolonged therapy with trimethoprim in doses higher than those recommended rarely occur but are reversible with discontinuation of therapy and administration of folinic acid.
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, anaphylactoid reactions, 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; website: www. mhra. gov.uk/yellowcard.
4.9 Overdose
Treat symptomatically, gastric lavage and forced diuresis can be used. Depression of haematopoiesis by trimethoprim can be counteracted by intramuscular injections of calcium folinate.
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 Preclinical safety data
There are no preclinical data of relevance to the prescriber additional to that included in other sections of SmPC.
6 PHARMACEUTICAL PARTICULARS
6.1
List of excipients
• Lactose monohydrate
• Povidone K-25
• Crospovidone
• Sodium starch glycolate (Type A)
• Magnesium stearate
6.2 Incompatibilities
None known
6.3 Shelf life
36 months
6.4 Special precautions for storage
Do not store above 25°C. Store in the original container.
6.5 Nature and contents of container
High density polystyrene with polythene lids and/or polypropylene containers with polythene lids and polyurethane or polythene inserts.
Blister pack - 25 micron PVC glass-clear/bluish rigid PVC (pharmaceutical grade) 20 micron hard tempered aluminium foil coated on the pull side with 6-7 gsm heat seal lacquer and printed on the bright side.
Pack sizes: 50, 100, 500, 1000, 5000 (Bulk pack), 6, 14 & 28 (blister pack)
6.6 Special precautions for disposal
No special instruction
MARKETING AUTHORISATION HOLDER
7
Accord Healthcare Limited Sage house , 319 Pinner Road North Harrow , Middlesex , HA1 4HF United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 20075/0291
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
02/03/09
10 DATE OF REVISION OF THE TEXT
13/12/2015