Treat symptomatically, gastric lavage and forced diuresis may be used. Depression of haematopoiesis by Thi Fen may be countered by intramuscular injections of calcium folinate.
Hypersensitivity to Thi Fen or any of the excipients. Pregnancy. Severe hepatic insufficiency. Severe renal insufficiency where blood levels cannot be regularly monitored. Megaloblastic anaemia and other blood dyscrasias. Thi Fen should not be administered to premature infants or children under 4 months of age.
None known
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. Thi Fen therapy may affect haematopoiesis
Nervous system disorders
Aseptic meningitis
Gastrointestinal disorders
Gastro-intestinal disturbances including nausea and vomiting, glossitis, sore mouth.
Hepatobiliary disorders
Disturbances in liver enzyme values, cholestatic jaundice.
Skin and subcutaneous tissue disorders
Pruritis, skin rashes, exfoliative dermatitis, urticaria.
More severe skin sensitivity reactions such as erythema multiforme, Stevens-Johnson Syndrome and ToxicEpidermal Necrolysis have been reported rarely.
Musculoskeletal and connective tissue 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 products 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.
There are no pre-clinical data of relevance to the prescriber additional to that included in other sections of the SmPC.
Treatment of susceptible infections caused by Thi Fen 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.
Consideration should be given to official guidance on the appropriate use of antibacterial agents
Pharmacotherapeutic Group: Systemic antibacterial. ATC Code: J01EA01
Mechanism of action: Thi Fen is a dihydrofolate reductase inhibitor which affects the nucleoprotein metabolism of micro-organisms by interference in the folic-folinic acid systems.
Thi Fen 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.
Thi Fen 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 1μg/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.
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 Thi Fen 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.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorbtion should not take this medicine.
None known.
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 Thi Fen 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 |
Thi Fen is removed by dialysis. However, it should not be administered to dialysis patients unless plasma concentrations can be estimated regularly.
Route of administration: Oral
No special requirements
