Group: antimicrobial agent
Tablet, 100 mg, 200 mg, [EDL]
Suspension, 50 mg/5 ml [EDL]
Solution for injection, 20 mg/5 ml 5 ml ampoule [EDL]

General information

Trimethoprim is a synthetic folateantagonist anti-infective. By inhibiting the synthesis of tetrahydrofolic acid, the metabolically active form of folic acid, trimethoprim inhibits bacterial thymidine synthesis.

Trimethoprim is readily absorbed from the GI tract. It distributes widely into body tissues and fluids including the CSF. The plasma half-life is 8-11 hours, it is metabolised in the liver and rapidly eliminated via the kidneys by glomerular filtration and tubular secretion.

Clinical information

Uses

Treatment of Pneumocystis carinii pneumonia (PCP) (with dapsone)

Dosage and administration

Treatment of Pneumocystis carinii pneumonia (PCP) in combination with dapsone

20 mg/kg/day oral/IV in 2-3 divided doses for 21 days or to complete a 21 day course of therapy for the treatment of PCP in combination with dapsone.

Trimethoprim may be administered as a slow IV bolus, or added to 100 ml Glucose 5% or sodium chloride 0.9% and infused over 30 minutes.

Contraindications

• Known hypersensitivity to trimethoprim
• Documented history of megaloblastic anaemia secondary to folate deficiency

Precautions

Reduce the dose in renal failure. If the creatinine clearance is between 10 and 25 ml/min, give the normal dose for three days and then half the normal dose. If the creatinine clearance is less than 10 ml/min give half the normal dose and monitor serum levels.

Trimethoprim increases serum levels of phenytoin; monitor for signs of phenytoin toxicity, and serum levels. The effect of coumarin anticoagulants may be enhanced.

Potentiation of folate deficiency may occur if trimethoprim is given with other antifolate drugs e.g. phenytoin. Folic acid can counteract the competitive blockade of folic acid metabolism and should not be used.

Overdosage

Overdose may produce nausea, vomiting, diarrhoea, mental depression, confusion, facial swelling, headache, bone marrow depression and slight elevation of liver transaminases. Acidification of the urine may enhance elimination of the drug. Haemodialysis may remove only moderate amounts of trimethoprim from the serum, peritoneal is ineffective in enhancing elimination.

Storage

Tablets should be stored in a tight, light resistant container at 15-30°C in a dry place.