Trimethoprim

Indications

Oral
Respiratory tract infections
Adult: Acute infection: 100 or 200 mg twice daily, alternatively, 200 or 300 mg daily as a single dose may be used. For initial UTI episodes: 100 mg every 12 hr or 200 mg every 24 hr for 10 days.
Child: 6-8 mg/kg/day in 2 divided doses. Alternatively, 6 wk-5 mth: 25 mg bid, 6 mth-5 yr: 50 mg bid, 6-12 yr: 100 mg bid.

CrCl (ml/min)	Dosage Recommendation
15-27	Normal dose for 3 days, thereafter half the normal doses.
<15	Half the normal dose from the start of the treatment.

Oral
Gastroenteritis
Adult: Acute infection: 100 or 200 mg twice daily, alternatively, 200 or 300 mg daily as a single dose may be used. For initial UTI episodes: 100 mg every 12 hr or 200 mg every 24 hr for 10 days.
Child: 6-8 mg/kg/day in 2 divided doses. Alternatively, 6 wk-5 mth: 25 mg bid, 6 mth-5 yr: 50 mg bid, 6-12 yr: 100 mg bid.

CrCl (ml/min)	Dosage Recommendation
15-27	Normal dose for 3 days, thereafter half the normal doses.
<15	Half the normal dose from the start of the treatment.

Oral
Susceptible infections
Adult: Acute infection: 100 or 200 mg twice daily, alternatively, 200 or 300 mg daily as a single dose may be used. For initial UTI episodes: 100 mg every 12 hr or 200 mg every 24 hr for 10 days.
Child: 6-8 mg/kg/day in 2 divided doses. Alternatively, 6 wk-5 mth: 25 mg bid, 6 mth-5 yr: 50 mg bid, 6-12 yr: 100 mg bid.

CrCl (ml/min)	Dosage Recommendation
15-27	Normal dose for 3 days, thereafter half the normal doses.
<15	Half the normal dose from the start of the treatment.

Oral
Uncomplicated urinary tract infections
Adult: Acute infection: 100 or 200 mg twice daily, alternatively, 200 or 300 mg daily as a single dose may be used. For initial UTI episodes: 100 mg every 12 hr or 200 mg every 24 hr for 10 days.
Child: 6-8 mg/kg/day in 2 divided doses. Alternatively, 6 wk-5 mth: 25 mg bid, 6 mth-5 yr: 50 mg bid, 6-12 yr: 100 mg bid.

CrCl (ml/min)	Dosage Recommendation
15-27	Normal dose for 3 days, thereafter half the normal doses.
<15	Half the normal dose from the start of the treatment.

Oral
Long term prophylaxis of urinary tract infection
Adult: 100 mg at night.
Child: 6 mth-5 yr: 25 mg at night; 6-12 yr: 50 mg at night. Alternatively, 1-2 mg/kg at night.

CrCl (ml/min)	Dosage Recommendation
15-27	Normal dose for 3 days, thereafter half the normal doses.
<15	Half the normal dose from the start of the treatment.

Oral
Pneumocystis (carinii) jiroveci pneumonia
Adult: 5 mg/kg tid for 21 days, in combination with dapsone. Max: 20 mg/kg/day

CrCl (ml/min)	Dosage Recommendation
15-27	Normal dose for 3 days, thereafter half the normal doses.
<15	Half the normal dose from the start of the treatment.

Intravenous
Respiratory tract infections
Adult: 200 mg every 12 hr by Inj or infusion.
Child: 8 mg/kg daily in 2-3 divided doses.

CrCl (ml/min)	Dosage Recommendation
15-27	Normal dose for 3 days, thereafter half the normal doses.
<15	Half the normal dose from the start of the treatment.

Intravenous
Gastroenteritis
Adult: 200 mg every 12 hr by Inj or infusion.
Child: 8 mg/kg daily in 2-3 divided doses.

CrCl (ml/min)	Dosage Recommendation
15-27	Normal dose for 3 days, thereafter half the normal doses.
<15	Half the normal dose from the start of the treatment.

Intravenous
Treatment and prophylaxis of urinary tract infections
Adult: 200 mg every 12 hr by Inj or infusion.
Child: 8 mg/kg daily in 2-3 divided doses.

CrCl (ml/min)	Dosage Recommendation
15-27	Normal dose for 3 days, thereafter half the normal doses.
<15	Half the normal dose from the start of the treatment.

Special Populations: Moderate to severe renal impairment: Creatinine clearance 15-27 mL/min: Normal dose for 3 days, then reduce to 1/2; <15 mL/min; 1/2 normal dose from start of treatment.

Contraindications

Hypersensitivity, serious haematological disorders, severe renal impairment, megaloblastic anaemia secondary to folate depletion.

Warnings / Precautions

Renal and hepatic impairment, porphyria, patients with potential folate deficiency, elderly, pregnancy, lactation, children with fragile X chromosome associated with mental retardation. Perform regular haematological examination.

Adverse Reactions

Nausea, vomiting, glossitis, pruritus, skin rash, fever, hyponatremia, hyperkalaemia, photosensitivity, liver enzyme elevation, , raised serum creatinine and BUN, blood dyscrasias, cholestatic jaundice, anaphylaxis, aseptic meningitis.
Potentially Fatal: Stevens-Johnson syndrome, toxic epidermal necrolysis.

Overdose Reactions

Nausea, vomiting, dizziness, headache, mental depression, confusion, and bone marrow depression. Empty stomach by gastric lavage, followed by supportive and symptomatic treatment. Urine acidification increase renal elimination of trimethoprim. Peritoneal dialysis not effective in drug elimination while haemodialysis can remove moderate amounts of trimethoprim.

Drug Interactions

Concurrent use increased risk of blood dyscrasias with azathioprine, methotrexate, pyrimethamine; increased risk of hyperkalaemia with ACE inhibitors; increased risk of hyponatraemia when used with both potassium-sparing diuretics and thiazides; increased risk of bleeding with warfarin; increased risk of lithium toxicity; increased digoxin, phenytoin, procainamide, lamivudine, stavudine, repaglinide, rosiglitazone, dofetilide serum levels; decreased ciclosporin levels. Concurrent use with dapsone increased serum levels of both and increased risk of dapsone toxicity.
See Below for More trimethoprim Drug Interactions

Lab Interactions

May interfere with serum methotrexate assay (where dihydrofolate reductase is used) and cause false elevation of creatinine (in Jaffe reaction).

Mechanism of Actions

Trimethoprim inhibits the conversion of bacterial dihydrofolic acid to tetrahydrofolic acid which is important for the synthesis of DNA. It may be bacteriostatic or bactericidal depending on growth conditions. It is active against a wide range of gm-ve and gm+ve aerobes, as well as some protozoa.
Absorption: Almost completely absorbed from the GI tract
Distribution: Widely distributed into body tissues and fluids. Apparent Vd ranges from 100-120 L. 45% bound to plasma proteins. Crosses placenta readily.
Metabolism: 10-20% metabolised by liver to oxide and hydroxylated metabolites
Excretion: 40-60% excreted by the kidneys as unchanged drug within 24 hr; small amounts excreted in faeces via the bile.