Chemical formula: C₁₄H₁₈N₄O₃ Molecular mass: 290.318 g/mol PubChem compound: 5578
Trimethoprim interacts in the following cases:
Trimethoprim may induce folate deficiency in patients predisposed to folate deficiency such as those receiving concomitant folate antagonists or anticonvulsants.
| Creatinine Clearance (ml/sec) | Plasma creatinine (micromole/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 may potentiate the anticoagulant effect of warfarin and other coumarins.
In elderly patients concurrently taking diuretics, particularly thiazides, there is an increased incidence of thrombocytopenia with purpura. Rare cases of hyponatraemia have been reported in patients treated with trimethoprim and potassium sparing diuretics and/or thiazide diuretics. Hyperkalaemia may be exacerbated by concomitant administration of potassium sparing diuretics and/or thiazide diuretics, potassium supplements, potassium-containing salt substitutes, renin-angiotensin system inhibitors (eg: ACE inhibitors or renin angiotensin receptor blockers), other potassium increasing substances (eg: heparin) and aldosterone antagonists (eplerenone). Monitoring of potassium should be undertaken as appropriate.
Increased risk of hyperkalaemia.
The likelihood of hyperkalaemia is increased when ACE inhibitors are taken with trimethoprim.
Reports of contraceptive failure after taking trimethoprim as trimethoprim may possibly reduce the contraceptive effect of oestrogens.
Inactivated by antibacterials.
Increased risk of ventricular arrhythmia.
Trimethoprim may increase the risk for bone marrow aplasia. Cytotoxic agents such as azathioprine, mercaptopurine and methotrexate increase the risk of haematological toxicity when given with trimethoprim.
An increased risk of nephrotoxicity has been reported with the use of trimethoprim and cyclosporin.
Plasma concentrations of trimethoprim and dapsone may increase when taken together.
Serum levels increased with trimethoprim.
Trimethoprim may increase the plasma concentration of lamivudine.
Careful monitoring of patients treated with digoxin or phenytoin is advised as trimethoprim may increase plasma concentration of these agents by increasing their elimination half-life.
Trimethoprim increases plasma concentration of procainamide.
The anti-folate effect may be increased if there is concomitant administration with trimethoprim.
Monitoring of blood glucose is advised if co-administered with repaglinide.
Trimethoprim may enhance the hypoglycaemic effects of repaglinide.
Rifampicin may decrease trimethoprim concentration.
Close monitoring of serum electrolytes is advised in patients at risk of hyperkalaemia.
Elevations in serum potassium have been observed in some patients treated with trimethoprim. Patients at risk for the development of hyperkalaemia include those with renal insufficiency, poorly controlled diabetes mellitus, or those using concomitant potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, renin angiotensin system inhibitors (eg: ACE inhibitors or renin angiotensin receptor blockers), or those patients taking other drugs associated with increases in serum potassium (e.g. heparin). If concomitant use of the above-mentioned agents is deemed appropriate, monitoring of serum potassium is recommended.
Trimoptin may interfere with diagnostic tests including serum methotrexate assay where dihydrofolate reductase is used and the Jaffe reaction for creatinine.
Trimethoprim should not be given to pregnant women, premature infants or infants during the first few weeks of life.
Trimethoprim is excreted in breast milk. This should be kept in mind when considering administration to breast feeding women.
No studies on the effects of ability to drive and use machines have been performed. Trimethoprim has minor effects on the ability to drive or use machines. It may cause ataxia, syncope, uveitis or vertigo and therefore caution should be advised if a patient experiences any of these effects.
The following list of undesirable effects have been reported by health care professionals. Sometimes it may be difficult to distinguish reactions caused by the condition being treated from adverse drug reactions, which means that not all the listed reactions were caused by drug administration.
The frequencies of the undesirable effects listed below are categorised as follows: Very common ≥1/10, Common ≥1/100 and <1/10, Uncommon ≥1/1000 and <1/100, Rare ≥1/10,000 and <1/1000, Very rare <1/10,000, Not known cannot be estimated from the available data.
Common: Monilial overgrowth.
Very rare: Leucopenia, neutropenia, thrombocytopenia, pancytopaenia, bone marrow depression, agranulocytosis, aplastic anaemia, haemolytic anaemia, eosinophilia, purpura, haemolysis.
Fatalities have been reported (especially in the elderly, or those with impairment of renal or hepatic function in whom careful monitoring is advised), however, the majority of haematological changes are mild and reversible when treatment is stopped.
Very rare: Hypersensitivity, anaphylaxis, angioedema, drug fever, allergic vasculitis resembling Henoch-Schoenlein purpura, periarteritis nodosa, systemic lupus erythematosus.
Very common: Hyperkalaemia.
Very rare: Hypoglycaemia, hyponatraemia, anorexia.
Close supervision is recommended when trimethoprim is used in elderly patients or in patients taking high doses as these patients may be more susceptible to hyperkalaemia and hyponatraemia.
Very rare: Depression, hallucinations, confusional states, agitation, anxiety, abnormal behaviour, insomnia and nightmares.
Common: Headache.
Very rare: Dyskinesias, aseptic meningitis, tremor, ataxia, dizziness, lethargy, syncope, paraesthesiae, convulsions, peripheral neuritis, vertigo, tinnitus.
Aseptic meningitis was rapidly reversible on withdrawal of the drug, but recurred in a number of cases on re-exposure to either co-trimoxazole or to trimethoprim alone.
Very rare: uveitis
Very rare: Cough, shortness of breath, wheeze, epistaxis.
Common: Nausea, diarrhoea, vomiting, gastrointestinal upset.
Very rare: Constipation, glossitis, stomatitis, pseudomembranous colitis, pancreatitis.
Very rare: Elevation of serum transaminases, elevation of bilirubin levels, disturbances of liver enzyme values, cholestatic jaundice, hepatic necrosis. Cholestatic jaundice and hepatic necrosis may be fatal.
Common: Skin rashes, urticaria, pruritus.
Very rare: Photosensitivity, exfoliative dermatitis, fixed drug eruption, erythema multiforme, erythema nodusum, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous dermatitis, purpura. Lyell’s syndrome (toxic epidermal necrolysis) carries a high mortality.
Very rare: Arthralgia, myalgia.
Very rare: Impaired renal function (sometimes reported as renal failure), haematuria. Trimethoprim may affect haemopoiesis.
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 national reporting system HPRA Pharmacovigilance: Website: www.hpra.ie.
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