Trimethoprim (TMP)

Antibiotic Class:

Trimethoprim [2, 4-diamino-5- (3’, 4’, 5’-trimethoxybenzyl) pyrimidine] is a diaminopyrimidine.

Antimicrobial Spectrum:

Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Listeria monocytogenes, Escherichia coli, Shigella dysenteriae, Salmonella typhi, Salmonella enteritidis, Klebsiella pneumoniae, Serratia marcescens, Proteus mirabilis, Haemophilus influenzae, Pasteurella multocida, Bordetella pertussis. Trimethoprim also has activity against Pneumocystis carinii, Toxoplasma gondii, Plasmodium falciparum.

Mechanism of Action:

Trimethoprim inhibits thymidine and DNA synthesis.

Pharmacodynamics

No data

Pharmacokinetics:

Cmax: 1-2mcg/mL; Half-life: 10-12; Volume of distribution: 100-120 L; Table 7

Trimethoprim is rapidly absorbed following oral administration with a high bioavailability. Approximately 44% of trimethoprim is bound to plasma proteins. Trimethoprim achieves high concentrations in breast milk.

Adverse Effects:

GI – nausea, vomiting

Hematologic – pancytopenia, agranulocytosis, macrocytic anemia, thrombocytopenia

Skin – toxic erythema, erythema nodosum, fixed local eruption, erythema multiforme, Lyell’s syndrome, Exfoliative dermatitis, urticaria, necrotizing vasculitis, photodermatitis, toxic erythema

Renal – transient blood urea and creatinine elevations, crystalluria, acute interstitial nephritis

CNS – headache, confusion, depression, aseptic meningitis

Dosage:

Oral: 100mg and 200mg tablets

         50mg/5ml suspension

Dosing in adults:

Urinary tract infection: 100mg PO q12h or 200mg PO q24h x 10 days

Dosing in children:

Acute otitis media: (≥6 months old) 10mg/kg suspension divided PO q12h x 10 days

Disease state based dosing:

Renal failure:  CrCl 15-30 mL/min, 50 mg every 12 hr; CrCl less than 15 mL/min, not recommended

Hepatic failure:  No dosage adjustment necessary.

Contraindications/Warnings/Precautions:

Contraindications: megaloblastic anemia due to folate deficiency

Precautions: patients with possible folate deficiency, impaired renal function

Drug Interactions:

Other diaminopyrimidines-pyrimethamine, azathioprine, or methotrexate are potentiated by TMP, resulting in severe leucopenia.

Pregnancy:

Category C. Trimethoprim interferes with folate metabolism.

Monitoring Requirements:

Therapeutic:  Monitor signs and symptoms of infection.  Monitor white blood cell count, culture and susceptibility

Toxic: Monitor renal function tests, serum potassium.

Brand names/Manufacturer: 

Proloprim Ò/Allergan, Primsol/Medicis pharmaceuticals, Trimpex/Roche pharmaceuticals