trimethoprim (Rx)

Frequency Not Defined

Aseptic meningitis

Fever

Maculopapular rash (3-7% at 200 mg/day; incidence higher with larger daily doses)

Erythema multiforme

Exfoliative dermatitis

Pruritus (common)

Phototoxic skin eruptions

Stevens-Johnson syndrome

Toxic epidermal necrolysis

Hyperkalemia

Hyponatremia

Epigastric distress

Glossitis

Nausea

Vomiting

Leukopenia

Megaloblastic anemia

Methemoglobinemia

Neutropenia

Thrombocytopenia

Liver enzyme elevation

Cholestatic jaundice

BUN and creatinine increased

Anaphylaxis

Hypersensitivity reactions

Contraindications

Hypersensitivity

Megaloblastic anemia due to folate deficiency

Cautions

Decreases urinary potassium excretion; may cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia

Large doses or long term therapy may interfere with hematopoiesis; the presence of clinical signs, such as sore throat, fever, pallor, or purpura may be early indications of serious blood disorders; monitor for signs/symptoms of hematologic disorders

If clinical signs of blood disorder noted, obtain a complete blood count and discontinue drug if significant reduction in count of any blood element found

Prolonged use may cause fungal or bacterial superinfection, including clostridium difficile-associated diarrhea and pseudomembranous colitis; may occur >2 months postantibiotic treatment

Hypersensitivity reactions reported

Use caution in patients with renal or hepatic impairment

Use caution in patients with potential for folate deficiency, including malnourished, chronic anticonvulsant therapy, or elderly; folates may be administered concomitantly without interfering with antibacterial action of trimethoprim

Some dosage forms may contain benzyl alcohol and derivatives; avoid in neonates

Not indicated for prophylactic or prolonged administration in otitis media at any age

Pregnancy Category: C

Lactation: enters breast milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Inhibits dihydrofolate reductase, which in turn inhibits folic acid reduction to tetrahydrofolate, causing inhibition of microorganism growth

Absorption

Readily and extensive

Time to peak, serum: 1-4 hr

Distribution

Widely into body tissues and fluids (middle ear, prostate, bile, aqueous humor, CSF); crosses placenta; enters breast milk

Protein binding: 42-46%

Metabolism

Partially hepatic

Elimination

Half-life: 8-14 hr; prolonged in renal impairment

Excretion: urine (60-80%) as unchanged drug