TRIMETHOPRIM

Trimethoprim is a synthetic antibacterial available in tablet form for oral administration. Each scored white tablet contains 100 mg trimethoprim. Trimethoprim is 5-[(3,4,5-trimethoxyphenyl)methyl]-2,4-pyrimidinediamine. It is a white to light yellow, odorless, bitter compound with a molecular weight of 290.32 and the molecular formula C 14 H 18 N 4 O 3. The structural formula is: Inactive Ingredients Anhydrous Lactose, Microcrystalline cellulose, Pregelatinized Starch, Sodium Starch Glycolate Type A, Magnesium Stearate. FDA approved dissolution test specifications differ from USP. structure

INDICATIONS & USAGE To reduce the development of drug-resistant bacteria and maintain the effectiveness of trimethoprim tablets and other antibacterial drugs, trimethoprim tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. For the treatment of initial episodes of uncomplicated urinary tract infections due to susceptible strains of the following organisms: Escherichia coli , Proteus mirabilis , Klebsiella pneumoniae , Enterobacter species, and coagulase-negative Staphylococcus species, including S. saprophyticus . Cultures and susceptibility tests should be performed to determine the susceptibility of the bacteria to trimethoprim. Therapy may be initiated prior to obtaining the results of these tests.

DOSAGE & ADMINISTRATION The usual oral adult dosage is 100 mg of trimethoprim every 12 hours or 200 mg of trimethoprim every 24 hours, each for 10 days. The use of trimethoprim in patients with a creatinine clearance of less than 15 mL/min is not recommended. For patients with a creatinine clearance of 15 to 30 mL/min, the dose should be 50 mg every 12 hours.

Trimethoprim is contraindicated in individuals hypersensitive to trimethoprim and in those with documented megaloblastic anemia due to folate deficiency

The adverse effects encountered most often with trimethoprim were rash and pruritus. Dermatologic Rash, pruritus, and phototoxic skin eruptions. At the recommended dosage regimens of 100 mg b.i.d. or 200 mg q.d., each for 10 days, the incidence of rash is 2.9% to 6.7%. In clinical studies which employed high doses of trimethoprim, an elevated incidence of rash was noted. These rashes were maculopapular, morbilliform, pruritic, and generally mild to moderate, appearing 7 to 14 days after the initiation of therapy. Hypersensitivity Rare reports of exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell Syndrome), and anaphylaxis have been received. Gastrointestinal Epigastric distress, nausea, vomiting, and glossitis. Elevation of serum transaminase and bilirubin has been noted, but the significance of this finding is unknown. Cholestatic jaundice has been rarely reported. Hematologic Thrombocytopenia, leukopenia, neutropenia, megaloblastic anemia, and methemoglobinemia. Metabolic Hyperkalemia, hyponatremia. Neurologic Aseptic meningitis has been rarely reported. Miscellaneous Fever, and increases in BUN and serum creatinine levels.

Trimethoprim may inhibit the hepatic metabolism of phenytoin. Trimethoprim, given at a common clinical dosage, increased the phenytoin half-life by 51% and decreased the phenytoin metabolic clearance rate by 30%. When administering these drugs concurrently, one should be alert for possible excessive phenytoin effect