Pharmacy Editor: Jay W. Marks, MD

GENERIC NAME: trimethoprim

BRAND NAMES: Trimpex; Proloprim, Primsol

DRUG CLASS AND MECHANISM: Trimethoprim is a synthetic (man-made) antibiotic that interferes with the production of tetrahydrofolic acid, a chemical that is necessary in order for bacteria and human cells to produce proteins. Trimethoprim inhibits production of tetrahydrofolic acid by inhibiting the enzyme responsible for making tetrahydrofolic acid from dihydrofolic acid. Trimethoprim inhibits the bacterial enzyme more than the corresponding human enzyme. Therefore, trimethoprim has less effect on the production of tetrahydrofolic acid by humans. Trimethoprim is effective against a wide variety of bacteria. Trimethoprim was first approved by the FDA in combination with sulfamethoxazole (e.g., Bactrim, Septra) in 1973. It was approved as a stand-alone drug in 1980.

PRESCRIPTION: Yes

GENERIC AVAILABLE: Yes

PREPARATIONS: Tablets: 100, and 200 mg. Solution: 50 mg/5 ml

STORAGE: Tablets should be kept at room temperature, 15-30°C (59-86°F).

PRESCRIBED FOR: Trimethoprim is used for the treatment of urinary tract infections, traveler's diarrhea, respiratory and middle ear infections, and, when combined with either sulfamethoxazole or dapsone, for prevention and treatment of Pneumocystis infections.

DOSING: The usual dose is 100 mg every 12 hours or 200 mg every 24 hours for 10 days. As with all antibiotics, it is important to complete the entire course of trimethoprim even if symptoms improve early in therapy. Persons with kidney diseases may need to receive lower doses. (Diseased kidneys may not eliminate trimethoprim adequately from the body, and levels of trimethoprim may increase in the body and lead to side effects.)

DRUG INTERACTIONS: Changes in one patient's mental status occurred when a combination of trimethoprim and sulfamethoxazole was given with amantadine (Symmetrel).

Blood levels of phenytoin (Dilantin) may be increased by treatment with trimethoprim. This may lead to side effects associated with phenytoin such as dizziness, and reduced attention. Trimethoprim also may increase blood levels of digoxin (Lanoxin) and warfarin (Coumadin) and lead to serious toxic effects.

Anemia, due to a reduction in folic acid, can occur in persons receiving trimethoprim in combination with divalproex, valproic acid, methotrexate, pyrimethamine, triamterene, or trimetrexate.

The combination of trimethoprim and cyclosporine can increase the risk of kidney damage from cyclosporine.

When trimethoprim and dapsone are used together, increased blood concentrations of both drugs can occur, sometimes with side effects that include a toxic condition called methemoglobinemia.

Rifampin can increase the elimination of trimethoprim by the kidneys and may reduce the effectiveness of trimethoprim.

PREGNANCY: Although there are no human studies that have examined the effects of trimethoprim on the fetus, animal studies have shown adverse effects. Therefore, the physician must weigh the potential risks to the fetus against the potential benefits to the mother when considering trimethoprim therapy for pregnant women.

NURSING MOTHERS: Trimethoprim is distributed into breast milk in high concentrations. Use of trimethoprim by mothers who are breast-feeding should be avoided.

SIDE EFFECTS: The most common side effects associated with trimethoprim are gastrointestinal. They include loss of appetite, nausea, vomiting, diarrhea, abdominal pain, abnormal taste, and swelling of the tongue. Taking trimethoprim with food may reduce some of these side effects.

Trimethoprim may cause anemia due to a deficiency of folic acid. The anemia usually is mild and resolves when the trimethoprim is stopped. Patients who are folate-deficient, such as malnourished, alcoholic, geriatric, or pregnant patients, may be at greater risk for developing anemia with trimethoprim. Warning signs of anemia include white or bluish fingernails and unusual tiredness and weakness. Prolonged therapy can result in low platelet counts, low white blood cell counts, and other toxic effects on the blood cells.

The most common side effects related to the skin are rash and itching. Rarely, the rash can progress to peeling or blistering. Some patients have photosensitivity reactions, that is, they develop skin rashes on parts of their body that are exposed to the sun.

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