Trimethoprim/Sulfamethoxazole (Co-trimoxazole; TMP-SMZ)

A to Z Drug Facts

(try-METH-oh-prim/suhl-fuh-meth-OX-uh-zole)

Bactrim, Bactrim D.S., Bactrim IV, Bactrim Pediatric, Cotrim, Cotrim D.S., Cotrim Pediatric, Septra, Septra DS, Septra IV, Sulfatrim, Uroplus DS, Uroplus SS,  Apo-Sulfatrim, Bactrim Roche, Novo-Trimel, Novo-Trimel D.S., Nu-Cotrimox, Pro-Trin, Roubac, Septra DS, Septra Injection

Class: Anti-infective

 Action Sulfamethoxazole (SMZ) inhibits bacterial synthesis of dihydrofolic acid by competing with PABA. Trimethoprim (TMP) blocks production of tetrahydrofolic acid by inhibiting the enzyme dihydrofolate reductase. This combination blocks two consecutive steps in bacterial biosynthesis of essential nucleic acids and proteins and is usually bactericidal.

 Indications

Oral/parenteral: Treatment of UTIs caused by susceptible strains of bacteria, shigellosis enteritis and Pneumocystis carinii pneumonitis. Oral: Treatment of acute otitis media and acute exacerbations of chronic bronchitis; reatment of traveler's diarrhea. Unlabeled use(s): Treatment of cholera, salmonella-type infections and nocardiosis; revention of recurrent UTIs in women; prophylaxis of bacterial infections in susceptible patients; treatment of prostatitis; prophylaxis of Pneumocystis carinii pneumonitis.

 Contraindications Hypersensitivity to sulfonamides; megaloblastic anemia caused by folate deficiency; pregnancy at term; lactation; infants < 2 mo of age.

 Route/Dosage

UTIs, Shigellosis, Acute Otitis Media

ADULTS: PO 160 mg TMP/800 mg SMZ q 12 hr for 10–14 days and 5 days for shigellosis. IV 8–10 mg/kg/day (based on TMP) in 2–4 divided doses q 6–12 hr for up to 14 days for severe UTIs and 5 days for shigellosis. CHILDREN > 2 MO: PO 8 mg/kg TMP/40 mg/kg SMZ daily in 2 divided doses q 12 hr for 10 days and 5 days for shigellosis.

Pneumocystis Carinii Pneumonitis

ADULTS: PO 20 mg/kg TMP/100 mg/kg SMZ daily in divided doses q 6 hr for 14 days. IV 15–20 mg/kg/day (based on TMP) in 3–4 divided doses for up to 14 days.

Traveler's Diarrhea

ADULTS: PO 160 mg TMP/800 mg SMZ q 12 hr for 5 days.

Exacerbation of Chronic Bronchitis

ADULTS: PO 160 mg TMP/800 mg SMZ q 12 hr for 14 days.

 Interactions

Cyclosporine: May cause decrease in therapeutic effect of cyclosporine and increased risk of nephrotoxicity. Methotrexate: May displace methotrexate from protein-binding sites, thus increasing free methotrexate levels. Phenytoin: Trimethoprim may inhibit metabolism of phenytoin or other hydantoins. Procainamide: Trimethoprim may inhibit renal elimination of procainamide and its metabolites. Sulfonylureas: May increase hypoglycemic response to sulfonylureas because of displacement from protein-binding sites or inhibition of hepatic metabolism. Warfarin: May cause prolonged PT. INCOMPATIBILITIES: Do not mix with other drugs or solutions other than D5W.

 Lab Test Interferences Can interfere with serum methotrexate assay as determined by competitive binding protein technique when bacterial dihydrofolate reductase is used as binding protein. May interfere with Jaffe alkaline picrate reaction assay for creatinine, resulting in overestimations.

 Adverse Reactions

CV: Allergic myocarditis. CNS: Headache; depression; seizures; aseptic meningitis; insomnia; hallucinations. DERM: Local reaction, pain, and irritation on IV administration; hypersensitivity reactions including rash; urticaria; photosensitization; generalized skin eruptions. EENT: Glossitis; stomatitis. GI: Nausea; vomiting; anorexia; abdominal pain; diarrhea; pseudomembranous enterocolitis; pancreatitis; esophageal ulcers. GU: Renal failure; interstitial nephritis; toxic nephrosis with oliguria or anuria; crystalluria. HEPA: Hepatitis; hepatic necrosis. HEMA: Agranulocytosis; aplastic, hemolytic or megaloblastic anemia; hrombocytopenia; leukopenia; neutropenia; hypoprothrombinemia; eosinophilia; ethemoglobinemia. Pulmonary infiltrates; cough; shortness of breath. OTHER: Arthralgia; myalgia; hypersensitivity reactions including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, serum sickness, anaphylactoid reactions, angioedema, drug fever, chills, systemic lupus erythematosus, periarteritis nodosa; conjunctival and scleral injection.

 Precautions

Pregnancy: Category C. Do not use at term because of risk of neonatal kernicterus. Lactation: Undetermined. Not recommended during nursing because sulfonamides are excreted in breast milk and may cause kernicterus. Premature infants and infants with hyperbilirubinemia or G-6-PD deficiency are also at risk for adverse effects. Children: Not recommended for infants < 2 mo. Elderly patients: Are at increased risk of severe adverse reactions. Special risk patients: Use drug with caution in patients with possible folate deficiency (eg, elderly patients, chronic alcoholics, patients undergoing anticonvulsant therapy, patients with malabsorption syndromes or malnutrition), patients with severe allergy or bronchial asthma, patients who have sulfite sensitivity and G-6-PD-deficient individuals. Ulceration: Take tablets with water or food to prevent lodging in esophagus and subsequent ulceration. Hematologic effects: Sulfonamide-associated deaths, although rare, have occurred from hypersensitivity of respiratory tract, Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias. Both components can interfere with hematopoiesis. IV use at high doses for extended periods of time may cause bone marrow depression. Patients with AIDS: Incidence of side effects, especially rash, fever and leukopenia, is greatly increased. Renal and hepatic impairment: Use drug with caution. Dosage adjustment may be required. Streptococcal pharyngitis: Do not use for streptococcal pharyngitis. Sulfonamides: Are chemically similar to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycemic agents. Goiter production, diuresis, and hypoglycemia occur rarely in patients receiving sulfonamides. Cross-sensitivity may occur.

 Administration/Storage

• Administer with full glass of water.
• May administer with food if GI upset occurs.
• For IV infusion, must dilute in 75 or 125 ml of D5W only. Administer each dose over 60–90 min. Flush IV line after infusion. Do not use IV solution if cloudy or precipitates are noted.
• If local irritation or inflammation because of extravascular infiltration occurs, discontinue infusion and restart at another site.
• Avoid rapid or direct IV injection. Do not inject IM.
• Shake oral suspension well before use.
• Store IV solution at room temperature. Do not refrigerate. Discard prepared IV solution if not used within 2 hr (75 ml) or 6 hr (125 ml).
• Store tablets or suspension at room temperature in a tight, light-resistant container.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies. Note decreased renal or hepatic function and sensitivity to sulfonamides (including sulfonylureas, or thiazide diuretics) and trimethoprim.
• Obtain culture and sensitivity before beginning drug therapy.
• Monitor I&O.
• Encourage fluid intake.
• Monitor renal function during prolonged treatment.
• Notify physician of GI upset, fever, chills, headache, rash, decreased urine output, wheezing, shortness of breath, dizziness, sore throat, unusual bleeding or bruising or arthralgia.

 Patient/Family Education

• Advise patient to complete full course of therapy.
• Encourage patient to maintain adequate fluid intake.
• Advise patient to take tablet with full glass of water.
• Educate patient and family to report any signs of superinfection such as fever, vaginitis, oral candidiasis and fatigue.
• Instruct patient to report these symptoms to physician: skin rash, sore throat, fever, or unusual bruising or bleeding.
• Caution patient to avoid exposure to sunlight and to use sunscreen or wear protective clothing to avoid photosensitivity reaction.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts