TRIMETHOPRIM-SULFAMETHOXAZOLE (TMP-SMZ)

TRIMETHOPRIM-SULFAMETHOXAZOLE (TMP-SMZ)
(tri-meth'o-prim-sul-fa-meth'ox-a-zole)
Bactrim, Bactrim DS, Co-Trim, Septra, Septra DS
Classifications: urinary tract agent; sulfonamide;
Therapeutic: urinary tract antiinfective
Prototype: Trimethoprim
Pregnancy Category: C

Availability

80 mg TMP/400 mg SMZ, 160 mg TMP/800 mg SMZ tablets; 40 mg TMP/200 mg SMZ/5 mL suspension

Action

Fixed combination of sulfamethoxazole (SMZ), an intermediate-acting antiinfective sulfonamide, and trimethoprim (TMP), a synthetic antiinfective. Both components of the combination are synthetic folate antagonist antiinfectives. Mechanism of action is principally enzyme inhibition that prevents bacterial synthesis of essential nucleic acids and proteins.

Therapeutic Effect

Effective against Pneumocystis carinii pneumonitis, shigellosis enteritis, and severe complicated UTIs due to most strains of the Enterobacteriaceae.

Uses

Pneumocystis carinii pneumonitis, shigellosis enteritis, and severe complicated UTIs. Also children with acute otitis media due to susceptible strains of Haemophilus influenzae, and acute episodes of chronic bronchitis in adults.

Unlabeled Uses

Isosporiasis; prevention of traveler's diarrhea; cholera; genital ulcers caused by Haemophilus ducreyi; prophylaxis for P. carinii pneumonia in neutropenic patients.

Contraindications

Hypersensitivity to TMP, SMZ, sulfonamides, or bisulfites, carbonic anhydrase inhibitors; group A beta-hemolytic streptococcal pharyngitis; megaloblastic anemia due to folate deficiency; creatinine clearance <15 mL/min; G6PD deficiency; hyperkalemia; porphyria; pregnancy (category C), lactation. Not recommended for infants <2 mo.

Cautious Use

Impaired kidney or liver function; bone marrow depression; possible folate deficiency; severe allergy or bronchial asthma; hypersensitivity to sulfonamide derivative drugs (e.g., acetazolamide, thiazides, tolbutamide).

Route & Dosage

Systemic Infections
Adult: PO 160 mg TMP/800 mg SMZ q12h
Child: PO >2 mo, <40 kg, 4 mg/kg/d TMP q12h; >40 kg, 160 mg TMP/800 mg SMZ q12h

Pneumocystis carinii Pneumonia
Adult: PO 15–20 mg/kg/d TMP divided q6h infused over 60–90 min

Prophylaxis for Pneumocystis carinii Pneumonia
Adult: PO 160 mg TMP/800 mg SMZ q24h
Child: PO 150 mg/m² TMP/750 mg/m² SMZ b.i.d. 3 consecutive d/wk (max: 320 mg TMP/d)

Renal Impairment
Cl_cr 10–30 mL/min: reduce dose by 50%

Administration

Oral

Give with a full glass of desired fluid.
Maintain adequate fluid intake (at least 1500 mL/d) during therapy.
Store at 15°–30° C (59°–86° F) in dry place protected from light. Avoid freezing.

Adverse Effects (≥1%)

Skin: Mild to moderate rashes (including fixed drug eruptions), toxic epidermal necrolysis. GI: Nausea, vomiting, diarrhea, anorexia, hepatitis, pseudomembranous enterocolitis, stomatitis, glossitis, abdominal pain. Urogenital: Kidney failure, oliguria, anuria, crystalluria. Hematologic: Agranulocytosis (rare), aplastic anemia (rare), megaloblastic anemia, hypoprothrombinemia, thrombocytopenia (rare). Body as a Whole: Weakness, arthralgia, myalgia, photosensitivity, allergic myocarditis.

Diagnostic Test Interference

May elevate levels of serum creatinine, transaminase, bilirubin, alkaline phosphatase.

Interactions

Drug: May enhance hypoprothrombinemic effects of oral anticoagulants; may increase methotrexate toxicity. Alcohol may cause disulfiram reaction.

Pharmacokinetics

Absorption: Readily from GI tract. Peak: 1–4 h. Distribution: Widely distributed, including CNS; crosses placenta; distributed into breast milk. Metabolism: In liver. Elimination: In urine. Half-Life: 8–10 h TMP, 10–13 h SMZ.

Nursing Implications

Assessment & Drug Effects

Be aware that IV Septra contains sodium metabisulfite, which produces allergic-type reactions in susceptible patients: Hives, itching, wheezing, anaphylaxis. Susceptibility (low in general population) is seen most frequently in asthmatics or atopic nonasthmatic persons.
Lab tests: Baseline and followup urinalysis; CBC with differential, platelet count, BUN and creatinine clearance with prolonged therapy.
Monitor coagulation tests and prothrombin times in patient also receiving warfarin. Change in warfarin dosage may be indicated.
Monitor I&O volume and pattern. Report significant changes to forestall renal calculi formation. Also report failure of treatment (i.e., continued UTI symptoms).
Older adult patients are at risk for severe adverse reactions, especially if liver or kidney function is compromised or if certain other drugs are given. Most frequently observed: thrombocytopenia (with concurrent thiazide diuretics); severe decrease in platelets (with or without purpura); bone marrow suppression; severe skin reactions.
Be alert for overdose symptoms (no extensive experience has been reported): nausea, vomiting, anorexia, headache, dizziness, mental depression, confusion, and bone marrow depression.

Patient & Family Education

Report immediately to physician if rash appears. Other reportable symptoms are sore throat, fever, purpura, jaundice; all are early signs of serious reactions.
Monitor for and report fixed eruptions to physician. This drug can cause fixed eruptions at the same sites each time the drug is administered. Every contact with drug may not result in eruptions; therefore, patient may overlook the relationship.
Drink 2.5–3 L (1 L is approximately equal to 1 qt) daily, unless otherwise directed.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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