sulfamethoxazole-trimethoprim

Action

Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA). Trimethoprim inhibits enzymes of folic acid pathways.

Availability

Injection: 80 mg/ml sulfamethoxazole and 16 mg/ml trimethoprim

Suspension: 200 mg sulfamethoxazole and 40 mg trimethoprim/5 ml

Tablets: 400 mg sulfamethoxazole and 80 mg trimethoprim (single strength); 800 mg sulfamethoxazole and 160 mg trimethoprim (double strength)

Indications and dosages

➣ Urinary tract infections caused by susceptible organisms

Adults: One double-strength tablet or two single-strength tablets or 20 ml suspension P.O. q 12 hours for 10 to 14 days

Children ages 2 months and older: 40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim P.O. q 12 hours for 10 days

➣ Severe urinary tract infections caused by susceptible organisms

Adults and children ages 2 months and older: 8 to 10 mg/kg (based on trimethoprim component) I.V. q 6, 8, or 12 hours for up to 14 days

➣ Shigellosis caused by susceptible strains of Shigella flexneri or Shigella sonnei

Adults: One double-strength tablet or two single-strength tablets or 20 ml suspension P.O. q 12 hours for 10 to 14 days. Alternatively, 8 to 10 mg/kg (based on trimethoprim component) I.V. q 6, 8, or 12 hours for 5 days.

Children ages 2 months and older: 40 mg/kg (sulfamethoxazole) and 8 mg/kg (trimethoprim) P.O. q 12 hours for 5 days. Alternatively, 8 to 10 mg/kg (based on trimethoprim component) I.V. q 6, 8, or 12 hours for up to 5 days.

➣ Acute exacerbation of chronic bronchitis caused by susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae

Adults: One double-strength tablet or two single-strength tablets or 20 ml suspension P.O. q 12 hours for 10 to 14 days

➣ Pneumocystis jiroveci pneumonia

Adults and children older than 2 months: 75 to 100 mg/kg (sulfamethoxazole) and 15 to 20 mg/kg (trimethoprim) P.O. daily in equally divided doses q 6 hours for 14 to 21 days. Alternatively, 15 to 20 mg/kg (based on trimethoprim component) I.V. q 6 to 8 hours for up to 14 days.

➣ Prophylaxis of P. jiroveci pneumonia

Adults: One double-strength tablet P.O. daily

Children ages 2 months and older: 750 mg/m² (sulfamethoxazole) and 150 mg/m² (trimethoprim) P.O. b.i.d. in equally divided doses on 3 consecutive days each week. Total dosage should not exceed 1,600 mg sulfamethoxazole and 320 mg trimethoprim.

➣ Traveler's diarrhea caused by susceptible strains of enterotoxigenic Escherichia coli

Adults: One double-strength tablet or two single-strength tablets or 20 ml suspension q 12 hours for 5 days

➣ Acute otitis media caused by susceptible strains of S. pneumoniae or H. influenzae

Children ages 2 months and older: 40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim P.O. q 12 hours for 10 days

Off-label uses

• Granuloma inguinale

• Toxoplasmic encephalitis (as primary prophylaxis)

Dosage adjustment

• Renal impairment

Contraindications

• Hypersensitivity to sulfonamides, trimethoprim, sulfonylureas, thiazides, or loop diuretics

• Porphyria

• Marked renal or hepatic impairment

• Megaloblastic anemia caused by folate deficiency

• Pregnancy at term or when premature birth is possible

• Infants younger than 2 months (except in P. jiroveci pneumonia prophylaxis)

Precautions

Use cautiously in:

• urinary obstruction, renal or hepatic disease, bronchial asthma, G6PD deficiency, group A beta-hemolytic streptococcal infection, blood dyscrasias

• history of multiple allergies

• elderly patients

• pregnant (before term) or breastfeeding patients

• children.

Administration

• Dilute each 5 ml of I.V. drug in 125 ml of dextrose 5% in water.

• Infuse I.V. over 60 to 90 minutes. Avoid rapid infusion.

• Don't mix with other drugs or solutions. Don't refrigerate. Use within 6 hours after dilution.

Adverse reactions

CNS: headache, depression, hallucinations, insomnia, drowsiness, fatigue, apathy, anxiety, ataxia, vertigo, polyneuritis, peripheral neuropathy, seizures

CV: allergic myocarditis or pericarditis

EENT: periorbital edema, optic neuritis, transient myopia, tinnitus

GI: nausea, vomiting, abdominal pain, stomatitis, glossitis, dry mouth, pancreatitis, anorexia, pseudomembranous colitis

GU: hematuria, proteinuria, crystalluria, toxic nephrosis with oliguria and anuria, renal failure

Hematologic: megaloblastic anemia, agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, hemolytic anemia

Hepatic: jaundice, hepatitis, hepatocellular necrosis

Respiratory: shortness of breath, pleuritis, allergic pneumonitis, pulmonary infiltrates, fibrosing alveolitis

Skin: generalized skin eruption, urticaria, pruritus, alopecia, local irritation, exfoliative dermatitis, photosensitivity reaction, epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome

Other: irritation at I.V. site, chills, drug fever, hypersensitivity reactions including anaphylaxis, serum sickness, lupus-like syndrome

Interactions

Drug-drug. Cyclosporine: increased nephrotoxicity

Dapsone: increased blood levels of both drugs

Hydantoins, zidovudine: increased blood levels of these drugs

Indomethacin, probenecid: increased sulfamethoxazole blood level

Methotrexate: increased risk of bone marrow suppression

Oral anticoagulants: increased anticoagulant effect

PABA, PABA-derived local anesthetics: inhibited sulfamethoxazole action

Sulfonylureas: increased risk of hypoglycemia

Thiazide diuretics: increased thrombocytopenic effects

Uricosuric drugs: increased uricosuric effects

Drug-diagnostic tests. Bilirubin, blood urea nitrogen, creatinine, eosinophils, transaminases: increased levels

Granulocytes, hemoglobin, platelets, white blood cells: decreased levels

Urine glucose tests: false-positive results

Drug-herbs. Dong quai, St. John's wort: increased risk of photosensitivity

Drug-behaviors. Sun exposure: increased risk of photosensitivity

Patient monitoring

See Monitor CBC with white cell differential. Watch for evidence of blood dyscrasias.

See Stay alert for erythema multiforme. Report early signs before condition can progress to Stevens-Johnson syndrome.

• Monitor patient for signs and symptoms of superinfection, including fever, tachycardia, and chills.

See Monitor liver function tests and assess for evidence of hepatitis.

See Check kidney function tests weekly. Evaluate patient's fluid intake, urine output, and urine pH. Report hematuria, oliguria, or anuria right away.

• Monitor neurologic status. Report seizures, hallucinations, or depression.

Patient teaching

• Advise patient to take on regular schedule as prescribed, along with a full glass of water. Tell him to drink plenty of fluids to minimize crystal formation in urine.

• If suspension is prescribed, make sure patient has a specially marked measuring spoon or other device so he can measure doses accurately.

• Instruct patient to complete full course of treatment even if he starts to feel better.

See Teach patient to recognize and immediately report signs and symptoms of hypersensitivity, especially rash.

See Inform patient that drug can cause blood disorders, GI and liver problems, serious skin reactions, and other infections. Describe key warning signs and symptoms (easy bruising or bleeding, severe diarrhea, unusual tiredness, yellowing of skin or eyes, sore throat, rash, cough, mouth sores, fever). Tell him to report these right away.

See Urge patient to promptly report scant or bloody urine or inability to urinate.

• Tell patient to contact prescriber if he develops depression.

• Teach patient effective ways to counteract photosensitivity effect. Advise him that dong quai and St. John's wort increase phototoxicity risk and should be avoided during therapy.

• Advise female patient to inform prescriber if she is pregnant. Tell her not to take drug near term.

• Caution female patient not to breastfeed, because she could pass drug effects to infant.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.