Sulfamethoxazole and trimethoprim

Generic name: Sulfamethoxazole and trimethoprim

Drug class: Antibiotic combination (sulfonamide and dihydrofolate reductase inhibitor)

Dosage form: Oral tablets, oral suspension, intravenous infusion

Route of administration: Oral, intravenous

Dose:

• Adults: For urinary tract infections, one double-strength tablet (800 mg sulfamethoxazole and 160 mg trimethoprim) every 12 hours for 10 to 14 days. For acute exacerbations of chronic bronchitis, a similar regimen for 14 days. Dosage may vary based on infection type and severity.
• Pediatrics: Dosing is weight-based and varies by age and infection type. Consult a pediatric dosing chart or healthcare provider for specific recommendations.

Mechanism of action: Sulfamethoxazole inhibits bacterial dihydropteroate synthase, blocking the conversion of para-aminobenzoic acid (PABA) to dihydrofolic acid, a precursor of folic acid. Trimethoprim inhibits bacterial dihydrofolate reductase, preventing the conversion of dihydrofolic acid to tetrahydrofolic acid, another folic acid precursor. This dual inhibition disrupts bacterial DNA and protein synthesis, leading to bactericidal effects.

Drug usage cases:

• Urinary tract infections
• Acute exacerbations of chronic bronchitis
• Shigellosis (bacillary dysentery)
• Traveler’s diarrhea
• Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment
• Toxoplasmosis prophylaxis and treatment
• Acute otitis media (middle ear infections)
• Sinusitis
• Acute exacerbations of chronic obstructive pulmonary disease (COPD)
• Melioidosis

Drug contraindications:

• Hypersensitivity to trimethoprim, sulfonamides, or any component of the formulation
• History of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides
• Documented megaloblastic anemia due to folate deficiency
• Severe hepatic impairment or marked liver parenchymal damage
• Severe renal insufficiency (creatinine clearance <15 mL/min) where renal function cannot be monitored
• Infants less than 2 months of age
• Pregnancy (due to potential risk of kernicterus in the newborn)
• Breastfeeding (due to potential risk of kernicterus in the nursing infant)

Side effects:

• Gastrointestinal disturbances: nausea, vomiting, anorexia
• Hypersensitivity reactions: skin rash, urticaria, pruritus
• Hematologic effects: thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia
• Hepatic effects: jaundice, elevated liver enzymes, hepatic necrosis
• Renal effects: crystalluria, hematuria, nephrotoxicity
• Electrolyte disturbances: hyperkalemia, hyponatremia
• Hematologic effects: megaloblastic anemia (especially in patients with folate deficiency)
• Photosensitivity reactions: sunburn-like reactions upon exposure to sunlight
• Hypoglycemia: especially in patients with diabetes or those on hypoglycemic agents
• Hypothyroidism: fatigue, weight gain, cold intolerance

Warnings:

• Serious skin reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis
• Hematologic reactions: monitor blood counts regularly; discontinue if significant abnormalities occur
• Hepatic reactions: monitor liver function tests; discontinue if signs of hepatic injury develop
• Renal reactions: ensure adequate hydration; monitor renal function, especially in patients with pre-existing renal impairment
• Electrolyte imbalances: monitor serum potassium levels, especially in patients with renal impairment or those on potassium-sparing diuretics
• Photosensitivity: advise patients to avoid excessive sun exposure and use protective measures
• Hypoglycemia: monitor blood glucose levels in diabetic patients; adjust hypoglycemic therapy as needed
• Hypothyroidism: monitor thyroid function tests; adjust thyroid hormone replacement therapy as needed
• Drug interactions: monitor for potential interactions with anticoagulants, methotrexate, phenytoin, and other medications

Use during pregnancy or breastfeeding:

Pregnancy: The use of sulfamethoxazole and trimethoprim during pregnancy is generally not recommended, especially during the third trimester, due to potential risks such as kernicterus in the newborn. If the potential benefits justify the use, it should be prescribed with caution and under close medical supervision.

Breastfeeding: Sulfamethoxazole and trimethoprim are excreted in breast milk and may pose a risk to the nursing infant, including the potential for kernicterus. Caution is advised when administering this combination to breastfeeding mothers, and it should be used only if the potential benefits outweigh the risks. Alternative treatments may be considered.