Products
Trimethoprim and sulfamethoxazole are commercially available in tablet and syrup form (Bactrim, generics). The drug has been approved in many countries since 1969. The Bactrim syrup is no longer available, but a generic is available (Nopil syrup). The fixed combination of the two active ingredients is also called cotrimoxazole.
Structure and properties
Trimethoprim (C14H18N4O3, Mr = 290.3 g/mol) is a trimethoxybenzylpyrimidine. It exists as a white to yellowish white powder and is very slightly soluble in water. Sulfamethoxazole (C10H11N3O3S, Mr = 253.3 g/mol) is a sulfonamide. It exists as a white crystalline powder that is practically insoluble in water.
| Trimethoprim | Sulfamethoxazole |
Effects
Trimethoprim and sulfamethoxazole (ATC J01EE01) have bactericidal properties due to synergistic actions. The individual agents have bacteriostatic effects only. The antibacterial properties are due to blockade of the microorganisms’ folic acid metabolism at two different sites. Trimethoprim inhibits dihydrofolic acid reductase, and sulfamethoxazole inhibits dihydrofolic acid synthetase.
Indications
For the treatment of bacterial infectious diseases with susceptible germs. The drugs are used, for example, against respiratory infections, infections of the genitourinary system, and infections of the gastrointestinal tract. A typical indication is acute cystitis (bladder infection) in women.
Dosage
According to the SmPC. The drugs are usually taken in the morning and evening, 12 hours apart and after meals. The usual duration of treatment is 3 to 5 days. For the treatment of cystitis, administration of a single dose is also possible.
Contraindications
- Hypersensitivity, including to other sulfonamides.
- Marked liver parenchymal damage
- Severe renal insufficiency
- Megaloblastic anemia due to folic acid deficiency.
- Premature or newborn infants during the first six weeks of life.
- Pregnancy in the last trimester
- Combination with dofetilide
Full details of precautions and interactions can be found in the drug label.
Interactions
Drug-drug interactions have been described with the following agents:
- Digoxin
- Phenytoin
- Tricyclic antidepressants
- Methotrexate
- Antidiabetic drugs
- Oral contraceptives
- Indomethacin
- Diuretics
- Anticoagulants
- Ciclosporin
- Pyrimethamine
- Amantadine
- Dofetilide (contraindicated)
Adverse effects
The most common possible adverse effects include loss of appetite, nausea, vomiting, diarrhea, fever, hyperkalemia, blood count abnormalities, and a maculopapular rash with itching.