Trimethoprim and Sulfamethoxazole
- Atc Codes:J01EE01
- CAS Codes:738-70-5#56585-33-2#723-46-6
- PHARMGKB ID:738-70-5#56585-33-2#723-46-6
Table of contents
- Brand Names
- Drug Combinations
- Chemistry
- Pharmacologic Category
- Mechanism of Action
- Therapeutic Use
- Unlabeled Use
- Pregnancy and Lactation Implications
- Contraindications
- Warnings and Precautions
- Adverse Reactions
- Caution and personalized dose adjustment in patients with the following genotypes
- Other genes that may be involved
- Substrate of
- Inhibits
- Drug Interactions
- Nutrition/Nutraceutical Interactions
- Dosage
- Pharmacokinetics and Pharmacodynamics
- Special Considerations
Brand Names
Europe
Austria: Bactrim Forte, Cotribene, Cotrimoxazol, Eusaprim; Estonia: Bactrim, Berlocid, Biseptol; Finland: Cotrim; France: Bactrim, Cotrimoxazole; Germany: Berlocid, Cotrim, Cotrimox, Cotrimoxazol, Cotrimstada, Drylin, Eusaprim, Kepinol, Sigaprim, TMS forte; Greece: Bactrimel, Oradin, Septrin, Solfoton; Hungary: Cotripharm, Sumetrolim; Ireland: Septrin; Italy: Bactrim; Latvia: Bactrim, Berlocid, Biseptol; Lithuania: Berlocid, Biseptol, Co-Trimoxazol; Luxembourg: Bactrim, Cotrim, Cotrimoxazole, Eusaprim; Malta: Deprim Tablets, Septrin; Netherlands: Bactrimel, Co Trimoxazol, Eusaprim; Poland: Apo-Sulfatrim, Bactrim, Biseptol, Duo-Septol, Groseptol, Septrin, Two-Septol; Portugal: Bactrim, Cotrimoxazol, Septrin; Romania: Biseptrim, Bitrim, Co-Trim Ell, Epitrim, Septrin, Sumetrolim, Tagremin; Slovakia: Biseptol, Bismoral, Cotrimoxazol; Slovenia: Primotren; Spain: Septrin, Soltrim; Sweden: Bactrim, Eusaprim; UK: Co-Trimoxazole, Septrin.
North America
Canada: Apo Sulfatrim, Novo-Trimel, Nu-Cotrimox, Protrin, Septra Injection, Trisulfa; USA: Bactrim, Septra, Sulfamethoprim, Sulfamethoxazole and Trimethoprim, Sulfatrim.
Latin America
Argentina: Adrenol, Bacticel, Bactrim, Co-Trimexazol, Cotrizol-G, Danferane, Dosulfin Fuerte, Netocur, Novidrine, Tritenk, Urisept; Brazil: Assepium, Bacfar, Bacprotin, Bac-Sulfitrin, Bacteracin, Bactrim, Bactrisan, Bactrizol, Bactropin, Batrox, Benectrin, Diazol, Dientrin, Infectrin, Medtrim, Neotrin, Roytrin, Sulfemethoxazole+Trimetropina, Teutrin, Tricban, Trimexazol, Uropol; Mexico: Anitrim, Apotrinelax, Bacpiryl, Bactelan, Bactide, Bactilen, Bactiver, Bactrim, Bactropin, Bateral, Batrizol, Bioprim, Bisultrim, Dertrin, Dibaprim, Ectaprim, Esteprim, Eutrim, Fartoprin, Fectri, Kaltrim, Maxtrim, Mixange, Neofatrim, Octiban, Odisulfan, Pisatrina, Polibatrin, Pribac, Protaxol, Protrim, Septrin, Servitrim, Soltrim, Sulfawal, Sulfort, Sulprim, Sultral, Thriazol, Tribakin, Trimetoger, Trimetox, Trimetropina con Sulfametoxazol, Trimexazol, Trimexole, Trimzol, TS-BAC, Vanadyl.
Asia
Japan: Bactramin, Baktar, Daiphen.
Drug combinations
Trimethoprim, Attapulgite, and Sulfamethoxazole
Trimethoprim, Bromhexine, and Sulfamethoxazole
Trimethoprim, Ammonium, Guaifenesin, and Sulfamethoxazole
Trimethoprim, Bromhexine, Guaiacol, and Sulfamethoxazole
Trimethoprim, Clophedianol, Guaifenesin, Oxatomide, and Sulfamethoxazole
Chemistry
Trimethoprim: C~14~H~18~N~4~O~3~. Mw: 290.32. 2,4-Pyrimidinediamine, 5-[(3,4,5-trimethoxyphenyl)methyl]. CAS-738-70-5 (1964).
Trimethoprim Sulfate: (C~14~H~18~N~4~O~3~)2.H~2~SO~4~. Mw: 678.71. 2,4-Diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine sulfate (2:1). CAS-56585-33-2 (1984).
Sulfamethoxazole: C~10~H~11~N~3~O~3~S. Mw: 253.28. (1) Benzenesulfonamide, 4-amino-N-(5-methyl-3-isoxazolyl)-; (2) N1-(5-Methyl-3-isoxazolyl)sulfanilamide. CAS-723-46-6 (1962).
Drug Combination
Trimethoprim and Sulfamethoxazole.
Pharmacologic Category
Antibacterials; Sulfonamides. (ATC-Code: J01EE01).
Mechanism of action
Sulfamethoxazole interferes with bacterial folic acid synthesis and growth via inhibition of dihydrofolic acid formation from para-aminobenzoic acid. Trimethoprim inhibits dihydrofolic acid reduction to tetrahydrofolate resulting in sequential inhibition of enzymes of folic acid pathway.
Therapeutic use
Oral treatment of urinary tract infections due to E. coli, Klebsiella and Enterobacter sp, M. morganii, P. mirabilis and P. vulgaris. Acute otitis media in children. Acute exacerbations of chronic bronchitis in adults due to susceptible strains of H. influenzae or S. pneumoniae. Treatment and prophylaxis of Pneumocystis jiroveci pneumonitis. Traveler’s diarrhea due to enterotoxigenic E. coli. Treatment of enteritis caused by Shigella flexneri or Shigella sonnei. I.V. treatment of severe or complicated infections when oral therapy is not feasible, for documented Pneumocystis jiroveci pneumonitis, empiric treatment of Pneumocystis jiroveci pneumonitis in immune-compromised patients. Treatment of documented or suspected shigellosis, typhoid fever, Nocardia asteroides infection, or other infections caused by susceptible bacteria.
Pregnancy and lactiation implications
Should not be used at term to avoid kernicterus in newborn. Should be used during pregnancy only if benefits outweigh risks since folic acid metabolism may be affected. Sulfonamides are excreted in low concentrations in breast milk.
Unlabeled use
Cholera and Salmonella-type infections and nocardiosis. Chronic prostatitis. As prophylaxis in neutropenic patients with P. jiroveci infections, in leukemia patients, and in patients following renal transplantation, to decrease incidence of Pneumocystis jiroveci pneumonitis. Treatment of Cyclospora infection, typhoid fever, Nocardia asteroides infection. Prophylaxis against urinary tract infection.
Contraindications
Hypersensitivity to any sulfa drug, trimethoprim, or any component of the formulation. Megaloblastic anemia due to folate deficiency. Infants <2 months of age. Marked hepatic damage or severe renal disease (if patient not monitored). Pregnancy (at term). Breast-feeding.
Warnings and precautions
Fatalities associated with severe reactions including agranulocytosis, aplastic anemia and other blood dyscrasias have occurred. Fatalities associated with severe reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have occurred. Fatalities associated with hepatic necrosis have also occurred. May cause hyperkalemia (associated with high doses of trimethoprim). May cause hypoglycemia, particularly in the malnourished, or patients with renal or hepatic impairment. Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea and pseudomembranous colitis. Use with caution in allergies or asthma, in hepatic or renal impairment, and in thyroid dysfunction. Incidence of adverse effects appears to be increased in patients with AIDS. Sulfonamides may cause euphoria, restlessness, irritability, disorientation, panic, and delusions. Use with caution in the elderly (greater risk for more severe adverse reactions), in G6PD deficiency (dose-related hemolysis may occur), and in potential folate deficiency (malnourished, chronic anticonvulsant therapy, or elderly). Slow acetylators may be more prone to adverse reactions. Injection vehicle may contain sodium metabisulfite and benzyl alcohol, associated with «gasping syndrome» in neonates.