トリメトプリム

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Antibiotics (Bacteriostatic)

Pharmaceuticals -> Used in Switzerland

Pharmaceuticals

log Kow = 0.91

0.6

0.92

less than 1 mg/mL at 75 °F (NTP, 1992)

... Very slightly soluble in water and slightly soluble in alcohol.

Soluble in N,N-dimethylacetamide (DMAC) at 13.86; benzyl alcohol at 7.29; propylene glycol at 2.57; chloroform at 1.82; methanol at 1.21; ether at 0.003; benzene at 0.002 g/100 ml at 25 °C.

In water, 400 mg/l @ 25 °C

6.15e-01 g/L

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents, Urinary; Antibacterial Agents; Folic Acid Antagonists

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Access group antibiotics

Active Ingredients (Trimethoprim) -> FDA Greenbook

Pharmaceuticals -> UK Veterinary Medicines Directorate List

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

390 to 397 °F (NTP, 1992)

199-203 °C

199 - 203 °C

Trimethoprim is an odorless white powder. Bitter taste. (NTP, 1992)

Solid

This chemical does not meet GHS hazard criteria for 7.9% (11 of 140) of reports.

Danger

H302 (85%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P264, P270, P273, P280, P301+P317, P318, P319, P330, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 140 reports by companies from 21 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

Chemical: 2,4-Pyrimidinediamine, 5-[(3,4,5-trimethoxyphenyl)methyl]-

Trimethoprim: Does not have an individual approval but may be used under an appropriate group standard

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Trimethoprim and sulfadiazine tablets. (a) Each tablet contains 30 mg (5 mg of trimethoprim and 25 mg of sulfadiazine), 120 mg (20 mg of trimethoprim and 100 mg of sulfadiazine), 480 mg (80 mg of trimethoprim and 400 mg of sulfadiazine) or 960 mg (160 mg of trimethoprim and 800 mg of sulfadiazine) ... (c) Conditions of use: (1) The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone or as an adjunct to surgery or debridement with associated infection. The drug is indicated where control of bacterial infection is required during the treatment of acute urinary tract infections, acute bacterial complications of distemper, acute respiratory tract infections, acute alimentary tract infections, wound infections, and abscesses. ... (6) The drug should not be used in patients showing marked liver parenchymal damage or blood dyscrasia, nor in those with a history of sulfonamide sensitivity. (7) Federal law restricts this drug to use by or on the order of a licensed veterinarian. /Trimethoprim and sulfadiazine/

Trimethoprim and sulfadiazine oral paste. (a) Each gram of oral paste contains 400 mg (67 mg of trimethoprim and 333 mg of sulfadiazine) ... (c) Conditions of use: ... (2) Indications for use: For horses where systemic anti-bacterial action against sensitive organisms is required during treatment of acute strangles, respiratory infections, acute urogenital infections, and wound infections and abscesses. /Trimethoprim and sulfadiazine/

Trimethoprim and sulfadiazine oral suspension. (a) Each ml of oral suspension contains 60 mg of drug (10 mg of trimethoprim and 50 mg of sulfadiazine) ... (c) Condition of use: Dogs: ... (2) Indications for use: The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone or as an adjunct to surgery or debridement with associated infection. The drug is indicated where control of bacterial infection is required during the treatment of acute urinary tract infections, acute bacterial complications of distemper, acute respiratory tract infections, acute alimentary tract infections, wound infections, and abscesses. ... Federal law restricts this drug to use by or on the order of a licensed veterinarian. /Trimethoprim and sulfadiazine/

For more FDA Requirements (Complete) data for TRIMETHOPRIM (7 total), please visit the HSDB record page.

Acute Tox. 4 (85%)

Acute toxicity (Oral) - Category 3

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Trimethoprim tablets should be stored in tight, light-resistant containers at 15-30 °C in a dry place.

Trimethoprim-sulfamethoxazole should be stored at room temp & not refrigerated. The multiple-dose vials should be used within 48 hr of initial entry. /Trimethoprim-sulfamethoxazole/

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Concomitant admin of trimethoprim or trimethoprim/sulfamethoxazole with methotrexate may incr bone marrow suppression, probably as an additive antifolate effect.

Concurrent use with trimethoprim or use of trimethoprim between courses of other folic acid antagonists, such as methotrexate or pyrimethamine, is not recommended because of the possibility of an increased incidence of megaloblastic anemia.

Trimethoprim may inhibit the metab of phenytoin, increasing the half-life of phenytoin by up to 50% & decreasing its clearance by 30%.

Concurrent use /with rifampin/ may significantly increase the elimination and shorten the elimination half-life of trimethoprim.

For more Interactions (Complete) data for TRIMETHOPRIM (15 total), please visit the HSDB record page.

TMP-SMZ is a well-known cause of acute drug-induced liver injury and typically has features suggestive of hypersensitivity much like other sulfonamides. In most recent case series from the United States and Europe, TMP-SMZ ranked among the top 5 causes of drug-induced idiosyncratic liver injury. The estimated incidence of liver injury after TMP-SMZ use ranges from 1 per 2,000 to 1 per 5,000 treated patients. The typical latency to onset is 2 to 8 weeks. Cases with shorter latencies are likely due to re-challenge after minor or forgotten toxicity with the previous exposures. At least half of cases are accompanied by signs and symptoms of hypersensitivity such as fever, rash, facial edema, lymphadenopathy, and peripheral eosinophilia (Case 1). Liver injury can be an accompanying finding in patients with DRESS syndrome, or more rarely, Stevens Johnson syndrome (SJS) or toxic epidermal necrosis (TEN). The most frequent pattern of initial enzyme elevations is mixed, but markedly cholestatic and markedly hepatocellular patterns occur. For unknown reasons, injury in children and young adults is more often hepatocellular, while cholestatic cases occur more frequently in the elderly. The course of the liver injury may be short-lived with rapid recovery or complicated and prolonged. Cases with cholestatic TMP-SMZ related liver injury are often prolonged and some are accompanied by varying degrees of bile duct injury and loss leading to vanishing bile duct syndrome and chronic cholestasis which, if severe, can lead to biliary cirrhosis, chronic liver failure, and death or need for liver transplantation. However, most cases of vanishing bile duct syndrome usually improve spontaneously over time, with gradual resolution of jaundice and symptoms, leaving minor alkaline phosphatase and GGT elevations that may persist for years.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 75(SRC), determined from a measured log Kow of 0.91(2) and a regression-derived equation(3), indicates that trimethoprim is expected to have high mobility in soil(SRC). Trimethoprim has a pKa of 7.12(4), which indicates it will partially exist in the protonated form in moist soils and cations adsorb to soil stronger than neutral compounds(SRC). Volatilization of trimethoprim from moist soil surfaces is not expected to be an important fate process(SRC) because cations are non-volatile and the neutral species has an estimated Henry's Law constant of 2.4X10-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Trimethoprim is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.9X10-9 mm Hg(SRC), determined from a fragment constant method(6). Trimethoprim is expected to biodegrade slowly in soils based upon biodegradation half-lives of approximately 100 and 75 days under anaerobic and aerobic conditions, respectively, in sediment(7).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 75(SRC), determined from a measured log Kow of 0.91(2) and a regression-derived equation(3), indicates that trimethoprim is not expected to adsorb to suspended solids and sediment(SRC). Trimethoprim has a pKa of 7.12(4), which indicates it will partially exist in the protonated form in water surfaces and the cation may adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.4X10-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5), and the fact that cations do not volatilize. According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Although trimethoprim absorbs light greater than 290 nm, it was shown to be stable in seawater exposed to sunlight(8). The half-lives of trimethoprim incorporated into sediment cores were approximately 100 and 75 days under anaerobic and aerobic conditions, respectively(9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), trimethoprim, which has a an estimated vapor pressure of 9.9X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase trimethoprim may be removed from the air by wet and dry deposition(SRC).

Trimethoprim is distributed into milk in concentrations approximately 125% those of concurrent maternal serum concentrations.

Trimethoprim is excreted into breast milk in low concns.

The Koc of trimethoprim is estimated as 75(SRC), using a measured log Kow of 0.91(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that trimethoprim is expected to have high mobility in soil(SRC). The pKa of trimethoprim is 7.12(4), which indicates that this compound will partially exist in the protonated form and cations adsorb to soil stronger than neutral compounds(SRC).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 & 1992, 2296 newborns had been exposed to the combination of trimethoprim-sulfamethoxazole during the 1st trimester. A total of 126 (5.5%) major birth defects were observed (98 expected). This incidence is suggestive of an association between the drug combination & congenital defects. Specific data were available for six defect categories, including (observed/expected) 37/23 cardiovascular defects ... .

Sulfonamide/trimethoprim combinations have been shown to cause a drop in the sperm count after 1 month of continuous treatment in males. Decreases varied between 7 & 88%. the authors theorized that trimethoprim deprived the spermatogenetic cells of active folate by inhibiting dihydrofolate reductase.

Single case report of Niikawa-Kuroki syndrome (mental & physical growth retardation & craniofacial anomalies) in non-Japanese girl.

Trimethoprim poisoning has been characterized by nausea, vomiting, headache, swollen face, epigastric pain, & weakness.

For more Human Toxicity Excerpts (Complete) data for TRIMETHOPRIM (11 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Trimethoprim

vLess-DILI-concern

4

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Trimethoprim and sulfadiazine tablets. (a) Each tablet contains 30 mg (5 mg of trimethoprim and 25 mg of sulfadiazine), 120 mg (20 mg of trimethoprim and 100 mg of sulfadiazine), 480 mg (80 mg of trimethoprim and 400 mg of sulfadiazine) or 960 mg (160 mg of trimethoprim and 800 mg of sulfadiazine) ... (c) Conditions of use: (1) The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone or as an adjunct to surgery or debridement with associated infection. The drug is indicated where control of bacterial infection is required during the treatment of acute urinary tract infections, acute bacterial complications of distemper, acute respiratory tract infections, acute alimentary tract infections, wound infections, and abscesses. ... (6) The drug should not be used in patients showing marked liver parenchymal damage or blood dyscrasia, nor in those with a history of sulfonamide sensitivity. (7) Federal law restricts this drug to use by or on the order of a licensed veterinarian. /Trimethoprim and sulfadiazine/

Trimethoprim and sulfadiazine oral paste. (a) Each gram of oral paste contains 400 mg (67 mg of trimethoprim and 333 mg of sulfadiazine) ... (c) Conditions of use: ... (2) Indications for use: For horses where systemic anti-bacterial action against sensitive organisms is required during treatment of acute strangles, respiratory infections, acute urogenital infections, and wound infections and abscesses. /Trimethoprim and sulfadiazine/

Trimethoprim and sulfadiazine oral suspension. (a) Each ml of oral suspension contains 60 mg of drug (10 mg of trimethoprim and 50 mg of sulfadiazine) ... (c) Condition of use: Dogs: ... (2) Indications for use: The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone or as an adjunct to surgery or debridement with associated infection. The drug is indicated where control of bacterial infection is required during the treatment of acute urinary tract infections, acute bacterial complications of distemper, acute respiratory tract infections, acute alimentary tract infections, wound infections, and abscesses. ... Federal law restricts this drug to use by or on the order of a licensed veterinarian. /Trimethoprim and sulfadiazine/

For more FDA Requirements (Complete) data for TRIMETHOPRIM (7 total), please visit the HSDB record page.

J01EE01

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

J01EA01

Trimethoprim exerts its antimicrobial effects by inhibiting an essential step in the synthesis of bacterial nucleic acids and proteins. It has shown activity against several species of gram-negative bacteria, as well as coagulase-negative _Staphylococcus_ species. Resistance to trimethoprim may arise via a variety of mechanisms, including alterations to the bacterial cell wall, overproduction of dihydrofolate reductase, or production of resistant dihydrofolate reductase. Rarely, trimethoprim can precipitate the development of blood disorders (e.g. thrombocytopenia, leukopenia, etc.) which may be preceded by symptoms such as sore throat, fever, pallor, and or purpura - patients should be monitored closely for the development of these symptoms throught the course of therapy. As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.

Trimethoprim is a reversible inhibitor of dihydrofolate reductase, one of the principal enzymes catalyzing the formation of tetrahydrofolic acid (THF) from dihydrofolic acid (DHF). Tetrahydrofolic acid is necessary for the biosynthesis of bacterial nucleic acids and proteins and ultimately for continued bacterial survival - inhibiting its synthesis, then, results in bactericidal activity. Trimethoprim binds with a much stronger affinity to bacterial dihydrofolate reductase as compared to its mammalian counterpart, allowing trimethoprim to selectively interfere with bacterial biosynthetic processes. Trimethoprim is often given in combination with sulfamethoxazole, which inhibits the preceding step in bacterial protein synthesis - given together, sulfamethoxazole and trimethoprim inhibit two consecutive steps in the biosynthesis of bacterial nucleic acids and proteins. As a monotherapy trimethoprim is considered bacteriostatic, but in combination with sulfamethoxazole is thought to exert bactericidal activity.

Trimethoprim is a bacteriostatic lipophilic weak base structurally related to pyrimethamine. It binds to and reversibly inhibits the bacterial enzyme dihydrofolate reductase, selectively blocking conversion of dihydrofolic acid to its functional form, tetrahydrofolic acid. This depletes folate, an essential cofactor in the biosynthesis of nucleic acids, resulting in interference with bacterial nucleic acid and protein production. Bacterial dihydrofolate reductase is approximately 50,000 to 60,000 times more tightly bound by trimethoprim than is the corresponding mammalian enzyme.

To determine the incidence & severity of hyperkalemia during trimethoprim therapy, 30 consecutive patients with acquired immunodeficiency syndrome receiving high-dose (20 mg/kg/day) trimethoprim were studied; in addition, the mechanism of trimethoprim-induced hyperkalemia was investigated in rats. Trimethoprim increased serum potassium concn by 0.6 mmol/l despite normal adrenocortical function & glomerular filtration rate. Serum potassium levels >5 mmol/l were observed during trimethoprim treatment in 15 of 30 patients. In rats, iv trimethoprim inhibited renal potassium excretion by 40% & increased sodium excretion by 46%. It was concluded that trimethoprim blocks apical membrane sodium channels in the mammalian distal nephron. As a consequence, the transepithelial voltage is reduced & potassium secretion is inhibited. Decreased renal potassium excretion secondary to these direct effects on kidney tubules leads to hyperkalemia in a substantial number of patients being treated with trimethoprim-containing drugs.

Trimethoprim half-life ranges from 8-10 hours, but may be prolonged in patients with renal dysfunction.

Trimethoprim has a serum half-life of approx 8-11 hr in adults with normal renal function. In adults with creatinine clearances of 10-30 or 0-10 ml/min, serum half-life of the drug may incr to 15 hr or >26 hr, respectively. Trimethoprim serum half-lives of about 7.7 & 5.5 hr have been reported in children <1 yr of age & between 1 & 10 yr of age, respectively.

Trimethoprim undergoes oxidative metabolism to a number of metabolites, the most abundant of which are the demethylated 3'- and 4'- metabolites, accounting for approximately 65% and 25% of the total metabolite formation, respectively. Minor products include N-oxide metabolites (<5%) and benzylic metabolites in even smaller quantities. The parent drug is considered to be the therapeutically active form. The majority of trimethoprim biotransformation appears to involve CYP2C9 and CYP3A4 enzymes, with CYP1A2 contributing to a lesser extent.

Trimethoprim is metabolized in the liver to oxide and hydroxylated metabolites ... .

The pharmacokinetics were studied of sulfadimethoxine (SDM) or sulfamethoxazole (SMX) in combination with trimethoprim (TMP) administered as a single oral dose (25 mg + 5 mg/kg bw) to 2 groups of 6 healthy pigs. The elimination half-lives of SMX & TMP were quite similar (2-3 hr); SDM had a relatively long half-life of 13 hr. Both sulfonamides (S) were exclusively metabolized to N4-acetyl derivatives but to different extents. The main metabolic pathway for TMP was O-demethylation & subsequent conjugation. In addition, the plasma concns of these drugs & their main metabolites after medication with different in-feed concns were determined. The drug (S:TMP) concns in the feed were 250:50, 500:100, & 1000:200 mg/kg. Steady-state concns were achieved within 48 hr of feed medication, twice daily (SDM+TMP) or 3 times/day (SMX+TMP). Protein binding of SDM & its metabolite was high (>93%), whereas SMX, TMP & their metabolites showed moderate binding (48-75%). Feed medication with 500 ppm sulfonamide combined with 100 ppm TMP provided minimum steady-state plasma concns (C(ss,min)) higher than the concn required for inhibition of the growth of 90% of Actinobacillus pleuropneumoniae strains (n=20).

AN164J8Y0X

TRIMETHOPRIM

Established Pharmacologic Class [EPC] - Dihydrofolate Reductase Inhibitor Antibacterial

Mechanisms of Action [MoA] - Dihydrofolate Reductase Inhibitors

Mechanisms of Action [MoA] - Cytochrome P450 2C8 Inhibitors

Mechanisms of Action [MoA] - Organic Cation Transporter 2 Inhibitors

Substances capable of killing agents causing urinary tract infections or of preventing them from spreading.

Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585)

Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)

Drugs used in the treatment of movement disorders. Most of these act centrally on dopaminergic or cholinergic systems. Among the most important clinically are those used for the treatment of Parkinson disease (ANTIPARKINSON AGENTS) and those for the tardive dyskinesias.

Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2C8.

Steady-state concentrations are achieved after approximately 3 days of repeat administration. Average peak serum concentrations of approximately 1 µg/mL (Cmax) are achieved within 1 to 4 hours (Tmax) following the administration of a single 100mg dose. Trimethoprim appears to follow first-order pharmacokinetics, as a single 200mg dose results in serum concentrations approximately double that of a 100mg dose. The steady-state AUC of orally administered trimethoprim is approximately 30 mg/L·h.

Approximately 10-20% of an ingested trimethoprim dose is metabolized, primarily in the liver, while a large portion of the remainder is excreted unchanged in the urine. Following oral administration, 50% to 60% of trimethoprim is excreted in the urine within 24 hours, approximately 80% of which is unchanged parent drug.

Trimethoprim is extensively distributed into various tissues following oral administration. It distributes well into sputum, middle ear fluid, and bronchial secretions. Trimethoprim distributes efficiently into vaginal fluids, with observed concentrations approximately 1.6-fold higher than those seen in the serum. It may pass the placental barrier and into breast milk. Trimethoprim is also sufficiently excreted in the feces to markedly reduce and/or eliminate trimethoprim-susceptible fecal flora.

Following oral administration, the renal clearance of trimethoprim has been variably reported between 51.7 - 91.3 mL/min.

Trimethoprim is widely distributed into body tissues & fluids including the aqueous humor, middle ear fluid, saliva, lung tissue, sputum, seminal fluid, prostatic tissue & fluid, vaginal secretions, bile, bone, & /cerebrospinal fluid/. The apparent volume of distribution of trimethoprim in adults with normal renal function ranges from 100-120 l. ... Trimethoprim is 42-46% bound to plasma proteins. Trimethoprim readily crosses the placenta, & amniotic fluid concns are reported to be 80% of concurrent maternal serum concns.

Only small amounts of trimethoprim are excreted in feces via biliary elimination. Trimethoprim may be moderately removed by hemodialysis.

Veterinary antimicrobial agent

Has a broad spectrum of antimicrobial activity and extends the spectrum of sulfamethoxazole to include many urinary and systemic pathogens untreatable by this sulfa drug alone.

MEDICATION (VET)

MEDICATION

Use (kg) in Switzerland (2009): >250

Prepn from guanidine and beta-ethoxy-3,4,5-trimethoxybenzylbenzalnitrile

Trimethoprim /is a/ drug that /is/ made from vanillin.

Preparations: Tablets, 100 and 200 mg.

Component of Bactrin and Septra

Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

See sulfamethoxazole, sulfadiazine, sulfametrole, sulfamoxole, and sulfalene for list of trade names of mixtures with trimethoprim.

Authorized or allowed for use in aquaculture in certain European countries.

Solid phase reactions between trimethoprim & sulfamethoxazole were investigated by IR spectrometry & differential scanning calorimetry in 4 tablet formulations. Heating & humidity were found to enhance the conditions for reactions, with the most likely manufacturing step causing reactions being wet granulation. Mixing, grinding & compression of powders caused no interactions.