Sulfamethizole

270.33

270.33

205-641-1

25W8454H16

757327

DTXSID5023615

C47736

Crystals from water|Colorless crystal

B - Blood and blood forming organs|D - Dermatologicals|J - Antiinfectives for systemic use|S - Sensory organs

2935904000

135

0.5

Sulfamethizole is a white powder. (NTP, 1992)

1.4704 (rough estimate)

208 °C

176°C (rough estimate)

259.1±30.7 °C

1.6440 (estimate)

>40.5 [ug/mL]

2-8°C

2.06X10-9 mm Hg at 25 deg C (est)

LD50 oral in rat: 3500mg/kg

Henry's Law constant = 2.63X10-14 atm-cu m/mol at 25 °C (est)

pKa1 = 2.1 /amine/; pKa2 = 5.3 /R1SO2NHR2 moiety/

155.2 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]|152.2 Ų [M+H]+ [CCS Type: TW]|157.8 Ų [M+H]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]|171.2 Ų [M+Na]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]

The electronic absorption spectra of the Cu(II), Ni(II) and Co(II) chelates of the Schiff bases synthesized from 5-bromo-salicylaldehyde and sulfamethoxypyridazine, sulfamethizole and sulfafurazole (sulfisoxazole) were studied in dimethyl sulfoxide solution. All the chelates showed an intense charge transfer absorption band at the blue end of the visible region. The stereochemical characteristics of the chelates were illustrated by means of the absorptions caused by the d-d transitions. The Ni(II) and Co(II) chelates are 6 coordinated in all cases.|The Cu(II), Co(II) and Ni(II) chelates of the Schiff bases formed from 5-bromo-salicylaldehyde and sulfamethizole, sulfamethoxypyridazine and sulfafurazole(sulfisoxazole) were synthesized and an atomic absorption spectrometric method for the determination of the metal content of the chelates is described. The stoichiometry was found to be 1:1 for all compounds. The metal content determined by the described method agreed with theoretical values. Structure analysis by infrared spectrometry and x-ray diffraction is also included. Thermostability of these Schiff bases was investigated using a thermogravimetric method. Decomposition began at 200-290 °C for the Schiff bases, while chelates began to decompose at 60-120 °C. Stable oxides were formed by all chelated at 530-800 °C. The orders and the activation energies of some decomposition reactions were calculated for the chelates on the basis of the thermograms.|The formation and stability of copper, cobalt and nickel chelates of the Schiff bases synthesized from the 5-bromo derivatives of salicylaldehyde, sulfamethoxypyridazine, sulfamethizole and sulfisoxazole (sulfafurazole) were studied in an absolute ethanol-acetone (70:30 v/v) solution.|Hydroxyl radical reaction rate constant = 2.39X10-11 cu cm/molec-sec at 25 °C (est)

Insoluble in water.

Azo, Diazo, Azido, Hydrazine, and Azide Compounds

NONH for all modes of transport

2

43

36/37

WP0875000

Xi

P280

H317

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.

Oral dosage form new animal drugs. Sulfamethizole and methenamine mandelate tablets. ... Each tablet contains 250 milligrams of sulfamethizole and 250 milligrams of methenamine mandelate. ... Conditions of use. (1) The drug is indicated for the treatment of urinary tract infections in dogs and cats such as cystitis, nephritis, prostatitis, urethritis, and pyelonephritis. It is also used as an aid in the management of complications resulting from surgical manipulations of the urinary tract such as removal of calculi from the bladder, in ureterostomies, and in instrumentation of the urethra and bladder. ... Federal law restricts this drug to use by or on the order of a licensed veterinarian. /Sulfamethizole and methenamine mandelate tablets/|The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Sulfamethizole is included on this list.|The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies discontinued drug products. Sulfamethizole is included on this list.

Briggs GG et al; Drug Preg Lactation 324-377 1984. Drugs in pregnancy and lactation: A reference guide to fetal and neonatalrisk (Drugs S-Z).

Flammability data is lacking for this compound. It is probably non-flammable. (NTP, 1992)

|Warning|H317 (98.68%): May cause an allergic skin reaction [Warning Sensitization, Skin]|P261, P272, P280, P302+P352, P321, P333+P313, P363, and P501|Aggregated GHS information provided by 76 companies from 3 notifications to the ECHA C&L Inventory.

This compound is not very flammable but any fire involving this compound may produce dangerous vapors. You should evacuate the area. All firefighters should wear full-body protective clothing and use self-contained breathing apparatuses. You should extinguish any fires involving this chemical with a dry chemical, carbon dioxide, foam, or halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, you should dampen the solid spill material with alcohol, then transfer the dampened material to a suitable container. Use absorbent paper dampened with alcohol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with alcohol followed by washing with a strong soap and water solution. Do not reenter the contaminate area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

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)

Leachate samples were collected on September 6, 2000, down gradient from the Norman Municipal Landfill research site in central Oklahoma; the landfill was established in the 1920s and closed in 1985(1). Sulfamethizole was tested for but not detected, reporting limit 0.10 ug/L(1). Sulfamethizole was not detected in final effluents of eight wastewater treatment plants in five Canadian cities, sampled in 2002; detection limit 0.004 ug/L(2). The compound has been detected in the secondary effluent of a waste water treatment plant in Berlin, Germany at a concentration of 0.006 ug/L(2).

These medications /coumarin- or indandione-derivative anticoagulants; hydantoin anticonvulsants or oral antidiabetic agents/ may be displaced from protein binding sites and/or their metabolism may be inhibited by some sulfonamides, resulting in increased or prolonged effects and/or toxicity; dosage adjustments may be necessary during and after sulfonamide therapy. /Sulfonamides/|Concurrent use of bone marrow depressants with sulfonamides may increase the leukopenic and/or thrombocytopenic effects; if concurrent use is required, close observation for myelotoxic effects should be considered. /Sulfonamides/|Concurrent long-term use of sulfonamides /with estrogen-containing, oral contraceptives/ may result in increased incidence of breakthrough bleeding and pregnancy. /Sulfonamides/|Concurrent use /of cyclosporine/ with sulfonamides may increase the metabolism of cyclosporine, resulting in decreased plasma concentration and potential transplant rejection, and additive nephrotoxicity; plasma cyclosporine concentrations and renal function should be monitored. /Sulfonamides/|For more Interactions (Complete) data for SULFAMETHIZOLE (12 total), please visit the HSDB record page.

LD50 Rat oral 3500 mg/kg

Patients with acquired immunodeficiency syndrome (AIDS) may have a greater incidence of side/adverse effects, especially rash, fever, and leukopenia, than do non-AIDS patients. /Sulfonamides/|Acute hemolytic anemia may occur during the first week of therapy as a result of sensitization or glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. This reaction may also occur in the fetus or premature infant in whom G-6-PD is normally deficient. /Sulfonamides/|Except as concurrent adjunctive therapy with pyrimethamine in the treatment of congenital toxoplasmosis, use of sulfonamides is contraindicated in infants up to 2 months of age. Sulfonamides compete for bilirubin binding sites on plasma albumin, increasing the risk of kernicterus in the newborn. Also, because the acetyltransferase system is not fully developed in the newborn, increased blood concentrations of the free sulfonamide can further increase the risk of kernicterus. /Sulfonamides/|Because sulfonamides are distributed into milk, and because of the potential for serious adverse reactions from the drugs in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the woman. Because of the risk of kernicterus in infants younger than 2 months of age, use of sulfonamides is contraindicated in lactating women who are nursing such infants. /Sulfonamides/|Elderly patients may be at increased risk of severe side/adverse effects. Severe skin reactions, generalized bone marrow depression, and decreased platelet count (with or without purpura) are the most frequently reported severe side/adverse effects in the elderly. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients who are receiving diuretics, primarily thiazides, concurrently with sulfamethoxazole. The potential for these problems should also be considered for elderly patients taking other sulfonamide medications. /Sulfonamides/

98-99%

Sulfamethizole's production and use as a human and veterinary antibiotic(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 47(SRC), determined from a log Kow of 0.54(2) and a regression-derived equation(3), indicates that sulfamethizole is expected to have very high mobility in soil(SRC). The pKa1 and pKa2 values for sulfamethizole are 2.1 and 5.3(4), respectively, indicating that this compound will partially exist in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of the neutral species from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.6X10-14 atm-cu m/mole(SRC), using a fragment constant estimation method(6). Sulfamethizole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.1X10-9 mm Hg(SRC), determined from a fragment constant method(7). In general, sulfonamide antimicrobials are not readily biodegraded and persist in soils(8).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 47(SRC), determined from a log Kow of 0.54(2) and a regression-derived equation(3), indicates that sulfamethizole is not expected to adsorb to suspended solids and sediment(SRC). A pKa1 and pKa2 of 2.1 and 5.3(4), respectively, indicate sulfamethizole will exist partially in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(5). By analogy to structurally similar sulfamethoxazole which did not undergo hydrolysis under field conditions(9), hydrolysis of sulfamethizole is not expected to be an important environmental fate process(SRC). 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). In general, sulfonamide antimicrobials are not readily biodegraded(8).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), sulfamethizole, which has an estimated vapor pressure of 2.1X10-9 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 sulfamethizole may be removed from the air by wet or dry deposition(SRC). Sulfamethizole contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).

By analogy to structurally similar sulfamethoxazole which did not undergo hydrolysis under field conditions(1), hydrolysis of sulfamethizole is not expected to be an important environmental fate process(SRC). Amphoteric sulfonamides behave as weak acids and are much more soluble in alkaline than acidic environments(2); they form salts in strongly acid or basic solutions(3). Sulfamethizole is expected to be readily photodegraded in most natural waters as the anionic form is most susceptible to direct photodegradation. In aqueous solution, direct photolysis rates under natural sunlight were reported as <0.3X10-5/sec (pH 2.4); 0.5X10-5/sec (pH 5.2); 1.3X10-5/sec (pH 6.7); 1.3X10-5/sec (pH 8.6), resulting in sulfanilic acid(4). Sulfamethizole contains chromophores that absorb at wavelengths >290 nm(5) and therefore may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for sulfamethizole(SRC), using a log Kow of 0.54(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of sulfamethizole is estimated as 47(SRC), using a log Kow of 0.54(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that sulfamethizole is expected to have very high mobility in soil. The pKa1 and pKa2 for sulfamethizole are 2.1 and 5.3(4), respectively, indicating that this compound will partially exist in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(6,7), suggesting that mobility may be much lower in some soils(SRC). Treated waste water effluent containing sulfamethizole was applied to soil columns over 23 days; the compound was not detected (detection limit 0.05 ug/L) in the drainage samples(8).

The Henry's Law constant for the neutral species of sulfamethizole is estimated as 2.6X10-14 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that the neutral species is expected to be essentially nonvolatile from moist soil surfaces(2). A pKa1 and pKa2 of 2.1 and 5.3(3), respectively, indicate sulfamethizole will exist partially in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(4). Sulfamethizole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.1X10-9 mm Hg(SRC), determined from a fragment constant method(5).

GROUNDWATER: Sulfamethizole was detected in groundwater downgradient of a landfill in Grindsted, Denmark, which was in operation from 1930-1977 and received pharmaceutical waste from 1962-1975(2). Sulfamethizole concentrations in ug/L and at 5.5 m depth (distance from landfill in meters): 100 (0); at 7 meter depth: 900 (0), 540 (15), 50 (37), <20 (50); at 8.5 meter depth: 230 (0), 900 (15), 310 (37), 20 (50); and at 10 meter depth: 210 (0), 70 (37), 70 (50), <20|DRINKING WATER: Sulfamethizole was not detected in finished water samples from a drinking water conventional treatment facility located in a heavily populated, highly urbanized US drainage basin that treats an average of 62 Mgal/day, providing potable water to an estimated 850,000 people; samples collected over 4 consecutive weeks during November and December, reporting level 0.05 ug/L(1).|SURFACE WATER: Sulfamethizole has been listed as one of the common drugs that the US Geological Survey has been monitoring in lakes and streams(1). It was detected at a frequency of 1% of 104 US streams sampled from 1999-2000, median concentration of 0.13 ug/L, detection limit of 0.05 ug/L(2). It was not detected in 76 water samples collected during 2001 upstream and downstream of select towns and cities in Iowa during high-, normal-, and low-flow conditions, detection limit 0.05 ug/L(3). Sulfamethizole was not detected in 12 stream and raw water samples collected in a heavily populated, highly urbanized US drainage basin during November and December 2001, reporting level of 0.10 ug/L(4).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 1,635 workers (255 of these were female) were potentially exposed to sulfamethizole in the US(1). Occupational exposure to sulfamethizole may occur through inhalation and dermal contact with this compound at workplaces where sulfamethizole is produced or used. Use data indicate that the general population may be exposed to sulfamethizole via dermal contact and administration of pharmaceutical products containing sulfamethizole(SRC).

For the treatment of urinary tract infection

Anti-Infective Agents /SRP: Antibacterial/|Sulfamethizole is indicated in the treatment of urinary tract infections (primarily pyelonephritis, pyelitis, and cystitis) in the absence of obstructive uropathy or foreign bodies, when these infections are caused by susceptible strains of the following organisms: Escherichia coli, Klebsiella-Enterobacter, Staphylococcus aureus, Proteus mirabilis, and Proteus vulgaris. /Included in US product label/|Sulfonamides are indicated in the treatment of chancroid caused by Hemophilus ducreyi. However, other agents such as erythromycin and ceftriaxone, are considered to be first line agents. /Sulfonamides; Included in US product labeling/|Sulfonamides are indicated in the treatment of endocervical and urethral infections caused by Chlamydia trachomatis. However, other agents, such as doxycycline and azithromycin, are considered to be first line agents. /Sulfonamides; Included in US product labeling/|For more Therapeutic Uses (Complete) data for SULFAMETHIZOLE (17 total), please visit the HSDB record page.

The number of conditions for which the sulfonamides are therapeutically useful and constitute drugs of first choice has been reduced sharply by the development of more effective antimicrobial agents and by the gradual increase in the resistance of a number of bacterial species to this class of drugs. /Sulfonamides/|Many of the adverse effects that have been attributed to the sulfonamides appear to be hypersensitivity reactions. The incidence of hypersensitivity reactions appears to increase with increased sulfonamide dosage. Although cross-sensitization has been reported to occur between the various anti-infective sulfonamides, some diuretics such as acetazolamide and the thiazides, some goitrogens, and sulfonylurea antidiabetic agents, the association between hypersensitivity to sulfonamide anti-infectives and subsequent sensitivity reactions to non-anti-infective sulfonamides (e.g., thiazides, sulfonylurea antidiabetic agents, furosemide, dapsone, probenecid) appears to result from a predisposition to allergic reactions in general rather than to cross-sensitivity to the sulfa moiety per se. /Sulfonamides/|Various dermatologic reactions, including rash, pruritus, urticaria, erythema nodosum, erythema multiforme (Stevens-Johnson syndrome), Lyell's syndrome (may be associated with corneal damage), Behcet's syndrome, toxic epidermal necrolysis, and exfoliative dermatitis, have been reported in patients receiving sulfonamides. Because photosensitivity may also occur, patients should be cautioned against exposure to UV light or prolonged exposure to sunlight. A relatively high proportion of fatalities has occurred as a result of the Stevens-Johnson syndrome, especially in children. Although long-acting sulfonamides (which are no longer commercially available) have been associated most often with the Stevens-Johnson syndrome, other sulfonamides also have been reported to cause this reaction. The physician should be alert to the signs, including high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis, which may precede the onset of the cutaneous lesions of the Stevens-Johnson syndrome. If a rash develops during therapy, the sulfonamide should be discontinued at once. In rare instances, a skin rash may precede a more serious reaction such as Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, and/or serious blood disorders. /Sulfonamides/|Fever, which may develop 7-10 days after the initial sulfonamide dose, is a common adverse effect of sulfonamide therapy. Serum sickness syndrome or serum sickness-like reactions (e.g., fever, chills, rigors, flushing, joint pain, urticarial eruptions, conjunctivitis, bronchospasm, leukopenia), have been reported; rarely, anaphylactoid reactions and anaphylaxis may occur. Lupus erythematosus-like syndrome, disseminated lupus erythematosus, angioedema, vasculitis, vascular lesions including periarteritis nodosa and arteritis, cough, shortness of breath, chills, pulmonary infiltrates, pneumonitis (which may be associated with eosinophilia), fibrosing alveolitis, pleuritis, pericarditis with or without tamponade, allergic myocarditis, hepatitis, hepatic necrosis with or without immune complexes, parapsoriasis varioliformis acuta, alopecia, conjunctival and scleral injection, periorbital edema, and arthralgia have also been reported. /Sulfonamides/|For more Drug Warnings (Complete) data for SULFAMETHIZOLE (27 total), please visit the HSDB record page.

Sulfamethizole is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.

Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. (See all compounds classified as Anti-Infective Agents.)

Rapidly absorbed.|Sulfamethizole is readily absorbed form the GI tract. Following oral administration of a single 2-g dose of sulfamethizole in a limited number of patients, blood concentrations of approximately 30 ug/mL were attained within 1 hour. Peak blood concentrations of about 60 ug/mL were reached within 2 hours followed by a gradual decrease to 6.6 ug/mL within eight hours and to 5 ug/mL within 12 hours. Approximately 2-11% of sulfamethizole present in the blood is in the N4-acetylated form.|Sulfamethizole is distributed into most body tissues but does not appear to diffuse into the CSF of patients with normal meninges. Sulfamethizole is approximately 90% bound to plasma proteins. Since the drug is rapidly eliminated in urine, the manufacturer states that accumulation of sulfamethizole in tissues outside the urinary tract is minimal|Sulfamethizole...is a rapidly eliminated sulfonamide; concentrations of drug in blood are thus low after administration of conventional doses.|Approximately 80% of an administered dose is recoverable within eight hours; approximately 98% is cleared in 15 to 24 hours. Sulfamethizole is cleared by the kidney at a rate only 10 to 20% lower than that of creatinine.|For more Absorption, Distribution and Excretion (Complete) data for SULFAMETHIZOLE (21 total), please visit the HSDB record page.

Hepatic.|Approximately 95% of a given dose of sulfamethizole is not metabolized; less than 5% is acetylated. As a consequence, almost all of a given dose of sulfamethizole is present in its active form in the body.|Renal clearance values of metabolite N4-acetylsulfonamides are 6-20 times higher than their parent compd. Sulfamethizole is acetylated very little.|Although the liver is the major site of metabolism, sulfonamides may also be metabolized in other body tissues. Most sulfonamides are metabolized mainly by N4-acetylation. The degree of acetylation, which is a function of time, varies from less than 5% for sulfamethizole to up to 40% for sulfadiazine. The N4-acetyl metabolites, which do not possess antibacterial activity, have greater affinity for plasma albumin than does the nonacetylated drug and are usually less soluble than the parent sulfonamide, particularly in acidic urine. Like acetyl derivatives, glucuronide derivatives do not possess antibacterial activity; however, glucuronide derivatives are water soluble, appear to resemble the nonacetylated sulfonamide in plasma binding capacity, and have not been associated with adverse effects. /Sulfonamides/

3-8 hours|Sulfonamides are generally classified as short-acting, intermediate-acting, or long-acting depending on the rate at which they are absorbed and eliminated. Sulfamethizole, sulfasalazine, and sulfisoxazole are generally considered to be short-acting sulfonamides and reportedly have plasma half-lives of about 4-8 hours. Sulfadiazine and sulfapyridine are generally considered to be intermediate-acting sulfonamides and reportedly have plasma half-lives of about 7-17 hours. /Sulfonamides/

Sulfamethizole is a competitive inhibitor of bacterial enzyme dihydropteroate synthetase. The normal para-aminobenzoic acid (PABA) substrate is prevented from binding. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.|Sulfonamides are usually bacteriostatic in action. Sulfonamides interfere with the utilization of p-aminobenzoic acid (PABA) in the biosynthesis of tetrahydrofolic acid (the reduced form of folic acid) cofactors in susceptible bacteria. Sulfonamides are structural analogs of PABA and appear to interfere with PABA utilization by competitively inhibiting the enzyme dihydropteroate synthase, which catalyzes the formation of dihydropteroic acid (a precursor of tetrahydrofolic acid) from PABA and pteridine; however, other mechanism(s) affecting the biosynthetic pathway also may be involved. Compounds such as pyrimethamine and trimethoprim, which block later stages in the synthesis of folic acid, act synergistically with sulfonamides. Only microorganisms that synthesize their own folic acid are inhibited by sulfonamides; animal cells and bacteria which are capable of utilizing folic acid precursors or preformed folic acid are not affected by these drugs. The antibacterial activity of the sulfonamides is reportedly decreased in the presence of blood or purulent body exudates. /Sulfonamides/|The sulfonamides are structural analogs of para-aminobenzoic acid (PABA) and competitively inhibit an enzymatic step (dihydropterate synthetase) during which PABA is incorporated into the synthesis of dihydrofolic acid (folic acid). Because dihydrofolate synthesis is reduced, the levels of tetrahydrofolate (folinic acid) formed from dihydrofolate diminish. Tetrahydrofolate is an essential component of the coenzymes responsible for single carbon metabolism in cells. Acting as antimetabolites to PABA, sulfonamides eventually block, in a complex fashion, several enzymes. These enzymes include those needed for the biogenesis of purine bases; for the transfer of desoxyuridine to thymidine; and for the biosynthesis of methionine, glycine, and formylmethionyl-transfer-RNA. This results in suppression of protein synthesis, impairment of metabolic processes, and inhibition of growth and multiplication of those organisms that cannot use preformed folate. The effect is bacteriostatic, although a bactericidal action is evident at the high concentrations that may be found in urine.

SYMPTOMS: Contact with, and especially ingestion of, this chemical may produce any of the following symptoms: nausea, diarrhea, anorexia, headache, depression, hallucinations, convulsions, fever, chills, skin eruptions or dermatitis. ACUTE/CHRONIC HAZARDS: This compound may be toxic and an irritant. It may cause skin eruptions on contact, by inhalation or on ingestion. Exposure at elevated levels may also lead to shock. (NTP, 1992)

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. If symptoms (such as redness or irritation) develop, immediately transport the victim to a hospital. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, anaphylaxis, and hemolysis if they occur. Replace fluid losses resulting from gastroenteritis with intravenous crystalloids. Maintain steady urine flow with fluids to alleviate crystalluria ... Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. Most antibiotics are excreted unchanged in the urine, so maintenance of adequate urine flow is important. The role of forced diuresis is unclear. Hemodialysis is not usually indicated, except perhaps in patients with renal dysfunction and a high level of a toxic agent. /Antibacterial agents/

/SIGNS AND SYMPTOMS/ The acute signs and symptoms associated with sulfonamide overdosage include anorexia, nausea, and colicky abdominal pain, vertigo, headache, drowsiness and unconsciousness. Pyrexia, hematuria and crystalluria have been reported. Blood dyscrasias and jaundice are late manifestations of overdose.|/CASE REPORTS/ Case report of a 50-yr-old man with renal dysfunction who developed oxidant hemolysis while on sulfamethizole therapy is described.|/EPIDEMIOLOGY STUDIES/ Eleven hundred cases of drug induced liver disease have been reported in Denmark from 1978 to 1987, including 52 fatal cases. Approximately 100 new cases have been reported every year since 1987. The definition and classification of drug induced liver disease are presented together with a review of the most common patho-anatomical pictures and pathogenic mechanisms, followed by a description of symptoms and paraclinical abnormalities for each of the ten most common drugs causing serious liver disease. Individual cases of liver disease caused by paracetamol, sulfamethizole and androgenic steroid hormones are presented. ... Finally there are some proposals for diminishing the number of and the severity of drug induced liver disease.|/EPIDEMIOLOGY STUDIES/ ... The risk of adverse birth and neonatal outcome, and miscarriage in women who used sulfamethizole during pregnancy /was investigated/. The association between use of sulfamethizole and adverse birth and neonatal outcome was investigated in a case-control and a cohort study in Denmark. /Investigators/ used data from the Prescription Database, the Birth Registry and the Hospital Discharge Registry in North Jutland County to study any association between sulfamethizole use and first recorded miscarriage. The cohort analysis included 3484 women who received a prescription for sulfamethizole from 30 days before conception to date of delivery, and 60175 women who did not use a sulphonamide-containing drug during pregnancy or 30 days before conception. The case-control analysis included 3347 women who had a miscarriage, of whom 90 had taken sulfamethizole, and 22599 primiparous controls who had a live birth. Among women who received prescriptions for sulfamethizole, adjusted odds ratios and 95% confidence intervals for adverse birth outcome were: malformation 1.17 (0.95-1.43); low birth weight 0.69 (0.49-0.98); pre-term birth 1.12 (0.97-1.30); stillbirth 1.02 (0.61-1.68); neonatal jaundice 1.14 (0.38-3.46); and for receiving a prescription for sulfamethizole within 1 week before miscarriage 1.66 (0.92-2.99). /Investigators/ found no increased risk of congenital malformation, stillbirth or pre-term birth, and no association between use of sulfamethizole late in pregnancy and risk of neonatal jaundice. There was an increased risk of miscarriage after exposure to sulfamethizole during the week before miscarriage, but further studies are needed to evaluate whether this increased risk is causal.|/OTHER TOXICITY INFORMATION/ Various dermatologic reactions, including rash, pruritus, urticaria, erythema nodosum, erythema multiforme (Stevens-Johnson syndrome), Lyell's syndrome (may be associated with corneal damage), Behcet's syndrome, toxic epidermal necrolysis, and exfoliative dermatitis, have been reported in patients receiving sulfonamides. Because photosensitivity may also occur, patients should be cautioned against exposure to UV light or prolonged exposure to sunlight. A relatively high proportion of fatalities has occurred as a result of the Stevens-Johnson syndrome, especially in children. Although long-acting sulfonamides (which are no longer commercially available) have been associated most often with the Stevens-Johnson syndrome, other sulfonamides also have been reported to cause this reaction. The physician should be alert to the signs, including high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis, which may precede the onset of the cutaneous lesions of the Stevens-Johnson syndrome. If a rash develops during therapy, the sulfonamide should be discontinued at once. In rare instances, a skin rash may precede a more serious reaction such as Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, and/or serious blood disorders. /Sulfonamides/

FNA, Sulfamethizol

Oral tablets: 500 mg (sulfamethizole), Thiosulfil Forte (scored), Wyeth-Ayerst|MARKETED AS A 4% AQUEOUS SOLN, PH 7.3-7.4. /SODIUM SALT/|SULFAMETHIZOLE IS AVAILABLE IN TABLETS CONTAINING 250, 500, OR 1000 MG & IN SUSPENSIONS OF 250 MG/5 ML OR 500 MG/5 ML.|Thiosnifil-A (Ayerst), Proklar (O'Neal, Jones & Feldman), component of Azotrex (Bristol), and component of Suladyne (Reid-Provident).

Benzenesulfonamide, 4-amino-N-(5-methyl-1,3,4-thiadiazol-2-yl)-: ACTIVE

HIGH-PRESSURE LIQ CHROMATOGRAPHY WAS USED FOR THE SEPARATION & DETECTION OF SULFANILAMIDES IN PHARMACEUTICAL PREPN.|QUALITATIVE ANALYSIS OF 14 SULFA DRUGS AND THEIR INDIVIDUAL QUANTITATIVE DETERMINATIONS WERE PERFORMED BY GAS-LIQUID CHROMATOGRAPHY.|THE RATE OF EXTRACTIVE ALKYLATION OF 24 STRUCTURALLY RELATED SULFONAMIDES WAS STUDIED WITH RESPECT TO THE ALKYLATING AGENT AND ORGANIC SOLVENT.|A THIN-LAYER CHROMATOGRAPHIC SYSTEM WAS USED FOR THE SEPARATION OF A SERIES OF SULFONAMIDES.|For more Analytic Laboratory Methods (Complete) data for SULFAMETHIZOLE (31 total), please visit the HSDB record page.

Analyte: sulfamethizole; matrix: milk; procedure: high-performance liquid chromatography with ultraviolet detection at 265 nm; limit of detection: 1.8 ppb|Analyte: sulfamethizole; matrix: milk; procedure: high-performance liquid chromatography with ultraviolet detection at 254 nm and thermospray mass spectrometry; limit of detection: 2 ng (HPLC-UV); 5-20 ng (TMS)|Analyte: sulfamethizole; matrix: tissue (kidney, muscle); procedure: high-performance liquid chromatography with ultraviolet detection at 270 nm and fluorescence detection [395 nm (excitation) and 495 nm (emission)] following post-column reaction; limit of detection: 0.5-5 ppb|Analyte: sulfamethizole; matrix: tissue (liver, muscle); procedure: high-performance liquid chromatography with ultraviolet detection at 270 nm|For more Clinical Laboratory Methods (Complete) data for SULFAMETHIZOLE (6 total), please visit the HSDB record page.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals -> Animal Drugs -> Approved in Taiwan