Sulfisoxazole

267.3

267.30

204-858-9

740T4C525W

757343|683536|38588|33807|13120

DTXSID6021292

C47740

Colorless prisms|White to slightly yellowish crystalline powder

J - Antiinfectives for systemic use|S - Sensory organs

29350030

107

1

Sulfisoxazole is an odorless white to yellowish crystalline powder. Slightly bitter taste. Acid to litmus. (NTP, 1992)

1.40 g/cm³

194 °C

482.2±55.0 °C(Predicted)

245.4±31.5 °C

1.6630 (estimate)

H2O: <0.1 g/100 mL at 22.5 ºC;acetone: complete50 mg/ml

2-8°C

5.08X10-8 mm Hg at 25 deg C (est)

LD50 orally in mice: 6800 mg/kg (Seki)

Odorless

Bitter

ACID TO LITMUS

5None

Henry's Law constant = 1.06X10-12 atm-cu cm/mol at 25 °C (est)

5|pKa1 = 1.5 /amino group/; pKa2 = 5.0 /R1SO2NHR2 moiety/

159.1 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]|157.4 Ų [M+H]+ [CCS Type: TW]

Mol wt: 309.34. Should not be confused with N4-acetyl sulfisoxazole which is a metabolite. Tasteless crystals; mp 193-194 °C. Sol (mg/mL): 0.07 in water; 4.93 in methanol; 5.7 in 95% ethanol; 0.94 in ether; 29.0 in chloroform /Acetyl sulfisoxazole/|Hydroxyl radical reaction rate constant = 3.24X10-11 cu cm/molec-sec at 25 °C (est)

May be sensitive to prolonged exposure to air and light. Sensitive to heat. Slightly soluble in water.

Amines, Phosphines, and Pyridines

IRRITANT

NONH for all modes of transport

2

36/37/38

26-36

WO9100000

Xi

Stable. Incompatible with strong oxidizing agents.

P305 + P351 + P338

H315-H319-H335

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.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl sulfisoxazole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.|Oral dosage form new animal drugs. Sulfisoxazole tablets. ... Specifications. Each tablet contains 260 milligrams (4 grains) of sulfisoxazole. ... Indications for use. Use in dogs and cats as an aid in treatment of bacterial pneumonia and bacterial enteritis when caused by organisms sensitive to sulfisoxazole..|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. Sulfisoxazole is included on this list.

NTP TR No 138; Route: oral, gavage; Species: rats and mice. NTIS No PB288779/AS.[NTP; Division of Toxicology Research and Testing; Management Status Report; 07/07/93; p.27]|Storer RD et al; Mutation Research 368 (2): 59-101 1996. Revalidation of the in vitro alkaline elution/rat hepatocyte assay for DNA damage: Improved criteria for assessment of cytotoxicity and genotoxicity and results for 81 compounds.|Berman S; New England Journal of Medicine 332: 1560-1565 June 8, 1995. Otitis media in children.|Miyagawa M et al; Mutation Research 343 (2-3): 157-183 1995. The in vivo-in vitro replicative DNA synthesis (RDS) test with hepatocytes prepared from male B6C3F1 mice as an early prediction assay for putative nongenotoxic (Ames-negative) mouse hepatocarcinogens.|For more Special Reports (Complete) data for SULFISOXAZOLE (19 total), please visit the HSDB record page.

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)

|Warning|H315 (95.45%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 44 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

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. STORAGE PRECAUTIONS: You should protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store under refrigerated temperatures. (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)

Sulfisoxazole was detected at a maximum concentration of 0.034 ug/L, median concentration of 0.019 ug/L, in final effluents of five of eight wastewater treatment plants located in five Canadian cities, sampled during 2002(1).

LD50=6800 mg/kg (Orally in mice)

It has been reported that sulfisoxazole may prolong the prothrombin time in patients who are receiving anticoagulants, including warfarin. This interaction should be kept in mind when /sulfisoxazole/ is given to patients already on anticoagulant therapy, and prothrombin time or other suitable coagulation test should be monitored.|It has been proposed that sulfisoxazole competes with thiopental for plasma protein binding. In one study involving 48 patients, intravenous sulfisoxazole resulted in a decrease in the amount of thiopental required for anesthesia and in a shortening of the awakening time. It is not known whether chronic oral doses of sulfisoxazole would have a similar effect.|Sulfonamides can displace methotrexate from plasma protein-binding sites, thus increasing free methotrexate concentrations. Studies in man have shown sulfisoxazole infusions to decrease plasma protein-bound methotrexate by one-fourth.|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/|For more Interactions (Complete) data for SULFISOXAZOLE (17 total), please visit the HSDB record page.

LD50 Rabbit oral 20000 mg/kg|LD50 Rabbit oral >1000 mg/kg bw|LD50 Rat oral 10000 mg/kg|LD50 Mice oral 6800 mg/kg bw

A bioassay of sulfisoxazole for possible carcinogenicity was conducted by admin the chemical by gavage to Fischer 344 rats and B6C3Fl mice. Groups of 50 rats of each sex and 50 mice of each sex were admin sulfisoxazole suspended in aqueous 0.5% carboxymethyl cellulose 7 days/wk at one of two doses, either 100 or 400 mg/kg body weight for the rats and either 500 or 2,000 mg/kg for the mice. Vehicle controls consisted of groups of 50 rats of each sex and 50 mice of each sex that were administered only the aqueous 0.5% carboxymethyl cellulose. Untreated controls consisted of groups of 50 rats of each sex and 50 mice of each sex. The dosed groups of the rats and mice were administered the chemical by gavage for 103 wk, then observed for 1 to 3 additional wk; the vehicle control groups were similarly administered 0.5% carboxymethyl cellulose alone. All surviving rats and mice were /sacrificed/ at wk 104 to 106. ... It is concluded that under the conditions of this bioassay, sulfisoxazole was not carcinogenic for either Fischer 344 rats or B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Negative; Female Rats: Negative; Male Mice: Negative; Female Mice: Negative.

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/|Patients with acquired immunodeficiency syndrome (AIDS) may have a grater incidence of side/adverse effects, especially rash, fever, and leukopenia, than do non-AIDS patients. /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/|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/|For more Populations at Special Risk (Complete) data for SULFISOXAZOLE (8 total), please visit the HSDB record page.

Sulfisoxazole'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), a Koc value of 58(2), indicates that sulfisoxazole is expected to have very high mobility in soil(SRC). Volatilization from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.1X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Sulfisoxazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.1X10-18 mm Hg(SRC), determined from a fragment constant method(4). In general, sulfonamide antimicrobials are not readily biodegraded and persist in soils(5).|AQUATIC FATE: Based on a classification scheme(1), a Koc value of 58(SRC), determined from a structure estimation method(2), indicates that sulfisoxazole is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.1X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(6), an estimated BCF of one(SRC), from its log Kow of 1.01(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Sulfisoxazole is expected to be readily photodegraded in most natural waters as the anionic form is susceptible to direct photodegradation(5). In general, sulfonamide antimicrobials are not readily biodegraded(9).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), sulfisoxazole, which has an estimated vapor pressure of 5.08X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase sulfisoxazole is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 12 hours(SRC), calculated from its rate constant of 3.2X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). The anionic form is susceptible to direct photodegradation(4).

The rate constant for the vapor-phase reaction of sulfisoxazole with photochemically-produced hydroxyl radicals has been estimated as 3.2X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 12 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). By analogy to structurally similar sulfamethoxazole which did not undergo hydrolysis under field conditions(4), hydrolysis of sulfisoxazole 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(3); they form salts in strongly acid or basic solutions(2). Sulfisoxazole is expected to be readily photodegraded in most natural waters as the anionic form is susceptible to direct photodegradation. In aqueous solution, direct photolysis rates under natural sunlight were reported as 7X10-5/sec (pH 2.5); 6X10-5/sec (pH 4.1); 4X10-5/sec (pH 5.2); 3.5X10-5/sec (pH 6.8); 1.7X10-5/sec (pH 10.7), resulting in sulfanilic acid(5); corresponding half-lives are 2.75, 3.21, 4.81, 5.4, and 11.3 hours, respectively(SRC).

An estimated BCF of 1 was calculated in fish for sulfisoxazole(SRC), using a log Kow of 1.01(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 sulfisoxazole using a clay loam (pH 6.2, organic content 3.1%) was reported as 58, Kd = 1.5(1). According to a classification scheme(2), this Koc value suggests that sulfisoxazole is expected to have very high mobility in soil. The pKa1 and pKa2 of sulfisoxazole are 1.5 and 5.0(3), 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(4). 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(5,6), suggesting that mobility may be much lower in some soils(SRC).

The Henry's Law constant for sulfisoxazole is estimated as 1.6X10-12 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that sulfisoxazole is expected to be essentially nonvolatile from water and moist soil surfaces(2). Sulfisoxazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.1X10-8 mm Hg(SRC), determined from a fragment constant method(3).

Six lactating women, ages 19-27 yr, were given 4 oral doses of sulfisoxazole, one g every 6 hr, during the first 24 hr of the collection period. Half-lives in milk were 7.2 hr for sulfisoxazole (I) and 8.9 hr for its major metabolite, N4-acetylsulfisoxazole (II). The milk to serum ratio for II was approximately fourfold that for I, reflecting the greater diffusion of the metabolite into milk. Total I recovered in breast milk during the 48 hr collection period accounted for less than 1% of the maternal dose in all patients, with a mean recovery of 0.45%. The drug was secreted predominantly as the acetylated metabolite, which comprised 77% of total drug recovered, whereas 23% appeared as the parent compound.|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/|/Sulfisoxazole/ is excreted in human milk.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 5,506 workers (3,068 of these were female) were potentially exposed to sulfisoxazole in the US(1). Occupational exposure to sulfisoxazole may occur through inhalation and dermal contact with this compound at workplaces where sulfisoxazole is produced or used. Use data indicate that the general population may be exposed to sulfisoxazole via administration of medication containing this compound(SRC).

For the treatment of severe, repeated, or long-lasting urinary tract infections, meningococcal meningitis, acute otitis media, trachoma, inclusion conjunctivitis, nocardiosis, chancroid, toxoplasmosis, malaria and other bacterial infections.

Anti-Infective Agents /SRP: Antibacterial/|Acute, recurrent or chronic urinary tract infections (primarily pyelonephritis, pyelitis and cystitis) due to susceptible organisms (usually Escherichia coli, Klebsiella-Enterobacter, staphylococcus, Proteus mirabilis and, less frequently, Proteus vulgaris) in the absence of obstructive uropathy or foreign bodies. /Included in US product label/|Meningococcal meningitis where the organism has been demonstrated to be susceptible. Haemophilus influenzae meningitis as adjunctive therapy with parenteral streptomycin. /Included in US product label/|Meningococcal meningitis prophylaxis when sulfonamide-sensitive group A strains are known to prevail in family groups or larger closed populations. (The prophylactic usefulness of sulfonamides when group B or C infections are prevalent has not been proven and in closed population groups may be harmful.) Important Note: In vitro sulfonamide susceptibility tests are not always reliable. The test must be carefully coordinated with bacteriologic and clinical response. When the patient is already taking sulfonamides, follow-up cultures should have aminobenzoic acid added to the culture media. /Included in US product label/|For more Therapeutic Uses (Complete) data for SULFISOXAZOLE (26 total), please visit the HSDB record page.

/Sulfisoxazole/ is contraindicated in the following patient populations: patients with a known hypersensitivity to sulfonamides; infants less than 2 months of age (except in the treatment of congenital toxoplasmosis as adjunctive therapy with pyrimethamine); pregnant women at term; and mothers nursing infants less than 2 months of age.|Use in pregnant women at term, in infants less than 2 months of age and in mothers nursing infants less than 2 months of age is contraindicated because sulfonamides may promote kernicterus in the newborn by displacing bilirubin from plasma proteins.|Fatalities associated with the administration of sulfonamides, although rare, have occurred due to severe reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias.|Sulfonamides, including sulfisoxazole, should be discontinued at the first appearance of skin rash or any sign of an adverse reaction.|For more Drug Warnings (Complete) data for SULFISOXAZOLE (34 total), please visit the HSDB record page.

Many bacteria become highly resistant to sulfonamides during therapy. Once resistance develops, cross resistance to other sulfonamides is usual. Resistance may be minimized by initiating treatment promptly with adequate doses & continuing...for sufficient period to eradicate infection. /Sulfonamides/

Sulfisoxazole 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.)

The mean urinary excretion recovery following oral administration of sulfisoxazole is 97% within 48 hours, of which 52% is intact drug, with the remaining as the N4-acetylated metabolite. It is excreted in human milk.|Following oral administration, sulfisoxazole is rapidly and completely absorbed; the small intestine is the major site of absorption, but some of the drug is absorbed from the stomach. Sulfonamides are present in the blood as free, conjugated (acetylated and possibly other forms) and protein-bound forms. The amount present as "free" drug is considered to be the therapeutically active form. Approximately 85% of a dose of sulfisoxazole is bound to plasma proteins, primarily to albumin; 65% to 72% of the unbound portion is in the nonacetylated form.|Maximum plasma concentrations of intact sulfisoxazole following a single 2-g oral dose of sulfisoxazole to healthy adult volunteers ranged from 127 to 211 ug/mL (mean, 169 ug/mL) and the time of peak plasma concentration ranged from 1 to 4 hours (mean, 2.5 hours). ... After multiple-dose oral administration of 500 mg /four times a day/ to healthy volunteers, the average steady-state plasma concentrations of intact sulfisoxazole ranged from 49.9 to 88.8 ug/mL (mean, 63.4 ug/mL).|Following a single 4-g dose of acetyl sulfisoxazole to healthy volunteers, maximum plasma concentrations of sulfisoxazole ranged from 122 to 282 ug/mL (mean, 181 ug/mL) for the pediatric suspension and occurred between 2 and 6 hours postadministration. /Acetyl-sulfisoxazole/|Wide variation in blood levels may result following identical doses of a sulfonamide. Blood levels should be measured in patients receiving sulfonamides at the higher recommended doses or being treated for serious infections. Free sulfonamide blood levels of 50 to 150 ug/mL may be considered therapeutically effective for most infections, with blood levels of 120 to 150 ug/mL being optimal for serious infections. The maximum sulfonamide level should not exceed 200 ug/mL, since adverse reactions occur more frequently above this concentration.|For more Absorption, Distribution and Excretion (Complete) data for SULFISOXAZOLE (25 total), please visit the HSDB record page.

N1-acetyl sulfisoxazole is metabolized to sulfisoxazole by digestive enzymes in the gastrointestinal tract and is absorbed as sulfisoxazole. This enzymatic splitting is presumed to be responsible for slower absorption and lower peak blood concentrations than are attained following administration of an equal oral dose of sulfisoxazole. With continued administration of acetyl sulfisoxazole, blood concentrations approximate those of sulfisoxazole. /Acetyl-sulfisoxazole/|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/|Identified urinary metabolites of sulfafurazole are acetylsulphisoxazole, sulphisoxazole-N-glucuronide, sulphisoxazole-N-sulphonate and sulphanilamide.|In man it is excreted in urine as unchanged sulfisoxazole (56%), N(4)-acetyl derivative (18%), N(4)-glucuronide (3.4%), N(4)-sulfate (1.0%) & a second glucuronide which is probably N(2)-glucuronide of sulfisoxazole.|Saturable metabolism of sulfisoxazole N1-acetyl in the rat during the initial pass of the drug from the intestinal lumen through the liver following oral administration of the drug (saturable first-pass metabolism) was investigated. The fraction of the total amount of drug recovered from the urine as the N4-conjugate fraction was apparent following the intravenous administration of sulfisoxazole acetyl or the oral administration of sulfisoxazole at the same dose levels.

The elimination half-life of sulfisoxazole ranged from 4.6 to 7.8 hours after oral administration. The elimination of sulfisoxazole has been shown to be slower in elderly subjects (63 to 75 years) with diminished renal function (creatinine clearance, 37 to 68 mL/min).|The half-life of elimination from plasma ranged from 5.4 to 7.4 hr. /Acetyl-sulfisoxazole/|The half-life of sulfafurazole is approximately 6 hours.

Sulfisoxazole is a competitive inhibitor of the enzyme dihydropteroate synthetase. It inhibits bacterial synthesis of dihydrofolic acid by preventing the condensation of the pteridine with para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.|The sulfonamides are bacteriostatic agents and the spectrum of activity is similar for all. Sulfonamides inhibit bacterial synthesis of dihydrofolic acid by preventing the condensation of the pteridine with aminobenzoic acid through competitive inhibition of the enzyme dihydropteroate synthetase. Resistant strains have altered dihydropteroate synthetase with reduced affinity for sulfonamides or produce increased quantities of aminobenzoic 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/

SYMPTOMS: Symptoms of exposure to this chemical include anaphylaxis, generalized allergic reactions, angioneurotic edema, arteritis, vasculitis, myocarditis, serum sickness, conjunctival and scleral injection, periarteritis nodosa, systemic lupus erythematosus, tachycardia, palpitations, syncope, cyanosis, rash, urticaria, pruritus, erythema multiforme, Stevens-Johnson syndrome, toxi epidermal necrolysis, exfoliative dermatitis, photosensitivity, goiter production, diuresis, hypoglycemia, nausea, emesis, abdominal pain, anorexia, diarrhea, glossitis, stomatitis, flatulence, salivary gland enlargement, gastrointestinal hemorrhage, pseudomembranous enterocolitis, melena, pancreatitis, hepatic dysfunction, jaundice, hepatocellular necrosis, crystalluria, hematuria, creatinine elevation, nephritis and toxic nephrosis with oliguria and anuria; leukopenia, agranulocytosis, aplastic anemia, eosino philia, clotting disorders, arthralgia, chest pain, myalgia, headache, dizziness, peripheral neuritis, paresthesia, convulsions, tinnitus, vertigo, ataxia edema, pyrexia, drowsiness, weakness, fatigue, rigors, lassitude, flushing, hearing loss, insomnia and pneumonitis. It may cause blood dyscrasias, sore throat, fever, cough, shortness of breath, pallor, pulmonary infiltrates and death. Other symptoms may include colic, vomiting, unconsciousness, thrombocytopenia, purpura, hemolytic anemia, intracranial hypertension, psychosis, hallucinations, disorientation, depression, anxiety, hypersensitivity reactions, blood disorders, acute renal failure and urinary retention. ACUTE/CHRONIC HAZARDS: When heated to decomposition, this compound emits very toxic fumes of sulfur oxides and nitrogen oxides. (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. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. 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/

/HUMAN EXPOSURE STUDIES/ /Investigators/ identified 40 patients (25 men and 15 women) who developed calculi composed totally or partially of sulfonamides (acetylsulfamethoxazole, sulfadiazine, and acetylsulfisoxazole) between 1980 and 1987. The incidence of sulfonamide stones is less than 1% of stones. Patient characteristics were determined from questionnaires sent to the patients and attending physicians. The majority of patients developed symptoms 1 to 4 weeks after beginning sulfonamide therapy. The bladder was the most common stone location. Obstruction of the urinary system by the acetyl derivatives of the drug is the most serious consequence of sulfonamide therapy. Early recognition of drug-related stones is essential to protect patients from recurrences, reduce the risk of renal complications, and avoid continuing ineffective therapeutic regimens.|/HUMAN EXPOSURE STUDIES/ Adverse reactions severe enough to require discontinuation of sulfafurazole administration occurred with an incidence of 3.1% in a series of 1002 treated patients. Skin rashes, eosinophilia and drug fever were the common manifestations.|/SIGNS AND SYMPTOMS/ The amount of a single dose of sulfisoxazole that is associated with symptoms of overdosage or is likely to be life-threatening has not been reported. Signs and symptoms of overdosage reported with sulfonamides include anorexia, colic, nausea, vomiting, dizziness, headache, drowsiness and unconsciousness. Pyrexia, hematuria and crystalluria may be noted. Blood dyscrasias and jaundice are potential late manifestations of overdosage.|/CASE REPORTS/ A 35-year-old man demonstrated sulfisoxazole diolamine-induced photosensitivity during treatment for staphylococcal blepharitis. This reaction was easily avoided by applying the ointment at bedtime and covering the eyelids during sun-bathing while in therapy. A drug-induced photosensitivity reaction should be considered in cases of staphylococcal blepharitis resistant to or aggravated by eyelid-margin therapy with sulfonamides.|For more Human Toxicity Excerpts (Complete) data for SULFISOXAZOLE (15 total), please visit the HSDB record page.

Ammonium Salt Sulfisoxazole

Pediatric Suspension (raspberry flavored), containing acetyl sulfisoxazole equivalent to approximately 0.5 gm sulfisoxazole per teaspoonful (5 mL) - bottles of 16 oz (1 pint); Roche|Sulfisoxazole, USP (Gantrisin, Sk-soxazole, & others)...available in 500 mg tablets for oral use.|Gantrisin (Hoffmann-La Roche), SK-Soxazole (Smith Kline & French).

Benzenesulfonamide, 4-amino-N-(3,4-dimethyl-5-isoxazolyl)-: ACTIVE

RESONANCE RAMAN SPECTROMETRY WAS APPLIED TO THE DETERMINATIONS OF 8 COLORLESS SULFONAMIDE DRUGS THAT EXHIBITED NO RESONANCE RAMAN EFFECT WITH ARGON ION LASER EXCITATION. THE LIMITS OF DETECTION WERE APPROX 2X10-8 MOLES. SULFISOXAZOLE GAVE COLORED DERIV IN A COMMON CHEM REACTION SYSTEM, AND THE RESONANCE RAMAN SPECTRA OF THE DERIV HAD CHARACTERISTIC SPECTRAL PATTERNS.|REVERSED-PHASE THIN-LAYER CHROMATOGRAPHY SEPARATION OF 10 KINDS OF SYNTHETIC SULFONAMIDE ANTIBACTERIALS INCL SULFISOXAZOLE IS DESCRIBED.|A REVERSED-PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) METHOD IS USED TO QUANTITATE N1-ACETYLSULFISOXAZOLE AND THE RELATED MFG IMPURITY SULFISOXAZOLE. A TLC PROCEDURE IS DESCRIBED TO COMPLEMENT THE HPLC QUANTITATION.|N-BROMOPHTHALIMIDE WAS USED IN DETERMINATION OF SULFISOXAZOLE BY TITRATION.|For more Analytic Laboratory Methods (Complete) data for SULFISOXAZOLE (22 total), please visit the HSDB record page.

ANALYTICAL METHODS FOR SULFAFURAZOLE. SAMPLE MATRIX: PLASMA. ASSAY PROCEDURE: HIGH PERFORMANCE LIQUID CHROMATOGRAPHY WITH UV DETECTION. LIMIT OF DETECTION: 2.0 MG/L. PENG GW ET AL; RES COMMUN CHEM PATHOL PHARMACOL 18: 233 (1977).|AN AUTOMATED COLORIMETRIC METHOD FOR DETERMINATION OF SULFISOXAZOLE IN HUMAN PLASMA AND URINE WAS DEVELOPED AND TESTED IN VITRO AND IN VIVO. THE LOWER LIMIT OF DETECTION WAS 2 MCG/ML.|A HIGH-PRESSURE LIQ CHROMATOGRAPHIC METHOD THAT USES A MOBILE PHASE WITH THE PH AND IONIC STRENGTH ADJUSTED TO THAT OF BLOOD IS DESCRIBED. THE MOBILE PHASE WAS METHANOL-WATER (5 AND 95%) FOR SULFONAMIDES. THE METHOD PROVIDES QUICK AND RELIABLE LIPOPHILICITY MEASUREMENT.|SULFONAMIDES WERE DETERMINED IN SWINE LIVER BY COLLISION-INDUCED DISSOCIATION/MASS ANALYZED ION KINETIC ENERGY SPECTROMETRY.|For more Clinical Laboratory Methods (Complete) data for SULFISOXAZOLE (8 total), please visit the HSDB record page.

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