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Pharmaceutical

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Antibiotics (Sulfonamide)

Pharmaceuticals -> Listed in ZINC15

log Kow = 1.01

0.9

0.83

Colorless prisms

White to slightly yellowish crystalline powder

less than 1 mg/mL at 72.5 °F (NTP, 1992)

White to off-white, odorless, crystalline powder. Sol in alcohol; freely sol in water. /Diethanolamine salt/

Soluble in alcohol

SOL IN DIETHYL ETHER (1 IN 800); SOL IN 5% AQ SODIUM BICARBONATE (1 IN 30)

1 G IN ABOUT 6700 ML WATER; SOL IN DIL HYDROCHLORIC ACID; 1 G IN ABOUT 10 ML BOILING ALCOHOL

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antibacterial Agents; Sulfonamides

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

383 to 388 °F (NTP, 1992)

194 °C

MP: 191 °C

MP: 195-198 °C

194 °C

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

Solid

Warning

H315 (95.6%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 45 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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.

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.

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.

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)

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.

LC50; Species: Ictalurus punctatus (Channel catfish); Conditions: freshwater, static, 17 °C, hardness 42 mg/L CaCO3; Concentration: < or =100 mg/L for 48 hr

LC50; Species: Lepomis macrochirus (Bluegill); Conditions: freshwater, static, 12 °C, hardness 42 mg/L CaCO3; Concentration: < or =100 mg/L for 48 hr

LC50; Species: Oncorhynchus mykiss (Rainbow trout); Conditions: freshwater, static, 12 °C, hardness 42 mg/L CaCO3; Concentration: < or =100 mg/L for 48 hr

LC50; Species: Salmo trutta (Brown trout); Conditions: freshwater, static, 12 °C, hardness 42 mg/L CaCO3; Concentration: < or =100 mg/L for 48 hr

For more Ecotoxicity Values (Complete) data for SULFISOXAZOLE (6 total), please visit the HSDB record page.

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).

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.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=127-69-5]

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).

/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.

Sulfafurazole (Sulfisoxazole)

Group 3: Not classifiable as to its carcinogenicity to humans

Volume 24: (1980) Some Pharmaceutical Drugs

1987

1987

Sulfisoxazole

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 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.

S - Sensory organs

J - Antiinfectives for systemic use

QS - Sensory organs

QJ - Antiinfectives for systemic use

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 <i>p</i>-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.

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/

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.

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.

740T4C525W

SULFISOXAZOLE

Established Pharmacologic Class [EPC] - Sulfonamide Antimicrobial

Chemical Structure [CS] - Sulfonamides

Sulfisoxazole is a Sulfonamide Antimicrobial.

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.

THERAP CAT: Antibacterial

THERAP CAT (VET): Antibacterial

MEDICATION (VET)

MEDICATION

CHEM INT FOR SULFISOXAZOLE DERIVATIVES

(1972) 2.64X10+7 GRAMS

(1975) 1.43X10+7 GRAMS (PRINCPL CUSTMS DISTS)

(1972) GREATER THAN 4.54X10+5 GRAMS

(1975) GREATER THAN 4.54X10+5 GRAMS

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).

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

Pharmaceuticals