SULFASALAZINE

Chemistry - Sulfasalazine is basically a molecule of sulfapyridine linked by a diazo bond to thediazonium salt of salicylic acid. It occurs as an odorless, bright yellow to brownish-yellow finepowder. Less than 0.1 mg is soluble in 1 ml of water and about 0.34 mg is soluble in 1 ml of alcohol. It is also known as salazosulfapyridine or salicylazosulfapyridine.

Storage, Stability, Compatibility

Sulfasalazine tablets (either plain or enteric-coated) should bestored at temperatures less than 40°C and preferably at room temperature (15-30°C) in well-closedcontainers. The oral suspension should be stored at room temperature (15-30°C); avoid freezing.

Pharmacology - SULFASALAZINE

While the exact mechanism of action for its therapeutic effects in treating colitisin small animals has not been determined, it is believed that after sulfasalazine is cleaved intosulfapyridine and 5-aminosalicylic acid (5-ASA, mesalamine) by bacteria in the gut the antibacterial(sulfapyridine) and/or anti-inflammatory (5-ASA) activity alters the symptoms/course of thedisease. Levels of both drugs in the colon are higher then by giving them orally as separate agents.
Uses, Indications - Sulfasalazine is used for the treatment of inflammatory bowel disease in dogsand cats.

Pharmacokinetics - SULFASALAZINE

Only about 10-33% of an orally administered dose of sulfasalazine is absorbed. Apparently, some of this absorbed drug is then excreted unchanged in the bile. Unabsorbedand biliary excreted drug is cleaved into 5-ASA and sulfapyridine in the colon by bacterial flora.
The sulfapyridine component is rapidly absorbed, but only a small percentage of the 5-ASA isabsorbed.
Absorbed sulfapyridine and 5-ASA are hepatically metabolized and then renally excreted.

Contraindications, Precautions, Reproductive Safety

Sulfasalazine is contraindicated in animals hypersensitive to it, sulfonamides or salicylates. It is also contraindicated in patients withintestinal or urinary obstructions. It should be used with caution in animals with preexisting liver, renal or hematologic diseases. Because cats can be sensitive to salicylates (see the aspirin monograph), use caution when using this drug in that species.
Although sulfasalazine has not been proven to be harmful to use during pregnancy and incidencesof neonatal kernicterus in infants born to women taking sulfasalazine are low, it should only beused when clearly indicated. In laboratory animal studies (rats, rabbits), doses of 6 times normal(human) caused impairment of fertility in male animals This effect is thought to be caused by thesulfapyridine component and was reversible upon discontinuation of the drug.

Adverse Effects, Warnings

Although adverse effects do occur in dogs, with keratoconjunctivitissicca (KCS) reported most frequently, they are considered to occur relatively uncommonly. Otherpotential adverse effects include cholestatic jaundice, hemolytic anemia, leukopenia, vomiting, decreased sperm counts and an allergic dermatitis.
Cats can occasionally develop anorexia and vomiting which may be alleviated through the use ofthe enteric-coated tablets. Anemias secondary to sulfasalazine are also potentially possible in cats.

Overdosage, Acute Toxicity

Little specific information is available regarding overdoses with thisagent, but because massive overdoses could cause significant salicylate and/or sulfonamide toxicity, standard protocols (empty stomach, cathartics, etc.) should be considered. Urine alkalinization andforced diuresis may also be beneficial in selected cases.

Drug Interactions

Sulfasalazine shares the interactive potential with other sulfonamides and maydisplace highly protein bound drugs, such as methotrexate, warfarin, phenylbutazone, thiazide diuretics, salicylates, probenicid and phenytoin. Although the clinical significanceof these interactions is not entirely clear, patients should be monitored for enhanced effects of thedisplaced agents.
Antacids may decrease the oral bioavailability of sulfonamides if administered concurrently.
Sulfasalazine may decrease the bioavailability of folic acid or digoxin; enhanced digoxin monitoring is warranted if both drugs are necessary and folic acid supplementation may be required withchronic therapy.
Ferrous sulfate or other iron salts may decrease the blood levels of sulfasalazine if administered concurrently; clinical significance is unknown.