SULFASALAZINE

(for veterinary information only)

BRAND NAME: AZULFIDINE, SULFAZINE

AVAILABLE IN
500 mg TABLETS

BACKGROUND

Colitis is another word for “inflammation of the colon (large intestine)". Clinical signs include bloody or mucous diarrhea with urgency and sometimes vomiting. Since the colon is the very last portion of the intestinal tract (following the mouth, esophagus, stomach, and small intestine), medications must reach the colon in one of two ways. They must either resist digestion all the way down until they get to their final destination in the colon or they must be absorbed into the body earlier in the digestion, enter the bloodstream and reach the colon through its blood supply. Sulfasalazine utilizes the former mechanism.

Sulfasalazine is created by bonding a sulfa antibiotic called “sulfapyridine” to a salt of salicylic acid (aspirin). The bond is intact all the way down the intestinal tract until it is cleaved in the colon by resident bacteria releasing the two component molecules. The sulfa antibiotic is absorbed into the body and has minimal effect but the salicylic acid exerts its famous anti-inflammatory effects locally. Essentially a salve is applied to the surface of the inflamed colon.

HOW THIS MEDICATION IS USED

Sulfasalazine is used in the treatment of colitis. Sulfasalazine is given as a tablet three times daily, which makes it somewhat less convenient to use than other medications commonly used for colitis (metronidazole, tylosin). It is usually not given for courses longer than 3 weeks due possible side effects on tear production (see below).

SIDE EFFECTS

Sulfasalazines most common side effects are GI related: appetite loss, nausea, diarrhea etc. In humans approximately 30% of people taking sulfasalazine report some kind of GI side effect and it is felt this statistic can be extrapolated to animals.

Other potential side effects stem from the sulfapyridine portion of the sulfasalazine compound. Sulfa drugs have numerous well documented side effects which we will now describe but it is important to know that these issues occur in less than 4% of people.

• Joint inflammation
  A broad inflammatory syndrome has been observed in some individuals sensitive to trimethoprim sulfa and might be seen with the use of other sulfas. This includes arthritis, fever, muscle soreness, kidney inflammation, and even inflammation in the eye. This syndrome has been formally studied and has been found to occur almost exclusively after a previous uneventful exposure to sulfa and occurs 8-20 days after therapy has started. The Doberman pinscher seems to be over-represented and complete recovery can be expected within one week of discontinuing the medication.
• Skin rashes
  Drug related skin reactions do not have characteristic appearances; in fact, they can have any appearance. They do, however, begin around the start of treatment with the offending drug and vanish with cessation of administration of the offending drug. Any drug of any kind can produce a drug reaction in the skin; sulfa is somewhat over-represented in cases of skin related drug eruptions.
• Inability to produce adequate tears
  Sulfa drugs of any kind are capable of disrupting tear function. Classically, this occurs after long term therapy (i.e. weeks to months) of use but occasionally certain individuals suffer from dry eyes after only one dose of sulfa. In most cases, tear function resumes normally after the drug is discontinued but occasionally the effect is long term or permanent despite withdrawal of the drug. This is the most common sulfa drug side effect seen in animals.
  
• Hepatitis
  Liver failure can result when a sensitive individual receives this medication. Nausea, jaundice, and all the other complications that occur with liver failure of any origin may result. Discontinuing the medication should lead to recovery. If the liver is biopsied during its state of failure, changes associated with sulfa reaction are characteristic (i.e. it should be possible via biopsy to determine if a failing liver was caused by an idiosynchratic sulfa reaction).
• Blood dyscrasias
  Blood dyscrasia is the development abnormal blood cells or proportions of different blood cells. Blood dyscrasias might lead to immune dysfunction, bleeding tendency, or other problems depending on which blood cells are affected. With sulfa antibiotics, loss of red blood cells, platelets, and white blood cells have been reported. This syndrome is typically part of the joint inflammation syndrome.

It should be noted that the above side effects are a list of the classical side effects reported with sulfa antibiotics in general; they do not refer to sulfasalazine specifically. The sulfa moiety of sulfasalazine demonstrates side effects only rarely with tear production problems being the only one of any likelihood. The others are potential side effects as they have been seen with closely related drugs.

INTERACTIONS WITH OTHER DRUGS

The sulfa moiety of sulfasalazine, once absorbed into the body, is quickly bound to a protein carrier (i.e. once inside the body, it travels through the circulation coupled with blood proteins.) If the patient is concurrently taking other drugs that rely on protein carriers to travel in the circulation, the sulfa may “bump” these other drugs off the carrier. Once a drug is “bumped” off the carrier, it is able to act on its target tissue. This means that protein-bound drugs are stronger in patients concurrently taking sulfas. Drugs which may be enhanced in this way include: methotrexate (a cancer chemotherapy agent), warfarin (an anti-coagulant used both therapeutically and as the active ingredient in rat poisons), thiazide diuretics, aspirin, and phenytoin (an anti-seizure drug).

Digoxin (a heart medication), may work less effectively in the presence of sulfasalazine.

CONCERNS AND CAUTIONS

Cats are sensitive to salicylates. This medication is used in dogs or with dosage adjustments for cats.

This drug may effect male fertility.

When sulfasalazine has been given to pregnant women, birth defects have occasionally arisen. It is best not to use this medication during pregnancy.

Many experts recommend a tear production test ("Schirmer Tear Test") prior to administration of sulfa medications. Do not be surprised if your veterinarian recommends this.

It has been noted that the only side effect of
reasonable likelihood is decreased tear production.
It is important to watch for squinting of the eyes
or apparent eye discomfort. If this is noted,
sulfasalazine should be discontinued
and the veterinarian informed promptly.

Sulfasalazine is a brightly orange colored medication.
If the patient vomits, as colitis patients sometimes do,
the orange dye is not easily removed from fabric including carpet.

Page last updated: 5/18/2019