SULFASALAZINE

Medically reviewed by ehealthlyf.com on Feb 11, 2023

What is sulfasalazine?

Sulfasalazine is a disease-modifying anti-rheumatic drug (DMARD) that is used to treat and manage autoimmune diseases, such as rheumatoid arthritis and an inflammatory bowel disease called ulcerative colitis. It is a slow-acting DMARD. 

Sulfasalazine is used off-label for Crohn’s disease, ankylosing spondylitis, and psoriatic arthritis. It helps to lessen your body’s pain and swelling by limiting the damage that rheumatoid arthritis can do to your joints.

The US Food and Drug Administration (FDA) has approved a standard tablet (Azulfidine) and an enteric-coated tablet (Azulfidine EN-tabs) of sulfasalazine. 

Delayed release, enteric-coated tablets are recommended for people who experience gastrointestinal side effects such as nausea and vomiting.

Chemistry

Sulfasalazine consists of an anti-inflammatory, 5-amino salicylic acid (5-ASA, mesalamine, or mesalazine), and the antibiotic sulfapyridine, which are linked by a bond.

Mechanism of action

Sulfasalazine belongs to the aminosalicylates group of medicines. It is not fully understood how sulfasalazine works. Sulfasalazine cannot be absorbed by the small intestine because it is too large, but bacteria in the colon can break the bond between 5-ASA and sulfapyridine, allowing 5-ASA to treat ulcerative colitis locally in the colon. A mixture of unchanged, hydroxylated, and glucuronidated sulfapyridine is eliminated in urine. Sulfasalazine and its metabolites have a range of immunomodulatory effects.

What are the ingredients in a sulfasalazine tablet?

Active ingredient: 

Sulfasalazine

Inactive ingredients:

Azulfidine tablets contain silicon dioxide, unspecified povidone, magnesium stearate, and corn starch.

Azulfidine EN-tablets (delayed release enteric coated): white wax, carnauba wax, cellacefate, magnesium stearate, polyethylene glycol 20000, unspecified povidone, propylene glycol, glyceryl stearate SE, silicon dioxide, corn starch, talc.

Generic versions may contain different ingredients. So check the label for a complete list of ingredients.

What is sulfasalazine used for?

Standard sulfasalazine tablets are used for:

• To treat mild to moderate ulcerative colitis.
• As adjunctive therapy in severe ulcerative colitis.
• To increase the time between severe ulcerative colitis attacks.

Delayed release enteric coated sulfasalazine tablets are used for:

• To treat mild to moderate ulcerative colitis, particularly those who cannot take standard, uncoated sulfasalazine tablets because of gastrointestinal side effects that are not caused by high blood levels of sulfapyridine and its metabolites. This applies to patients who experience nausea and vomiting after the first few doses as well as those who experience symptoms even after their dose is lowered.
• As adjunctive therapy in severe ulcerative colitis
• To extend the intervals between acute ulcerative colitis attacks.
• To treat rheumatoid arthritis in patients who do not respond to salicylates or other nonsteroidal anti-inflammatory drugs(NSAIDs)
• To treat paediatric patients with polyarticular-course juvenile rheumatoid arthritis who do not respond to salicylates or other NSAIDs.

Dosage

Tablets: 500 mg

Delayed release enteric-coated tablets: 500 mg

Ulcerative colitis

3-4g per day PO (orally) divided TID (three times a day) after meals.

While it may start at 1-2g per day, >4 g per day can increase the risk of toxicity.

Maintenance: 2 g per day, divided into doses at <8 hours intervals when endoscopic examination confirms improvements.

Dosing modifications

• Reduce dose by 50% and gradually increase to the desired dose over several days; stop therapy for 5-7 days if GI intolerance persists and re-introduce at a lower daily dose

Rheumatoid arthritis

Delayed tablets: 0.5–1 g per day PO divided BID (two times a day) increase weekly to a maintenance dose of 2 g per day PO divided BID. After giving it for 12 weeks, the dose may be increased to 3 g per day if the response is insufficient.

Suggested dosing schedule for adult rheumatoid arthritis

Crohns disease(off label)

3-6g per day PO in divided doses for up to 16 weeks.

Juvenile Rheumatoid arthritis-polyarticular course

Children > 6 years – 30 to 50 mg per kg of body weight daily in two evenly divided doses. The maximum dose is typically 2 g per day. Initially, a dose of a quarter to a third of the planned maintenance dose should be used and increased weekly until reaching the maintenance dose after one month.

Administration

• Take after meals 
• Administer equally divided doses

Who should not take sulfasalazine?

Do not take sulfasalazine if you are:

• Allergic to sulfasalazine, its metabolites, sulfonamides or salicylates, or any of the other ingredients in sulfasalazine.
• Have intestinal or urinary obstruction
• Have porphyria

What should I say to the doctor before taking sulfasalazine?

You should tell all your medical conditions if you have,

• History of recurring or chronic infections
• Underlying conditions or taking other drugs which may make you more susceptible to infections
• Severe allergy or bronchial asthma
• Glucose 6-phosphate dehydrogenase deficiency

How should I take sulfasalazine?

• Take exactly as directed.
• Tablets should be taken after meals, in doses that are evenly distributed.
• Do not break, crush, or chew the enteric-coated, delayed-release tablets,  instead swallow them whole.
• Follow the directions on your prescription label carefully, and ask your doctor or pharmacist if you have any questions or if you don’t understand anything.
• Drink plenty of fluids while taking sulfasalazine.
• Do not stop taking sulfasalazine on your own accord; instead, wait until your doctor instructs you to.
• Do not change the dosage in any way; only take as directed.

What should I do if I forget to take a dose?

You can take the missed dose as soon as you remember it. If it approaches your next dose, then skip the missed one and carry on with your regular dosing schedule. 

What happens if I overdose?

If you take too much sulfasalazine, call the Poison Control Helpline at 1-800-222-1222, or go to the hospital right away.  Information will also be available at https://www.poisonhelp.org/help. If the victim has fallen, had a seizure, is having difficulty breathing, or cannot be roused, call emergency services at 911 right away.

Symptoms of overdose include:

• Nausea 
• Vomiting
• Stomach pain
• Tiredness
•  seizures

What are the side effects of sulfasalazine?

The most frequent side effects of sulfasalazine are:

• Anorexia
• Headache
• Nausea
• Vomiting
• Gastric distress
• Reversible oligospermia

Less frequent side effects are:

• Skin rash
• Pruritus
• Urticaria
• Fever
• Heinz body anaemia
• Hemolytic anaemia
• Cyanosis
• Orange-yellow discolouration of urine or skin

Sulfasalazine can cause serious side effects including

• Hepatic, renal, and hematologic toxicity 
• Some patients’ deaths have been associated with hypersensitivity reactions, agranulocytosis, aplastic anaemia, other blood dyscrasias, renal and liver damage, irreversible neuromuscular and central nervous system changes, and fibrosing alveolitis. Tell your doctor if you got a sore throat, fever, pallor, purpura, or jaundice while taking sulfasalazine.

Complete blood counts and urine analyses should be done frequently while using sulfasalazine.

• Oligospermia and infertility
• Serious infections including fatal sepsis and pneumonia
• Severe cutaneous adverse reactions

Drug reactions with systemic symptoms and eosinophilia (DRESS)

Early signs of such reactions include fever or swollen lymph nodes (lymphadenopathy), and these may be seen even if the rash has not developed.

• Other severe cutaneous adverse reactions include exfoliating dermatitis, stevens-johnson syndrome, toxic epidermal necrolysis, and acute generalised exanthematous pustulosis.
• Sun sensitivity
• Hearing changes
• mental/mood changes
• Painful urination
• Goitre
• Numbness or tingling of hands/ feet
• Signs of low blood sugar(eg. Hinger, cold sweat, blurred vision, weakness, fast heartbeat)

Postmarketing side effects of sulfasalazine have been reported and include the following:

• Blood dyscrasias: Pseudomononucleosis
• Cardiac disorder: myocarditis
• Hepatobiliary disorder: Reports of hepatotoxicity, including elevated liver function test(SGOT/AST/SGPT/ALT, GGT, LDH, alkaline phosphatase, bilirubin), yellowing of skin and eyes, cholestatic jaundice
• Metabolism and nutrition system disorder: Folate deficiency
• Renal and urinary disorder: Nephrolithiasis

Interactions

Inform your physician of all the medications you take, including prescription and non-prescription drugs, vitamins, and herbal supplements. Especially tell your doctor if you take digoxin or folic acid. Sulfasalazine may reduce the absorption of these drugs. Sulfasalazine used in combination with methotrexate may increase the risk of gastrointestinal adverse effects, mainly nausea.

• Sulfasalazine has no serious interactions with other drugs.
• Some of the interactions of sulfasalazine include:
• Ketorolac
• Ketorolac intranasal
• Live vaccines of measles, mumps, rubella and varicella 
• Methotrexate
• Pemetrexed

You should always carry a list of all your prescriptions with you and give it to your doctor or pharmacist. Consult your doctor if you have any questions or concerns about your health. 

Pregnancy and breastfeeding

A study suggests that sulfasalazine is not associated with foetal malformations. But some babies born to mothers who used sulfasalazine while pregnant have been reported to have neural tube defects. This may be related to the medication’s capacity to reduce folic acid absorption and metabolism.

Sulfasalazine and sulfapyridine pass through the placenta. Thus, it is recommended only in much-needed conditions.

• Sulfasalazine and its metabolites pass into breast milk and there is an increased risk of kernicterus in newborns.
• Limited data also suggest that it may cause infants to develop bloody stools or diarrhoea.

Therefore, inform your doctor if you are pregnant or breastfeeding while taking sulfasalazine.

Storage and disposal of the medication

• Store at 25-degree celsius (77 degrees Fahrenheit), excursions permitted to 15-30 degrees Celsius (59-86 degrees Fahrenheit)
• Keep this medication in a tightly closed container it came in and out of reach of children
• Keep away from moisture
• In order to prevent pets, children, and other people from ingesting leftover medication, it should be disposed of in a specific manner.
• Utilising a medicine take-back programme is the best way to get rid of your prescription drugs. Talk to your pharmacist or contact your local garbage/ recycling department to learn about the take-back program in your community.

What are the warnings and precautions for sulfasalazine? (Patient education)

Warnings

• Do not take Azulfidine or Azulfidine EN tablets if you are allergic to sulfasalazine or other ingredients contained in these drugs
• Keep out of reach of children
• Seek immediate medical attention or dial a poison control centre in the event of an overdose. 

Sulfasalazine may cause your skin to be more sensitive to sunlight than normal. Exposure to sunlight, even for a brief period of time, may cause a skin rash, itching, redness, or other discolouration of the skin or severe sunburn. When you begin to take sulfasalazine:

• If at all possible, avoid being in the sun, especially between the hours of 10 a.m. and 4 p.m.
• Wear protective clothing including a hat and sunglasses.
• Apply a sunblock that has a skin protection factor of at least 15. Some patients may require products with higher SPF 
• Wear a lip balm with an SPF number of a minimum of 15.

FAQs

1. What are the long-term consequences of sulfasalazine use?

It may include serious allergic reactions, low blood cell counts, infections, heart, liver, and kidney damage, nerve or muscle problems, a low sperm count, sun sensitivity, and severe skin reactions. Your urine or skin may turn orange,  but this is usually harmless and goes away when the medicine is stopped.

2. Does sulfasalazine cause high blood pressure?

Sulfasalazine has not been associated with high blood pressure (hypertension). Additionally, high blood pressure is not mentioned as a side effect in the product information from the manufacturer. Common side effects of sulfasalazine include loss of appetite, headache, vomiting, and stomach upset.

3. Does sulfasalazine cause hair loss?

Sulfasalazine has been linked to hair loss (alopecia) in one case report of a severe allergic reaction (Drug Rash with Eosinophilia and Systemic Symptoms, or DRESS), but this side effect is not common. Auto-immune conditions such as rheumatoid arthritis (RA) and lupus can be associated with hair loss.

4. Does sulfasalazine cause weight gain?

Sulfasalazine may cause kidney problems that lead to fluid buildup in your body and weight gain. You may have puffy eyes, swelling in your arms, ankles, or feet, or little or no urination. If any of these symptoms apply to you, contact your doctor right away.

References

1. Micromedex
2. National Library of Medicine Azulfidine EN- Tabs Product Label.
3. National Library of Medicine Azulfidine Product Label.
4. Sulfasalazine: Side Effects, Dosage, Uses and More ( Healthline).
5. Sulfasalazine: Generic, Uses, Side Effects, Dosages, Interaction, Warnings(rxlist.com)
6. Sulfasalazine: Uses, Dosage, Side Effects, Warnings- Drugs.com.