Azulfidine (Sulfasalazine)

Do you have arthritis or ulcerative colitis? IYou may be prescribed sulfasalazine for these conditions. However, like any medication, it should be taken carefully after you review the instructions and make sure it's appropriate for you. Learn more about sulfasalazine so you can get the benefits of treatment and avoid unexpected side effects.

What Is Azulfidine (Sulfasalazine)?

Sulfasalazine is a medication available as tablets taken by mouth. Azulfidine is the brand name of this medicine.

Why is Azulfidine prescribed to patients? Conditions such as rheumatoid arthritis, juvenile arthritis, and ulcerative colitis can cause significant pain. Azulfidine is a medicine that helps reduce pain and inflammation. In many cases, it is prescribed after other medications have already been tried without enough benefit. This drug is used to reduce swelling, which is one of the main symptoms of many types of arthritis. Patients with mild stomach pain may also benefit from Azulfidine (sulfasalazine). If the pain is more severe, additional medicines may be prescribed along with sulfasalazine.

How to Take Sulfasalazine

"How should I take Azulfidine (sulfasalazine)?" is an important question to ask your healthcare professional, because the dosage may vary. Several factors can affect your dosing schedule. The most important is your current health condition. If your condition is more severe, you may be prescribed a higher dose. Be sure to tell your doctor about all of your health conditions, as the dose may need to be adjusted from the general instructions. Pay attention to how your body reacts when you take the drug for the first time. Age is also an important factor in deciding how much medicine you should take.

Sulfasalazine conventional and delayed-release tablets are taken by mouth. The daily dose should be divided into equal doses and taken after meals. Delayed-release tablets should be swallowed whole.

Dosage for Ulcerative Colitis

The dosage of sulfasalazine (Azulfidine) varies depending on age and the condition being treated.

For the treatment of ulcerative colitis, the interval between doses of sulfasalazine given as conventional or delayed-release tablets should not exceed 8 hours. Response to sulfasalazine in patients with ulcerative colitis can be assessed using clinical signs such as fever, weight changes, and the degree and frequency of diarrhea and bleeding, as well as by sigmoidoscopy and evaluation of biopsy samples.

Continuing sulfasalazine treatment may be necessary even after symptoms, including diarrhea, have been brought under control. When endoscopic examination confirms satisfactory improvement, the sulfasalazine dose may be reduced to a maintenance dose.

If diarrhea returns, the dose should be increased to the previously effective amount. Patients with ulcerative colitis should be advised that the disease rarely goes away completely, and that ongoing use of maintenance doses of sulfasalazine may lower the risk of relapse.

The usual initial adult dosage of sulfasalazine given as conventional or delayed-release tablets for treating ulcerative colitis is 3-4 g daily, given in equally divided doses. In some patients, starting treatment with 1-2 g daily may help reduce gastrointestinal (GI) side effects. Although doses as high as 12 g daily have been used, doses above 4 g daily are associated with a higher rate of side effects.

Some clinicians recommend avoiding doses above 4 g a day unless the serum concentration of total sulfapyridine and the patient's phenotype are known. The usual adult maintenance dose is 2 g daily in 4 divided doses. However, some clinicians recommend a lower maintenance dose of 1-1.5 g daily to help prevent side effects. The effectiveness of maintenance therapy is related to dose, but the possible benefit of doses above 2 g daily must be weighed against the higher risk of side effects and the need for closer monitoring.

When sulfasalazine is given as conventional tablets for treating ulcerative colitis in children 2 years of age and older, the usual initial dosage is 40-60 mg/kg/day in 3-6 divided doses. The usual maintenance dosage is 30 mg/kg/day in 4 divided doses. When sulfasalazine is given as delayed-release tablets for treating ulcerative colitis in children 6 years of age and older, the usual initial dosage is 40-60 mg/kg/day in 3-6 divided doses. The usual maintenance dosage is 30 mg/kg/day in 4 divided doses.

Dosage for Rheumatoid Arthritis

The medicine can be taken at 18 years of age. For the treatment of rheumatoid arthritis, the interval between doses of sulfasalazine given as delayed-release tablets is usually 12 hours. The usual adult dosage of sulfasalazine given as delayed-release tablets for managing rheumatoid arthritis is 2-3 g daily in equally divided doses. It may be helpful to start treatment with 0.5-1 g daily to reduce GI side effects. Do not start with a high dose of Azulfidine, as it may cause stomach pain.

A response to sulfasalazine, shown by improvement in the number and extent of actively inflamed joints, may occur after 4-12 weeks of therapy. Patients receiving sulfasalazine doses above 2 g daily should be carefully monitored.

Dosage for Juvenile Arthritis

The usual dosage of sulfasalazine given as delayed-release tablets for managing polyarticular course juvenile rheumatoid arthritis in children 6 years of age and older is 30-50 mg/kg/day in 2 equally divided doses; the maximum dosage usually is 2 g daily. To reduce GI intolerance, the manufacturer recommends starting sulfasalazine in children at 1/4 to 1/3 of the planned maintenance dose and increasing the dose at weekly intervals until the planned maintenance dose is reached, usually by week 4.

Take as Directed

Azulfidine does not work quickly. It can take time for the medicine to start working. Follow your doctor's instructions and take the drug for as long as needed to treat your condition. If your condition is severe, treatment may need to continue longer. Do not stop taking the drug whenever you want, because side effects may occur. Your condition may get worse if you stop taking sulfasalazine without medical advice.

Another important point is to take the drug exactly as prescribed. If you take it at irregular intervals or do not follow the instructions, you may be less likely to get the full benefit. You are more likely to notice improvement only if you take the prescribed amount regularly. The medicine works by building up to a certain level in your body to help treat the cause of your condition.

"How will I know if the drug is working for me?" In general, your joint pain may improve or become milder than it was before treatment.

Sulfasalazine Side Effects

Like any medication, this medicine can cause unwanted effects. That does not mean you will definitely have side effects while taking it. Still, it is important to know about the possible reactions you may experience. Some side effects of Azulfidine (sulfasalazine) are more common, while others are rare but may be more serious. Knowing what side effects the drug can cause can help you understand what to expect during treatment.

In general, severe side effects caused by sulfasalazine are uncommon, but milder side effects occur often. Side effects usually begin within a few days to 12 weeks after starting sulfasalazine treatment, especially when the dose is above 4 g daily.

Patients with Ulcerative Colitis

Clinical experience to date indicates that the incidence of sulfasalazine-induced side effects in patients with ulcerative colitis is generally similar to that reported in patients with rheumatoid arthritis. The most common side effects associated with sulfasalazine therapy in patients with ulcerative colitis are loss of appetite, headache, nausea, vomiting, stomach upset, and reversible oligospermia.

Other side effects reported in patients with ulcerative colitis include itching, hives, rash, fever, Heinz body anemia, hemolytic anemia, and cyanosis. Side effects reported in patients with rheumatoid arthritis receiving sulfasalazine include nausea, dyspepsia, headache, abdominal pain, vomiting, fever, dizziness, stomatitis, rash, itching, abnormal liver function test results, leukopenia, and thrombocytopenia; reversible immunoglobulin suppression, rarely accompanied by clinical findings, has been observed in sulfasalazine-treated patients with rheumatoid arthritis.

Patients with Rheumatoid Arthritis

There do not appear to be drug-induced side effects that are specific to patients with rheumatoid arthritis. However, rash occurs more often in patients with rheumatoid arthritis than in those with ulcerative colitis, affecting 13% and 3.3% of patients respectively. Most patients with side effects, except rashes, have serum total sulfapyridine concentrations above 50 mcg/mL. The ability to acetylate sulfasalazine may affect the onset and severity of side effects. In one study, 86% of patients who experienced side effects were slow acetylators of sulfapyridine.

GI Effects

Loss of appetite can happen while taking sulfasalazine. Many patients report reduced appetite during treatment. In some cases, this is linked to nausea, which may also occur with sulfasalazine. Headache and sometimes dizziness are also common side effects that may appear for a short time and go away without any special treatment.

Nausea, vomiting, stomach upset, diarrhea, and loss of appetite occur frequently in patients receiving sulfasalazine. The manufacturers suggest that GI intolerance that occurs after the first few doses of sulfasalazine is probably caused by irritation of the lining of the digestive tract and may be relieved by spreading the total daily dose more evenly over the day or by using enteric-coated tablets. However, there have been no definitive studies comparing the toxicity of enteric-coated and uncoated tablets.

Symptoms that occur after the first few days of sulfasalazine treatment are probably due to high serum concentrations of total sulfapyridine. They may improve by cutting the dose in half and gradually increasing it over several days. If symptoms continue, the drug should be stopped for 5-7 days, and treatment should then be restarted at a lower daily dose.

There have been isolated reports of enteric-coated sulfasalazine tablets passing through the digestive tract intact in some patients, possibly because of a lack of intestinal esterases needed to break down the enteric coating. Additional enteric-coated tablets should not be taken if this happens.

Sensitivity Reactions

You may also notice itching. This can be a sign of an allergic reaction.

If a hypersensitivity reaction occurs during sulfasalazine treatment, the drug should be stopped right away. Desensitization to sulfasalazine is sometimes used when restarting treatment is considered necessary in a patient who has had a hypersensitivity reaction to the drug. However, desensitization should not be attempted in patients with a history of agranulocytosis, toxic epidermal necrolysis, fibrosing alveolitis, or anaphylactoid reaction while receiving sulfasalazine.

Specialized references should be consulted for specific information on desensitization procedures and dosage. Although various desensitization procedures have been reported to be effective, many regimens use an initial sulfasalazine dosage of 50-250 mg daily, which is then doubled every 4-7 days until the desired therapeutic dosage is attained. If symptoms of sensitivity recur, the drug should be discontinued.

If you have a fever, pale skin, unexplained spots, other skin problems, a sore throat, or sudden pain when urinating, call your doctor right away.

Other Adverse Effects

A few cases of pulmonary eosinophilia and at least one fatality from fibrosing alveolitis have been reported in patients receiving sulfasalazine. Sulfasalazine may turn alkaline urine and skin an orange-yellow colour.

Some men notice a lower sperm count after starting this medication. If this happens, it is considered one of the possible side effects. After treatment with sulfasalazine (Azulfidine), sperm count generally returns to normal.

It is impossible to predict exactly which side effects of Azulfidine you may experience, because each body reacts differently. The side effects listed here have been reported in patients, but that does not mean you will have any of them. You may also experience a side effect that is not listed here.

What Other Drugs Will Affect Sulfasalazine?

It's important to check which medications may interact with sulfasalazine before starting treatment. Some interactions may affect how well the medication works. It may not work as expected, or it may take longer to start helping. Here is how sulfasalazine may interact with the following drugs.

• Folic acid. Azulfidine can prevent folic acid from being fully absorbed. Vitamin B9 may need to be taken at a higher dose if you use this drug together with a vitamin supplement. However, do not increase the dose without talking to your doctor.
• Heart medications. If your doctor has prescribed heart medicines, make sure they do not interact with sulfasalazine; otherwise, they may be less effective. For example, digoxin should not be combined with Azulfidine without medical guidance, because sulfasalazine can affect its absorption.
• Disease-modifying antirheumatic drugs. Some drugs in this group may increase side effects when taken together with sulfasalazine (Azulfidine). Many patients report nausea when taking methotrexate together with sulfasalazine (Azulfidine).

The drugs listed above are only examples of medications that can interact with Azulfidine. The full list may be longer. Be sure to tell your doctor if you are taking other medications along with sulfasalazine to help avoid unexpected side effects. Your pharmacist or doctor can advise whether you should continue taking the drug or whether Azulfidine should be taken only after you finish treatment with another medication.

Overdose

Make sure you do not take more than the prescribed dose. Taking too much may cause nausea, stomach pain, and other unwanted effects. If you take too much of the drug, go to the emergency room, as large doses of Azulfidine can be poisonous. Do not wait to get medical help if you realize you have taken too much.

Missed Dose

Some people take an extra dose when they realize they missed one. You should take the missed dose only if you remember it soon after. If it is almost time for your next dose, do not take a double dose, as this may lead to overdose.

Important Warnings

Review the important warnings to help avoid serious side effects, some of which can be fatal.

Refills

Your healthcare professional may authorize refills when prescribing Azulfidine. This means you may not need a new prescription every time you run out and need more medication.

Clinical Monitoring

Clinical monitoring is important to make sure the drug is affecting your body as expected. During treatment with Azulfidine, you will need regular doctor visits and standard blood tests. At the start of treatment, blood tests may be needed more often because of the risk of infection associated with the medicine. You may also need tests to check how your liver is working, since the drug can affect this organ. If you have kidney problems, tell your doctor so they can order kidney tests to help prevent possible side effects.

Your Diet

You can usually continue eating the same foods as before. The main thing to keep in mind is that sulfasalazine affects how folic acid is absorbed. That is why you should ask your doctor whether you need an extra dose of folic acid.

Sun Sensitivity

Avoid sunbathing and tanning while you are being treated with sulfasalazine. The drug can make your skin more sensitive to the sun. If you take this medication during the summer, use sunscreen with UV protection.

Is Sulfasalazine Safe to Use During Pregnancy or While Breastfeeding?

Reproduction studies in rats and rabbits using sulfasalazine dosages up to 6 times the usual human dosage have not shown evidence of harm to the fetus. Sulfasalazine has been used to treat inflammatory bowel disease, including Crohn's disease and ulcerative colitis, during pregnancy.

Although fetal abnormalities have occasionally been reported in infants born to women with inflammatory bowel disease who received sulfasalazine alone or with corticosteroids during pregnancy, most evidence suggests that sulfasalazine is not associated with a substantial risk of teratogenicity and that the potential benefits of treatment generally appear to outweigh the possible risks in pregnant women with this disease.

Although most experience with sulfasalazine in pregnancy has been in women with inflammatory bowel disease, the safety of the drug in pregnant women with rheumatoid arthritis is not expected to be different. Sulfasalazine treatment can generally be continued in pregnant women with rheumatoid arthritis. Some clinicians consider sulfasalazine the disease-modifying antirheumatic drug (DMARD) of choice in women who are planning a pregnancy or who are pregnant. The risk of sulfasalazine-induced kernicterus in newborns exposed during the last trimester appears to be low. Agranulocytosis has been reported in a newborn whose mother received sulfasalazine and corticosteroid therapy throughout pregnancy.

The effect of the drug on later growth, development, and functional maturation in children whose mothers received sulfasalazine during pregnancy has not been determined. Because there are no adequate and controlled studies to date of sulfasalazine in pregnant women, the drug should be used during pregnancy only when clearly needed.

Impaired male fertility was observed in reproduction studies in rats using sulfasalazine dosages of 800 mg/kg/day. Oligospermia, abnormal sperm forms, impaired sperm motility, and infertility have occurred in men receiving sulfasalazine; however, these effects appear to be reversible after the drug is stopped. These effects appear to be caused by sulfapyridine, not 5-aminosalicylic acid (mesalamine), acting on sperm maturation.

Are you breastfeeding and thinking about taking sulfasalazine (Azulfidine)? You should know that the baby can receive some of the medicine through breast milk. You should not take the drug without a doctor's advice. Otherwise, your baby may experience side effects that may not be fatal but can still be serious.

Mutagenicity and Carcinogenicity

In carcinogenicity studies in rats and mice, male rats had a higher incidence of transitional cell papillomas in the urinary bladder, female rats had a higher incidence of urinary bladder transitional cell papilloma of the kidney, and male and female mice had a higher incidence of hepatocellular adenoma or carcinoma.

Allergy Warning

It is important to tell your doctor about any allergic reactions you have ever had while taking medicines that contain the same active ingredient as Azulfidine. Take the risk of an allergic reaction seriously, as it can be fatal. If you are not sure whether you are allergic to sulfa drugs, use extra caution. Take a small dose and watch how your body reacts. Call emergency services right away if you have trouble breathing or develop a sore throat.

Pediatric Precautions

The safety and effectiveness of sulfasalazine in children under 2 years of age with ulcerative colitis have not been established. The safety and effectiveness of sulfasalazine for managing polyarticular-course juvenile rheumatoid arthritis in children 6-16 years of age is supported by evidence from adequate and well-controlled studies in adults.

Warnings for People with Certain Health Conditions

• People with asthma.
• People with porphyria.

These warnings apply to people in the groups listed above. If you have either of these conditions and use Azulfidine, you may have side effects and your condition may get worse.

Storage

Store Azulfidine at room temperature. Do not refrigerate it, and avoid damp places. The recommended storage temperature is 20-25°C (68-77°F).