Azulfidine (Sulfasalazine)

Do you have arthritis or ulcerative colitis? If so, you may be prescribed sulfasalazine. However, like any medicine, it should be taken carefully after you have checked the instructions and made sure it is suitable for you. Learn more about sulfasalazine so you can get the benefits of treatment and help avoid unexpected side effects.

What Is Azulfidine (Sulfasalazine)?

Sulfasalazine is a medicine that comes as tablets to take by mouth.

Why is Azulfidine prescribed? Conditions such as rheumatoid/juvenile arthritis and ulcerative colitis can cause significant pain. Azulfidine is a medicine that helps relieve pain and reduce inflammation. In the UK, this medicine is usually prescribed when other treatments have already been tried but have not worked well enough. This medicine also helps to reduce swelling, which is a key symptom of many types of arthritis. Patients with mild stomach pain may benefit from Azulfidine (sulfasalazine). If the pain is severe, other medicines may be prescribed alongside sulfasalazine.

How to Take Sulfasalazine

"How should I take Azulfidine (sulfasalazine)?" is an important question to ask your healthcare professional, as the dose can vary. Several factors can affect your dosing schedule, and the most important is your current health condition. If your condition is more severe, you may be prescribed a higher dose. Tell your doctor about all your health problems, as the dose in the general instructions may need to be lowered or increased. Pay attention to how your body reacts when you take the medicine for the first time. Age is also important when deciding how much medicine you should take.

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

Dosage for Ulcerative Colitis

The dose 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 standard 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 diarrhoea and bleeding, as well as by sigmoidoscopy and assessment of biopsy samples.

It may be necessary to continue sulfasalazine treatment even when clinical symptoms, including diarrhoea, have been brought under control. When endoscopic examination confirms satisfactory improvement, the sulfasalazine dose may be reduced to a maintenance dose.

If diarrhoea returns, the dose should be increased to the previously effective dose. Patients with ulcerative colitis should be advised that the condition rarely goes away completely, and that continuing maintenance doses of sulfasalazine may reduce the risk of relapse.

The usual initial adult dose of sulfasalazine given as standard or delayed-release tablets for treating ulcerative colitis is 3-4 g daily, 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 dose-related. Still, 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 standard tablets for treating ulcerative colitis in children aged 2 years and over, the usual initial dose is 40-60 mg/kg/day in 3-6 divided doses. The usual maintenance dose is 30 mg/kg/day in 4 divided doses. When sulfasalazine is given as delayed-release tablets for treating ulcerative colitis in children aged 6 years and over, the usual initial dose is 40-60 mg/kg/day in 3-6 divided doses. The usual maintenance dose is 30 mg/kg/day in 4 divided doses.

Dosage for Rheumatoid Arthritis

The medicine can be taken from 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 dose 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 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 treatment. Patients receiving sulfasalazine doses above 2 g daily should be carefully monitored.

Dosage for Juvenile Arthritis

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

Take as Directed

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

Another important point is that treatment is most likely to work when you take the medicine exactly as prescribed. If you take it at irregular intervals or do not follow the instructions, you are less likely to get the full benefit. You are most likely to notice a positive effect 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 that the drug works for me?" The answer is simple: your joint pain should improve or become milder than it was before treatment.

Sulfasalazine Side Effects

Like any medicine, this treatment may cause side effects. This does not mean you will definitely get them, but it is important to know what might happen. Some side effects of Azulfidine (sulfasalazine) are more common, while others are rare but can be more serious. Knowing about them can help you understand what to expect during treatment.

In general, serious sulfasalazine-related side effects are uncommon, but milder side effects happen fairly often. They usually begin within a few days to 12 weeks after starting treatment, especially when the dose is above 4 g daily.

Patients with Ulcerative Colitis

Clinical experience so far suggests that the rate of sulfasalazine-related side effects in patients with ulcerative colitis is generally similar to that reported in patients with rheumatoid arthritis. The most common side effects linked to sulfasalazine treatment in patients with ulcerative colitis are anorexia, headache, nausea, vomiting, gastric discomfort, and reversible oligospermia.

Other side effects reported in patients with ulcerative colitis include pruritus, urticaria, rash, fever, Heinz body anaemia, haemolytic anaemia, and cyanosis. Side effects reported in patients with rheumatoid arthritis receiving sulfasalazine include nausea, dyspepsia, headache, abdominal pain, vomiting, fever, dizziness, stomatitis, rash, pruritus, abnormal liver function test values, 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 any 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, apart from rashes, have serum total sulfapyridine concentrations above 50 mcg/mL. The ability to acetylate sulfasalazine may influence when side effects begin and how severe they are. In one study, 86% of patients with side effects were slow acetylators of sulfapyridine.

GI Effects

You may notice that you do not feel like eating while taking sulfasalazine. Many patients report a reduced appetite during treatment. In some cases, this is linked to nausea, which can also happen with sulfasalazine. Headaches and sometimes dizziness are also common side effects, and they may appear for a short time and then go away without any special treatment.

Nausea, vomiting, gastric discomfort, diarrhoea, and anorexia occur frequently in patients taking sulfasalazine. Manufacturers suggest that GI intolerance after the first few doses is probably caused by irritation of the lining of the gut and may be eased by spreading the total daily dose more evenly across 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 appearing after the first few days of sulfasalazine treatment are probably due to high serum concentrations of total sulfapyridine. They may improve if the dose is halved and then increased gradually over several days. If symptoms continue, the medicine should be stopped for 5-7 days, and treatment restarted at a lower daily dose.

There have been isolated reports of enteric-coated sulfasalazine tablets passing through the GI tract intact in some patients, possibly because of a lack of intestinal esterases needed to break down the enteric coating. If this happens, no more enteric-coated tablets should be taken.

Sensitivity Reactions

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

If a hypersensitivity reaction occurs during sulfasalazine treatment, the medicine should be stopped immediately. Desensitisation to sulfasalazine may be used when restarting treatment is considered necessary in a patient who has had a hypersensitivity reaction to the medicine. However, desensitisation should not be attempted in patients with a history of agranulocytosis, toxic epidermal necrolysis, fibrosing alveolitis, or anaphylactoid reaction while taking sulfasalazine.

Specialist references should be consulted for detailed information on desensitisation procedures and dosing. Although various desensitisation procedures have been reported to work, many regimens use an initial sulfasalazine dose of 50-250 mg daily, which is then doubled every 4-7 days until the required therapeutic dose is reached. If symptoms of sensitivity return, the medicine should be stopped.

If you develop a fever, pale skin, unexplained spots, other skin problems, a sore throat, or sudden discomfort when passing urine, call your doctor straight away.

Other Adverse Effects

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

Some men notice that their sperm count decreases after they start taking this medicine. Do not worry if this happens, as it is a known side effect. After treatment with sulfasalazine (Azulfidine) stops, sperm count usually returns to normal.

It is impossible to predict exactly which side effects of Azulfidine you may experience, because everyone 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 even have a side effect that is not listed here.

What Other Drugs Will Affect Sulfasalazine?

It is important to check which medicines interact with sulfasalazine before starting treatment. Some interactions can affect how the medicine works. It may not work as expected, or it may take longer to start working. Below are some examples of how sulfasalazine interacts with other medicines.

• Folic acid. Azulfidine prevents folic acid from being fully absorbed. Vitamin B9 may need to be taken at a higher dose if you use this medicine together with a supplement. However, you should not increase the dose without your doctor's advice.
• Heart medicines. If your doctor has prescribed heart medicines, make sure they do not interact with sulfasalazine, otherwise they may not work as well. For example, digoxin should not be combined with Azulfidine. You may absorb less of the heart medicine because sulfasalazine can affect how well it is absorbed.
• Disease-modifying antirheumatic drugs. Some medicines 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 medicines mentioned above are only examples of drugs that can interact with Azulfidine. The list may be longer. You are strongly advised to tell your doctor if you are taking any other medicines while using sulfasalazine to help avoid unexpected and potentially life-threatening side effects. In the UK, your pharmacist can advise whether you should continue taking this medicine or whether Azulfidine should be taken only after you have finished a course of another treatment.

Overdose

Make sure you do not take too much of this medicine. If you take a larger dose, you may have nausea, stomach pain, and other unwanted effects. If you think you have taken too much, go to A&E immediately, as large doses of Azulfidine can be poisonous. Do not wait if you realise you have taken more than prescribed.

Missed Dose

Many people take an extra dose when they realise they have missed one. This is only appropriate if you remember the missed dose soon afterwards. If it is nearly time for your next dose, do not take two doses together, as this may lead to an overdose.

Important Warnings

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

Refills

In the UK, your prescriber may authorise repeat supplies of Azulfidine. This means you may not need a new prescription every time the medicine runs out and you need more.

Clinical Monitoring

Clinical monitoring is important to make sure the medicine is having the right effect on your body. During Azulfidine treatment, you will need to see your doctor regularly and have routine blood tests. You should be aware that treatment with sulfasalazine often involves several blood tests at the start because of the risk of infection linked to the medicine. As well as blood tests, you may need tests to check your liver, as the medicine can affect this organ. If you have kidney problems, tell your doctor, as they may also arrange kidney tests to help prevent possible side effects.

Your Diet

You can carry on eating the same foods as usual. The main thing to remember is that sulfasalazine affects the absorption of folic acid. 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 taking sulfasalazine. The medicine can make your skin more sensitive to the sun. If you are taking it during summer, use a cream with UV protection.

Is Sulfasalazine Safe to Use During Pregnancy or While Breastfeeding?

Reproduction studies in rats and rabbits using sulfasalazine doses up to 6 times the usual human dose 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 linked to 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 medicine 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 to become pregnant or who are pregnant. The risk of sulfasalazine-induced kernicterus in newborn babies exposed during the last trimester appears to be low. Agranulocytosis has been reported in a newborn whose mother received sulfasalazine and corticosteroid treatment throughout pregnancy.

The effect of the medicine 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 well-controlled studies to date in pregnant women using sulfasalazine, the medicine should be used during pregnancy only when clearly needed.

Impairment of male fertility was seen in reproduction studies in rats using sulfasalazine doses of 800 mg/kg/day. Oligospermia, abnormal sperm forms, impaired sperm motility, and infertility have occurred in men taking sulfasalazine; however, these effects appear to be reversible after the medicine 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 will receive some of the medicine through breast milk. You should not take this medicine without your doctor's advice. Otherwise, your baby may have side effects that are not fatal but can still be serious.

Mutagenicity and Carcinogenicity

In carcinogenicity studies in rats and mice, an increased incidence of urinary bladder transitional cell papillomas was observed in male rats, an increased incidence of urinary bladder transitional cell papilloma of the kidney was observed in female rats, and an increased incidence of hepatocellular adenoma or carcinoma was observed in male and female mice.

Allergy Warning

Tell your doctor if you have ever had an allergic reaction to any medicine containing the same active ingredient as Azulfidine. Allergic reactions can be serious and, in some cases, life-threatening, so this risk should not be ignored. If you are unsure whether you are allergic to sulfonamide medicines, do not test this yourself by taking a small dose. Seek medical advice instead.

Paediatric precautions

The safety and effectiveness of sulfasalazine in children under 2 years of age with ulcerative colitis have not been established. For polyarticular-course juvenile rheumatoid arthritis in children aged 6-16 years, evidence from adequate and well-controlled studies in adults supports the safety and effectiveness of sulfasalazine.

Warnings for people with certain health conditions

• Patients with asthma.
• Patients with porphyria.

These warnings apply to people in the groups listed above. If they use Azulfidine, they may have side effects, and their condition may get worse.

Storage

Store Azulfidine at room temperature. Do not refrigerate it or keep it in damp places. The recommended storage temperature is 20–25°C.