Azulfidine

Sulfasalazine may cause side effects. Sulfasalazine causes temporary infertility in males. Fertility returns when the medicine is stopped. It can also cause your urine or skin to turn yellowish-orange; this effect is harmless.

Tell your doctor if any of these symptoms are severe or do not go away:

• diarrhea
• headache
• loss of appetite
• upset stomach
• vomiting
• stomach pain

If you have any of the following symptoms, stop taking sulfasalazine and call your doctor immediately:

• skin rash
• itching
• hives
• swelling
• sore throat
• fever
• joint or muscle aches
• pale or yellow skin
• difficulty swallowing
• tiredness
• unusual bleeding or bruising
• weakness

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Azulfidine is a prescription medication used to treat the symptoms of ulcerative colitis including bowel inflammation, diarrhea (stool frequency), rectal bleeding, and abdominal pain. Azulfidine EN-tabs (delayed-release tablets) is used to treat rheumatoid arthritis in adults and children when other medications have not worked.

Azulfidine belongs to a group of drugs called aminosalicylates. It works by reducing inflammation (swelling) inside the body.

Azulfidine comes as regular and delayed-release tablets (Azulfidine EN-tabs). It is usually taken four times daily after meals. Drink a full glass of water after taking Azulfidine to protect the kidneys and to prevent kidney stones.

Common side effects include loss of appetite, nausea or vomiting, and headache.

Azulfidine is a prescription medication used:

• in the treatment of mild to moderate ulcerative colitis, and as adjunctive therapy in severe ulcerative colitis; and
• for the prolongation of the remission period between acute attacks of ulcerative colitis

Azulfidine En-tabs (delayed-release tablet) is used to treat ulcerative colitis (as indicated above) as well as:

• in the treatment of patients with rheumatoid arthritis who have responded inadequately to salicylates or other nonsteroidal anti-inflammatory drugs; and
• in the treatment of pediatric patients with polyarticular-course1 juvenile rheumatoid arthritis who have responded inadequately to salicylates or other nonsteroidal anti-inflammatory drugs.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Do not take this medication if:

• you are allergic to sulfasalazine, its metabolites, sulfonamides or salicylates
• you have intestinal or urinary obstruction (blockage)
• you have porphyria (enzyme problems)

This medication may make your skin more sensitive to sunlight. Avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. 

You should not use sulfasalazine if you have porphyria, a blockage in your bladder or intestines, or if you are allergic to sulfa drugs, aspirin, or similar medicines called salicylates.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Sulfasalazine can weaken your immune system. Your blood may need to be tested often.

This medicine can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using sulfasalazine.

Take this medicine after a meal.

Do not crush, chew, or break an enteric coated pill. Swallow it whole. The pill has a special coating to protect your stomach. Breaking the pill will damage this coating.

For best results, keep using this medicine as directed. Sulfasalazine will not cure ulcerative colitis, but it can reduce the number of attacks you have.

If you are treating arthritis, do not stop using any of your other arthritis medicines until your doctor tells you to. Your symptoms may not improve right away when you start taking sulfasalazine, and you may still need your other medicines for awhile.

Store at room temperature away from moisture and heat.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Ulcerative Colitis

Adjunct for management of mild to moderate ulcerative colitis.145 146

Crohn’s Disease

Management of active Crohn’s disease†.101 102 103 105 107 108

May be useful in patients with mild to moderately active disease, especially those with ileocolonic or colonic involvement.107 108 157 May not be effective in patients with small bowel disease.157 Many clinicians recommend that the drug be used in patients with left-sided disease, restricted to the colon.159

Patients who have previously received corticosteroid therapy or have undergone surgical resection may fail to respond to sulfasalazine therapy.159 Those who have not received corticosteroids or have not undergone surgery may respond substantially better to sulfasalazine than to placebo.159

There is some evidence that concomitant therapy with sulfasalazine and corticosteroids may not be more effective than either drug alone,105 106 157 but some subgroups of patients may have a better response to combined therapy (e.g., those with disease localized in the colon).105

Does not appear to be useful for maintenance therapy once a remission has been attained or following surgical resection.102 104 107 108 157

Rheumatoid Arthritis in Adults

Management of rheumatoid arthritis in adults whose symptoms progress despite an adequate regimen of NSAIAs.119 121 146 147 148 149 150 151 152 153 154 155 One of several disease-modifying antirheumatic drugs (DMARDs) that can be used when DMARD therapy is appropriate.154 155

Usually used in conjunction with analgesic and/or NSAIA therapy, at least until the beneficial effects of sulfasalazine are apparent.146 Administration of sulfasalazine alone is not a complete treatment for rheumatoid arthritis.146

Has been used in conjunction with other DMARDs (e.g., azathioprine, gold compounds, hydroxychloroquine, methotrexate, penicillamine) and/or systemic corticosteroids.148 149 150

Juvenile Arthritis

Management of the signs and symptoms of polyarticular course juvenile rheumatoid arthritis in children who have not responded adequately to NSAIAs.115 146 Not recommended for management of systemic course juvenile rheumatoid arthritis because of the high frequency of adverse effects reported in children.146

Absorption

Bioavailability

About 10–15% of a sulfasalazine dose is absorbed as unchanged drug from the small intestine.145 146 a

Part of an oral dose of sulfasalazine passes intact into the colon where the azo-linkage is cleaved by intestinal flora to form sulfapyridine and 5-aminosalicylic acid (mesalamine).a Sulfapyridine is rapidly absorbed from the colon; only a small portion of the 5-aminosalicylic acid present in the colon is absorbed.a

Following administration of a single oral dose of sulfasalazine to healthy adults, peak serum sulfasalazine concentrations occur within 1.5–6 hours and peak serum sulfapyridine concentrations occur within 6–24 hours.a When delayed-release tablets are used, peak serum sulfasalazine concentrations occur within 3–12 hours and peak sulfapyridine concentrations occur within 12–24 hours.a

Plasma Concentrations

Mean serum concentration of total sulfapyridine (sulfapyridine and its metabolites) tends to be greater in patients who are slow acetylator phenotypes than in fast acetylator phenotypes.a

Distribution

Extent

In animals, relatively high concentrations of sulfasalazine are present in serous fluid, liver, and the intestinal wall.a Sulfapyridine is distributed to most body tissues.a

Unchanged sulfasalazine, sulfapyridine and its metabolites, and 5-aminosalicylic acid and its acetylated metabolite cross the placenta.100 124 125 135

Only small amounts of unchanged sulfasalazine are distributed into milk, but sulfapyridine concentrations in milk are about 30–60% of concurrent serum concentrations.145 146

Plasma Protein Binding

Sulfasalazine is >99.3% bound to albumin; sulfapyridine is 70% bound to albumin; acetylsulfapyridine (principal metabolite of sulfapyridine) is approximately 90% bound to plasma proteins.a

Elimination

Metabolism

Sulfasalazine is cleaved by intestinal flora in the colon to form sulfapyridine and 5-aminosalicylic acid.145

Following absorption, sulfapyridine undergoes hepatic N 4-acetylation and ring hydroxylation followed by conjugation with glucuronic acid.a A small portion of 5-aminosalicylic acid is absorbed and undergoes N 4-acetylation; the major portion is excreted in the feces.a The rate of metabolism of sulfapyridine and acetylsulfapyridine depends on the acetylator phenotype of the patient.145 146 d

Elimination Route

Most of a sulfasalazine dose is excreted in the urine.a Unchanged sulfasalazine accounts for up to 15%, sulfapyridine and its metabolites account for about 60%, and 5-aminosalicylic acid and its metabolites account for 20–33% of a dose.a

Although total fecal excretion of sulfasalazine and its metabolites depends on GI transit time and the activity of the intestinal bacteria; fecal excretion may account for about 5% of a daily dose (primarily as sulfapyridine metabolites).a

Half-life

Mean serum half-life of sulfasalazine is 5.7 hours following a single dose and 7.6 hours following multiple doses.a

Half-life of sulfapyridine is 8.4 hours following a single sulfasalazine dose and 10.4 hours following multiple sulfasalazine doses.a

Special Populations

In geriatric patients with rheumatoid arthritis, half-life of sulfasalazine and its metabolites may be increased.145 146

• If you have an allergy to sulfasalazine or any other part of Azulfidine (sulfasalazine tablets).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have a sulfa (sulfonamide) allergy, talk with your doctor.
• If you have any of these health problems: Bowel block, porphyria, or trouble passing urine.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Azulfidine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take after meals.
• To gain the most benefit, do not miss doses.
• Keep taking Azulfidine as you have been told by your doctor or other health care provider, even if you feel well.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

There is evidence that the incidence and severity of toxicity following overdosage are directly related to the total serum sulfapyridine concentration. Symptoms of overdosage may include nausea, vomiting, gastric distress, and abdominal pains. In more advanced cases, central nervous system symptoms such as drowsiness, convulsions, etc., may be observed. Serum sulfapyridine concentrations may be used to monitor the progress of recovery from overdosage.

There are no documented reports of deaths due to ingestion of large single doses of sulfasalazine.

Doses of Azulfidine tablets of 16 g per day have been given to patients without mortality. A single oral dose of 12 g/kg was not lethal to mice.

Instructions for Overdosage

Gastric lavage or emesis plus catharsis as indicated. Alkalinize urine. If kidney function is normal, force fluids. If anuria is present, restrict fluids and salt, and treat appropriately. Catheterization of the ureters may be indicated for complete renal blockage by crystals. The low molecular weight of sulfasalazine and its metabolites may facilitate their removal by dialysis.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of sulfasalazine tablets and enteric-coated tablets to treat ulcerative colitis in children younger than 2 years of age. Safety and efficacy have not been established in children younger than 2 years of age.

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of sulfasalazine enteric-coated tablets to treat juvenile rheumatoid arthritis in children. However, safety and efficacy have not been established in children younger than 6 years of age.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of sulfasalazine in the elderly.

Pregnancy

Breast Feeding

Studies suggest that this medication may alter milk production or composition. If an alternative to this medication is not prescribed, you should monitor the infant for side effects and adequate milk intake.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Ketorolac
• Methenamine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Amtolmetin Guacil
• Azathioprine
• Bromfenac
• Bufexamac
• Celecoxib
• Clonixin
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Dipyrone
• Droxicam
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Flurbiprofen
• Ibuprofen
• Indomethacin
• Ketoprofen
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Mercaptopurine
• Morniflumate
• Nabumetone
• Naproxen
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Phenylbutazone
• Piketoprofen
• Piroxicam
• Proglumetacin
• Propyphenazone
• Proquazone
• Riluzole
• Rofecoxib
• Sulindac
• Tenoxicam
• Tiaprofenic Acid
• Tolfenamic Acid
• Tolmetin
• Valdecoxib

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aminolevulinic Acid
• Cyclosporine
• Digoxin
• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergy to sulfa drugs or salicylates or
• Bowel blockage or
• Porphyria (enzyme problem) or
• Urinary bladder blockage—Should not be used in patients with these conditions.

• Asthma, bronchial—Use with caution. May increase risk of having an allergic reaction.

• Blood or bone marrow problems (eg, agranulocytosis, aplastic anemia) or
• Kidney disease or
• Liver disease—Use with caution. May make these conditions worse.

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency (a hereditary metabolic disorder affecting red blood cells)—May cause hemolytic anemia (blood disorder) in patients with this condition.

• Infection—May decrease your body's ability to fight infection.