Azathioprine

What is Azathioprine?

• Azathioprine (Azasan; Imuran) is an immunosuppressive antimetabolite used with other medications to prevent transplant rejection in people who received kidney transplants.
• It is also used to treat severe rheumatoid arthritis when other medications and treatments have not helped.

Azathioprine

Azathioprine 3d structure

What are the uses of this medicine?

• Azathioprine (Azasan; Imuran) is used as an adjunct for the prevention of rejection in kidney transplants. It is also indicated for the management of active rheumatoid arthritis to reduce signs and symptoms.
• Aspirin, non-steroidal anti-inflammatory drugs and/or low dose glucocorticoids may be continued during treatment of rheumatoid arthritis with azathioprine tablets.
• The combined use of azathioprine tablets with disease modifying anti-rheumatic drugs (DMARDs) has not been studied for either added benefit or unexpected adverse effects.

How does this medicine work?

• Azathioprine (ay" za thye' oh preen) is an imidazolyl derivative and prodrug of mercaptopurine that inhibits lymphocyte function by antagonism of purine metabolism, thus inhibiting DNA, RNA and subsequent protein synthesis.
• Azathioprine inhibits the maturation of T cells and blocks delayed hypersensitivity reactions; it also has antiinflammatory activity.

In prevention of rejection: The use of azathioprine for inhibition of renal homograft rejection is well established. The drug suppresses hypersensitivities of the cell-mediated type and causes variable alterations in antibody production. Suppression of T-cell effects, including ablation of T-cell suppression, is dependent on the temporal relationship to antigenic stimulus or engraftment. This agent has little effect on established graft rejections or secondary responses.

In autoimmune diseases:

• The mechanisms whereby azathioprine affects autoimmune diseases are not known.
• Azathioprine is immunosuppressive, delayed hypersensitivity and cellular cytotoxicity tests being suppressed to a greater degree than are antibody responses.
• In the rat model of adjuvant arthritis, azathioprine has been shown to inhibit the lymph node hyperplasia, which precedes the onset of the signs of the disease.
• Azathioprine is considered a slow-acting drug and effects may persist after the drug has been discontinued.

Who Should Not Use this medicine ?

This medicine cannot be used in patients:

• who have shown hypersensitivity to the drug.
• for treating rheumatoid arthritis in pregnant women.
• with rheumatoid arthritis previously treated with alkylating agents (cyclophosphamide, chlorambucil, melphalan, or others).

What drug interactions can this medicine cause?

• Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.

Be sure to mention any of the following:

• angiotensin converting enzyme (ACE) inhibitors such as benazepril (Lotensin), captopril, enalapril (Vasotec), fosinopril, lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), Ramipril (Altace), or trandolapril (Mavik)
• trimethoprim and sulfamethoxazole (Bactrim, Septra)
• ribavirin (Copegus, Rebetol, Virazole)
• allopurinol (Zyloprim)
• aminosalicylates such as mesalamine (Apriso, Asacol, Pentasa, others), olsalazine (Dipentum), and sulfasalazine (Azulfidine)
• anticoagulants ('blood thinners') such as warfarin (Coumadin)

Is this medicine FDA approved?

• Azathioprine was introduced into use in the early 1960s and represented a major breakthrough in the development of antirejection therapy, allowing for more widespread and successful use of kidney, heart and liver transplantation.
• Azathioprine was approved for use in the United States in 1968 and is still widely used in transplantation and in treatment of autoimmune conditions such as Crohn disease, rheumatoid arthritis and autoimmune hepatitis. Azathioprine is available generically and under the brand name of Imuran as tablets of 50, 75 and 100 mg; a parenteral formulation is also available.

How should this medicine be used?

Recommended dosage: In Renal Homotransplantation:

• The initial dose is usually 3 to 5 mg/kg daily, beginning at the time of transplant.
• Azathioprine tablets are usually given as a single daily dose on the day of, and in a minority of cases 1 to 3 days before, transplantation.
• Dose reduction to maintenance levels of 1 to 3 mg/kg daily is usually possible.

In Rheumatoid Arthritis:

• The initial dose should be approximately 1.0 mg/kg (50 to 100 mg) given as a single dose or on a twice-daily schedule.
• The dose may be increased, beginning at 6 to 8 weeks and thereafter by steps at 4-week intervals, if there are no serious toxicities and if initial response is unsatisfactory.
• Dose increments should be 0.5 mg/kg daily, up to a maximum dose of 2.5 mg/kg per day.
• Therapeutic response occurs after several weeks of treatment, usually 6 to 8.
• Maintenance therapy should be at the lowest effective dose, and the dose given can be lowered decrementally with changes of 0.5 mg/kg or approximately 25 mg daily every 4 weeks while other therapy is kept constant.

Administration:

• Azathioprine comes as a tablet to take by mouth.
• It is usually taken once or twice a day after meals.
• Take azathioprine at around the same times every day.
• If you are taking azathioprine to treat rheumatoid arthritis, your doctor may start you on a low dose and gradually increase your dose after 6-8 weeks and then not more than once every 4 weeks.
• Your doctor may gradually decrease your dose when your condition is controlled.
• If you are taking azathioprine to prevent kidney transplant rejection, your doctor may start you on a high dose and decrease your dose gradually as your body adjusts to the transplant.
• Azathioprine controls rheumatoid arthritis but does not cure it.
• It may take up to 12 weeks before you feel the full benefit of azathioprine.
• Azathioprine prevents transplant rejection only as long as you are taking the medication.
• Continue to take azathioprine even if you feel well. Do not stop taking azathioprine without talking to your doctor.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Azathioprine Tablets, 50 mg

This medicine is available in fallowing brand namesː

• Azasan; Imuran

What side effects can this medication cause?

The most common side effects of this medicine may include: Hematologic:

• Leukopenia
• thrombocytopenia
• pancytopenia

Gastrointestinal:

• Nausea and vomiting
• diarrhea
• fever
• malaise
• myalgias
• Vomiting with abdominal pain

Less coomon side effects may include:

• skin rashes, alopecia, fever, arthralgias, diarrhea, steatorrhea, negative nitrogen balance, reversible interstitial pneumonitis and hepatosplenic T-cell lymphoma.

• Long term use of azathioprine is associated with an increased risk for malignancy, including lymphoma and possibly hepatocellular carcinoma.

What special precautions should I follow?

• Severe leukopenia, thrombocytopenia, macrocytic anemia, and/or pancytopenia may occur in patients being treated with azathioprine tablets. Severe bone marrow suppression may also occur. It is suggested that patients on azathioprine tablets have complete blood counts, including platelet counts, weekly during the first month, twice monthly for the second and third months of treatment, then monthly or more frequently if dosage alterations or other therapy changes are necessary.
• Serious infections are a constant hazard for patients receiving chronic immunosuppression, especially for homograft recipients. Fungal, viral, bacterial, and protozoal infections may be fatal and should be treated vigorously. Reduction of azathioprine dosage and/or use of other drugs should be considered.
• Azathioprine may increase your risk of developing certain types of cancer, especially skin cancer and lymphoma (cancer that begins in the cells that fight infection).
• Azathioprine tablets can cause fetal harm when administered to a pregnant woman. Whenever possible, use of azathioprine tablets in pregnant patients should be avoided. This drug should not be used for treating rheumatoid arthritis in pregnant women.
• A gastrointestinal hypersensitivity reaction characterized by severe nausea and vomiting has been reported. These symptoms may also be accompanied by diarrhea, rash, fever, malaise, myalgias, elevations in liver enzymes, and occasionally, hypotension.
• Patients being started on azathioprine tablets should be informed of the necessity of periodic blood counts while they are receiving the drug and should be encouraged to report any unusual bleeding or bruising to their physician.
• Careful dosage instructions should be given to the patient, especially when azathioprine tablets are being administered in the presence of impaired renal function or concomitantly with allopurinol.
• Patients should be advised of the potential risks of the use of azathioprine tablets during pregnancy and during the nursing period. The increased risk of neoplasia following therapy with azathioprine tablets should be explained to the patient.
• Azathioprine is associated with minor, usually transient and asymptomatic elevations in serum aminotransferase levels during therapy and with rare instances of acute, cholestatic liver injury and, with long term use, noncirrhotic portal hypertension as a result of nodular regenerative hyperplasia or sinusoidal obstruction syndrome.
• Do not have any vaccinations during or after your treatment without talking to your doctor.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• marrow hypoplasia
• bleeding
• infection
• nausea
• vomiting
• diarrhea
• mild leukopenia
• mild abnormalities in liver function

Management of overdosage:

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• About 30% of azathioprine is bound to serum proteins, but approximately 45% is removed during an 8-hour hemodialysis.

Can this medicine be used in pregnancy?

• Pregnancy Category D.
• Azathioprine tablets can cause fetal harm when administered to a pregnant woman.
• Azathioprine tablets should not be given during pregnancy without careful weighing of risk versus benefit.
• Whenever possible, use of azathioprine tablets in pregnant patients should be avoided.
• This drug should not be used for treating rheumatoid arthritis in pregnant women.

Can this medicine be used in children?

• Safety and efficacy of azathioprine in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• azathioprine

Inactive ingredients:

• croscarmellose sodium
• lactose monohydrate
• magnesium stearate
• povidone
• starch, corn

Who manufactures and distributes this medicine?

Manufactured by:

• Cadila Healthcare Ltd.
• Ahmedabad, India

Distributed by:

• Zydus Pharmaceuticals USA Inc.
• Princeton, NJ

What should I know about storage and disposal of this medication?

• Store at 20° to 25° C (68° to 77° F) in a dry place and protect from light.

• Dailymed label info on Azathioprine
• FDA Azathioprine

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