Azathioprine (Oral)

Overview

What is Azathioprine?

Azathioprine is a drug that belongs to a group of medicines classified as immunosuppressive agents. Azathioprine is effective in lowering the body's natural immunity, which helps prevent rejection of an organ transplant such as a kidney. Azathioprine is also used to relieve swelling or pain in joints by suppressing the immune functions that cause these symptoms in patients diagnosed with rheumatoid arthritis. This medication is only available by prescription from a licensed medical doctor and comes in tablet form.

How does Azathioprine work?

Azathioprine works by weakening the body's immune system, keeping it from attacking or rejecting the transplanted kidney, allowing it to function normally. Patients with rheumatoid arthritis experience less damage from their immune systems attacking their joints.

What are the signs of a kidney transplant rejection?

After a kidney transplant, drugs such as Azathioprine are given to keep the body from rejecting the new organ because they see it as a foreign object. Transplant patients need to be aware of the signs of rejection which include:

• Pain at the site of the transplant
• Unwell feeling
• Irritability
• Flu-like symptoms
• Weight changes
• Swelling
• Changes in heart rate
• Less or less frequent urine

Organ rejection can be acute or chronic; it is fairly common to have an instance of acute rejection within 12 months of the kidney transplant. Sometimes this leads to chronic rejection, when the organ slowly loses its ability to function. Over time, rejection becomes less likely but the risk of rejection never goes away. It is vital to have regular check-ups and continue your medication regimen with Azathioprine as directed by your health provider.

What is rheumatoid arthritis?

Technically an autoimmune disease, rheumatoid arthritis causes pain, swelling and stiffness to the joints affecting the hands, feet and risks. Rheumatoid arthritis is a disease in which the body's immune system, normally attacking infections, attacks the cells the line the body's joints instead, causing them to become painful, stiff and swollen, eventually damaging bone. Women, family history and tobacco smokers are at risk for developing rheumatoid arthritis. No cure is available but immunosuppressant drugs such as Azathioprine are prescribed to ease symptoms and prevent joint damage.

Symptoms of rheumatoid arthritis include:

• Joint pain, swelling and stiffness
• Inflammation in other parts of the body
• Fatigue and lack of energy
• Fever
• Sweating
• Poor appetite
• Weight loss
• Dry eyes, if eyes are affected
• Chest pain, if the disease is present in the heart or lungs

What other diseases is Azathioprine prescribed for?

In addition to preventing kidney transplant rejection and alleviating symptoms of rheumatoid arthritis, Azathioprine is also prescribed for other autoimmune diseases such as Crohn's disease, ulcerative colitis and for multiple sclerosis.

Conditions treated

• Kidney transplant rejection protection, rheumatoid arthritis, Crohn's disease, ulcerative colitis

Type of medication

• Immunosuppressant

Side effects

Because Azathioprine affects the immune system, it may cause side effects in some patients. Not all patients experience side effects, but severe or prolonged side effects could be a sign of serious health issues and require medical attention. Contact your physician immediately if you experience the following common side effects:

• Black, tarry stools
• Bleeding gums
• Blood in stool or urine
• Chest pain
• Cough or hoarseness
• Fever or chills
• Lower back or side pain
• Pain or difficulty when urinating
• Tiny red skin rash
• Gasping for breath
• Throat soreness
• White spots, ulcers, sores on lips or in mouth
• Swelling of glands
• Bruising or bleeding unusually
• Fatigue or weakness at unexpected times

The following side effects are rarely reported by patients receiving treatment of Azathioprine, but they are possible. If you experience side effects such as these, contact your health professional right away:

• Tender abdomen or pain in the stomach
• Stools that are the color of clay
• Urine that is darker than normal
• Less than normal appetite
• Fast heartbeat
• Fever (sudden)
• Headaches
• Itchy skin
• Muscle or joint pain
• Nausea, vomiting, and diarrhea (severe)
• Redness or blisters on the skin
• Swollen lower legs or feet
• Abnormal feeling of discomfort or illness (sudden)
• Yellow tinged skin or eyes

The following side effects are possible but it is unknown how frequently they occur. If your side effects are present when you take Azathioprine, contact your health provider immediately:

• Abdominal or stomach cramps
• Diarrhea
• Difficulty with breathing
• Difficulty with moving
• Fat in the stool
• General feeling of illness
• Pale skin
• Sores on the skin
• Sudden loss of weight
• Troubled breathing with movement
• Weight loss

Some side effects of Azathioprine do not require medical treatment and typically disappear over time. You may experience side effects such as these:

• Nausea or vomiting (mild)
• Swollen joints
• Hair loss or thinning of the hair

If side effects such as these become prolonged or are considered severe, seek medical attention immediately.

Dosage

Azathioprine should be taken only as prescribed by your medical doctor; do not increase the dosage either in amount or frequency or take the medication longer than you are prescribed to. Taking too much of this medication may cause unwanted and dangerous side effects. Taking too little of this medication will not treat the condition you are taking it for.

Occasionally Azathioprine is prescribed in combination with other medicines. If so, your doctor will give you specific instructions on how to take these medicines together. Make sure you understand the instructions and ask questions if you are unclear on the medication plan.

Do not stop taking this medication without checking with your physician first.

Azathioprine may cause nausea or vomiting; to lessen this side effect, take the medication after meals or at bedtime. Consult your health provider if you continue to have problems with nausea when taking this medication.

Dosage will be different for different patients and prescribed to them based on their specific condition and symptoms. Follow your doctor's prescription or the directions on the label of your Azathioprine medication. The following information represents average doses; yours may be different.

For kidney transplant rejection

Dosage of Azathioprine is based on body weight and must be determine by your health provider. Typically, the starting dose for adults is 3 to 5 milligrams per kilogram of body weight per day, given as a single dose. The first dose of Azathioprine is given one to three days prior to the transplant or, sometimes, on the day of the transplant. Your doctor will adjust your dose after a certain period of time or as needed. Children who have had kidney transplants will have their dose of Azathioprine determined for them by their doctor.

For rheumatoid arthritis

Again, dosage is based on body weight in adults, with the starting dose for this treatment at one milligram per kilogram of body weight per day as a single dose. This may be divided into two doses or adjusted as needed, but will typically not exceed a total of 2.5 milligrams per kilogram of body weight per day. Prescription details for children with rheumatoid arthritis will be determined by their doctor.

Missing a dose does not mean you should catch up; if you are close to the time of your next dose, skip the missing dose and resume your medication schedule without double dosing. If you vomit after taking Azathioprine, contact your health professional for instructions on what to do about that dose.

Interactions

If you've experienced an unusual reaction or allergy to Azathioprine or any other drug treatments, inform your doctor before beginning treatment with this drug. Allergies to animals, foods, dyes or preservatives should also be disclosed to your health provider.

Studies in pediatric and geriatric age groups have not shown any age related side effects that were more of a risk with regard to the use of this drug. Prescription of Azathioprine to these patients will be at the doctor's discretion.

Pregnant women or women who may become pregnant should not be prescribed Azathioprine as it has demonstrated fetal risks. Options of therapy should be discussed with your health care professional.

No adequate data has been provided from studies on breastfeeding women to determine if Azathioprine passes risks on to breastfeeding infants. Discuss this treatment with your physician if you are breastfeeding.

It is of critical importance that your disclose your full medical history as well as details of any drugs you are currently taking or have taken in the recent past before you begin to use Azathioprine or any other drug. Include all information available on your prescription as well as non-prescription medication that you may be taking and details of any herbal, vitamin, and holistic supplements or treatments you are currently being treated with.

Azathioprine has been known to interact with and should not be taken with the following medication under any circumstances. Your physician may change to another treatment if you are taking:

• Febuxostat

Prescription doses of Azathioprine are not typically recommended with use of the drugs listed below but could be part of your overall health treatment plan. Your health care provider may choose to change dosage or frequency if you are prescribed one of these medications while taking Azathioprine:

• Adenovirus Vaccine, various types
• Alacepril
• Guerin Vaccine, Live
• Allopurinol
• Alfalfa
• Benazepril
• Bacillus of Calmette
• Captopril
• Black Cohosh
• Doxorubicin
• Cilazapril
• Enalapril Maleate
• Enalaprilat
• Influenza Virus Vaccine, Live
• Fosinopril
• Measles Virus Vaccine, Live
• Lisinopril
• Moexipril
• Mercaptopurine
• Mycophenolic Acid
• Mumps Virus Vaccine, Live
• Oxypurinol
• Olsalazine
• Perindopril
• Pentopril
• Quinapril
• Poliovirus Vaccine, Live
• Ribavirin
• Ramipril
• Rubella Virus Vaccine, Live
• Rotavirus Vaccine, Live
• Spirapril
• Smallpox Vaccine
• Sulfasalazine
• Sulfamethoxazole
• Typhoid Vaccine
• Trimethoprim
• Varicella Vaccine
• Zofenopril
• Trandolapril
• Yellow Fever Vaccine

Taking Azathioprine with the following medications increases the risks of some health risks, but could be unavoidable depending on your medical status. In that case, your doctor may alter your dosage amount, frequency or other instructions:

• Acenocoumarol
• Phenprocoumon
• Cyclosporine
• Warfarin

Consult your doctor to determine if certain foods or eating food at all with Azathioprine is recommended. Additionally, discuss use of alcoholic beverages, tobacco and illegal drugs and the possible effects on this medication.

These medical problems are known to affect the effectiveness and/or increase the risks associated with the treatment of Azathioprine. Make sure your doctor is aware of any conditions you have prior to treatment with this drug. These conditions include:

• Anemia
• Issues with bone marrow
• Inability to fight off infections
• Blood problems
• Bowel concerns such as vomiting, diarrhea or nausea
• Low white blood cells (known as Leukopenia)

Use of Azathioprine with the following medical conditions may worsen their symptoms or make the condition itself worse:

• Kidney disease
• Thrombocytopenia (low number of platelets)

Warnings

Before prescribing you Azathioprine, your doctor will discuss possible side effects and risks versus the benefits a treatment regime including this drug will give you. Prolonged use of Azathioprine requires regular office visits to your health provider to monitor undesired effects through blood and urine testing.

Do not use Azathioprine if you're pregnant as it can cause harm to the fetus. Use of a reliable birth control option is advised while being treated with Azathioprine. If it's possible that you've become pregnant while using Azathioprine, inform your health provider immediately.

Do not take Azathioprine in combination with the drug mercaptopurine, also known as Purinethol. Use of these two medications together could cause serious unwanted side effects.

If you are being treated for rheumatoid arthritis, make certain that your doctor knows if you currently or have in the past taken chlorambucil (Leukeran), cyclophosphamide (Cytoxan, Neosar) or melphalan (Alkeran) to treat your symptoms. Using these drugs in combination with Azathioprine may increase your risk for unwanted side effects, even if you are no longer taking the other drug. Talk to your doctor if you think of any questions with regard to these other drugs.

Azathioprine may increase your risk of getting certain types of cancer; specifically, risk is associated with lymphoma and other skin and lymph cancers as well as leukemia and other blood cancers. Talk to your health provider to determine the risks of cancer while taking Azathioprine.

Certain precautions may be taken to prevent development of skin cancer due to the increased risk posed by taking Azathioprine. It is recommended that patients on this treatment regimen use sunscreen or sunblock lotions with a sun protection factor (SPF) of at least 15 on a regular basis when going outside. Wear protective clothing including hats and stay out of direct sunlight during the hours of 10 a.m. and 3 p.m. Do not use tanning beds or sun lamps while under treatment with Azathioprine.

During your Azathioprine treatment and after you stop, it is important to avoid immunizations or vaccines without your doctor's approval. Azathioprine lowers your body's immune system, making vaccinations not work or, worse, infect you with the disease you're being inoculated for. Keep away from people in your household who receive live virus vaccines due to the risk that they could pass on the disease to you. Live vaccines include measles, mumps, influenza, poliovirus, rotavirus and rubella. Do not get physically close or stay in the same room with people who have had live vaccines for long periods of time. Direct any questions you have about this to your heal care provider.

Azathioprine will temporarily lower the white blood cells found in your body, which increases your chances of getting an infection. You may also have a lower number of blood platelets, which help your blood clot. For these reasons, take precautions while under treatment with Azathioprine to reduce the chances of dangerous bleeding or infection. People with infections of any kind should be avoided if possible. Consult your physician as soon as possible if you think you're coming down with an infection including symptoms of fever, pain or difficulty urinating, hoarseness, cough, chills, pain in the lower back or side. Notify your medical professional as soon as possible if unexpected bleeding or bruising occurs to any part of your body or if you observe stools that are black or tarry, blood in your stool or in your urine or small reddish spots on your skin. Use caution when performing oral hygiene with floss, toothpick or a toothbrush. Consult your doctor or dentist on gentler ways to perform good oral hygiene while under treatment with Azathioprine. Make sure you consult your doctor prior to getting dental work performed. Keep your hands away from the eye and nose area unless you have just washed your hands and haven't touched anything else since washing. Take care not to cut yourself when you are using a razor or nail clippers or cooking or other situations involving sharp objects. Do not participate in dangerous sports or other activities where you may be at risk for injury or bruising.

While being treated with Azathioprine, your risk of developing a serious brain infection called progressive multifocal leukoencephalopathy is higher. Avoid being people who are sick or who have infections while you are on this drug. Wash your hands often. Inform your doctor of any infection you may have before you begin treatment with Azathioprine. If you've ever had an infection that would not go away or that recurred, make sure your doctor is informed of this.

If you experience more than one of these symptoms while you are on a treatment regimen that includes Azathioprine, inform your doctor right away:

• Severe nausea or vomiting
• Diarrhea
• Fever
• Rash
• General discomfort or illness
• Muscle or joint pain
• Lightheadedness or dizziness
• Unusual tiredness or weakness

These symptoms could mean that your bowel has had a serious reaction to Azathioprine, requiring immediate medical attention.

Do not combine this medicine with any others unless specifically prescribed by your doctor. This includes all prescription and non-prescription medications as well as vitamin, herbal and holistic therapies you may take.

Storage

Azathioprine should be stored out of sight and reach of children and pets in the original container, kept closed for safety. Keep doses of this medication at room temperature and away from heat, moisture and light. Do not allow this medication to freeze.

Should you have expired Azathioprine or doses that you don't use, check with your physician or pharmacist on the safest way to dispose of this medication, if required.

Summary

Azathioprine is an immunosuppressive agent drug that is often prescribed for treatment of patients who have undergone a kidney transplant as part of their anti-rejection medication therapy. Other autoimmune diseases have also been shown to respond to treatment with Azathioprine, with patients of rheumatoid arthritis being treated with this drug as well.

Due to the immunosuppressive effects of this drug, use of Azathioprine can lead to certain risks and side effects. The most common of these is nausea or vomiting and swollen joints, which do not typically require medical attention. If, however, patients determine that these symptoms are severe or also experience others such as black, tarry stools, abdominal or stomach cramps, fever, headaches or other symptoms, they should seek medical attention immediately.

Prolonged treatment with Azathioprine leads to increased risk of certain cancers of the skin and lymph system (lymphoma) and blood (leukemia). Regular office visits including blood and urine tests to determine any unwanted effects should be scheduled for the patient's benefit. Use of sunblock with a strength of at least SPF 15 on a regular basis is also recommended.

Risk of infections and bleeding are also factors and it is advised that patients being treated with Azathioprine avoid situations that could cause bruising, bleeding or other traumas. Avoid people who have infections or demonstrate signs of sickness. Also avoid any people you come in close contact with who have had a live vaccine.

Azathioprine may react with other drugs, so it is encouraged that you disclose any and all drug therapies including prescription, non-prescription, vitamin or holistic treatments to your doctor before beginning a course of treatment with Azathioprine. Disclosure of your full medical history is also advised.

Store Azathioprine in medication its original, closed packaging at room temperature and out of sight and reach of children and pets. Do not expose this medication to heat, light or moisture and keep it from freezing. Dispose of unused or expired Azathioprine per your doctor or pharmacist's instructions on safe disposal.