In 1968 the Food and Drug Administration approved Azopi for use after an organ transplant to decrease the chance of the body rejecting the transplanted organ. However, Azopi is an experimental drug that can be used during treatment of cancers such as leukemia and lymphomas. In the body, Azopi is converted to mercaptopurine (6-MP) and thus has the same effects as that chemotherapy drug. They both are purine analogs that interfere with the metabolism of purine-based nucleotides found in DNA.
The use of Azopi results in killing cells such as T-lymphocytes. This is important in cancers such as lymphocytic leukemia. The idea is that if T-lymphocyte reproduction is inhibited by interfering with DNA synthesis, then the cancer cell reproduction will also be inhibited. Certain types of leukemia and lymphomas are treated with radiation and chemotherapy, which destroy dividing cells such as those in the bone marrow. As a result, the patient is no longer able to produce blood cells. To combat the loss of blood cells, a bone marrow transplant may be performed to provide the patient with healthy marrow. The body may react against the foreign bone marrow. Therefore, an additional benefit of Azopi use as an immunosuppressant could be to produce fewer white blood cells, thus interfering with the body's natural immune response to foreign proteins, such as those found on the cell surfaces of bone marrow coming from a bone marrow donor.
The dose of Azopi tablets required to prevent rejection and minimize toxicity will vary with individual patients; this necessitates careful management. The initial dose is usually 3 to 5 mg/kg daily, beginning at the time of transplant. Azopi 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. The dose of Azopi tablets should not be increased to toxic levels because of threatened rejection. Discontinuation may be necessary for severe hematologic or other toxicity, even if rejection of the homograft may be a consequence of drug withdrawal.
Azopi tablets, USP are indicated as an adjunct for the prevention of rejection in renal homotransplantation. Experience with over 16,000 transplants shows a 5-year patient survival of 35% to 55%, but this is dependent on donor, match for HLA antigens, anti-donor or anti-B-cell alloantigen antibody, and other variables. The effect of Azopi tablets on these variables has not been tested in controlled trials.
Azopi is an immunosuppressive antimetabolite. Each uncoated Azopi tablet intended for oral administration contains 25 mg or 75 mg or 100 mg of Azopi. In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, povidone and starch.
Azopi is chemically 6-[(1-methyl-4-nitro-1 H -im >H -purine. The structural formula of Azopi is:
Taking other medicines
Azopi can interact with medications used to treat gout, such as allopurinol and febuxostat. It’s also known to interact with some medications used to control high blood pressure, such as warfarin. So make sure to discuss what medications you’re on with your rheumatology team, as they might suggest starting you on an alternative DMARD.
Check with your doctor or pharmacist before starting any new medications. And remember to mention you’re on Azopi if you’re treated by anyone other than your usual rheumatology team.
You can carry on taking a non-steroidal anti-inflammatory drug (NSAID) or painkillers if needed, unless your doctor advises otherwise.
Don’t take over the counter preparations or herbal remedies without discussing this first with your doctor or pharmacist as some of them could react badly with Azopi.
Azopi carries a black-box warning because it may increase your risk of developing certain cancers such as lymphoma, leukemia, and skin cancer.
However, if you have a kidney transplant, you may be at a higher risk for developing cancer even if you don't take Azopi.
Tell your doctor if you've ever had cancer or if you've ever taken any of the following drugs:
Avoid unnecessary exposure to sunlight to decrease your risk of skin cancer while taking Azopi. You should wear protective clothing, sunglasses, and sunscreen when outdoors.
Some teenagers and young males who took this drug alone or with another medicine known as a tumor necrosis factor (TNF) blocker to treat Crohn's disease or ulcerative colitis developed a serious type of cancer called hepatosplenic T-cell lymphoma (HSTCL).
Azopi is not approved by the FDA to treat Crohn's or ulcerative colitis, but some doctors may prescribe the medicine off-label.
You should call your doctor immediately if you are taking the drug for Crohn's or ulcerative colitis and experience the following symptoms:
- Unexplained weight loss
- Stomach pain or tenderness
- Night sweats
- Easy bleeding or bruising
Azopi may also cause a decrease in blood cells in your bone marrow, which can lead to serious or life-threatening infections.
Certain medicines may also increase this risk when taken with Azopi. Tell your doctor if you are taking:
You should also call your doctor immediately if you experience any of the following symptoms:
- Pale skin
- Excessive fatigue
- Fast heartbeat
- Shortness of breath
- Difficulty sleeping
- Sore throat
- Other signs of an infection
Your health care provider will probably order tests to check your blood cells and liver enzymes during your treatment with Azopi.
Tell your doctor if you are allergic to Azopi or any other medications.
This medicine controls symptoms of rheumatoid arthritis, but it doesn't cure it. It might take up to 12 weeks before you feel the full benefits.
Don't stop taking Azopi without first talking to your doctor.
You should tell your doctor you are taking this drug before having any type of surgery, including a dental procedure.
Don't have any vaccinations during or after your treatment with Azopi without first talking to your healthcare provider.
Before taking this medicine, tell your doctor if you have or have had:
- Any type of infection
- Kidney disease
- Liver disease
- Any blood disorder
- TPMT deficiency (an enzyme disorder)
Leukopenia and/or thrombocytopenia are dose-dependent and may occur late in the course of therapy with Azopi tablets. Dose reduction or temporary withdrawal may result in reversal of these toxicities. Infection may occur as a secondary manifestation of bone marrow suppression or leukopenia, but the incidence of infection in renal homotransplantation is 30 to 60 times that in rheumatoid arthritis. Anemias, including macrocytic anemia and/or bleeding have been reported.
TPMT genotyping or phenotyping can help >CLINICAL PHARMACOLOGY, WARNINGS and PRECAUTIONS: Laboratory Tests). Death associated with pancytopenia has been reported in patients with absent TPMT activity receiving Azopi. 6, 20
There are medications and other medical conditions that can interact with Azopi. A medication called allopurinol is used to treat gout and can increase the effects and toxicity of Azopi because it interferes with the removal of Azopi from the body.
Both kidney disease and liver disease can increase the effects and toxicity of Azopi. Both diseases interfere with the removal of Azopi from the body. If the patient has either of these diseases, the physician may make adjustments in the dosage given.
Sally C. McFarlane-Parrott