Азатиоприн
Азатиоприн Uses, Dosage, Side Effects, Food Interaction and all others data.
Азатиоприн antagonizes purine metabolism and may inhibit synthesis of DNA, RNA, and proteins. It may also interfere with cellular metabolism and inhibit mitosis. Its mechanism of action is likely due to incorporation of thiopurine analogues into the DNA structure, causing chain termination and cytotoxicity.
Азатиоприн is an immunosuppressive agent which functions through modulation of rac1 to induce T cell apoptosis, as well as other unknown immunosuppressive functions. It has a long duration of action as it is given daily, and has a narrow therapeutic index. Patients should be counselled regarding the risk of malignancies of the skin and lymphomas.
| Trade Name | Азатиоприн |
| Availability | Prescription only |
| Generic | Azathioprine |
| Azathioprine Other Names | Azamun, Azathioprine, Azathioprinum, Azatioprina |
| Related Drugs | Entyvio, Humira, Stelara, Gilenya, Tysabri, Zeposia, Colazal, Vumerity, aspirin, prednisone |
| Type | |
| Formula | C9H7N7O2S |
| Weight | Average: 277.263 Monoisotopic: 277.038193193 |
| Protein binding | Azathioprine is 30% bound to proteins such as human serum albumin in circulation. |
| Groups | Approved |
| Therapeutic Class | Cytotoxic immunosuppressants |
| Manufacturer | |
| Available Country | Russia |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Азатиоприн is used for an adjunct for the prevention of rejection in renal homotransplantation. It is also used for the management of active rheumatoid arthritis to reduce signs and symptoms.
Renal Homotransplantation: Азатиоприн is used for 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 Азатиоприн on these variables has not been tested in controlled trials.
Rheumatoid Arthritis: Азатиоприн is used for the treatment of active rheumatoid arthritis (RA) to reduce signs and symptoms. Aspirin, non-steroidal anti-inflammatory drugs and/or low dose glucocorticoids may be continued during treatment with Азатиоприн. The combined use of Азатиоприн with disease modifying anti-rheumatic drugs (DMARDs) has not been studied for either added benefit or unexpected adverse effects. The use of Азатиоприн with these agents cannot be recommended.
Азатиоприн is also used to associated treatment for these conditions: Atopic Dermatitis (AD), Crohn's Disease (CD), Disseminated Sclerosis, Immune Thrombocytopenia, Kidney Transplant Rejection, Nephritis, Lupus, Pericarditis, Psoriasis, Rheumatoid Arthritis, Uveitis
How Азатиоприн works
Азатиоприн's mechanism of action is not entirely understood but it may be related to inhibition of purine synthesis, along with inhibition of B and T cells.
6-thioguanine triphosphate, a metabolite of azathioprine, modulates activation of rac1 when costimulated with CD28, inducing T cell apoptosis. This may be mediated through rac1's action on mitogen-activated protein kinase, NF-kappaB.
Dosage
Азатиоприн dosage
Renal Homotransplantation: The dose of Азатиоприн 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. Азатиоприн is 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 Азатиоприн 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 thehomograftmay be a consequence of drug withdrawal.
Rheumatoid Arthritis: Азатиоприн is usually given on a daily basis. 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; an adequate trial should be a minimum of 12 weeks. Patients not improved after 12 weeks can be considered refractory. Азатиоприн may be continued long-term in patients with clinical response, but patients should be monitored carefully, and gradual dosage reduction should be attempted to reduce risk of toxicities.
Maintenance therapyshould be at the lowesteffective 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. The optimum duration of maintenance Азатиоприн has not been determined. Азатиоприн can be discontinued abruptly, but delayed effects are possible.
Side Effects
Opportunistic infections especially in transplant patients receiving concomitant other immunosuppressants. Bone marrow depression, leucopenia, thrombocytopenia, nausea. Uncommonly, anaemia, hypersensitivity reactions, cholestasis, pancreatitis.
Toxicity
The oral LD50 in mice is 2500mg/kg and in rats is 400mg/kg.
Patients experiencing an overdose may present with bone marrow hypoplasia, bleeding, and infection, which may progress to death. Patients should be treated with supportive and symptomatic treatments. 8 hour hemodialysis may remove 45% of a dose from serum.
Precaution
Monitor FBC wkly during 1st 8 wk of therapy especially with high dose or severe renal/hepatic impairment. Inherited deficiency of thiopurine methyltransferase enzyme. Avoid excessive sun/UV exposure.
Interaction
Metabolism inhibited by allopurinol. Reduces the neuromuscular blockade of curare, tubocurarine but potentiates that of succinylcholine.
Food Interaction
- Take with food. Food reduces irritation.
Азатиоприн Drug Interaction
Major: adalimumab, adalimumabUnknown: aspirin, aspirin, duloxetine, duloxetine, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, pregabalin, pregabalin, esomeprazole, esomeprazole, hydroxychloroquine, hydroxychloroquine, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol
Азатиоприн Disease Interaction
Major: bone marrow depression, infections, renal dysfunctionModerate: liver disease
Volume of Distribution
Data regarding the volume of distribution of azathioprine is not readily available.
Elimination Route
Oral azathioprine is well absorbed, with a Tmax of 1-2h. Further data regarding the absorption of azathioprine is not readily available.
Half Life
The half life of azathioprine is approximately 5 hours.
Clearance
Data regarding the clearance of azathioprine is not readily available.
Elimination Route
Азатиоприн and mercaptopurine are not detectable in urine after 8 hours. Further data regarding the route of elimination of azathioprine are not available.
Pregnancy & Breastfeeding use
Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk
Contraindication
Азатиоприн should not be used for treating rheumatoid arthritis in pregnant women.Patients with rheumatoid arthritis previously treated with alkylating agents (cyclophosphamide, chlorambucil, melphalan, or others) may have a prohibitive risk of malignancy if treated with Азатиоприн
Special Warning
Use In Renal Dysfunction: Relatively oliguric patients, especially those with tubular necrosis in the immediate postcadaveric transplant period, may have delayed clearance of Азатиоприн or its metabolites, may be particularly sensitive to this drug, and are usually given lower doses. Procedures for proper handling and disposal of this immunosuppressive antimetabolite drug should be considered. Several guidelines on this subject have been published.25-31 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
Storage Condition
Азатиоприн should be stored at 15 to 25° C in a dry place and protected from light.
Innovators Monograph
You find simplified version here Азатиоприн
Азатиоприн contains Azathioprine see full prescribing information from innovator Азатиоприн Monograph, Азатиоприн MSDS, Азатиоприн FDA label
FAQ
What are the side effects of taking Азатиоприн?
- Increased stomach irritation, abdominal pain.
- Nausea and vomiting.
- Changes in hair color and texture, along with hair loss.
- Loss of appetite.
- Blood in the urine or stool.
- Unusual bruising.
- Fatigue.
- Development of mouth sores and ulcers.
Why is Азатиоприн bad for you?
This is the most serious warning from the Food and Drug Administration (FDA). A black box warning alerts doctors and patients about drug effects that may be dangerous. Long-term use of Азатиоприн may increase your risk of developing certain types of cancer, such as lymphoma, leukemia, and skin cancers.
Is Азатиоприн a steroid?
Азатиоприн is often referred to as a “steroid sparing agent” or “immunomodulator”. It allows the dose of steroids to be kept to a minimum and eventually stop. Азатиоприн is also used in other groups of patients including those with organ transplants, rheumatoid arthritis and psoriasis.
What are the long term effects of Азатиоприн?
The main theoretical risks of prolonged use would be the myelotoxicity, hepatotoxicity, and the development of cancer. In fact, serious bone marrow suppression or serious liver damage are uncommon, and can be minimized with proper use of the drug.
Does Азатиоприн make me tired?
Some people can have serious side effects when taking Азатиоприн. Stop taking your medicine and contact your specialist or a doctor immediately if: you feel tired all the time, dizzy or sick, or you are vomiting or have diarrhoea. you have a high temperature with shivering or chills, cough or a sore throat.
What is the best time of day to take Азатиоприн?
Азатиоприн is best taken on an empty stomach, at least 1 hour before or 3 hours after food or milk. But, if you find that Азатиоприн makes you feel nauseous or sick, or gives you stomach upset, try taking your Азатиоприн dose after food or at bedtime, or ask if you can divide your dose and take it twice a day.
What is the alternative to Азатиоприн?
Methotrexate is an alternative to azathioprine in neuromyelitis optica spectrum disorders with aquaporin-4 antibodies.
Can you take vitamin D with Азатиоприн?
No interactions were found between Азатиоприн and Vitamin D3.
Does Азатиоприн make me gain weight?
No, Азатиоприн itself is not causing your weight gain. Perhaps the drug is sufficiently controlling the disease to allow for more complete food absorption. If you're concerned about your weight, note that most weight reduction diets are well-tolerated in Crohn's disease patients.
What drugs interact with Азатиоприн?
Some products that may interact with this drug are: febuxostat, past or present use of certain cancer drugs (such as cyclophosphamide, melphalan), other drugs that weaken the immune system/increase the risk of infection (such as rituximab, tofacitinib). Azathioprine is very similar to mercaptopurine.
Does Азатиоприн lower my immune system?
Азатиоприн weakens your body's immune system, to help keep it from "rejecting" a transplanted organ such as a kidney. Organ rejection happens when the immune system treats the new organ as an invader and attacks it. Азатиоприн is used to prevent your body from rejecting a transplanted kidney.
Can Азатиоприн affect eyes?
Азатиоприн affects the way the body's immune system works, which can make you more likely to catch infections. Chicken pox or shingles can affect the eye, so if you develop either of these you should report to your doctor immediately.
How long does it take for Азатиоприн to start working?
It can take up to 8-12 weeks after you start taking Азатиоприн for you to see improvement in your arthritis. Blood work will have to be done every 4-8 weeks to monitor your blood counts. If you are pregnant or considering having a child, discuss this with your doctor before beginning this medication.
Does Азатиоприн affect fertility?
The immunosuppressive drugs Азатиоприн have not been shown to affect fertility.
Can Азатиоприн cause liver damage?
Азатиоприн can also cause an acute, clinically apparent liver injury that is typically cholestatic. This complication is uncommon but not rare, occurring in approximately one in a thousand treated patients.
How to start Азатиоприн?
Азатиоприн is usually given as tablets, taken once or twice daily. They should be swallowed whole and taken with or after food. Your doctor will advise you about the correct dose, which will depend on how much you weigh. But you'll usually start on a low dose of about 50mg, your doctor may increase this if necessary.
Why is Азатиоприн cytotoxic?
The cytotoxicity of Азатиоприн is due, in part, to the incorporation of 6-TGN into DNA. 6-MP undergoes two major inactivation routes (Figure 1). One is thiol methylation, which is catalyzed by the enzyme thiopurine S-methyltransferase (TPMT), to form the inactive metabolite methyl-6-MP (6-MeMP).
