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Generic Azathioprine ( Azathioprine )
Azathioprine
| Active ingredient | Azathioprine |
|---|---|
| Mechanism of action | Converted to 6-mercaptopurine; inhibits de novo purine synthesis |
| Common dose | Typically 1-3 mg/kg per day (adjusted for kidney function) |
| What is it used for? | Autoimmune diseases (e.g., rheumatoid arthritis, inflammatory bowel disease) and organ-transplant immunosuppression |
| Important information on taking | Take with food; monitor blood counts and liver enzymes regularly |
| Common side effects | Nausea, diarrhea, hepatotoxicity, opportunistic infections |
| Serious risks | Bone-marrow suppression, severe infections, malignancy (e.g., lymphoma) |
| Interactions | Allopurinol, other immunosuppressants, certain antivirals |
| Contraindications | Hypersensitivity to azathioprine or its metabolites; pregnancy or breastfeeding without specialist guidance |
| Legal status | Prescription-only medication in most jurisdictions |
Understanding Azathioprine and its purpose
Definition, therapeutic role, and mechanism of action of Azathioprine
Azathioprine is a synthetic purine analog that functions as a prodrug of 6-mercaptopurine. It is administered to suppress excessive immune activity in conditions such as organ transplant rejection and autoimmune diseases. After oral ingestion the drug is metabolized by hepatic enzymes to the active metabolite 6-mercaptopurine which is then converted to thio-inosinic acid within lymphocytes. Thio-inosinic acid inhibits de novo purine synthesis by antagonizing the activity of xanthine oxidase and by being incorporated into dna and rna leading to cytotoxicity in proliferating cells. The resulting depletion of guanine nucleotides impairs nucleic acid synthesis and prompts apoptosis of overactive immune cells. This targeted reduction of lymphocyte proliferation translates into the therapeutic effect of preventing graft rejection and modulating autoimmune pathology.
Pharmacological characteristics of Azathioprine
Azathioprine is an immunosuppressive medication used primarily to prevent organ transplant rejection and to treat certain autoimmune diseases. It belongs to the class of purine analogues that interfere with dna and rna synthesis in rapidly dividing immune cells. After oral administration the drug is converted by the hepatic pathway into 6-mercaptopurine which then is metabolized to active thioguanine nucleotides. These active metabolites inhibit several steps in purine biosynthesis leading to reduced proliferation of t lymphocytes. The suppression of t-cell activity modulates immune responses and helps maintain graft tolerance or diminish inflammatory attacks. Pharmacokinetically Azathioprine exhibits moderate oral absorption and a variable half-life influenced by individual metabolism. Genetic polymorphisms in the thiopurine methyltransferase enzyme can affect the clearance of the drug and its therapeutic efficacy. Overall it functions as a prodrug that ultimately limits immune cell activation through depletion of guanine nucleotides needed for nucleic acid synthesis.
Conditions treated with Azathioprine
| Inflammatory bowel disease (ulcerative colitis) | Azathioprine 2 mg/kg per day, divided 2-3 times, typically 6-12 months |
|---|---|
| Crohn's disease | Azathioprine 150-200 mg per day, usually 1-2 times, maintenance for 1-2 years |
| Organ transplantation (immunosuppression) | Azathioprine 50-150 mg per day, once or twice daily, lifelong adjunct therapy |
Side effects of Azathioprine
Side effects of Azathioprine
Azathioprine is sometimes prescribed to modulate the immune system. Common side effects include nausea, vomiting and mild liver enzyme elevation. Some individuals may experience skin rashes or itching without an allergic reaction. Blood cell counts can decrease leading to increased susceptibility to infections. Elevated uric acid levels may cause gout-like joint discomfort in certain patients. Regular monitoring of kidney function is recommended because the drug can affect renal clearance.
Essential considerations before taking Azathioprine
Azathioprine can cause nausea and vomiting in some patients. It may lower white blood cell counts increasing infection risk. The drug can affect liver function leading to elevated enzymes. Some individuals experience skin rash or itching as a reaction. Rarely it may cause pancreatitis requiring medical attention. Long term use has been linked to a slight increase in malignancy risk. Patients are monitored regularly for blood work and organ function.
Frequently observed responses to Azathioprine
- Nausea
- Vomiting
- Diarrhea
- Myelosuppression
- Rash
Azathioprine remains a cornerstone immunosuppressive agent for conditions such as organ transplantation, autoimmune hepatitis, and inflammatory bowel disease, offering reliable disease-modifying effects when used judiciously. Its efficacy is balanced by a well-characterized risk of bone-marrow suppression, hepatotoxicity, and increased susceptibility to infections, particularly in patients with pre-existing liver disease or concomitant myelosuppressive therapy. Regular complete blood-count monitoring, liver enzyme checks, and renal function assessments are essential during the first six months of treatment to detect adverse changes early. Patients should be counseled to report any unexplained fever, persistent sore throat, easy bruising, or jaundice promptly, as these may signal serious marrow or hepatic complications. Because Azathioprine is a prodrug metabolized by the enzyme tpmt, genetic testing or enzymatic activity screening can identify individuals at high risk for severe myelosuppression, allowing dose adjustments before therapy begins. Concomitant use with allopurinol dramatically raises Azathioprine levels and must be avoided unless dose reduction is carefully planned. Finally, prospective users should discuss vaccination status, pregnancy plans, and alternative therapies with their healthcare provider to ensure that the benefits of immunosuppression outweigh the potential risks in their unique clinical context.
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