Imuran 50 mg Tablets

Brand Name

Imuran is the established brand name under which this medication is distributed, highly regarded in medical circles for its role in managing immune-related conditions. It has become a cornerstone therapy for clinicians addressing specific autoimmune and transplant-related disorders.

International Nonproprietary Name (INN)

The active component of this drug is identified by its International Nonproprietary Name (INN) as azathioprine. This purine analogue is meticulously designed to exert immunosuppressive effects within the body’s complex immune system.

Forms of Release

Imuran is primarily available as film-coated tablets in strengths of 25 mg and 50 mg, tailored for oral administration to suit a range of patient needs. Additionally, an injectable powder for reconstitution is offered at 100 mg per vial, intended for intravenous use in acute or hospital settings where oral intake is impractical. These formulations ensure versatile delivery of azathioprine, accommodating both chronic maintenance and urgent therapeutic requirements.

Composition

The principal active ingredient in Imuran is azathioprine, which underpins its immunosuppressive capabilities. Alongside this key substance, the tablets include several inactive components to enhance stability and ease of use. These consist of lactose monohydrate, corn starch, and magnesium stearate as fillers and lubricants, with a coating of hypromellose and polyethylene glycol for protection and appearance. The injectable form contains azathioprine sodium, sterile for reconstitution with sodium chloride or water for injection. These supporting elements collectively maintain the drug’s integrity and facilitate its administration across its various applications.

Pharmacologic Properties

Pharmacodynamics

This medication influences the body by modulating the immune system’s activity. Azathioprine acts as a prodrug, rapidly metabolized into 6-mercaptopurine (6-MP), which disrupts purine synthesis—a critical process for DNA and RNA production in rapidly dividing cells like lymphocytes. By inhibiting this pathway, it suppresses the proliferation of T- and B-cells, key players in immune responses, thereby reducing inflammation and preventing rejection in organ transplants. It also interferes with adenine and guanine nucleotide formation, further dampening immune activation. This targeted suppression alleviates symptoms in autoimmune diseases and supports graft survival, offering a balanced approach to immune regulation.

Pharmacokinetics

The pharmacokinetic profile of Imuran outlines how azathioprine is processed within the body. After oral administration, it is absorbed variably from the gastrointestinal tract, with bioavailability ranging from 27% to 83%, peaking in plasma within 1 to 2 hours, minimally affected by food. Intravenous delivery achieves immediate levels. It is 30% bound to plasma proteins, distributing widely with a volume of approximately 0.8 L/kg, crossing into tissues including the placenta. Metabolism occurs primarily in the liver and erythrocytes via xanthine oxidase and thiopurine methyltransferase (TPMT), producing active 6-MP and inactive metabolites. Excretion is predominantly renal (50% as metabolites), with a half-life of 3 to 5 hours for azathioprine, though active metabolites persist longer, necessitating careful monitoring in organ dysfunction.

Indications for Use

This medication is prescribed for conditions involving excessive immune activity or transplant management, harnessing its capacity to temper immune responses across diverse clinical scenarios.

Diseases and Conditions

Imuran is indicated for preventing organ rejection in adult renal transplant recipients, used alongside other immunosuppressants to maintain graft function. It is also approved for severe rheumatoid arthritis in adults unresponsive to conventional therapies, reducing joint inflammation and damage. Additional uses include managing active Crohn’s disease and ulcerative colitis, mitigating flares in these inflammatory bowel diseases. Its immunosuppressive action makes it a critical tool for these autoimmune and transplant-related challenges.

Contraindications

While effective for many, certain conditions render this medication unsuitable due to significant risks, requiring thorough evaluation prior to initiation.

Conditions Prohibiting Use

Imuran is contraindicated in patients with known hypersensitivity to azathioprine or 6-mercaptopurine, as reactions could range from mild rashes to severe anaphylaxis. It is prohibited in individuals with severe infections or active malignancy (except in transplant contexts), given its immunosuppressive effects heightening these risks. Patients with severe hepatic or bone marrow dysfunction, such as cirrhosis or aplastic anemia, should avoid it due to potential toxicity exacerbation. It is also barred in pregnant women unless benefits outweigh fetal risks, and in those with TPMT deficiency without dose adjustment, ensuring safety in vulnerable populations.

Method of Administration and Dosage

How to Take

This medication is administered orally as tablets or intravenously, depending on the form. Tablets should be swallowed whole with ample water, preferably on an empty stomach to optimize absorption, though with food if gastrointestinal upset occurs. The injectable form is reconstituted and given as an IV infusion over 30–60 minutes in a clinical setting, avoiding bolus injection. Consistent timing—once or twice daily—supports steady levels, and patients should adhere to prescribed methods to maintain therapeutic efficacy.

Dosages for Adults and Children

Dosing varies by indication and patient, with pediatric use established for certain conditions. For renal transplantation in adults, Imuran starts at 3–5 mg/kg/day IV or orally on day one, tapering to 1–3 mg/kg/day for maintenance. In rheumatoid arthritis, adults begin at 1 mg/kg/day (50–100 mg), increasing by 0.5 mg/kg every 4–8 weeks to 2–3 mg/kg/day if needed. For inflammatory bowel disease, 1.5–2.5 mg/kg/day is typical. Children (e.g., transplant or autoimmune) follow similar weight-based dosing (1–3 mg/kg/day), adjusted for response and tolerability, with close monitoring due to higher sensitivity.

Dose Adjustment in Specific Conditions

Adjustments are essential in renal or hepatic impairment. In mild to moderate renal dysfunction (creatinine clearance 30–80 mL/min), doses are reduced by 25–50% (e.g., 0.75–2 mg/kg/day), with severe cases (below 30 mL/min) requiring further cuts or avoidance. Moderate hepatic impairment lowers doses to 0.5–1.5 mg/kg/day, with severe cases contraindicating use. TPMT deficiency necessitates 10–50% of standard doses, guided by genetic testing, while elderly patients may start at 1 mg/kg/day, with careful oversight for toxicity, balancing efficacy and safety.

Side Effects

This medication can provoke a range of adverse reactions, from mild to severe, and patients should be informed to ensure timely management.

Possible Adverse Reactions

Common effects include nausea, vomiting, or loss of appetite, often gastrointestinal in nature and transient. Bone marrow suppression—manifesting as leukopenia, thrombocytopenia, or anemia—occurs frequently, requiring blood count monitoring. Infections, from mild respiratory issues to severe opportunistic ones, rise due to immunosuppression. Liver enzyme elevations or rare hepatitis signal hepatotoxicity, while skin rashes or alopecia affect some users. Pancreatitis, interstitial lung disease, or malignancy risk (e.g., lymphoma) are rare but serious, with regular follow-ups critical to mitigate these outcomes.

Overdose

Symptoms of Overdose

Excessive intake of Imuran can trigger significant symptoms needing urgent care. These include severe nausea, vomiting, or diarrhea from gastrointestinal overload, alongside profound fatigue or pallor from bone marrow suppression. Infections or bleeding may emerge rapidly, with fever, bruising, or petechiae as signs. Liver dysfunction (jaundice, dark urine) or neurological effects (confusion, lethargy) could occur in extreme cases, highlighting the need for swift intervention.

First Aid Measures

In an overdose scenario, immediate action is vital. If the patient is conscious and ingestion was recent, contact emergency services or poison control without inducing vomiting unless advised. Maintain airway and vital signs while awaiting help. In medical settings, gastric lavage or activated charcoal may be used within an hour of ingestion to limit absorption, followed by supportive care—IV fluids, blood transfusions, or antibiotics as needed. Hemodialysis is ineffective due to rapid metabolism, but monitoring and symptom management are key.

Drug Interactions

Effects on Other Medications

This medication can alter co-administered drugs via metabolic interactions. It enhances toxicity of allopurinol by inhibiting xanthine oxidase, requiring allopurinol dose reductions (25% of normal). Warfarin efficacy may decrease, needing adjustments, while ACE inhibitors or co-trimoxazole heighten marrow suppression risks. Ribavirin co-use increases 6-MP toxicity, necessitating caution. Monitoring ensures safe combination therapy.

Compatibility with Alcohol and Food

Alcohol should be avoided with Imuran, as it exacerbates hepatotoxicity and gastrointestinal risks. Food may reduce absorption slightly, but taking it with meals can ease nausea, with no strict dietary limits beyond avoiding hepatotoxins. Consistency aids tolerability.

Special Precautions

Use During Pregnancy and Breastfeeding

This medication is Category D, used in pregnancy only if benefits outweigh risks due to teratogenicity (e.g., limb defects), with contraception required. Azathioprine enters breast milk; breastfeeding is discouraged due to immunosuppression risks in infants, with alternatives preferred.

Impact on Driving and Operating Machinery

Imuran may impair alertness due to fatigue or dizziness, especially early in use. Patients should avoid driving or machinery until they assess its effects, prioritizing safety.

Considerations for Elderly and Pediatric Patients

In elderly patients, this drug requires cautious dosing (e.g., 1 mg/kg/day) due to increased infection and marrow risks, with frequent monitoring. In children over 1 year, it’s used for transplants or autoimmune conditions (1–3 mg/kg/day), with close oversight for growth and toxicity, ensuring tailored care.