Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
AZATHIOPRINE SODIUM vs ASTAGRAF XL
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Azathioprine is a prodrug of 6-mercaptopurine. It inhibits purine synthesis by interfering with the synthesis of DNA, RNA, and cellular proteins, thereby suppressing immune responses.
Calcineurin inhibitor that binds to FKBP-12, forming a complex that inhibits calcineurin, thereby preventing dephosphorylation and nuclear translocation of NFAT, which reduces T-cell activation and cytokine production (e.g., IL-2).
Renal transplantation (adjunctive immunosuppression),Rheumatoid arthritis (active, severe, not responsive to conventional therapy),Off-label: Inflammatory bowel disease (Crohn's disease, ulcerative colitis), autoimmune hepatitis, systemic lupus erythematosus, vasculitis, myasthenia gravis, pemphigus vulgaris
Prophylaxis of organ rejection in kidney transplant recipients,Prophylaxis of organ rejection in liver transplant recipients,Prophylaxis of organ rejection in heart transplant recipients
1-2 mg/kg/day IV or oral, initially; maintenance 0.5-1 mg/kg/day IV or oral. For severe organ rejection: 3-5 mg/kg/day IV.
Initial oral dose of 0.1-0.15 mg/kg/day divided every 12 hours, with subsequent adjustments based on trough levels. Typical maintenance dose 0.05-0.15 mg/kg/day.
Terminal elimination half-life of azathioprine is approximately 3-5 hours; its active metabolite 6-mercaptopurine has a half-life of 0.5-1.5 hours. However, the pharmacodynamic effect (immunosuppression) persists longer due to intracellular accumulation of thioguanine nucleotides.
Terminal elimination half-life is approximately 43 hours (range 15.8–68.6 hours) in adult kidney transplant recipients. This long half-life supports once-daily dosing. In liver transplant patients, half-life ranges from 12 to 42 hours.
Primarily metabolized by xanthine oxidase (XO) and thiopurine methyltransferase (TPMT) to active and inactive metabolites. Also metabolized by aldehyde oxidase and glutathione S-transferase. Concomitant use with allopurinol (XO inhibitor) requires dose reduction.
Primarily hepatic via CYP3A4 and CYP3A5; undergoes extensive first-pass metabolism. Substrate of P-glycoprotein.
Primarily renal: approximately 50% as unchanged drug and metabolites (6-mercaptopurine, thiouric acid) within 24 hours. Biliary/fecal excretion accounts for minor fraction (<5%).
Primarily fecal (94.6%) via biliary elimination. Renal excretion accounts for approximately 2.4% of the dose, mainly as metabolites. Less than 1% is excreted unchanged in urine.
Approximately 30% bound to serum proteins, primarily albumin.
Approximately 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Apparent volume of distribution is 0.6-1.0 L/kg, indicating distribution into total body water and tissues.
Volume of distribution is 3.5–4.5 L/kg (wide distribution, indicating extensive tissue binding). High Vd reflects distribution into erythrocytes, lymphocytes, and tissues.
Oral bioavailability of azathioprine is approximately 60-70% (range 27-82%) due to first-pass metabolism. Intravenous administration yields 100% bioavailability.
Oral bioavailability is highly variable, approximately 20–30% (range 5–89%). Absorption is incomplete and inconsistent; food decreases absorption by up to 33%. The modified-release formulation (Astagraf XL) has a lower peak and more sustained absorption compared to immediate-release.
GFR 50-80 m L/min: no adjustment. GFR 30-50 m L/min: reduce dose by 25% to 50%. GFR 10-30 m L/min: reduce dose by 50% to 75%. GFR <10 m L/min: avoid or use with extreme caution.
For GFR <30 m L/min: reduce dose by 50% and monitor trough levels closely. No adjustment for GFR >30 m L/min.
Child-Pugh class A: no adjustment. Child-Pugh class B: reduce dose by 50%. Child-Pugh class C: avoid use.
Child-Pugh Class A: no adjustment. Class B: reduce dose by 25%. Class C: reduce dose by 50% and monitor trough levels frequently.
2-5 mg/kg/day IV or oral, divided every 12-24 hours; dose based on body weight (mg/kg).
Initial oral dose 0.15-0.2 mg/kg/day divided every 12 hours. Adjust to target trough levels of 5-15 ng/m L. Maximum dose 0.3 mg/kg/day.
Start at lower end of dosing range; monitor renal function and adjust accordingly. Consider reduced initial dose (e.g., 1 mg/kg/day) due to age-related decreased renal function.
Start at lower end of adult dosing range (0.05 mg/kg/day) and titrate slowly due to reduced renal function and increased risk of adverse effects. Monitor trough levels closely.
MALIGNANCY: Immunosuppression increases risk of lymphoma and other malignancies, particularly skin cancers. Monitor for neoplasia, especially in renal transplant patients.
Increased susceptibility to infection and possible development of lymphoma and other malignancies, particularly of the skin, due to immunosuppression. Increased nephrotoxicity, especially when used with other nephrotoxic drugs.
Hematotoxicity (leukopenia, thrombocytopenia, anemia) - monitor CBC. Hepatotoxicity - monitor liver function tests. Increased infection risk. Pancreatitis. Hypersensitivity reactions. Increased risk of malignancy (skin cancer, lymphoma). Use with caution in renal/hepatic impairment. Test for TPMT deficiency before use.
Nephrotoxicity, neurotoxicity (tremor, headache, seizures), hypertension, hyperkalemia, hyperglycemia, increased risk of infections and malignancies (especially skin), and lymphoproliferative disorders. Monitor blood pressure, renal function, electrolytes, and drug levels.
Hypersensitivity to azathioprine or 6-mercaptopurine. Severe active infection. Pregnancy (FDA Category D), especially first trimester. Lactation. Concomitant use with allopurinol (unless dose adjusted). TPMT deficiency (increased risk of severe myelotoxicity).
Hypersensitivity to tacrolimus or any component of the formulation; concurrent use with cyclosporine or other calcineurin inhibitors.
Avoid raw or undercooked meats and fish to reduce infection risk; no specific dietary restrictions; grapefruit juice has no known interaction.
Grapefruit juice significantly increases tacrolimus AUC and Cmax; avoid concurrent use. High-fat meals may decrease absorption; maintain consistent fat intake with each dose to ensure stable levels. Avoid taking with alcohol or herbal supplements like St. John's wort, which may reduce efficacy.
FDA Category D. Hematologic toxicity and immunosuppression in the neonate. Increased risk of congenital malformations (cleft palate, skeletal anomalies) and fetal growth restriction. First trimester exposure associated with highest risk; second and third trimester risks include intrauterine growth restriction and preterm birth.
Tacrolimus is classified as FDA Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. In animal studies, tacrolimus caused maternal toxicity and embryotoxicity at doses higher than those used clinically. First trimester exposure is associated with an increased risk of congenital anomalies, including cardiac malformations. Second and third trimester use has been linked with intrauterine growth restriction, preterm delivery, and transient neonatal hyperkalemia and renal dysfunction. Postnatal immunosuppression in the neonate may occur.
Contraindicated during breastfeeding due to potential immunosuppression and hematologic toxicity in the nursing infant. M/P ratio: Not established.
Tacrolimus is excreted into human breast milk with a milk-to-plasma (M/P) ratio of approximately 0.3. Limited data suggest low infant exposure (relative infant dose 0.5% of maternal weight-adjusted dose). However, because of potential for infant immunosuppression and growth effects, breastfeeding is generally not recommended unless benefits outweigh risks. Monitor infant for trough levels if breastfeeding.
Azathioprine dose may need to be reduced due to increased clearance in pregnancy; monitor 6-thioguanine nucleotide levels. Empiric dose adjustments not standardized; titrate to maintain therapeutic effect while minimizing myelotoxicity.
Pregnancy increases tacrolimus clearance due to expanded plasma volume and altered cytochrome P450 3A4 activity. Dose requirements may increase by 25-50% during the second and third trimesters. Therapeutic drug monitoring is essential, targeting trough levels 5-10 ng/m L. Postpartum, doses should be reduced to prepregnancy levels within 1-2 weeks as clearance normalizes.
Monitor CBC and LFTs weekly for first month, then biweekly for next 2 months, then monthly; dose reduction required with allopurinol coadministration (reduce to 25% of usual dose); screen for TPMT and NUDT15 deficiency before initiating therapy; avoid live vaccines; increased risk of lymphoproliferative disorders; use sun protection due to photosensitivity; pregnancy category D.
Monitor trough levels 5-15 ng/m L; avoid using with sirolimus due to increased risk of thrombotic microangiopathy; conversion from tacrolimus immediate-release is 1:1 (mg:mg) but monitor levels closely for 2 weeks; administer consistently with or without food to avoid fluctuations.
Take exactly as prescribed, do not stop without consulting your doctor.,Report any signs of infection (fever, sore throat, easy bruising or bleeding) immediately.,Use effective contraception during treatment and for at least 3 months after stopping.,Avoid live vaccines (e.g., MMR, varicella, nasal flu) while on this medication.,Limit sun exposure and use broad-spectrum sunscreen and protective clothing.,Do not take allopurinol without your doctor's knowledge.,Attend all scheduled blood tests to monitor for side effects.,May cause nausea; take with food if upset stomach occurs.
Take at the same time every day, consistently with or without food.,Do not crush, chew, or split the extended-release capsules; swallow whole.,Avoid grapefruit and grapefruit juice as they can increase drug levels and toxicity.,Report signs of infection (fever, sore throat), tremors, or changes in urine output immediately.,Minimize sun exposure and use sunscreen due to increased risk of skin cancer.,Do not change brand or formulation without consulting your transplant team.,Keep all appointments for blood level monitoring.
"Azathioprine may reduce the therapeutic efficacy and cardiotoxic effects of digitoxin by accelerating its metabolism through induction of cytochrome P450 enzymes, particularly CYP3A4. This interaction can lead to decreased digitoxin serum concentrations, potentially resulting in loss of heart rate control in patients with atrial fibrillation or heart failure. Conversely, the cardiotoxic risk of digitoxin is diminished, but the therapeutic goal may be compromised."
"Azathioprine and fingolimod both suppress lymphocyte function, leading to additive or synergistic immunosuppression. This combination increases the risk of severe infections, including opportunistic infections, due to profound immune system suppression. Clinically, patients may present with prolonged lymphopenia, increased susceptibility to infections, and potential reactivation of latent viruses such as JC virus (causing progressive multifocal leukoencephalopathy) or cytomegalovirus."
"Azathioprine, an immunosuppressant that acts as a prodrug for 6-mercaptopurine, can increase the myelosuppressive effects of benazepril, an ACE inhibitor. This interaction is likely due to additive bone marrow suppression, leading to an elevated risk of leukopenia, anemia, and thrombocytopenia, especially in patients with renal impairment or concomitant use of other myelosuppressive agents."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about AZATHIOPRINE SODIUM vs ASTAGRAF XL, answered by our medical review team.
AZATHIOPRINE SODIUM is a Immunosuppressant that works by Azathioprine is a prodrug of 6-mercaptopurine. It inhibits purine synthesis by interfering with the synthesis of DNA, RNA, and cellular proteins, thereby suppressing immune responses.. ASTAGRAF XL is a Immunosuppressant, Calcineurin Inhibitor that works by Calcineurin inhibitor that binds to FKBP-12, forming a complex that inhibits calcineurin, thereby preventing dephosphorylation and nuclear translocation of NFAT, which reduces T-cell activation and cytokine production (e.g., IL-2).. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between AZATHIOPRINE SODIUM and ASTAGRAF XL depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of AZATHIOPRINE SODIUM is: 1-2 mg/kg/day IV or oral, initially; maintenance 0.5-1 mg/kg/day IV or oral. For severe organ rejection: 3-5 mg/kg/day IV.. The standard adult dose of ASTAGRAF XL is: Initial oral dose of 0.1-0.15 mg/kg/day divided every 12 hours, with subsequent adjustments based on trough levels. Typical maintenance dose 0.05-0.15 mg/kg/day.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between AZATHIOPRINE SODIUM and ASTAGRAF XL in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. AZATHIOPRINE SODIUM is classified as Category D/X. FDA Category D. Hematologic toxicity and immunosuppression in the neonate. Increased risk of congenital malformations (cleft palate, skeletal anomalies) and fetal growth restrictio. ASTAGRAF XL is classified as Category C. Tacrolimus is classified as FDA Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. In animal studies, tacrolimus caused maternal toxicity an. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.