Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
PROGRAF 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
Calcineurin inhibitor; binds to FKBP-12, inhibits calcineurin, preventing dephosphorylation and nuclear translocation of NF-AT, thereby inhibiting T-cell activation and cytokine gene transcription.
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).
Prophylaxis of organ rejection in kidney, liver, and heart transplant recipients,Treatment of refractory acute cellular rejection after organ transplantation,Off-label: Severe atopic dermatitis, nephrotic syndrome, ulcerative colitis
Prophylaxis of organ rejection in kidney transplant recipients,Prophylaxis of organ rejection in liver transplant recipients,Prophylaxis of organ rejection in heart transplant recipients
Initial oral dose: 0.1-0.15 mg/kg/day divided into 2 doses (every 12 hours). IV dose: 0.03-0.05 mg/kg/day as continuous infusion. Adjunct with corticosteroids.
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 is approximately 8.7 hours (range 4-41 hours) in healthy volunteers; in liver transplant patients, half-life is approximately 11.7 hours (range 3.9-56 hours); prolonged in patients with hepatic impairment.
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 hepatic via CYP3A4 and CYP3A5; intestinal metabolism contributes. P-glycoprotein substrate.
Primarily hepatic via CYP3A4 and CYP3A5; undergoes extensive first-pass metabolism. Substrate of P-glycoprotein.
Primarily fecal (approximately 92%) with biliary excretion as the major route; renal excretion accounts for about 2.4% of the dose as unchanged drug and metabolites.
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.
99% bound primarily to albumin and alpha-1-acid glycoprotein; also binds to erythrocytes and lipoproteins.
Approximately 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Volume of distribution is approximately 0.99 L/kg (range 0.6-1.9 L/kg) in healthy subjects; higher values indicate extensive tissue distribution and binding to erythrocytes.
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 is approximately 17-25% (range 4-89%) in transplant patients, with high inter- and intra-subject variability; absorption is influenced by food.
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.
No specific GFR-based dose adjustment required, but monitor renal function closely due to nephrotoxicity. For severe renal impairment (Cr Cl <30 m L/min), reduce dose by 25-50% and monitor levels.
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 A: no adjustment. Child-Pugh B: reduce dose by 25%. Child-Pugh C: reduce dose by 50% and titrate based on trough levels.
Child-Pugh Class A: no adjustment. Class B: reduce dose by 25%. Class C: reduce dose by 50% and monitor trough levels frequently.
Oral: 0.1-0.3 mg/kg/day divided every 12 hours. IV: 0.03-0.05 mg/kg/day continuous infusion. Monitor trough concentrations.
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 due to potential age-related decline in renal function. Monitor renal function and tacrolimus levels closely.
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.
Increased risk of lymphomas and other malignancies, particularly skin cancer; increased susceptibility to infections. Only should be prescribed by physicians experienced in immunosuppressive therapy.
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.
Nephrotoxicity, neurotoxicity (tremor, headache, seizures), hypertension, hyperkalemia, hyperglycemia, thrombotic microangiopathy, risk of BK virus infection, increased risk of EBV-associated post-transplant lymphoproliferative disorder.
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 tacrolimus or any component of the formulation, concomitant use with cyclosporine, and patients with or at risk for congenital long QT syndrome.
Hypersensitivity to tacrolimus or any component of the formulation; concurrent use with cyclosporine or other calcineurin inhibitors.
Grapefruit and grapefruit juice increase tacrolimus levels, avoid. High-fat meals may decrease absorption; take consistently with or without food. Avoid potassium-rich foods if hyperkalemia risk.
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.
Pregnancy Category C. Risk in first trimester: increased risk of congenital malformations (animal studies); human data limited. Second and third trimester: potential for fetal growth restriction, prematurity, and neonatal toxicity (hyperkalemia, renal dysfunction). Use only if benefit outweighs risk.
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.
Excreted in breast milk; M/P ratio unknown. Weigh benefits of breastfeeding against potential risk of infant immunosuppression and renal toxicity. Consider avoiding or using alternative.
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.
Increased clearance and decreased bioavailability during pregnancy may necessitate higher doses; monitor trough concentrations frequently (every 1-2 weeks) and adjust to maintain therapeutic levels (typically 5-15 ng/m L for liver transplantation, adjust per indication). Increased dose requirements often seen in second and third trimesters.
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 trough levels 12 hours post-dose; target 5-20 ng/m L depending on organ. Avoid with live vaccines. Adjust dose for hepatic impairment. Cautious co-administration with nephrotoxic drugs. Grapefruit juice increases tacrolimus levels.
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 at the same time every day, 12 hours apart.,Do not eat grapefruit or drink grapefruit juice.,Report signs of infection, tremors, or changes in urine output.,Avoid live vaccines and limit sun exposure.,Do not stop abruptly; taper under medical supervision.
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.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about PROGRAF vs ASTAGRAF XL, answered by our medical review team.
PROGRAF is a Calcineurin Inhibitor that works by Calcineurin inhibitor; binds to FKBP-12, inhibits calcineurin, preventing dephosphorylation and nuclear translocation of NF-AT, thereby inhibiting T-cell activation and cytokine gene transcription.. 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 PROGRAF 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 PROGRAF is: Initial oral dose: 0.1-0.15 mg/kg/day divided into 2 doses (every 12 hours). IV dose: 0.03-0.05 mg/kg/day as continuous infusion. Adjunct with corticosteroids.. 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 PROGRAF 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. PROGRAF is classified as Category C. Pregnancy Category C. Risk in first trimester: increased risk of congenital malformations (animal studies); human data limited. Second and third trimester: potential for fetal grow. 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.