Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
PROGRAF vs ENVARSUS XR
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. Binds to FKBP-12, forming a complex that inhibits calcineurin phosphatase, thereby blocking T-cell activation and IL-2 transcription.
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 patients,Prophylaxis of organ rejection in liver transplant patients
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.
0.2 mg/kg/day orally once daily, with the morning meal, using extended-release tablets. Dose adjustments guided by trough concentrations.
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 half-life approximately 25-30 hours in stable renal transplant patients. Longer half-life (up to 50 hours) in patients with hepatic impairment.
Primarily hepatic via CYP3A4 and CYP3A5; intestinal metabolism contributes. P-glycoprotein substrate.
Primarily hepatic via CYP3A4 and CYP3A5; also metabolized by intestinal CYP3A4.
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%) with minor renal excretion (2.2% as unchanged drug). Biliary excretion is a significant route.
99% bound primarily to albumin and alpha-1-acid glycoprotein; also binds to erythrocytes and lipoproteins.
Approximately 99% bound to erythrocytes and 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.
0.9-1.4 L/kg in renal transplant patients; large volume indicates extensive tissue distribution, particularly to red blood cells.
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 approximately 15-25% with the extended-release formulation; reduced by high-fat meal, so should be taken consistently on an empty stomach.
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.
No specific GFR-based dose adjustment; however, due to nephrotoxicity, monitor renal function closely and reduce dose if renal impairment occurs. For patients with severe renal impairment (Cr Cl <30 m L/min), consider alternative immunosuppression.
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.
In patients with mild to moderate hepatic impairment (Child-Pugh A or B), reduce dose by 25%. For severe hepatic impairment (Child-Pugh C), reduce dose by 50% and monitor trough levels closely.
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.
For pediatric kidney transplant recipients: 0.2 mg/kg/day orally once daily, with morning meal. Adjust to target trough concentrations. Safety and efficacy not established for other indications in pediatrics.
Start at lower end of dosing range due to potential age-related decline in renal function. Monitor renal function and tacrolimus levels closely.
No specific dose adjustment; however, elderly patients may have increased susceptibility to nephrotoxicity and neurotoxicity. Use lowest effective dose, monitor renal function, and adjust based on trough levels.
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 malignancy (e.g., lymphoma, skin cancer).
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, hypertension, hyperkalemia, post-transplant diabetes mellitus, monitoring of blood concentrations required.
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.
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 and grapefruit juice increase tacrolimus exposure and must be avoided. High-fat meals may decrease absorption; consistency of food intake relative to dosing is recommended. Alcohol should be limited due to potential additive hepatotoxicity.
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.
Envarsus XR (tacrolimus) is classified as FDA Pregnancy Category C. In the first trimester, there is an increased risk of congenital anomalies (e.g., cardiac, renal) based on animal studies; human data are limited but suggest a possible small increase. During the second and third trimesters, risks include intrauterine growth restriction, preterm delivery, and transient neonatal hyperkalemia and renal dysfunction. Advise women of childbearing potential to use effective contraception.
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. The milk-to-plasma ratio is approximately 0.5 (range 0.12–0.75). Infant exposure is estimated to be <1% of the maternal weight-adjusted dose, which is considered low. However, due to potential for immunosuppression and adverse effects, breastfeeding is generally not recommended unless benefits outweigh risks. Monitor infant for signs of immunosuppression.
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 induces pharmacokinetic changes including increased volume of distribution, altered protein binding, and enhanced clearance of tacrolimus. Frequent monitoring of trough concentrations is essential to maintain therapeutic levels (target 5–10 ng/m L). Dose adjustments (increases of 20–50% or more) are often required, especially during the second and third trimesters. Postpartum, doses should be reduced to pre-pregnancy levels within 1–2 weeks.
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.
ENVARSUS XR is an extended-release formulation of tacrolimus; conversion from immediate-release tacrolimus requires close therapeutic drug monitoring due to altered pharmacokinetics. Administer consistently with or without food to minimize variability. Avoid grapefruit products. Monitor renal function, blood pressure, electrolytes, glucose, and trough tacrolimus levels. CYP3A4/5 inducers/inhibitors significantly affect tacrolimus exposure; adjust dose accordingly. Do not crush, chew, or split tablets.
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 exactly as prescribed, at the same time each day, with or without food but consistently.,Swallow whole; do not crush, chew, or break the tablet.,Avoid grapefruit and grapefruit juice.,Do not stop or change dose without consulting your doctor.,Report signs of infection (fever, sore throat), tremor, headache, changes in urination, or unusual bleeding.,Avoid live vaccines and limit sun exposure due to increased skin cancer risk.,Keep all appointments for blood tests to monitor drug levels and organ function.
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 ENVARSUS XR, 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.. ENVARSUS XR is a Calcineurin Inhibitor Immunosuppressant that works by Calcineurin inhibitor. Binds to FKBP-12, forming a complex that inhibits calcineurin phosphatase, thereby blocking T-cell activation and IL-2 transcription.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between PROGRAF and ENVARSUS XR 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 ENVARSUS XR is: 0.2 mg/kg/day orally once daily, with the morning meal, using extended-release tablets. Dose adjustments guided by trough concentrations.. 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 ENVARSUS XR 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. ENVARSUS XR is classified as Category C. Envarsus XR (tacrolimus) is classified as FDA Pregnancy Category C. In the first trimester, there is an increased risk of congenital anomalies (e.g., cardiac, renal) based on anima. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.