Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
PROGRAF vs LUPKYNIS
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 immunosuppressant that binds to cyclophilin A, inhibiting calcineurin activity, which prevents dephosphorylation and activation of nuclear factor of activated T-cells (NFAT), thereby reducing cytokine production and T-cell activation.
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
Treatment of lupus nephritis in combination with a background immunosuppressive therapy
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.
23.7 mg orally twice daily with food.
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 approximately 30 hours; supports once-daily dosing; steady-state reached by day 4.
Primarily hepatic via CYP3A4 and CYP3A5; intestinal metabolism contributes. P-glycoprotein substrate.
Primarily metabolized by CYP3A4; minor contribution from CYP3A5.
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 hepatic metabolism; <1% excreted unchanged in urine; approximately 66% of total radioactivity recovered in feces (mainly metabolites) and 22% in urine (mainly metabolites).
99% bound primarily to albumin and alpha-1-acid glycoprotein; also binds to erythrocytes and lipoproteins.
Greater than 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.
Apparent Vd/F ~24 L (approximately 0.34 L/kg assuming 70 kg); indicates distribution into 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 approximately 35% (range 20–50%) under fasting conditions; high-fat meal reduces Cmax and AUC by about 50%.
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 dose adjustment required for GFR ≥30 m L/min. Avoid use in severe renal impairment (GFR <30 m L/min) due to lack of data.
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. Child-Pugh Class B: Reduce dose to 15.8 mg orally twice daily. Child-Pugh Class C: Not recommended.
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.
Safety and efficacy not established in pediatric patients; no approved dose.
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 required; monitor renal function due to age-related decline.
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 risk of infection and lymphoma; increased risk of nephrotoxicity and hypertension; increased risk of neurotoxicity.
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 and hypertension require regular monitoring. Neurotoxicity including posterior reversible encephalopathy syndrome (PRES). Increased susceptibility to infections including opportunistic infections. Malignancies including lymphoma. Monitor for Epstein-Barr virus serology. Use with caution with CYP3A4 inhibitors and inducers. Avoid live vaccines.
Hypersensitivity to tacrolimus or any component of the formulation, concomitant use with cyclosporine, and patients with or at risk for congenital long QT syndrome.
Concurrent use with chronic immunosuppressive therapies other than mycophenolate mofetil (MMF) or mycophenolic acid (MPA). Known hypersensitivity to voclosporin 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.
Avoid grapefruit and grapefruit juice as they increase voclosporin exposure. No other specific food interactions are known.
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.
LUPKYNIS (voclosporin) is a calcineurin inhibitor. Based on animal studies, there is a risk of fetal harm in all trimesters. In rats and rabbits, voclosporin administration during organogenesis resulted in increased embryofetal mortality and reduced fetal weight at maternally toxic doses. There are no adequate human studies. Avoid use during pregnancy unless potential benefit outweighs risk.
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.
It is unknown if voclosporin is excreted in human milk. In animal studies, voclosporin and its metabolites were detected in milk of lactating rats. No M/P ratio available for humans. Due to potential for serious adverse reactions in nursing infants, advise women not to breastfeed during treatment and for 4 weeks after last dose.
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.
No specific dose adjustments are established for pregnancy. However, pregnancy can increase voclosporin clearance due to expanded plasma volume and enhanced metabolism. Consider therapeutic drug monitoring if available, and adjust dose to maintain therapeutic trough levels (target 30-60 ng/m L) as needed.
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 for hematuria, proteinuria, and e GFR during treatment. Lupkynis (voclosporin) is a calcineurin inhibitor; do not co-administer with other CNIs or strong CYP3A4 inhibitors. Reduce dose in patients with e GFR <45 m L/min per 1.73 m². Concomitant use with mycophenolate mofetil and corticosteroids is standard. Check blood pressure and serum potassium regularly. Live vaccines contraindicated.
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; do not stop or change dose without consulting your doctor.,You will need regular blood and urine tests to monitor kidney function and drug levels.,Report any signs of infection (fever, sore throat), high blood pressure (severe headache, vision changes), or changes in urine output/color.,Avoid grapefruit and grapefruit juice during treatment.,Do not receive live vaccines while taking this medication.,Use effective contraception during treatment and for 12 weeks after last dose if of childbearing potential.,Tell your doctor about all medications, including over-the-counter drugs and supplements.
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 LUPKYNIS, 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.. LUPKYNIS is a Calcineurin Inhibitor Immunosuppressant that works by Calcineurin inhibitor immunosuppressant that binds to cyclophilin A, inhibiting calcineurin activity, which prevents dephosphorylation and activation of nuclear factor of activated T-cells (NFAT), thereby reducing cytokine production and T-cell activation.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between PROGRAF and LUPKYNIS 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 LUPKYNIS is: 23.7 mg orally twice daily with food.. 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 LUPKYNIS 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. LUPKYNIS is classified as Category C. LUPKYNIS (voclosporin) is a calcineurin inhibitor. Based on animal studies, there is a risk of fetal harm in all trimesters. In rats and rabbits, voclosporin administration during . Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.