Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
TACROLIMUS vs LUPKYNIS
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Tacrolimus is a calcineurin inhibitor. It binds to FK506-binding protein 12 (FKBP12), forming a complex that inhibits calcineurin phosphatase activity. This prevents dephosphorylation and nuclear translocation of nuclear factor of activated T-cells (NFAT), thereby inhibiting transcription of interleukin-2 (IL-2) and other cytokines, leading to suppressed T-cell activation and proliferation.
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 patients receiving allogeneic liver, kidney, or heart transplants,Treatment of rejection in liver, kidney, and heart transplants,Off-label: Treatment of moderate to severe atopic dermatitis (topical),Off-label: Graft-versus-host disease (GVHD) prophylaxis and treatment
Treatment of lupus nephritis in combination with a background immunosuppressive therapy
0.1-0.2 mg/kg/day orally in two divided doses (immediate-release); 0.05-0.15 mg/kg/day orally once daily (extended-release); 0.01-0.05 mg/kg/day continuous IV infusion.
23.7 mg orally twice daily with food.
Terminal elimination half-life is approximately 8.7-21.7 hours in healthy volunteers and 18-41 hours in liver transplant recipients. Prolonged half-life in hepatic impairment requires dose adjustments.
Terminal elimination half-life approximately 30 hours; supports once-daily dosing; steady-state reached by day 4.
Primarily metabolized by cytochrome P450 3A4 (CYP3A4) and to a lesser extent by CYP3A5 in the liver and intestinal wall. It is a substrate of P-glycoprotein (ABCB1).
Primarily metabolized by CYP3A4; minor contribution from CYP3A5.
Primarily fecal (approximately 93%), with renal excretion accounting for about 2.4% of the unchanged drug. Biliary excretion is a minor route for 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).
Approximately 99% bound, primarily to albumin and alpha-1-acid glycoprotein.
Greater than 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Approximately 0.85-1.5 L/kg, reflecting extensive tissue distribution and binding to lymphocytes.
Apparent Vd/F ~24 L (approximately 0.34 L/kg assuming 70 kg); indicates distribution into tissues.
Oral: about 17-25% (variable due to first-pass metabolism and food effects); topical: minimal systemic absorption (less than 5% in healthy skin).
Oral bioavailability approximately 35% (range 20–50%) under fasting conditions; high-fat meal reduces Cmax and AUC by about 50%.
No standard dose adjustment for renal impairment; monitor renal function closely and reduce dose if nephrotoxicity occurs. For GFR < 30 m L/min, consider dose reduction by 50% and close monitoring.
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 Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: reduce dose by 75%; monitor 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.
0.15-0.3 mg/kg/day orally in two divided doses (immediate-release); 0.03-0.1 mg/kg/day continuous IV infusion; titrate to target trough levels.
Safety and efficacy not established in pediatric patients; no approved dose.
Start at lower end of dosing range (0.05-0.1 mg/kg/day orally); monitor renal function and trough levels closely due to age-related decline in renal function.
No specific dose adjustment required; monitor renal function due to age-related decline.
Increased susceptibility to infection and the possible development of lymphoma. Only physicians experienced in immunosuppressive therapy and management of transplant patients should prescribe tacrolimus. Patients receiving tacrolimus should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources.
Increased risk of infection and lymphoma; increased risk of nephrotoxicity and hypertension; increased risk of neurotoxicity.
Increased risk of lymphomas and other malignancies, particularly skin cancer,Increased susceptibility to infections, including opportunistic infections and reactivation of latent viruses (e.g., BK virus, CMV, EBV),Nephrotoxicity: acute and chronic renal impairment, monitor renal function closely,Neurotoxicity: tremors, headache, seizures, posterior reversible encephalopathy syndrome (PRES),Hyperkalemia: monitor serum potassium levels,Hypertension: monitor blood pressure and manage accordingly,Post-transplant diabetes mellitus: monitor blood glucose levels,Anaphylactic reactions: risk with intravenous formulation due to castor oil derivative (polyoxyl 60 hydrogenated castor oil) in some formulations,QT prolongation: caution in patients with risk factors or with drugs that prolong QT interval
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,Hypersensitivity to hydrogenated castor oil (present in some intravenous formulations)
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 by inhibiting CYP3A4 and must be avoided. High-fat meals decrease absorption; consistent timing relative to meals recommended.
Avoid grapefruit and grapefruit juice as they increase voclosporin exposure. No other specific food interactions are known.
First trimester: Increased risk of congenital malformations including cardiac anomalies. Second and third trimesters: Risk of fetal growth restriction, preterm delivery, and neonatal hyperkalemia. Tacrolimus crosses the placenta.
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.
Tacrolimus is excreted into breast milk. M/P ratio (concentration in milk:plasma) is approximately 0.3-0.9. It is recommended to use with caution; monitor infant for immunosuppression and tacrolimus trough levels.
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 dose requirements due to increased volume of distribution and clearance. Monitoring tacrolimus trough levels recommended every 1-2 weeks; dose adjustments to maintain therapeutic range (typically 5-15 ng/m L).
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 2-3 days after dose changes; target 5-15 ng/m L for most indications. Use with caution in renal impairment due to nephrotoxicity. Strong CYP3A4 interaction potential; avoid grapefruit and adjust azole antifungals. Hypomagnesemia common; supplement as needed.
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 consistently with or without food, but do not switch between.,Avoid grapefruit and grapefruit juice.,Report signs of infection, tremors, or kidney issues (swelling, decreased urine).,Do not take any new medications without consulting your doctor.,Use sun protection due to increased skin cancer risk.,Do not miss doses; if you do, take as soon as remembered unless near next dose.
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.
"Tacrolimus, a potent CYP3A4 inhibitor, significantly decreases the metabolism of citalopram, a CYP3A4 substrate, leading to elevated citalopram plasma concentrations. This pharmacokinetic interaction increases the risk of dose-dependent adverse effects such as QT prolongation, serotonin syndrome, and central nervous system toxicity. Clinical outcomes may include corrected QT (QTc) interval prolongation, increasing the risk of torsade de pointes, and enhanced serotonergic effects requiring careful monitoring."
"Tacrolimus, a calcineurin inhibitor, primarily induces nephrotoxicity through afferent arteriolar vasoconstriction and direct tubular injury. Etofenamate, a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX) enzymes, reduces prostaglandin synthesis, leading to decreased renal blood flow and glomerular filtration rate. Concomitant use synergistically impairs renal function, increasing the risk of acute kidney injury, hyperkalemia, and hypertension, particularly in patients with preexisting renal impairment or volume depletion."
"Tacrolimus, a calcineurin inhibitor and CYP3A4 substrate, may inhibit the metabolism of isoflurophate, a long-acting cholinesterase inhibitor used in glaucoma. This interaction can lead to increased systemic exposure of isoflurophate, potentially exacerbating cholinergic side effects such as bradycardia, hypersalivation, and bronchospasm. Clinically, patients may experience enhanced toxicity, including prolonged muscle weakness or respiratory depression, especially in those with compromised hepatic function."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about TACROLIMUS vs LUPKYNIS, answered by our medical review team.
TACROLIMUS is a Calcineurin Inhibitor that works by Tacrolimus is a calcineurin inhibitor. It binds to FK506-binding protein 12 (FKBP12), forming a complex that inhibits calcineurin phosphatase activity. This prevents dephosphorylation and nuclear translocation of nuclear factor of activated T-cells (NFAT), thereby inhibiting transcription of interleukin-2 (IL-2) and other cytokines, leading to suppressed T-cell activation and proliferation.. 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 TACROLIMUS 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 TACROLIMUS is: 0.1-0.2 mg/kg/day orally in two divided doses (immediate-release); 0.05-0.15 mg/kg/day orally once daily (extended-release); 0.01-0.05 mg/kg/day continuous IV infusion.. 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 TACROLIMUS 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. TACROLIMUS is classified as Category D/X. First trimester: Increased risk of congenital malformations including cardiac anomalies. Second and third trimesters: Risk of fetal growth restriction, preterm delivery, and neonat. 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.