Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ASTAGRAF XL 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 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).
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 transplant recipients,Prophylaxis of organ rejection in liver transplant recipients,Prophylaxis of organ rejection in heart transplant recipients
Treatment of lupus nephritis in combination with a background immunosuppressive therapy
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.
23.7 mg orally twice daily with food.
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.
Terminal elimination half-life approximately 30 hours; supports once-daily dosing; steady-state reached by day 4.
Primarily hepatic via CYP3A4 and CYP3A5; undergoes extensive first-pass metabolism. Substrate of P-glycoprotein.
Primarily metabolized by CYP3A4; minor contribution from CYP3A5.
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.
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 to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Greater than 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
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.
Apparent Vd/F ~24 L (approximately 0.34 L/kg assuming 70 kg); indicates distribution into tissues.
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.
Oral bioavailability approximately 35% (range 20–50%) under fasting conditions; high-fat meal reduces Cmax and AUC by about 50%.
For GFR <30 m L/min: reduce dose by 50% and monitor trough levels closely. No adjustment for GFR >30 m L/min.
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. Class B: reduce dose by 25%. Class C: reduce dose by 50% and monitor trough levels frequently.
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.
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.
Safety and efficacy not established in pediatric patients; no approved dose.
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.
No specific dose adjustment required; monitor renal function due to age-related decline.
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.
Increased risk of infection and lymphoma; increased risk of nephrotoxicity and hypertension; increased risk of neurotoxicity.
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.
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; concurrent use with cyclosporine or other calcineurin inhibitors.
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 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.
Avoid grapefruit and grapefruit juice as they increase voclosporin exposure. No other specific food interactions are known.
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.
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 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.
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.
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.
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 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.
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, 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.
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 ASTAGRAF XL vs LUPKYNIS, answered by our medical review team.
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).. 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 ASTAGRAF XL 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 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.. 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 ASTAGRAF XL 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. 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. 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.