Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
TACROLIMUS 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
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 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 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
Prophylaxis of organ rejection in kidney transplant recipients,Prophylaxis of organ rejection in liver transplant recipients,Prophylaxis of organ rejection in heart transplant recipients
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.
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 8.7-21.7 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 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 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 hepatic via CYP3A4 and CYP3A5; undergoes extensive first-pass metabolism. Substrate of P-glycoprotein.
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 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.
Approximately 99% bound, primarily to albumin and alpha-1-acid glycoprotein.
Approximately 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.
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: about 17-25% (variable due to first-pass metabolism and food effects); topical: minimal systemic absorption (less than 5% in healthy skin).
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 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.
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 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. Class B: reduce dose by 25%. Class C: reduce dose by 50% and monitor trough levels frequently.
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.
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 (0.05-0.1 mg/kg/day orally); monitor renal function and trough levels closely due to age-related decline in renal function.
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 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 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 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, 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,Hypersensitivity to hydrogenated castor oil (present in some intravenous formulations)
Hypersensitivity to tacrolimus or any component of the formulation; concurrent use with cyclosporine or other calcineurin inhibitors.
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.
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.
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.
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.
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.
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 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).
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 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 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 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 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.
"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 ASTAGRAF XL, 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.. 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 TACROLIMUS 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 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 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 TACROLIMUS 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. 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. 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.