Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ASTAGRAF XL vs PROTOPIC
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).
Tacrolimus, a calcineurin inhibitor, binds to FKBP-12 and inhibits calcineurin, thereby blocking dephosphorylation and nuclear translocation of NFAT, reducing transcription of pro-inflammatory cytokines (e.g., IL-2, IFN-γ) in T-cells.
Prophylaxis of organ rejection in kidney transplant recipients,Prophylaxis of organ rejection in liver transplant recipients,Prophylaxis of organ rejection in heart transplant recipients
Moderate to severe atopic dermatitis in non-immunocompromised patients where conventional therapy is inadvisable or ineffective,Prophylaxis of organ rejection in kidney or liver transplantation (systemic use, not topical),Off-label: Treatment of vitiligo, psoriasis, eczema of the face and neck (short-term)
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.
Apply a thin layer of 0.03% or 0.1% ointment to affected areas twice daily. Discontinue when lesions resolve. For adults, use 0.03% or 0.1%; 0.1% is not indicated for children.
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 half-life ranges from 6–20 hours in pediatric atopic dermatitis patients; prolonged in hepatic impairment (mean 8–35 hours).
Primarily hepatic via CYP3A4 and CYP3A5; undergoes extensive first-pass metabolism. Substrate of P-glycoprotein.
Primarily hepatic via CYP3A4; also metabolized by CYP3A5. Topical absorption results in minimal systemic exposure, but systemic metabolism follows oral route.
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 fecal (biliary) elimination of metabolites; <1% of parent drug excreted unchanged in urine.
Approximately 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
99% bound primarily to 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.
Vd/F ~ 30–50 L/kg after oral administration, indicating extensive tissue distribution; topical absorption negligible.
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.
Systemic bioavailability after topical application is <0.5% in adults with intact skin; increases in compromised skin barrier.
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. Tacrolimus is not significantly renally excreted and systemic absorption is minimal.
Child-Pugh Class A: no adjustment. Class B: reduce dose by 25%. Class C: reduce dose by 50% and monitor trough levels frequently.
No specific dose adjustment for Child-Pugh class A or B. For severe hepatic impairment (Child-Pugh C), use with caution; consider starting at lower concentration (0.03%) due to potential increased systemic exposure.
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.
Children (2-15 years): Apply 0.03% ointment twice daily. Do not use 0.1% in this age group. For children 2 years and older.
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. Use minimum effective amount; monitor for cutaneous infections.
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.
Long-term safety of topical calcineurin inhibitors has not been established. Although a causal relationship has not been established, rare cases of malignancy (e.g., lymphoma, skin cancer) have been reported in patients treated with topical calcineurin inhibitors. Therefore, continuous long-term use should be avoided, and application should be limited to areas of involvement.
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.
Increased risk of infections (including herpes simplex, eczema herpeticum); avoid use on malignant or premalignant skin conditions; use with caution in patients with netherton syndrome; may cause photosensitivity; avoid concurrent UV exposure; monitor for lymphadenopathy; not for use in children <2 years (safety not established).
Hypersensitivity to tacrolimus or any component of the formulation; concurrent use with cyclosporine or other calcineurin inhibitors.
Hypersensitivity to tacrolimus or any component of the formulation; use in patients with known or suspected malignancy at the application site; use in immunocompromised patients (relative).
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.
No known food interactions with topical PROTOPIC. However, if absorbed systemically (rare), grapefruit juice may increase tacrolimus levels; avoid excessive consumption of grapefruit juice while using PROTOPIC.
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.
Pregnancy Category C. Animal studies have shown embryotoxicity and teratogenicity at systemic exposures below human therapeutic levels. No adequate human studies in pregnant women. Risk cannot be ruled out; use only if potential benefit justifies potential risk to fetus. First trimester: avoid if possible. Second and third trimesters: limited data; systemic absorption minimal with topical use, but theoretical risk remains.
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.
Not known if tacrolimus is excreted in human milk after topical administration. Systemic absorption is minimal (<0.5%), but caution is advised due to potential for infant immunosuppression. M/P ratio: not available. Consider benefit of breast-feeding vs risk of infant exposure.
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 recommended for topical use due to minimal systemic absorption. However, limit application to smallest area and shortest duration needed. Avoid use on large areas, broken skin, or under occlusion to reduce systemic exposure.
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.
PROTOPIC (tacrolimus) is a topical calcineurin inhibitor used for atopic dermatitis. It is steroid-sparing, thus avoiding skin atrophy and tachyphylaxis. Apply as a thin layer to affected areas. Avoid occlusive dressings. Can be used on face, neck, and intertriginous areas where topical steroids are riskier. Monitor for burning/stinging upon application, which often improves with continued use. Warn patients about rare risk of lymphoma and skin malignancy; use only as second-line therapy for short-term and intermittent treatment. Do not use in immunocompromised patients or those with active skin infections.
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.
Apply PROTOPIC exactly as prescribed; do not use more than directed.,Wash hands after application unless treating hands.,Do not cover treated area with bandages or dressings unless instructed.,Expect mild burning or stinging especially in the first few days; this usually resolves with continued use.,Avoid sun exposure and use sunscreen; protect treated areas from natural and artificial sunlight.,Do not use on infected skin; tell your doctor if you have an infection.,PROTOPIC is for external use only; do not get in eyes, mouth, or nose.,Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding.,Store at room temperature away from moisture and heat.,Report any signs of skin infection, rash, or swollen lymph nodes to your doctor immediately.
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 PROTOPIC, 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).. PROTOPIC is a Topical Calcineurin Inhibitor that works by Tacrolimus, a calcineurin inhibitor, binds to FKBP-12 and inhibits calcineurin, thereby blocking dephosphorylation and nuclear translocation of NFAT, reducing transcription of pro-inflammatory cytokines (e.g., IL-2, IFN-γ) in T-cells.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ASTAGRAF XL and PROTOPIC 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 PROTOPIC is: Apply a thin layer of 0.03% or 0.1% ointment to affected areas twice daily. Discontinue when lesions resolve. For adults, use 0.03% or 0.1%; 0.1% is not indicated for children.. 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 PROTOPIC 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. PROTOPIC is classified as Category C. Pregnancy Category C. Animal studies have shown embryotoxicity and teratogenicity at systemic exposures below human therapeutic levels. No adequate human studies in pregnant women.. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.