Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
PROGRAF vs GENGRAF
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; binds to cyclophilin, inhibits calcineurin-dependent T-cell activation, preventing nuclear factor of activated T-cells (NF-AT) dephosphorylation and translocation, thereby reducing IL-2 and other cytokine gene transcription.
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
Prophylaxis of organ rejection in kidney, liver, and heart allogeneic transplants,Treatment of active rheumatoid arthritis (FDA-approved for moderate to severe),Treatment of psoriasis (FDA-approved for severe, recalcitrant cases),Off-label: nephrotic syndrome, aplastic anemia, ulcerative colitis, atopic dermatitis
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.
5-15 mg/kg/day orally in divided doses every 12 hours.
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 half-life is approximately 8.4 hours (range 5-18 hours) in adult volunteers; prolonged in hepatic impairment.
Primarily hepatic via CYP3A4 and CYP3A5; intestinal metabolism contributes. P-glycoprotein substrate.
Hepatic metabolism primarily via CYP3A4 enzyme; also substrate for CYP3A5. Metabolized to multiple metabolites with variable activity, including AM1 (hydroxylated), AM9 (N-demethylated), and AM4N (cyclized). Undergoes extensive first-pass metabolism.
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 biliary/fecal (94%); renal excretion accounts for 6% (0.1% unchanged).
99% bound primarily to albumin and alpha-1-acid glycoprotein; also binds to erythrocytes and lipoproteins.
90-98% bound to plasma proteins, primarily lipoproteins, 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.
3.5 L/kg (range 1.2-4.8 L/kg) in renal transplant recipients; distribution is extensive and variable.
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 is 30% (range 10-60%), variable due to first-pass metabolism and food effects.
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.
GFR <30 m L/min: reduce dose by 50%.
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; Class B: reduce dose by 50%; Class C: avoid use.
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.
4-10 mg/kg/day orally in divided doses every 12 hours; adjusted to target trough levels.
Start at lower end of dosing range due to potential age-related decline in renal function. Monitor renal function and tacrolimus levels closely.
Initiate at lower end of dosing range and titrate based on renal function and drug levels.
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 susceptibility to infection and development of lymphoma and other malignancies, particularly of the skin. Only physicians experienced in immunosuppressive therapy and management of transplant patients should prescribe cyclosporine.
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: Monitor renal function regularly; risk increased with high doses, other nephrotoxic drugs, or prolonged use.,Hepatotoxicity: Monitor liver function.,Hypertension: Common; require blood pressure control.,Neurotoxicity: Including tremor, convulsions, headache, and paresthesias.,Hyperkalemia: Monitor serum potassium, especially with potassium-sparing diuretics or ACE inhibitors.,Hypomagnesemia: Supplementation may be required.,Increased risk of infections and lymphoproliferative disorders.,Potential for anaphylactic reactions with IV formulation (due to Cremophor EL).,Carcinogenesis: Especially skin malignancies; minimize UV exposure.
Hypersensitivity to tacrolimus or any component of the formulation, concomitant use with cyclosporine, and patients with or at risk for congenital long QT syndrome.
Hypersensitivity to cyclosporine or any component of the formulation (including Cremophor EL for IV),Uncontrolled hypertension,Malignancy (except non-melanoma skin cancer) in patients with rheumatoid arthritis or psoriasis,Concomitant use with PUVA or UVB therapy, methotrexate, other immunosuppressive agents, or coal tar (for psoriasis patients),Abnormal renal function with uncontrolled hypertension (for psoriasis patients),Pregnancy (category C; additional risk of premature birth and low birth weight)
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.
Grapefruit and grapefruit juice increase cyclosporine levels and must be avoided. High-potassium foods (e.g., bananas, oranges, potatoes) may increase hyperkalemia risk; monitor intake. Avoid St. John's wort as it reduces drug levels.
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.
First trimester: Cyclosporine crosses the placenta. Limited human data, but no major malformations attributed. Second and third trimesters: Risk of intrauterine growth restriction, prematurity, and low birth weight. Consider risk-benefit; avoid if possible, but may be used if essential.
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.
Cyclosporine is excreted into breast milk. Milk-to-plasma ratio approximately 0.3-0.6. Potential for infant immunosuppression and growth inhibition. Weigh benefits against risks; monitor infant for adverse effects.
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.
Pregnancy reduces cyclosporine oral bioavailability and increases clearance; dose may need to be increased by 20-50% to maintain therapeutic trough levels. Frequent level monitoring recommended, especially in third trimester. Postpartum dose reduction likely 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 trough levels (target 100-400 ng/m L) and renal function closely. Calcineurin inhibitors cause nephrotoxicity; dose reduction may be necessary. Avoid use with potassium-sparing diuretics or ACE inhibitors due to hyperkalemia risk. Grapefruit increases levels; avoid coadministration. Remember to adjust dose for hepatic impairment.
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 with or without food consistently at the same times each day.,Do not consume grapefruit or grapefruit juice while on this medication.,Report signs of infection, tremors, or changes in urine output immediately.,Avoid live vaccinations and limit sun exposure due to increased skin cancer risk.,Do not stop or change dose without consulting your doctor.
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 GENGRAF, 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.. GENGRAF is a Calcineurin Inhibitor Immunosuppressant that works by Calcineurin inhibitor; binds to cyclophilin, inhibits calcineurin-dependent T-cell activation, preventing nuclear factor of activated T-cells (NF-AT) dephosphorylation and translocation, thereby reducing IL-2 and other cytokine gene transcription.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between PROGRAF and GENGRAF 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 GENGRAF is: 5-15 mg/kg/day orally in divided doses every 12 hours.. 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 GENGRAF 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. GENGRAF is classified as Category C. First trimester: Cyclosporine crosses the placenta. Limited human data, but no major malformations attributed. Second and third trimesters: Risk of intrauterine growth restriction,. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.