Prograf Granules

— THERAPEUTIC CATEGORIES —
  • Organ rejection prophylaxis
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Prograf Granules Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Tacrolimus 0.2mg, 1mg; per pkt; for oral susp.

    Pharmacological Class

    Immunosuppressant (calcineurin-inhibitor).

    See Also

    How Supplied

    Caps—100; Granules—50; Ampules—10

    Manufacturer

    Astellas Pharma US, Inc.

    Generic Availability

    YES

    Mechanism of Action

    Tacrolimus inhibits T-lymphocyte activation and proliferation. Experimental evidence suggests that tacrolimus binds to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin is then formed and the phosphatase activity of calcineurin inhibited.

    Prograf Granules Indications

    Indications

    Organ rejection prophylaxis in patients with allogeneic kidney, liver, heart, or lung transplants, in combination with other immunosuppressants.

    Prograf Granules Dosage and Administration

    Adult

    Give at least 6hrs after transplantation. If previously on IV infusion, initial oral dose may be given 8–12hrs post infusion. Liver (with corticosteroids only): initially 0.1–0.15mg/kg/day in two divided dose every 12hrs. Concomitant corticosteroid is recommended early post-transplantation. Heart or lung (with azathioprine or MMF): initially 0.075mg/kg/day in two divided doses every 12hrs; cystic fibrosis patients may require higher doses (lung transplant). Kidney (may be given within 24hrs of transplantation but should be delayed until renal function has recovered): initially 0.2mg/kg/day in two divided doses every 12hrs in combination with azathioprine; or 0.1mg/kg/day in two divided doses every 12hrs in combination with MMF/IL-2 receptor antagonist; black patients may require higher doses. Renal or hepatic impairment: use lowest effective dose. Post-op oliguria: give initial dose no sooner than 6hrs and within 48hrs of transplantation, but may be delayed until renal function recovers. See full labeling.

    Children

    Give at least 6hrs after transplantation. If previously on IV infusion, initial oral dose may be given 8–12hrs post infusion. Granules: mix only with 15–30mL of room temperature water and drink immediately; or may give susp via non-PVC oral syringe. Rinse cup/oral syringe with same volume of water and drink. Kidney: initially 0.3mg/kg/day in two divided doses every 12hrs. Liver: initially 0.15–0.2mg/kg/day in two divided doses every 12hrs. Heart or lung: initially 0.3mg/kg/day (0.1mg/kg/day if antibody induction treatment is administered) in two divided doses every 12hrs; cystic fibrosis patients may require higher doses (lung transplant). Switching between oral forms: use the same total daily dose.

    Administration

    Initiate oral therapy if possible. Give at least 6hrs after transplantation. If previously on IV infusion, initial oral dose may be given 8–12hrs post infusion. Take with or without food. Avoid grapefruit or grapefruit juice in combination with Prograf. Do not use simultaneously with cyclosporine; discontinue Prograf or cyclosporine at least 24 hours before initiating the other.

    Nursing Considerations

    Initiate oral therapy if possible. Give at least 6hrs after transplantation. If previously on IV infusion, initial oral dose may be given 8–12hrs post infusion. Take with or without food. Avoid grapefruit or grapefruit juice in combination with Prograf. Do not use simultaneously with cyclosporine; discontinue Prograf or cyclosporine at least 24 hours before initiating the other.

    Prograf Granules Contraindications

    Not Applicable

    Prograf Granules Boxed Warnings

    Boxed Warning

    Malignancies. Serious infections.

    Prograf Granules Warnings/Precautions

    Warnings/Precautions

    Increased risk of lymphomas and other malignancies (eg, skin) due to immunosuppression. Avoid sun, UV light. Increased risk of infections (eg, bacterial, viral, fungal, protozoal), including opportunistic infections. Monitor Epstein-Barr virus serology, development of infections during therapy. Oral forms are not interchangeable with other tacrolimus ext-rel products. Only physicians experienced in immunosuppressive therapy should prescribe Prograf. Risk of new onset diabetes after transplant (esp. Hispanic and black patients); monitor blood glucose. Hepatic or renal impairment; monitor and consider dose reduction. Obtain tacrolimus whole blood concentrations, serum creatinine, serum potassium, and fasting glucose periodically. Monitor and control BP. Avoid in congenital long QT syndrome. CHF, bradyarrhythmias, concomitant antiarrhythmic drugs, or electrolyte disturbances; consider obtaining ECGs and monitor electrolytes periodically. Discontinue or reduce dose if myocardial hypertrophy occurs. Risk for thrombotic microangiopathy (including hemolytic uremic syndrome and thrombotic thrombocytopenic purpura) esp. in those with severe infections, GVHD, HLA mismatch. Complete required immunizations prior to transplantation and treatment. IV: have epinephrine readily available. Elderly. Labor & delivery. Advise females and males of reproductive potential to use appropriate contraception prior to initiation. Pregnancy. Nursing mothers.

    Prograf Granules Pharmacokinetics

    Distribution

    Plasma protein bound: 99%.

    Metabolism

    Hepatic (CYP3A4). 

    Elimination

    Oral administration: fecal (92.6 ± 30.7%), renal (2.3 ± 1.1%). Half-life: 31.9 ± 10.5 hours (based on radioactivity); 48.4 ± 12.3 hours (based on tacrolimus concentrations).

    Prograf Granules Interactions

    Interactions

    Concomitant sirolimus (in liver/heart transplant), live vaccines: not recommended. Concomitant mTOR inhibitors (eg, sirolimus, everolimus) may increase risk of thrombotic microangiopathy. Concomitant strong CYP3A4 inhibitors/inducers or substrates: must adjust dosing regimen, closely monitor tacrolimus blood concentrations and for QT prolongation. Caution with mycophenolic acid; reduce dose of these as needed. Caution with potassium-sparing diuretics, ACEIs, ARBs. Avoid grapefruit or grapefruit juice. Additive nephrotoxicity with cyclosporine (discontinue at least 24hrs prior to initiating the other drug), aminoglycosides, ganciclovir, amphotericin B, cisplatin, NRTIs, protease inhibitors; if concomitant use, monitor renal function and tacrolimus blood levels; adjust doses of both drugs. May be potentiated by calcium channel blockers (eg, verapamil, diltiazem, nifedipine), antifungals (eg, voriconazole, posaconazole, itraconazole, fluconazole, ketoconazole), macrolides (eg, troleandomycin, clarithromycin, erythromycin), lansoprazole, omeprazole, chloramphenicol, cimetidine, cyclosporine, amiodarone, danazol, ethinyl estradiol, protease inhibitors (eg, nelfinavir, telaprevir, boceprevir, ritonavir), nefazodone, letermovir, schisandra sphenanthera extract, magnesium-aluminum-hydroxide, metoclopramide, cannabidiol (monitor; consider reducing tacrolimus dose). May be antagonized by carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. Johns wort, methylprednisolone, prednisone, caspofungin. Monitor closely with direct acting antiviral therapy; may need to adjust dose.

    Prograf Granules Adverse Reactions

    Adverse Reactions

    Tremor, headache, constipation, diarrhea, nausea, abdominal pain, insomnia, hypertension, renal dysfunction, fever, serious viral infections (eg, CMV, PML, PVAN), leukopenia, anemia, bronchitis, pericardial effusion, UTI, paresthesia, peripheral edema, hyperkalemia, hypomagnesemia, hyperlipidemia, hyperglycemia; nephrotoxicity or neurotoxicity (esp. in high doses), diabetes mellitus, posterior reversible encephalopathy syndrome (consider reduced dose or discontinue), malignancies (eg, lymphomas, skin), post-transplant lymphoproliferative disorder, myocardial hypertrophy, pure red cell aplasia, Torsade de Pointes; IV: anaphylaxis (monitor and discontinue if occurs).

    Prograf Granules Clinical Trials

    See Literature

    Prograf Granules Note

    Not Applicable

    Prograf Granules Patient Counseling

    See Literature

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