Generic Name and Formulations:
Tacrolimus 0.5mg, 1mg, 5mg; caps.

Company:
Astellas Pharma US, Inc.
Indications for PROGRAF:
Organ rejection prophylaxis in allogeneic hepatic transplant patients, in combination with corticosteroids; or in cardiac and renal transplant patients in combination with corticosteroids, azathioprine, or mycophenolate mofetil (MMF).

Limitations Of use:
Do not use simultaneously with cyclosporine. Reserve IV inj for patients unable to take oral caps. Concomitant sirolimus: not recommended in liver/heart transplant; safety and efficacy not established in kidney transplant.

Adult:
Give at least 6hrs after transplantation. If previously on IV infusion, initial oral dose may be given 8–12hrs post infusion. Hepatic: initially 0.1–0.15mg/kg/day in two divided dose every 12hrs. Cardiac: initially 0.075mg/kg/day in two divided doses every 12hrs. Concomitant corticosteroid is recommended early post-transplantation. Renal: 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 and IL-2 receptor antagonist; black patients may require higher doses. Renal or hepatic impairment: use lowest effective dose (see full labeling). Post-op oliguria: may delay therapy until renal function recovers.

Children:
Give at least 6hrs after transplantation. If previously on IV infusion, initial oral dose may be given 8–12hrs post infusion. Hepatic: initially 0.15–0.2mg/kg/day in two divided doses every 12hrs. Concomitant corticosteroid is recommended early post-transplantation.

Warnings/Precautions:
Increased risk of infections (eg, bacterial, viral, fungal, protozoal, cytomegalovirus), opportunistic infections including polyoma virus. Increased risk of lymphomas and other malignancies (eg, skin). Avoid sun, UV light. Diabetes: monitor for hyperglycemia. Hepatic or renal impairment; monitor and consider dose reduction. Obtain tacrolimus blood concentrations, serum creatinine, potassium, and fasting glucose periodically. 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. Pregnancy (Cat.C), nursing mothers: not recommended.

Interactions:
Concomitant sirolimus (see Indications), live vaccines: not recommended. Concomitant strong CYP3A4 inhibitors/inducers or substrates: must adjust dosing regimen, closely monitor tacrolimus blood concentrations and for QT prolongation. Avoid potassium-sparing diuretics, grapefruit juice, nelfinavir. Additive nephrotoxicity with cyclosporine (discontinue at least 24hrs prior to initiating the other drug), aminoglycosides, ganciclovir, amphotericin B, cisplatin. May be potentiated by calcium channel blockers (eg, diltiazem, nifedipine), antifungals (eg, fluconazole, ketoconazole), macrolides (eg, troleandomycin, clarithromycin, erythromycin), metoclopramide, lansoprazole, omeprazole, bromocriptine, chloramphenicol, cimetidine, cyclosporine, danazol, ethinyl estradiol, amiodarone, methylprednisolone, schisandra sphenanthera extract, protease inhibitors (eg, telaprevir, boceprevir, ritonavir), nefazodone, magnesium-aluminum-hydroxide. May be antagonized by carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, caspofungin, St. Johns Wort, sirolimus. Caution with mycophenolic acid.

See Also:
PROGRAF INJECTION

Pharmacological Class:
Immunosuppressant.

Adverse Reactions:
Tremor, headache, constipation, diarrhea, nausea, insomnia, hypertension, renal dysfunction, infections (eg,viral, cytomegalovirus, polyoma virus), hypophosphatemia, hyperkalemia, hypomagnesemia, hyperglycemia, nephrotoxicity or neurotoxicity (esp. in high doses), JC virus-associated progressive multifocal leukoencephalopathy, post-transplant 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, GI perforation; IV: anaphylactic reactions.

Metabolism:
Hepatic (CYP3A4); 99% protein bound.

Elimination:
Fecal (primary), renal.

Generic Availability:
YES

How Supplied:
Caps—100; Ampules—10