Prograf

Tacrolimus

Prophylaxis of organ rejection in patients receiving allogeneic liver or kidney transplants. Treatment of lupus nephritis.

Liver transplantation Adult Initially 0.1-0.15 mg/kg/day in 2 divided doses every 12 hr, to be administered no sooner than 6 hr after transplantation. In patients transferring from IV infusion to oral dosing, 1st oral dose should be given 8-12 hr after discontinuing IV infusion. Childn Initially 0.15-0.2 mg/kg/day in 2 divided doses every 12 hr. Kidney transplantation Adult Initially 0.2 mg/kg/day every 12 hr in 2 divided doses when in combination w/ azathioprine, or, 0.1 mg/kg/day every 12 hr in 2 divided doses when in combination w/ mycophenolate mofetil (MMF) & IL-2 receptor antagonist. Initial dose may be administered w/in 24 hr of transplantation. Lupus nephritis Adult 3 mg once daily after supper.

May be taken with or without food: Should be taken consistently either w/ food or w/o food. Avoid grapefruit juice.

Hypersensitivity.

Increased susceptibility to infection & possible development of lymphoma. Increased risk of development of post-transplant DM in Black & Hispanic kidney transplant patients. Hyperglycemia. Nephrotoxicity in high doses. Patients w/ persistent elevations of serum creatinine. Concomitant use w/ other nephrotoxic drugs. Do not use simultaneously w/ cyclosporine. Monitor serum K levels & do not use K-sparing diuretics during therapy. Neurotoxicity in high doses. Posterior reversible encephalopathy syndrome may develop. Risk of lymphoproliferative disorder in young childn who are at risk for primary EBV infection while immunosuppressed or who are switched to Prograf following long-term immunosuppression therapy. Increased risk for opportunistic infections & activation of latent viral infections including BK virus associated nephropathy & JC virus associated progressive multifocal leukoencephalopathy. Not recommended to use w/ sirolimus in heart transplant recipients. Not recommended w/ strong CYP3A4 inhibitors (eg, telaprevir, boceprevir, ritonavir, ketoconazole, itraconazole, voriconazole, clarithromycin) & inducers (eg, rifampin, rifabutin). Avoid use in patients w/ congenital long QT syndrome. Consider obtaining ECG & monitoring electrolytes (Mg, K, Ca) periodically during treatment in patients w/ CHF bradyarrhythmias, taking certain antiarrhythmic medications or other drugs that lead to QT prolongation, electrolyte disturbances eg, hypokalemia, hypocalcemia, hypomagnesemia. Avoid concomitant use w/ herbal prep containing St. John's wort. Risk factors for pure red cell aplasia (PRCA) eg, parvovirus B19 infection, underlying disease or concomitant drugs associated w/ PRCA. GI perforation. HTN; hyperkalemia; myocardial hypertrophy. Risk factor for the development of the CAD associated w/ systemic erythematosus especially in patients w/ lupus nephritis. DM. Limit exposure to sunlight & UV light. Regularly assess serum creatinine, K & fasting glucose; perform routine monitoring of metabolic & hematologic systems as clinically warranted. Patients w/ renal insufficiency. Post-transplant hepatic impairment. Use of appropriate contraception prior to starting treatment in females & males of reproductive potential. Pregnancy. Do not use in lactation. Ped patients w/ lupus nephritis & on kidney transplant.

Liver transplantation: Tremor, headache, diarrhea, HTN, nausea & abnormal renal function; diarrhea sometimes associated w/ other GI complaints eg, nausea & vomiting; hyperkalemia & hypomagnesemia; hyperglycemia. Kidney transplantation: Infection, tremor, HTN, abnormal renal function, constipation, diarrhea, headache, abdominal pain & insomnia. Lupus nephritis: Increased urinary β₂-microglobulin, increased urinary NAG, nasopharyngitis, hyperuricemia, leukocytosis, increased creatinine, diarrhea, increased BP & hyperglycemia.

Potential for additive or synergistic impairment of renal function w/ drugs that may be associated w/ renal dysfunction (eg, aminoglycosides, amphotericin B, & cisplatin). Additive/synergistic nephrotoxicity w/ cyclosporine. Rapid, sharp rise in levels after co-administration w/ strong CYP3A4 inhibitor, clarithromycin, despite initial dose reduction. Increased whole blood conc w/ CYP3A inhibitors (eg, diltiazem, nicardipine, nifedipine, verapamil; clotrimazole, fluconazole, itraconazole, ketoconazole, voriconazole; clarithromycin, erythromycin, troleandomycin; cisapride, metoclopramide; bromocriptine, chloramphenicol, cimetidine, cyclosporine, danazol, ethinyl estradiol, methylprednisolone, lansoprazole, omeprazole, PIs, nefazodone, Mg-Al-hydroxide, amiodarone, herbal products containing Schisandra sphenanthera extr, letermovir). Decreased whole blood conc w/ CYP3A inducers (eg, carbamazepine, phenobarb, phenytoin; rifabutin, caspofungin, rifampin; St. John's wort; sirolimus). Reduced levels w/ St. John's wort. Increased mean AUC & decreased mean C_max w/ Mg-Al-hydroxide. Decreased oral bioavailability & significant increase in clearance w/ rifampin (600 mg). Caution w/ HIV therapy eg, nephrotoxic drugs (eg, ganciclovir) or that are metabolized by CYP3A (eg, nelfinavir, ritonavir). Increased whole blood conc w/ most PIs (eg, ritonavir, telaprevir, boceprevir). May affect pharmacokinetics & increase conc of other drugs (eg, phenytoin). May affect CYP3A-mediated metabolism w/ grapefruit juice. Not recommended in combination w/ sirolimus in prevention of graft rejection. Avoid use w/ live vaccines. Potential for increased mycophenolic acid (MPA) exposure after crossover from cyclosporine to tacrolimus in patients concomitantly receiving MMF or MPA. Pharmacokinetics may be impacted by changes in liver function during direct acting antiviral therapy, related to clearance of HCV.

Immunosuppressants

L04AD02 - tacrolimus ; Belongs to the class of calcineurin inhibitors. Used as immunosuppressants.

Rx