Prograf

Tacrolimus

Prophylaxis of transplant rejection in liver, kidney or heart allograft recipients. Treatment of allograft rejection resistant to treatment w/ other immunosuppressive medicinal products. Cap 0.5 & 1 mg: RA not adequately responsive to conventional therapies. Lupus nephritis (where the effect of steroids is insufficient or administration of steroids is difficult because of their adverse reactions).

Prophylaxis of liver transplant rejection Adult PO Initially 0.1-0.2 mg/kg/day in 2 divided doses approx 12 hr after surgery. IV Initially 0.01-0.05 mg/kg/day as a continuous 24-hr infusion. Childn PO Initially 0.3 mg/kg/day in 2 divided doses. IV Initially 0.05 mg/kg/day as a continuous 24-hr infusion. Prophylaxis of kidney transplant rejection Adult PO Initially 0.2-0.3 mg/kg/day in 2 divided doses approx 24 hr after surgery. IV Initially 0.05-0.1 mg/kg/day as a continuous 24-hr infusion. Childn PO Initially 0.3 mg/kg/day in 2 divided doses. IV 0.075-0.1 mg/kg/day as a continuous 24-hr infusion. Prophylaxis of heart transplant rejection Adult PO Initially 0.075 mg/kg/day in 2 divided doses 5 days after surgery. IV 0.01-0.02 mg/kg/day as a continuous 24-hr infusion. Childn w/o Ab induction Initially 0.03-0.05 mg/kg/day as a continuous 24-hr infusion, then PO 0.3 mg/kg/day 8-12 hr after discontinuing IV therapy. W/ Ab induction PO Initially 0.1-0.3 mg/kg/day in 2 divided doses. Treatment of allograft rejection in liver & kidney transplantation Increased Prograf doses, supplemental corticosteroid therapy & introduction of short courses of mono-/polyclonal Ab have been used to manage rejection episodes. Conversion to Prograf: Begin w/ initial oral dose recommended for primary immunosuppression. Treatment of allograft rejection in heart transplantation Increased Prograf doses, supplemental corticosteroid therapy & introduction of short courses of mono-/polyclonal Ab have been used to manage rejection episodes. Adult Conversion to Prograf: Initially 0.15 mg/kg/day in 2 divided doses. Childn Conversion to Prograf: Initially 0.2-0.3 mg/kg/day in 2 divided doses. Treatment of allograft rejection after lung transplantation PO Initially 0.1-0.15 mg/kg/day. Treatment of allograft rejection after pancreas transplantation PO Initially 0.2 mg/kg/day. Treatment of allograft rejection after intestinal transplantation PO Initially 0.3 mg/kg/day. RA PO Adult 3 mg once daily. Elderly Initially 1.5 mg once daily for 4 wk. May be increased to 3 mg once daily. Lupus nephritis (LN) PO Adult 3 mg once daily.

RA & LN: Should be taken with food: Take after dinner. Avoid grapefruit juice. Transplant: Should be taken on an empty stomach: Take at least 1 hr before or 2-3 hr after meals. Avoid grapefruit juice.

Hypersensitivity to tacrolimus, to any of the excipients, or other macrolides. Inj: Hypersensitivity to polyoxyethylene hydrogenated castor oil or structurally related compd.

Monitor significant changes in BP, ECG, neurological & visual status, fasting blood glucose levels, electrolytes (particularly K), liver & renal function tests, haematology parameters, coagulation values & plasma protein determinations during initial post-transplant period. Reports of GI perforation. Perform extra monitoring of tacrolimus conc during episodes of diarrhoea. Risk of cardiomyopathy; monitor high-risk patients receiving substantial immunosuppression using echocardiography or ECG pre- & post-transplant (eg, initially at 3 mth & then at 9-12 mth). May prolong QT interval & cause Torsades de Pointes. Reports of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders. Perform EBV-VCA serology before starting treatment. Increase risk of infections including opportunistic infections eg, BK virus-associated nephropathy & JC virus-associated progressive multifocal leukoencephalopathy; viral hepatitis eg, hepatitis B & C reactivation & de novo infection, as well as hepatitis E. Risk of posterior reversible encephalopathy syndrome. Reports of eye disorders, sometimes progressing to loss of vision. Cases of pure red cell aplasia. Limit exposure to sunlight & UV light. Rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Hypersensitivity to peanut or soya. Concomitant use w/ strong CYP3A4 inhibitors or inducers. Avoid concomitant use w/ St. John's wort or other herbal prep; combined administration w/ ciclosporin; high K intake or K-sparing diuretics; drugs known to have nephrotoxic or neurotoxic effects; live attenuated vaccines. May cause visual & neurological disturbances. Patients w/ severe liver impairment. Pregnancy. Women should not breast-feed while on treatment. RA: Use is limited only in patients w/ persisting symptoms despite appropriate therapies w/ NSAIDs or other antirheumatic drugs. Discontinue use if any abnormality is noted. Interstitial pneumonia may be aggravated in patients w/ RA-associated interstitial pneumonia. Concomitant use w/ methotrexate, other antirheumatic drugs, or anti-TNF α drugs in RA patients. Use in surgery eg, artificial joint replacement. Childn. LN: Patients in acute phase w/ high disease activity. Renal disorder may be aggravated. Patients should also receive appropriate therapy for coronary diseases eg, hyperlipidemia or HTN. Long-term use. Childn.

Transplantation: Hyperglycaemic conditions, DM, hyperkalaemia; insomnia; tremor, headache; HTN; diarrhoea, nausea; renal impairment. RA: Abnormal renal function (increased BUN, increased creatinine), GI disorders (abdominal pain, diarrhea, nausea), impaired glucose tolerance (increased HbA1C & increased blood glucose). LN: Increased urinary β2-microglobulin, increased urinary NAG, nasopharyngitis, hyperuricemia, leukocytosis, increased creatinine, diarrhea, increased BP, hyperglycemia.

Increased tacrolimus blood levels w/ CYP3A4 inhibitors: antifungal agents eg, ketoconazole, fluconazole, itraconazole, voriconazole, isavuconazole; erythromycin; HIV PIs eg, ritonavir, nelfinavir, saquinavir, HCV PIs eg, telaprevir, boceprevir; & the combination of ombitasvir & paritaprevir w/ ritonavir, when used w/ or w/o dasabuvir; letermovir; cobicistat; tyrosine kinase inhibitors nilotinib & imatinib; clotrimazole, clarithromycin, josamycin, nifedipine, nicardipine, diltiazem, verapamil, amiodarone, danazol, ethinylestradiol, omeprazole, nefazodone, herbal remedies containing extr of Schisandra sphenanthera; bromocriptine, cortisone, dapsone, ergotamine, gestodene, lidocaine, mephenytoin, miconazole, midazolam, nilvadipine, norethisterone, quinidine, tamoxifen, troleandomycin; grapefruit juice; lansoprazole, ciclosporin. Increased tacrolimus blood levels w/ other active substances known to have high affinity for plasma proteins (eg, NSAIDs, oral anticoagulants, oral antidiabetics); prokinetic agents (eg, metoclopramide); cimetidine; Mg-Al hydroxide. Decreased tacrolimus blood levels w/ rifampicin, phenytoin, St. John's wort; phenobarb; maintenance doses of corticosteroids; carbamazepine, metamizole, INH. Increased or decreased tacrolimus blood levels w/ high dose prednisolone or methylprednisolone. May affect metabolism of CYP3A4 substrates. Prolonged t_½ of ciclosporin. Synergistic/additive nephrotoxic effects w/ ciclosporin. Increased blood levels of phenytoin. Reduced clearance of steroid-based contraceptives. Changes in mycophenolic acid exposures when switching combination therapy from ciclosporin to tacrolimus. Increased toxic effects w/ medicinal products known to have nephrotoxic or neurotoxic effects (eg, aminoglycosides, gyrase inhibitors, vancomycin, sulfamethoxazole + trimethoprim, NSAIDs, ganciclovir or acyclovir). Enhanced nephrotoxicity w/ amphotericin B & ibuprofen. Increased risk of hyperkalaemia w/ high K intake or K-sparing diuretics (eg, amiloride, triamterene, spironolactone). Immunosuppressants may affect the response to vaccination & vaccination during treatment w/ tacrolimus may be less effective.

Immunosuppressants / Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

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

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