Advagraf

Tacrolimus

Prophylaxis of transplant rejection in adult kidney or liver allograft recipients. Treatment of allograft rejection resistant to treatment w/ other immunosuppressants in adults.

Prophylaxis of kidney transplant rejection Initially 0.2-0.3 mg/kg/day once daily in the morning w/in 24 hr after surgery. Prophylaxis of liver transplant rejection Initially 0.1-0.2 mg/kg/day once daily in the morning approx 12-18 hr after surgery. Treatment of allograft rejection Increased doses of tacrolimus, supplemental corticosteroid therapy, & introduction of short courses of mono-/polyclonal Ab have been used to manage rejection episodes. Treatment of allograft rejection after kidney or liver transplantation Conversion from other immunosuppressants to Advagraf: Begin w/ the initial oral dose recommended for primary immunosuppression. Treatment of allograft rejection after heart transplantation Initially 0.15 mg/kg/day once daily in the morning. Treatment of allograft rejection after lung transplantation Initially 0.1-0.15 mg/kg/day. Treatment of allograft rejection after pancreas transplantation Initially 0.2 mg/kg/day. Treatment of allograft rejection after intestinal transplantation Initially 0.3 mg/kg/day.

Should be taken on an empty stomach: Take at least 1 hr before or 2-3 hr after meals. Swallow whole, do not chew/crush. Avoid grapefruit & grapefruit juice.

Hypersensitivity to tacrolimus, to any of the excipients, or other macrolides.

Monitor 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 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. Limited experience in non-Caucasian patients & patients at elevated immunological risk (eg, retransplantation, evidence of panel reactive Ab). 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. Not recommended for use in childn <18 yr.

Tremor, renal impairment, hyperglycaemic conditions, DM, hyperkalaemia, infections, HTN & insomnia.

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, norethindrone, quinidine, tamoxifen, (triacetyl)oleandomycin; 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, cisapride); 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, cotrimoxazole, 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

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

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