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 the completion of surgery. Prophylaxis of liver transplant rejection Initially 0.1-0.2 mg/kg/day once daily in the morning approx 12-18 hr after the completion of surgery. Allograft rejection after kidney or liver transplantation For conversion from other immunosuppressants to once daily tacrolimus monohydrate, treatment should begin w/ the initial oral dose recommended in kidney & liver transplantation respectively for prophylaxis of transplant rejection. Allograft rejection after heart transplantation Adult In those converted to tacrolimus monohydrate, initially 0.15 mg/kg/day once daily in the morning. Allograft rejection after transplantation of other allografts Lung-transplanted patient Initially 0.10-0.15 mg/kg/day; pancreas-transplanted patient Initially 0.2 mg/kg/day; intestinal transplantation Initially 0.3 mg/kg/day.

Should be taken on an empty stomach: Take in the morning on an empty stomach (at least 1 hr before or 2-3 hr after meal). Cap to be taken immediately following removal from the blister. Swallow whole w/ water. Avoid grapefruit juice.

Hypersensitivity to tacrolimus & to other macrolides.

Maintain patients on a single formulation of tacrolimus w/ the corresponding daily dosing regimen. Treatment w/ other immunosuppressive medicinal products; prophylaxis of transplant rejection in adult heart allograft recipients. Monitor the following parameters during the initial post-transplant period on a routine basis: BP, ECG, neurological & visual status, fasting blood glucose levels, electrolytes (particularly K), liver & renal function tests, haematology parameters, coagulation values & plasma protein determinations. Concomitant use w/ strong CYP3A4 inhibitors/inducers; St. John's wort-containing herbal prep; ciclosporin (avoid combined administration & in patients previously receiving ciclosporin); high K intake or K-sparing diuretic; nephrotoxic or neurotoxic drugs; live attenuated vaccines. Significant change in blood levels during diarrhoea episodes. Increased risk of cardiac disorders in pre-existing heart disease, corticosteroid usage, HTN, renal or hepatic dysfunction, infections, fluid overload & oedema. May prolong QT interval & cause torsades de pointes. Patients w/ risk factors for QT prolongation, including w/ personal or family history of QT prolongation, CHF, bradyarrhythmias & electrolyte abnormalities; diagnosed or suspected congenital long QT syndrome. May increase risk of lymphoproliferative disorders & malignancies when in concomitant w/ immunosuppressives eg, antilymphocytic Abs (eg, basiliximab, daclizumab). Limit exposure to sunlight & UV light. Increased risk for opportunistic infections eg, BK virus-associated nephropathy & JC virus-associated progressive multifocal leukoencephalopathy. Perform radiological procedure (eg, MRI) if patients present w/ symptoms indicating posterior reversible encephalopathy syndrome eg, headache, altered mental status, seizures, & visual disturbances. Adequately control BP & seizure, & discontinue use immediately if posterior reversible encephalopathy syndrome is diagnosed. Pure red cell aplasia. Non-Caucasians & those at elevated immunological risk (eg, retransplantation, evidence of panel reactive Abs); severe liver impairment. Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Hypersensitivity to peanut or soya. May cause visual & neurological disturbances which may be enhanced if administered w/ alcohol. May affect ability to drive & use machines. Use of appropriate contraception prior to starting treatment in females & males of reproductive potential. Pregnancy. Do not use in lactation. Not recommended in childn <18 yr.

Headache, tremor; diarrhoea, nausea; renal impairment; DM, hyperglycaemic conditions, hyperkalaemia; abnormal LFT; HTN; insomnia. Ischaemic coronary artery disorders, tachycardia; anaemia, thrombocytopenia, leukopenia, abnormal RBC analyses, leukocytosis; nervous system disorders, seizures, disturbances in consciousness, peripheral neuropathies, dizziness, paraesthesias & dysaesthesias, impaired writing; eye disorders, blurred vision, photophobia; tinnitus; parenchymal lung disorders, dyspnoea, pleural effusion, cough, pharyngitis, nasal congestion & inflammations; GI signs & symptoms, vomiting, GI & abdominal pains; GI inflammatory conditions, haemorrhages, ulceration & perforation; ascites, stomatitis & ulceration, constipation, dyspeptic signs & symptoms, flatulence, bloating & distension, loose stools; renal failure, acute renal failure, toxic nephropathy, renal tubular necrosis, urinary abnormalities, oliguria, bladder & urethral symptoms; rash, pruritus, alopecias, acne, increased sweating; arthralgia, back pain, muscle spasms, pain in extremity; metabolic acidoses, other electrolyte abnormalities, hyponatraemia, fluid overload, hyperuricaemia, hypomagnesaemia, hypokalaemia, hypocalcaemia, decreased appetite, hypercholesterolaemia, hyperlipidaemia, hypertriglyceridaemia, hypophosphataemia; increased blood alkaline phosphatase, increased wt; primary graft dysfunction; thromboembolic & ischaemic events, vascular hypotensive disorders, haemorrhage, peripheral vascular disorders; febrile disorders, pain & discomfort, asthenic conditions, oedema, disturbed body temp perception; bile duct disorders, hepatocellular damage & hepatitis, cholestasis & jaundice; confusion & disorientation, depression, anxiety symptoms, hallucination, mental disorders, depressed mood, mood disorders & disturbances, nightmare.

May increase whole blood trough conc & increase risk of serious adverse reactions (eg, neurotoxicity, QT prolongation) w/ grapefruit or grapefruit juice; moderate or weak CYP3A4 inhibitors eg, antifungal agents (eg, fluconazole, isavuconazole, clotrimazole, miconazole), macrolides (eg, azithromycin), Ca channel blockers (eg, nifedipine, nicardipine, diltiazem, verapamil), amiodarone, danazol, ethinylestradiol, lansoprazole, omeprazole, HCV antivirals (elbasvir/grazoprevir & glecaprevir/pibrentasvir), CMV antiviral (letermovir), & tyrosine kinase inhibitors (nilotinib, crizotinib & imatinib) & (Chinese) herbal remedies containing extr of Schisandra sphenanthera; bromocriptine, cortisone, dapsone, ergotamine, gestodene, lidocaine, mephenytoin, midazolam, nilvadipine, norethisterone, quinidine, tamoxifen; prokinetic agents eg, metoclopramide, cimetidine & Mg-Al-hydroxide. May increase whole blood trough conc & synergistic/additive nephrotoxic effects w/, & prolonged t_½ of ciclosporin. May enhance nephrotoxic or neurotoxic effects w/ products known to have nephrotoxic or neurotoxic effects (eg, aminoglycosides, gyrase inhibitors, vancomycin, sulfamethoxazole + trimethoprim, NSAIDs, ganciclovir, acyclovir, amphotericin B, ibuprofen, cidofovir, foscarnet). May increase whole blood trough conc & increase risk of serious adverse reactions (eg, nephrotoxicity, neurotoxicity, QT prolongation) which requires close monitoring w/ strong CYP3A4 inhibitors eg, antifungal agents (eg, ketoconazole, itraconazole, posaconazole, voriconazole), macrolides (eg, telithromycin, troleandomycin, clarithromycin, josamycin, erythromycin), HIV PIs (eg, ritonavir, nelfinavir, saquinavir), HCV PIs (eg, telaprevir, boceprevir, & combination of ombitasvir & paritaprevir w/ ritonavir, when used w/ & w/o dasabuvir), nefazodone, pharmacokinetic enhancer (cobicistat), & kinase inhibitors (idelalisib, ceritinib). May decrease whole blood trough conc & increase risk of rejection w/ strong CYP3A4 inducers eg, rifampicin, phenytoin, carbamazepine, apalutamide, enzalutamide, mitotane, or St. John's wort (Hypericum perforatum); moderate CYP3A4 inducers eg, metamizole, phenobarb, INH, rifabutin, efavirenz, etravirine, nevirapine; maintenance doses of corticosteroids. Possible interactions w/ products/other active substances known to have high affinity for plasma proteins eg, NSAIDs, oral anticoagulants, oral antidiabetics. May have impact on blood levels (increase or decrease) w/ high dose prednisolone or methylprednisolone. May have impact on pharmacokinetics by changes in liver function during, & may decrease blood levels w/ direct-acting antiviral therapy, related to clearance of hepatitis virus. May be associated w/ hyperkalaemia, or may increase pre-existing hyperkalaemia w/ high K intake, or K-sparing diuretics (eg, amiloride, triamterene, or spironolactone); other agents that increase serum K eg, trimethoprim & cotrimoxazole (trimethoprim/sulfamethoxazole). Increased blood level of phenytoin. May reduce clearance of steroid-based contraceptives leading to increased hormone exposure. Potentially decrease clearance & increase t_½ of pentobarbital & antipyrine. May interfere w/ mycophenolic acid's enterohepatic cycle potentially having to reduce plasma level & efficacy of mycophenolic acid. May affect response to vaccination; avoid use of live attenuated vaccines.

Immunosuppressants

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

Rx