Astellas Pharma


Concise Prescribing Info
Tacrolimus monohydrate
Prophylaxis of transplant rejection in adult kidney or liver allograft recipients. Kidney or liver allograft rejection resistant to treatment w/ other immunosuppressive medicinal products in adult patients.
Dosage/Direction for Use
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 Advagraf, treatment should begin w/ the initial oral dose recommended in kidney & liver transplantation, respectively for prophylaxis of transplant rejection.
Should be taken on an empty stomach: Take at least 1 hr before or 2-3 hr after a meal. Swallow whole, do not chew/crush. Avoid consumption of grapefruit & grapefruit juice.
Hypersensitivity to tacrolimus & to other macrolides.
Special Precautions
Observe medication errors including inadvertent, unintentional or unsupervised substitution of immediate- or prolonged-release tacrolimus formulations. Treatment of allograft rejection resistant to treatment w/ other immunosuppressives in adults; prophylaxis of transplant rejection in adult heart allograft recipients. Monitor relevant 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. Concomitant use w/ strong CYP3A4 inhibitors/inducers; herbal prep containing St. John's wort; ciclosporin; high K intake or K-sparing diuretics; nephrotoxic or neurotoxic drugs; live attenuated vaccines. GI perforation. Monitor high-risk patients receiving substantial immunosuppression, using procedures eg, echocardiography or ECG pre- & post-transplant; consider dose reduction if abnormalities develop. Patients w/ risk factor for QT prolongation, including w/ a personal or family history of QT prolongation, CHF, bradyarrhythmias & electrolyte abnormalities. Patients diagnosed or suspected to have congenital long QT syndrome or acquired QT prolongation; concomitantly using known QT prolonging-medications; induce electrolyte abnormalities; increase tacrolimus exposure. Carefully monitor EBV-PCR during treatment. Limit exposure to sunlight & UV light. Increased risk for opportunistic infections eg, BK virus-associated nephropathy & JC virus-associated progressive multifocal leukoencephalopathy; consider differential diagnosis in immunosuppressed patients w/ deteriorating hepatic or renal function or neurological symptoms. Discontinue immediately, adequate BP & seizure control is advised if posterior reversible encephalopathy syndrome is diagnosed. Pure Red Cell Aplasia. Non-Caucasians & at elevated immunological risk. Patients w/ rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Hypersensitivity to peanut or soya. May cause visual & neurological disturbances & may be enhanced w/ alcohol. Dose reduction in patients w/ severe liver impairment. Pregnancy & lactation. Not recommended for use in childn <18 yr.
Adverse Reactions
DM, hyperglycaemic conditions, hyperkalaemia; insomnia; headache, tremor; HTN; diarrhoea, nausea; abnormal liver function tests; renal impairment. Anaemia, thrombocytopenia, leukopenia, abnormal RBC analyses, leukocytosis; metabolic acidoses, other electrolyte abnormalities, hyponatraemia, fluid overload, hyperuricaemia, hypomagnesaemia, hypokalaemia, hypocalcaemia, decreased appetite, hypercholesterolaemia, hyperlipidaemia, hypertriglyceridaemia, hypophosphataemia; confusion & disorientation, depression, anxiety symptoms, hallucination, mental disorders, depressed mood, mood disorders & disturbances, nightmare; nervous system disorders, seizures, disturbances in consciousness, peripheral neuropathies, dizziness, paraesthesias & dysaesthesias, impaired writing; eye disorders, blurred vision, photophobia; tinnitus; ischaemic CAD, tachycardia; thromboembolic & ischaemic events, vascular hypotensive disorders, haemorrhage, peripheral vascular disorders; parenchymal lung disorders; dyspnoea, pleural effusion, cough, pharyngitis, nasal congestion & inflammations; vomiting, GI & abdominal pains, GI signs & symptoms, inflammatory conditions, haemorrhages, ulceration & perforation, ascites, stomatitis & ulceration, constipation, dyspeptic signs & symptoms, flatulence, bloating & distension, loose stools; bile duct disorders, hepatocellular damage & hepatitis, cholestasis & jaundice; rash, pruritus, alopecias, acne, increased sweating; arthralgia, back pain, muscle spasms, pain in extremity; renal failure, acute renal failure, toxic nephropathy, renal tubular necrosis, urinary abnormalities, oliguria, bladder & urethral symptoms; febrile disorders, pain & discomfort, asthenic conditions, oedema, disturbed body temp perception, increased blood alkaline phosphatase, increased wt; primary graft dysfunction.
Drug Interactions
Potentially increase tacrolimus blood levels w/ CYP3A4 inhibitors [eg, ketoconazole, fluconazole, itraconazole, voriconazole, macrolide antibiotic (erythromycin), HIV PIs (eg, ritonavir, nelfinavir, saquinavir) or HCV PIs (eg, telaprevir, boceprevir) & letermovir; clotrimazole, clarithromycin, josamycin, nifedipine, nicardipine, diltiazem, verapamil, amiodarone, danazol, ethinylestradiol, omeprazole, nefazodone, Schisandra sphenanthera extr; bromocriptine, cortisone, dapsone, ergotamine, gestodene, lidocaine, mephenytoin, miconazole, midazolam, nilvadipine, norethindrone, quinidine, tamoxifen, (triacetyl) oleandomycin; grapefruit juice; lansoprazole & ciclosporin]; NSAIDs, oral anticoagulants, oral antidiabetics. May increase systemic exposure of tacrolimus by prokinetic agents (eg, metoclopramide & cisapride), cimetidine, Mg & Al hydroxide. Potentially decrease tacrolimus blood levels w/ CYP3A4 inducers (eg, rifampicin, phenytoin, St. John's wort; phenobarb; corticosteroid maintenance doses; carbamazepine, metamizole & INH). Potential increase or decrease tacrolimus blood levels w/ high-dose prednisolone or methylprednisolone for the treatment of acute rejection. Prolonged t½ of ciclosporin. Increased blood level of phenytoin. May reduce clearance of steroid-based contraceptives. May potentially decrease clearance & increase t½ of pentobarbital & antipyrine. May increase nephrotoxic or neurotoxic effects w/ aminoglycosides, gyrase inhibitors, vancomycin, co-trimoxazole, NSAIDs, ganciclovir or aciclovir. Enhanced nephrotoxicity w/ amphotericin B & ibuprofen. May increase pre-existing hyperkalaemia w/ high K intake or K-sparing diuretics (eg, amiloride, triamterene, or spironolactone). Avoid live attenuated vaccines.
MIMS Class
ATC Classification
L04AD02 - tacrolimus ; Belongs to the class of calcineurin inhibitors. Used as immunosuppressants.
Advagraf PR cap 5 mg
Advagraf PR cap 0.5 mg
Advagraf PR cap 1 mg
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