Advagraf

Tacrolimus (as monohydrate)

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

Treatment of allograft rejection after heart transplantation Initially 0.15 mg/kg once daily in the morning. Prophylaxis of kidney transplant rejection 0.2-0.3 mg/kg once daily in the morning w/in 24 hr after completion of surgery. Prophylaxis of liver transplant rejection 0.1-0.2 mg/kg once daily in the morning approx 12-18 hr after completion of surgery. Conversion of Prograf-treated patients to Advagraf Convert on 1:1 (mg:mg) total daily dose basis. Administer in the morning.

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 consumption of grapefruit & grapefruit juice.

Hypersensitivity to tacrolimus or other macrolides.

Hypersensitivity to peanut or soya. Discontinue therapy immediately if posterior reversible encephalopathy (PRES) is diagnosed. Increased risk of developing lymphoproliferative disorders; for opportunistic infections (bacterial, fungal, viral & protozoal). Risk of thrombotic microangiopathy. GI perforation; cardiomyopathies; EBV-associated lymphoproliferative disorders; pure red cell aplasia. May prolong the QT interval & cause Torsades de Pointes. Pre-existing heart disease, corticosteroid usage, HTN, renal or hepatic dysfunction, infections, fluid overload, oedema. Patients w/ risk factors for & personal or family history of QT prolongation, CHF, bradyarrhythmias & electrolyte abnormalities; diagnosed or suspected congenital long QT syndrome or acquired QT prolongation; patients on concomitant drugs known to prolong QT interval, induce electrolyte abnormalities or known to increase tacrolimus exposure. May cause visual & neurological disturbances. Non-Caucasian & patients at elevated immunological risk. Monitor BP, ECG, neurological & visual status, fasting blood glucose levels, electrolytes (particularly K), liver & renal function tests, haematology parameters, coagulation values, plasma protein determinations; blood levels when given w/ CYP3A4 inhibitors/inducers, or during diarrhoea episodes. Regularly monitor maternal blood glucose; monitor & control BP during pregnancy. Early & frequent monitoring of blood level w/in 1st few days of coadministration w/ CYP3A4 inhibitors & monitor for renal function, QT prolongation w/ ECG, & other side effects. EBV-viral capsid antigen serology should be ascertained before starting treatment & carefully monitor EBV-PCR. Limit sun & UV light exposure. Avoid coadministration w/ St. John's wort, ciclosporin, live attenuated vaccines; high K intake or K-sparing diuretics. Concurrent use w/ drugs known to have neurotoxic effects; nephrotoxic drugs; mammalian target of rapamycin (mTOR) inhibitors. Galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Impaired renal function. Severe liver impairment. Females & males of reproductive potential should use appropriate contraception prior to start of therapy. Increased hyperglycemia in pregnant women w/ diabetes including gestational diabetes. Exacerbated HTN in pregnant women & increased pre-eclampsia. Not to be used during lactation. Prematurity, birth defects/congenital anomalies, low birth wt & fetal distress in infants exposed to treatment in utero. Not recommended for use in childn <18 yr.

DM, hyperglycaemic conditions, hyperkalaemia; insomnia; headache, tremor; HTN; diarrhoea, nausea; abnormal LFTs; 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; 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; 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. TEN (Lyell's syndrome). SJS.

Increased blood levels w/ CYP3A4 inhibitors, antifungal agents (eg, ketoconazole, fluconazole, itraconazole & voriconazole), erythromycin, HIV PIs (eg, but not limited to ritonavir, nelfinavir, saquinavir), HCV PIs (eg, but not limited to telaprevir, boceprevir), or letermovir, clotrimazole, clarithromycin, josamycin, nifedipine, nicardipine, diltiazem, amiodarone, verapamil, danazol, ethinylestradiol, omeprazole, nefazodone, Schisandra sphenanthera extr, grapefruit juice. Potential inhibition of metabolism w/ bromocriptine, cortisone, dapsone, ergotamine, gestodene, lidocaine, mephenytoin, miconazole, midazolam, nilvadipine, norethindrone, quinidine, tamoxifen, (triacetyl)oleandomycin. Increased whole blood conc w/ lansoprazole & ciclosporin. Drugs known to have high affinity for plasma proteins eg, NSAIDs, oral anticoagulants/antidiabetics. Increased systemic exposure w/ prokinetics (eg, metoclopramide & cisapride), cimetidine & Mg-Al hydroxide. Decreased blood levels w/ rifampicin, phenytoin, St. John's wort, phenobarb, corticosteroids, carbamazepine, metamizole, INH, caspofungin. Increased or decreased blood levels w/ high dose prednisolone or methylprednisolone. May potentially decrease clearance & increase t½ of pentobarbital & antipyrine. Prolonged t_½ of ciclosporin. Increased blood level of phenytoin. Reduced clearance of steroid-based contraceptives. Increased nephrotoxic or neurotoxic effects w/ aminoglycosides, gyrase inhibitors, vancomycin, cotrimoxazole, NSAIDs, ganciclovir, aciclovir. Enhanced nephrotoxicity w/ amphotericin B, ibuprofen. Increased pre-existing hyperkalaemia w/ high K intake or K-sparing diuretics (eg, amiloride, triamterene or spironolactone). Live attenuated vaccines. Direct-acting antiviral therapy.

Immunosuppressants

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

S