TACROGRAF

What it is

TACROGRAF contains tacrolimus monohydrate equivalent to tacrolimus 0.5 mg, 1 mg, or 5 mg per hard gelatin capsule. Tacrolimus is a macrolide lactone with potent in vitro and in vivo immunosuppressive activity. It inhibits the formation of cytotoxic lymphocytes primarily responsible for graft rejection and suppresses T cell activation and T helper cell dependent B cell proliferation.

Approved indications —

Liver allograft transplantation in adults and children. — Kidney allograft transplantation in adults and children. — Lung allograft transplantation in adults and children. — Heart allograft transplantation in adults and children.

Dosing overview

The oral daily dose should be taken in two divided doses, in the morning and in the evening, on an empty stomach or at least one hour before or two to three hours after a meal to achieve maximal absorption. Tacrolimus doses should be adjusted according to individual patient requirements. Higher mg/kg doses may be required in children compared with adults to achieve the same tacrolimus blood concentration; initial oral doses should be 0.15 to 0.30 mg/kg/day as two divided doses. Monitoring of tacrolimus whole blood concentrations in conjunction with other laboratory and clinical parameters is considered an essential aid to patient management.

Key safety warnings

Post-transplant insulin-dependent diabetes mellitus was reported in kidney transplant patients, with a median time to onset of 68 days; insulin dependence was reversible in 15 per cent of these patients at one year and in 50 per cent at two years post-transplant. The risk-benefit ratio should be carefully considered before using tacrolimus in kidney patients with a pre-transplant diabetic condition. Neurological and CNS disorders have been reported with tacrolimus therapy, including tremor, headache, changes in motor function, sensory function or mental status, insomnia, seizures, coma and delirium. Posterior reversible encephalopathy syndrome has been reported in patients treated with tacrolimus; if patients present with symptoms such as headache, altered mental status, seizures and visual disturbances, a radiological procedure should be performed and immediate discontinuation of systemic tacrolimus is advised. Tacrolimus can cause both acute and chronic renal function impairment due to its vasoconstrictive effect on renal vasculature, toxic tubulopathy and tubular-interstitial effects. These changes have been observed to be dose dependent and improvements have been associated with reduced dosing. Tacrolimus should not be used simultaneously with ciclosporin; tacrolimus or ciclosporin should be discontinued at least 24 hours prior to initiating the other. Mild to severe hyperkalaemia was reported in patients treated with tacrolimus, especially in patients with renal impairment; serum potassium levels should be monitored and potassium sparing diuretics should not be used during tacrolimus therapy. Patients treated with tacrolimus are at increased risk of developing lymphomas and other malignancies, particularly of the skin; the risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. Tacrolimus predisposes patients to the development of bacterial, fungal, parasitic and viral infections; over suppression of the immune system can increase susceptibility to opportunistic infections, sepsis and fatal infections such as BK virus associated nephropathy, JC virus associated progressive multifocal leukoencephalopathy and CMV infection. Hypertension is a common adverse effect of tacrolimus therapy; antihypertensive therapy may be required. Tacrolimus may prolong the QT interval and may cause Torsade de Pointes.

Contraindications

Hypersensitivity to tacrolimus or other macrolides, or to other ingredients of the capsules.

PBS listing

Information about PBS listing for TACROGRAF is not provided in the source documents.

Regulatory history

TACROGRAF received initial ARTG registration on 8 August 2011. The brand TACROGRAF comprises six ARTG registrations for tacrolimus 0.5 mg, 1 mg and 5 mg capsules in bottle and blister pack formats, all first listed on 18 August 2011.