EVEROCAN

What it is

EVEROCAN contains everolimus, a white to faintly yellow powder that is practically insoluble in water but soluble in organic solvents such as ethanol and methanol. It is supplied as an uncoated tablet. EVEROCAN is available in four strengths: 0.25 mg, 0.5 mg, 0.75 mg and 1 mg tablets.

Approved indications

— Prophylaxis of organ rejection in adult patients at mild to moderate immunological risk receiving an allogeneic renal transplant. — Prophylaxis of organ rejection in adult patients at mild to moderate immunological risk receiving an allogeneic cardiac transplant. — Prophylaxis of organ rejection in adult patients receiving an allogeneic hepatic transplant.

Dosing overview

For kidney and heart transplantation, an initial dose regimen of 0.75 mg twice a day is recommended for the general population, administered as soon as possible after transplantation. For liver transplantation, the dose of 1.0 mg twice a day is recommended with the initial dose approximately 4 weeks after transplantation. The daily dose should always be given orally in two divided doses, consistently either with or without food and at the same time as ciclosporin microemulsion or tacrolimus, and tablets should be taken whole and not crushed before use. Everolimus has a narrow therapeutic index which may require adjustments in dosing to maintain therapeutic response and safety, and routine everolimus whole blood therapeutic drug level monitoring is recommended. Patients achieving everolimus whole blood trough levels ≥3.0 ng/mL have been found to have a lower incidence of biopsy-proven acute rejection compared with patients whose trough levels are below 3.0 ng/mL, and the upper limit to the therapeutic range is recommended at 8 ng/mL.

Key safety warnings

Patients on a regimen of immunosuppressive medicinal products, including everolimus, are at increased risk of developing infections especially with opportunistic pathogens, and fatal infections and sepsis have been reported. Among opportunistic conditions are polyomavirus infections including BK virus-associated nephropathy which can lead to kidney graft loss and potentially fatal JC virus-associated progressive multiple leukoencephalopathy; these infections should be considered in the differential diagnosis of immunosuppressed patients with deteriorating kidney graft function or neurological symptoms. Patients receiving everolimus are at increased risk of developing lymphomas or other malignancies, particularly of the skin, and the absolute risk seems related to the duration and intensity of immunosuppression rather than to the use of a specific agent. Patients should be monitored regularly for skin neoplasms and advised to minimise exposure to UV light, sunlight and use appropriate sunscreen. Concomitant use of everolimus and ciclosporin microemulsion or tacrolimus has been associated with increased serum cholesterol and triglycerides that may require treatment, and patients receiving everolimus should be monitored for hyperlipidemia and, if necessary, treated with lipid-lowering agents and appropriate dietary adjustments. In renal and cardiac transplant, everolimus may potentiate the renal toxicity of ciclosporin, and everolimus with full-dose ciclosporin increases the risk of renal dysfunction; reduced doses of ciclosporin are required for use in combination with everolimus in order to avoid renal dysfunction. Cases of interstitial lung disease, implying lung intraparenchymal inflammation and/or fibrosis of non-infectious etiology, some fatal, have occurred in patients receiving everolimus; mostly, the condition resolves after discontinuation of everolimus and/or addition of glucocorticoids, however, fatal cases have also occurred. Everolimus has been shown to increase the risk of new onset diabetes mellitus after transplant, and blood glucose concentrations should be monitored closely in patients treated with everolimus.

Contraindications

Everolimus is contraindicated in patients with a known hypersensitivity to everolimus, sirolimus or to any of the excipients.

PBS listing

EVEROCAN 0.75 mg tablets are listed on the PBS with an ex-manufacturer price of A$397.81. EVEROCAN 1 mg tablets are listed on the PBS with an ex-manufacturer price of A$530.42. EVEROCAN 0.5 mg tablets are listed on the PBS with an ex-manufacturer price of A$265.21. EVEROCAN 0.25 mg tablets are listed on the PBS with an ex-manufacturer price of A$151.93. The 0.75 mg and 1 mg strengths have four PBS items each with restrictions that include streamlined and unrestricted categories, whilst the 0.5 mg and 0.25 mg strengths have three PBS items each with streamlined and unrestricted restrictions.

Regulatory history

EVEROCAN was first listed on the ARTG on 2021-04-21 across all four strengths (0.25 mg, 0.5 mg, 0.75 mg and 1 mg) under licence category RE.