Everolimus

CLINICAL USE

Prophylaxis of acute rejection in allogenic renal and cardiac transplants, in combination with ciclosporin and prednisolone

DOSE IN NORMAL RENAL FUNCTION

0.75 mg twice daily(Titrate according to levels – see ‘Other Information)

PHARMACOKINETICS

Molecular weight :958.2

%Protein binding :74

%Excreted unchanged in urine : <5

Volume of distribution (L/kg) :235–449 litres

half-life – normal/ESRD (hrs) :18–35/Unchanged

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Dose as in normal renal function

<10 : Dose as in normal renal function

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Unknown dialysability. Dose as in normal renal function

HD :Unknown dialysability. Dose as in normal renal function

HDF/high flux :Unknown dialysability. Dose as in normal renal function

CAV/VVHD :Unknown dialysability. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Ciclosporin: increases everolimus AUC by 168% and Cmax by 82%Rifampicin: decreases everolimus levels by factor of 3. Increase dose ×3 and monitor levels

Antifungals: fluconazole, ketoconazole, itraconazole increase everolimus blood levels

Antibacterials: erythromycin, clarithromycin increase everolimus levels. Rifabutin, rifampicin decrease everolimus levelsAnticonvulsants: carbamazepine, phenobarbital, phenytoin decrease everolimus levelsSt John’s wort: decreases everolimus levels

Grapefruit juice: increases everolimus levels

ADMINISTRATION

Reconstition

–

Route

Oral

Rate of Administration

–

Comments

–

OTHER INFORMATION

None of the metabolites contributes significantly to the immunosuppressive activity of everolimusC max and AUC are reduced by 60% and 16% respectively when everolimus is taken with a high fat meal. Take doses consistently either with or without food to achieve consistent blood levelsPatients achieving whole-blood trough levels of ≥3.0 ng/mL have been found to have a lower incidence of biopsy-proven acute rejection

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