Indications: Breast cancer, advanced:

Treatment of advanced hormone receptor-positive, HER2-negative breast cancer in postmenopausal women (in combination with exemestane and after letrozole or anastrozole failure)

Pancreatic neuroendocrine tumors:

Treatment of advanced, metastatic or unresectable pancreatic neuroendocrine tumors (PNET) Limitations of use: Not indicated for the treatment of functional carcinoid tumors.

Renal angiomyolipoma with tuberous sclerosis complex

Treatment of renal angiomyolipoma with tuberous sclerosis complex (TSC) not requiring immediate surgery Renal cell carcinoma, advanced (Afinitor only): Treatment of advanced renal cell cancer (RCC) after sunitinib or sorafenib failure.

Subependymal giant cell astrocytoma Treatment of subependymal giant cell astrocytoma (SEGA) associated with TSC which requires intervention, but cannot be curatively resected.

Liver transplantation (Zortress only):

Prophylaxis of organ rejection in liver transplantation (in combination with corticosteroids and reduced doses of tacrolimus).

Renal transplantation (Zortress only):

Prophylaxis of organ rejection in renal transplant patients at low to moderate immunologic risk (in combination with basiliximab induction and concurrent with corticosteroids and reduced doses of cyclosporine).

Cautions: monitor blood-glucose concentration, serum- triglycerides and serum-cholesterol before treatment and periodically thereafter.

concomitant use of drugs that increase risk of bleeding. history of bleeding disorders.

monitor renal function before treatment and periodically thereafter.

reduce dose or discontinue if severe Side effects occur. Contra-indications: Hypersensitivity to everolimus, sirolimus, other rapamycin derivatives, or any component of the formulation.

Renal Impairment: No dosage adjustment is necessary.

Hepatic Impairment: Mild impairment (Child-Pugh class A): Breast cancer, PNET, RCC, renal angiomyolipoma: Reduce dose to 7.5 mg once daily

if not tolerated, may further reduce to 5 mg once daily. Liver or renal transplantation:

Reduce initial dose by ~33% (individualize subsequent dosing based on therapeutic drug monitoring (target trough concentration: 3 to 8 ng/ml).

SEGA: U.S. labeling:

Adjustment to initial dose may not be necessary subsequent dosing is based on therapeutic drug monitoring (monitor ~2 weeks after initiation, dosage modifications, or after any change in hepatic status; target trough concentration: 5 to 15 ng/ml).

Canadian labeling:

Initial: Patients ≥18 years of age:

75% of usual dose based on calculated BSA (rounded to the nearest strength). Assess trough concentrations ~2 weeks after initiation, dosage modifications, or after any change in hepatic status.

Target trough concentration:

5 to 15 ng/ml (may increase dose within the target range to achieve higher concentrations as tolerated).

Patients <18 years of age: Use is not recommended. Moderate impairment (Child-Pugh class B):

Breast cancer, PNET, RCC, renal angiomyolipoma:

Reduce dose to 5 mg once daily if not tolerated, may further reduce to 2.5 mg once daily. Liver or renal transplantation:

Reduce initial dose by ~50% (individualize subsequent dosing based on therapeutic drug monitoring) (target trough concentration: 3 to 8 ng/ml).

SEGA: U.S. labeling:

Adjustment to initial dose may not be necessary subsequent dosing is based on therapeutic drug monitoring (monitor ~2 weeks after initiation, dosage modifications, or after any change in hepatic status) (target trough concentration: 5 to 15 ng/ml).

Canadian labeling:

Initial: Patients ≥18 years of age: 50% of usual dose based on calculated BSA (rounded to the nearest strength). Assess trough concentrations ~2 weeks after initiation, dosage modifications, or after any change in hepatic status. Target trough concentration: 5 to 15 ng/ml (may increase dose within the target range to achieve higher concentrations as tolerated).

Patients <18 years of age: Use is not recommended. Severe impairment (Child-Pugh class C):

Breast cancer, PNET, RCC, renal angiomyolipoma:

If potential benefit outweighs risks, a max. dose of 2.5 mg once daily may be used. Liver or renal transplantation: Reduce initial dose by ~50% (individualize subsequent dosing based on therapeutic drug monitoring) (target trough concentration: 3 to 8 ng/ml).

SEGA: U.S. labeling: Reduce initial dose to 2.5 mg/m2 once daily (or current dose by ~50%) subsequent dosing is based on therapeutic drug monitoring (monitor ~2 weeks after initiation, dosage modifications, or after any change in hepatic status; target trough concentration: 5 to 15 ng/ml).

Pregnancy: manufacturer advises avoid (toxicity in animal studies) effective contraception must be used during and for up to 8 weeks after treatment.

Breast-feeding: manufacturer advises avoid

Side Effects: Most common : diarrhoea, dry mouth, abdominal pain, dysphagia, anorexia, taste disturbance, chest pain, hypertension, hyperlipidaemia, hypercholesterolaemia, peripheral oedema, pneumonitis (including interstitial lung disease), asthenia, fatigue, headache, insomnia, convulsions, irritability, increased susceptibility to infections (including pneumonia, aspergillosis, and candidiasis), hyperglycaemia, hypoglycaemia, dehydration, renal failure, electrolyte disturbance, arthralgia, eyelid oedema, epistaxis, skin and nail disorders (including hand-foot syndrome).

less commonly:

congestive heart failure, flushing, agitation, aggression, rhabdomyolysis and impaired wound healing.

hepatitis B reactivation and haemorrhage also reported Dose: renal cell carcinoma, neuroendocrine tumours of pancreatic origin, hormone-receptor-positive breast cancer: ADULT over 18 years: 10 mg once daily.