Everolimus

Mechanism :

Everolimus is a macrolide immunosuppressant and a mechanistic target of rapamycin (mTOR) inhibitor which has antiproliferative and antiangiogenic properties, and also reduces lipoma volume in patients with angiomyolipoma.
Reduces protein synthesis and cell proliferation by binding to the FK binding protein-12 (FKBP-12), an intracellular protein, to form a complex that inhibits activation of mTOR) serine-threonine kinase activity.

Indication :

Tuberous sclerosis complex-associated partial-onset seizures
Tuberous sclerosis complex-associated subependymal giant cell astrocytoma
Neuroendocrine tumors: Progressive pancreatic neuroendocrine tumors (PNET)
Renal cell carcinoma
Liver and renal transplantation

Contraindications :

Clinically significant hypersensitivity to everolimus, other rapamycin derivatives, or any component of the formulation.

Dosing :

Tuberous sclerosis complex-associated partial-onset seizures:

Oral: Initial 5 mg/m² once daily; continue until disease progression or unacceptable toxicity.

Tuberous sclerosis complex-associated subependymal giant cell astrocytoma:

Oral: 4.5 mg/m² once daily; continue until disease progression or unacceptable toxicity.

Adverse Effect :

Stomatitis, constipation, infections, asthenia, fatigue, cough, diarrhea, rash, anemia, nausea, anorexia, edema, peripheral, dyspnea, pyrexia, vomiting, headache, epistaxis, decreased lymphocytes, increased glucose, pneumonitis, pruritus, dry skin, menstrual irregularities, hypertension, hemorrhage, tachycardia, congenital heart failure.

Interaction :

Angiotensin-Converting Enzyme Inhibitors: Everolimus may enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors.
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
CYP3A4 Inducers: May decrease the serum concentration of Everolimus.
CYP3A4 Inhibitors: May increase the serum concentration of Everolimus.
Efavirenz: May decrease the serum concentration of Everolimus.
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants.

Renal Dose :

Dose in Renal Impairment GFR (mL/min)

20-50	Dose as in normal renal function
10-20	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

Hepatic Dose :

Tuberous sclerosis complex (TSC)-associated subependymal giant cell astrocytoma (SEGA) or partial-onset seizures:
Mild to moderate hepatic impairment: Dosing should be based on therapeutic drug monitoring every 1-2 weeks after initiation maintaining target trough concentration 5 to 15 ng/mL. Adjust the dose using the equation: new dose = current dose x (target concentration divided by current concentration). The maximum dose increment at any titration must not exceed 5 mg.
Severe hepatic impairment: Reduce initial dose to 2.5 mg/sqm once daily. Subsequent dosing is based on therapeutic drug monitoring 2 weeks after initiation maintaining target trough concentration 5 to 15 ng/mL.

Renal and liver transplant rejection prophylaxis
Mild hepatic impairment: Reduce the initial daily dosage by approximately one-third; adjust dose as per trough levels maintaining target trough concentration of 3 to 8 ng/mL.
Moderate and Severe hepatic impairment: Reduce the initial daily dosage by approximately one-half; adjust dose as per trough levels maintaining target trough concentration of 3 to 8 ng/mL.