Trade Names:Afinitor- Tablet 5 mg- Tablet 10 mg
Inhibitor of mammalian target of rapamycin (mTOR), which is a serine-threonine kinase. Everolimus binds to an intracellular protein, resulting in an inhibitory complex formation and inhibition of mTOR kinase activity.
T max is 1 to 2 h. C max is dose-proportional between 5 and 10 mg. Steady-state is achieved within 2 wk with once-daily dosing. High-fat meals reduce C max and AUC by 60% and 16%, respectively.
Protein binding is approximately 74%.
Everolimus is a substrate for CYP3A4 and P-glycoprotein (Pgp). Six metabolites have been identified and are approximately 100 times less active than everolimus.
Elimination half-life is approximately 30 h. Recovery in the feces and urine is 80% and 5%, respectively.
No influence of CrCl (25 to 178 mL/min) has been detected.Hepatic Function Impairment
The average AUC in subjects with moderate hepatic function impairment is twice that found in subjects with healthy hepatic function. Dose reduction is recommended in patients with moderate hepatic function impairment. Administration is not recommended in patients with severe hepatic function impairment.Elderly
No effect of age on pharmacokinetics has been observed.Gender
No effect of gender on pharmacokinetics has been observed.Race
Average exposure is higher in Japanese patients compared with non-Japanese patients. Oral Cl is 20% higher in black patients compared with white patients. The importance of these differences in safety and efficacy has not been established.
Treatment of advanced renal cell carcinoma after failure of sunitinib or sorafenib.
Hypersensitivity to rapamycin derivatives or any component of the product.
PO 10 mg once daily.Dose ModificationAdults
POManagement of severe and/or intolerable adverse reactions
Temporarily reduce dosage to 5 mg once daily.Hepatic function impairment
Reduce dosage to 5 mg once daily in patients with moderate hepatic function impairment. Do not use in patients with severe hepatic function impairment.Strong CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin)
Consider increasing dose in 5 mg increments to 20 mg once daily. However, no clinical data are available.
Store at 59° to 86°F. Protect from light and moisture.
Ketoconazole, a strong CYP3A4 inhibitor and Pgp inhibitor, increases everolimus C max and AUC by 3.9- and 15-fold, respectively. Moderate CYP3A4 inhibitors and Pgp inhibitors (eg, erythromycin, verapamil) increase everolimus C max and AUC by approximately 2- and 4-fold, respectively.CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin)
Everolimus C max and AUC may be reduced. Strong CYP3A4 inducers may reduce everolimus C max and AUC by approximately 60%.Food
High-fat meals reduce the C max and AUC; however, everolimus may be taken without regard to meals.Live vaccines
Avoid taking live vaccines during use of everolimus.
None well documented.
Hypertension (4%); tachycardia (3%); CHF (1%).
Asthenia (33%); fatigue (31%); pyrexia (20%); headache (19%); insomnia (9%); dizziness (7%); paresthesia (5%); dysphagia (4%).
Rash (29%); pruritus (14%); dry skin (13%); hand-foot syndrome, nail disorder (5%); erythema, onychoclasis, skin lesion (4%); acniform dermatitis (3%).
Epistaxis (18%); eyelid edema, pharyngolaryngeal pain (4%); rhinorrhea (3%); conjunctivitis (2%).
Stomatitis (44%); diarrhea (30%); nausea (26%); anorexia (25%); vomiting (20%), dysgeusia (10%); abdominal pain (9%); dry mouth (8%); hemorrhoids (5%).
Decreased hemoglobin (92%); increased cholesterol (77%); increased triglycerides (73%); increased glucose (57%); decreased lymphocytes (51%); increased creatinine (50%); decreased phosphate (37%); increased AST (25%); increased ALT, decreased platelets (23%); decreased neutrophils (14%); increased bilirubin (3%).
Peripheral edema (25%); weight decrease (9%); exacerbation of preexisting diabetes mellitus (2%).
Extremity pain (10%); jaw pain (3%).
Cough (30%); dyspnea (24%); pneumonitis (14%); pleural effusion (7%).
Infections and infestations (37%); mucosal inflammation (19%); chest pain (5%); chills (4%); renal failure (3%).
Monitor renal function, including BUN or serum creatinine, CBC, fasting blood glucose, and lipid profile prior to therapy and periodically thereafter. When possible, achieve glucose and lipid control prior to starting therapy.
Category D .
Safety and efficacy not established.
No overall differences in safety or efficacy have been observed in patients 65 yr of age and older compared with younger subjects.
Renal function impairment is not expected to alter drug exposure and no dosage adjustment is recommended.
Dosage reduction in patients with moderate hepatic function impairment is recommended. Because use in patients with severe hepatic function impairment has not been evaluated, avoid administration.
Because everolimus has immunosuppressive properties, patients may be predisposed to infections, especially from opportunistic pathogens.
May occur. Consider the possibility in patients who present with nonspecific respiratory signs and symptoms.
Mouth ulcers, oral mucositis, and stomatitis may occur.
Clinical experience is limited.
Copyright © 2009 Wolters Kluwer Health.