Everolimus

Brands

DEA Class; Rx

Common Brand Names; Afinitor, Zortress, Afinitor Disperz

  • Antineoplastics, mTOr Kinase Inhibitors

Macrolide immunosuppressant analog of sirolimus; inhibits the mammalian target of rapamycin (mTOR), a serine-threonine kinase
Afinitor is used for certain patients with breast cancer, neuroendocrine tumors of pancreatic, GI, or lung origin, renal cell carcinoma, and certain tuberous sclerosis complex (TSC)-associated conditions (e.g., subependymal giant cell astrocytoma (SEGA), renal angiomyolipoma, and partial-onset seizures); Zortress is used for kidney or liver transplant rejection prophylaxis
May increase the risk for infection

Indicated in postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane after failure of treatment with letrozole or anastrozole

Indicated for advanced renal cell carcinoma (RCC) after failure with sunitinib or sorafenib

Indicated for progressive neuroendocrine tumors (PNET) located in the pancreas that are not surgically resectable or are metastatic; also indicated for well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung

Indicated for the treatment of noncancerous kidney tumors (renal angiomyolipomas) with tuberous sclerosis complex (TSC) in patients not requiring immediate surgery

Indicated in patients with TSC for the treatment of SEGA that requires therapeutic intervention but cannot be curatively resected

Indicated for the adjunctive treatment of patients with TSC-associated partial onset seizures

Indicated for prophylaxis of organ rejection in patients with low-moderate immunologic risk

Use in combination with reduced doses of cyclosporine, as well as basiliximab and corticosteroids

Indicated for prophylaxis of allograft rejection in adult liver transplant recipients in combination with reduced doses of tacrolimus and with corticosteroids

Hypersensitivity to everolimus or rapamycin (sirolimus) derivatives

  • Stomatitis (44%)
  • Constipation (38%)
  • Infections (37%)
  • Asthenia (33%)
  • Fatigue (31%)
  • Cough (30%)
  • Diarrhea (30%)
  • Rash (29%)
  • Anemia (26%)
  • Nausea (26%)
  • Anorexia (25%)
  • Edema, peripheral (25-45%)
  • Dyspnea (24%)
  • Pyrexia (20%)
  • Vomiting (20%)
  • Headache (19%)
  • Epistaxis (18%)
  • Decreased lymphocytes, Grade 3 (16%)
  • Increased glucose, Grade 3 (15%)
  • Pneumonitis (14%)
  • Pruritus (14%)
  • Dry skin (13%)
  • Decreased Hgb, Grade 3 (12%)
  • Menstrual irregularities (11%)

For patients with increased risk for skin cancer, exposure to sunlight and ultraviolet light should be limited by wearing protective clothing and using sunscreen with a high protection factor

Non-infectious pneumonitis is a class effect on rapamycin derivatives; non-infectious pneumonitis was reported in up to 19% of patients treated with Afinitor/Afinitor Disperz in clinical trials, some cases were reported with pulmonary hypertension (eg, pulmonary arterial hypertension) as a secondary (see Dosage Modifications)

For Grade 2 to 4 noninfectious pneumonitis, withhold or permanently discontinue therapy based on severity; corticosteroids may be indicated until clinical symptoms resolve; administer prophylaxis when concomitant use of corticosteroids or other immunosuppressive agents required; the development of pneumonitis has been reported even at a reduced dose

Radiation sensitization and recall, in some cases severe, involving cutaneous and visceral organs (including radiation esophagitis and pneumonitis) reported in patients treated with radiation prior to, during, or subsequent to treatment; monitor patients closely when therapy administered during or sequentially with radiation treatment

Continue therapy without dose alteration in patients who develop radiological changes

Elicits immunosuppressive effects and may increase risk for infections; some of infections have been severe (eg, sepsis, septic shock, or resulting in multisystem organ failure) or fatal; incidence of Grade 3 and 4 infections up to 10% and up to 3%, respectively reported; incidence of serious infections was reported at a higher frequency in patients less than 6 years of age; monitor for signs and symptoms and treat promptly

Pneumocystis jiroveci pneumonia, some with a fatal outcome, reported; this may be associated with concomitant use of corticosteroids or other immunosuppressive agents; antimicrobial prophylaxis for Pneumocystis jiroveci (carinii) pneumonia and prophylaxis for cytomegalovirus (CMV) recommended in transplant recipients

Based on animal studies and mechanism of action therapy can cause fetal harm when administered to pregnant woman; there are limited case reports of use in pregnant women; however, these reports are not sufficient to inform about risks of birth defects or miscarriage; advise pregnant women of potential risk to fetus

There are no data on presence of everolimus in human milk, effects on breastfed infant or on milk production

Adults

Zortress: Maximum dosage is based on everolimus trough concentrations (target of 3 to 8 ng/mL).
Afinitor: 10 mg/day for advanced hormone receptor-positive breast cancer, advanced renal cell carcinoma, and renal angiomyolipoma with tuberous sclerosis complex (TSC); maximum dosage is based on everolimus trough concentrations (target of 5 to 15 ng/mL) for the treatment of subependymal giant cell astrocytoma (SEGA) associated with TSC.
Afinitor Disperz: Maximum dosage is based on everolimus trough concentrations (target of 5 to 15 ng/mL) for the treatment of SEGA and partial seizures associated with TSC.

Geriatric

Zortress: Maximum dosage is based on everolimus trough concentrations (target of 3 to 8 ng/mL).
Afinitor: 10 mg/day for advanced hormone receptor-positive breast cancer, advanced renal cell carcinoma, and renal angiomyolipoma with tuberous sclerosis complex (TSC); maximum dosage is based on everolimus trough concentrations (target of 5 to 15 ng/mL) for the treatment of subependymal giant cell astrocytoma (SEGA) associated with TSC.
Afinitor Disperz: Maximum dosage is based on everolimus trough concentrations (target of 5 to 15 ng/mL) for the treatment of SEGA and partial seizures associated with TSC.

Adolescents

Zortress: Safety and efficacy have not been established.
Afinitor: Maximum dosage is based on everolimus trough concentrations (target of 5 to 15 ng/mL) for the treatment of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC).
Afinitor Disperz: Maximum dosage is based on everolimus trough concentrations (target of 5 to 15 ng/mL) for the treatment of SEGA and partial seizures associated with TSC.

Children

2 to 12 years:
Zortress: Safety and efficacy have not been established.
Afinitor: Maximum dosage is based on everolimus trough concentrations (target of 5 to 15 ng/mL) for the treatment of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC).
Afinitor Disperz: Maximum dosage is based on everolimus trough concentrations (target of 5 to 15 ng/mL) for the treatment of SEGA and partial seizures associated with TSC.
1 year:
Zortress: Safety and efficacy have not been established.
Afinitor/Afinitor Disperz: Maximum dosage is based on everolimus trough concentrations (target of 5 to 15 ng/mL) for the treatment of SEGA associated with TSC.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Everolimus 

tablet (Afinitor)

  • 2.5mg
  • 5mg
  • 7.5mg
  • 10mg

tablet for oral suspension (Afinitor Disperz)

  • 2mg
  • 3mg
  • 5mg

tablet (Zortress)

  • 0.25mg
  • 0.5mg
  • 0.75mg
  • 1mg
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