Names and pronunciation
(e-ve-ro′li-mus) Afinitor, Afinitor Disperz, Zortress
Source page 534
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Individual generic drug information
Extracted information for everolimus only.
(e-ve-ro′li-mus) Afinitor, Afinitor Disperz, Zortress
Source page 534
Func. class.: Antineoplastic— miscellaneous
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Chem. class.: Kinase inhibitor
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Do not confuse: everolimus/sirolimus/tacrolimus/ temsirolimus
Source page 535
ACTION: Proliferation signal inhibitor that inhibits mammalian target of rapamycin (mTOR); this pathway is dys- regulated in cancer
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USES: Renal cell cancer in those with failed treatment with SORAfenib or SUNI- tinib kidney transplant rejection prophy- laxis with cycloSPORINE, subependymal giant cell astrocytoma, progressive pan- creatic neuroendocrine tumor (PNET) with unresectable locally advanced/meta- static disease, breast cancer hormone receptor positive/HER-2 negative, renal angiomyolipoma, tuberous sclerosis complex, liver transplant rejection prophylaxis
Source page 535
Extracted information for everolimus only.
CONTRAINDICATIONS: Breast- feeding; hypersensitivity to this product, Rapamune, Torisel, pregnancy Precautions: Children, renal/hepatic disease, diabetes mellitus, hyperlipid- emia, pleural effusion
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Black Box Warning: lmmunosuppres- sion, infection, renal artery thrombosis, renal impairment, renal vein thrombo- sis, neoplastic disease, heart trans- plant Black Box Warning: Increase: nephro- toxicity—immunosuppressants Increase: everolimus effect—CYP3A4 inhibitors (strong, moderate), antifun- gals, calcium channel blockers, cimeti- dine, danazol, erythromycin, cyclo- SPORINE, HIV-protease inhibitors Decrease: everolimus effect—CYP3A4 inducers, carBAMazepine, PHENobarbital, phenytoin, rifamycin, rifapentine Decrease: effect of live vaccines Drug/Herb • St. John’s wort: may decrease effect of everolimus Drug/Food • Alters bioavailability; use consistently with/without food; do not use with grape- fruit juice Drug/Lab Test Increase: bilirubin, calcium, cholesterol, glucose, potassium, lipids, phosphate, triglycerides, uric acid Decrease: calcium, glucose, potassium, magnesium, phosphate Black Box Warning: Immunosuppres- sion: CBC with differential during treat- ment monthly; if leukocytes <3000/mm3 or platelets <100,000/mm3, product should be discontinued or reduced; de- creased hemoglobin level may indicate bone marrow suppression • Hepatic/renal studies: AST, ALT, amylase, bilirubin, creatinine, phos- phate, and for hepatotoxicity: dark urine, jaundice, itching, light-colored stools; product should be discontinued • Pneumonitis: continuing cough, dys- pnea, pleural effusion baseline and during treatment, use corticosteroids if needed, if severe, reduce dose or discontinue Black Box Warning: Infection: bacterial fungal infections can occur and are more common with combination immunosup- pression therapy; assess for fever, cough, dyspnea, fatigue Black Box Warning: May result in graft loss within 30 days after trans- plantation • Obtain everolimus blood levels in kid- ney transplant, hepatic disease, CYP3A4 inducers, inhibitors • Pregnancy/breastfeeding: avoid in pregnancy; use adequate contraception during and for 12 wk after final dose; re- port exposure to the National Transplant Pregnancy Registry (877-955-6877); do not breastfeed Black Box Warning: To report fever, rash, severe diarrhea, chills, sore throat, fatigue; serious infections may occur; to report clay-colored stools, cramping (hepatotoxicity) Black Box Warning: To avoid crowds, persons with known infections to reduce risk for infection • Not to use with grapefruit juice • To avoid individuals recently vacci- nated with live vaccines; children may require accelerated vaccine schedule be- fore treatment • That frequent lab tests are required • That product may decrease male, fe- male fertility • That drinking alcohol is not recom- mended • To take consistently with or without food • To report vision changes, weight gain, edema, shortness of breath, impaired wound healing • Pregnancy: to notify prescriber if pregnancy is planned or suspected; to use contraception prior to, during, and 12 wk after product discontinued; to avoid breastfeeding
Source pages 535, 536, 537
SIDE EFFECTS CNS: Headache, insomnia, paresthe- sia, chills, fever, seizure, personality changes, insomnia, dizziness, weakness, fatigue CV: Hypertension, peripheral edema EENT: Blurred vision, photophobia, eye- lid edema, epistaxis, sinusitis, cataracts, conjunctivitis GI: Nausea, vomiting, diarrhea, constipa- tion, stomatitis, anorexia, abdominal pain, dysgeusia, hepatic artery thrombosis GU: Renal failure, UTI, infertility HEMA: Anemia, leukopenia, thrombocy- topenia, hemolytic uremic syndrome, thrombotic microangiopathy, thrombotic thrombocytopenia, purpura INTEG: Rash, acne, leukocytoclastic vasculitis META: Hyperglycemia, increased creat- inine, hyperlipidemia, hypophosphate- mia, weight loss, hypertriglyceridemia RESP: Pleural effusion SYST: Angioedema, anaphylaxis, lym- phoma
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INTERACTIONS
Source page 536
Extracted information for everolimus only.
DOSAGE AND ROUTES Prophylaxis (Zortress) • Adult: PO 0.75 mg q12hr with cyclo- SPORINE in combination with basilix- imab, corticosteroids, reduced doses of cycloSPORINE Liver transplant rejection prophylaxis • Adult: PO 1 mg bid starting at least 30 days after transplant in combination with reduced-dose tacrolimus and corticoste- roids Advanced renal cancer (Afinitor) • Adult: PO 10 mg daily as long as clinically beneficial; with strong 3A4 in- ducers 10 mg daily, then may increase by 5-mg increments to 20 mg daily Progressive neuroendocrine tumor (PNET) (Afinitor only) • Adult: PO 10 mg daily, reduce dose to 5 mg daily if intolerable adverse reac- tions occur Subependymal giant-cell astrocytoma (SEGA) (Afinitor E only) • Adult/adolescent/child: 4.5 mg/m2 daily, then titrate to a target trough of 5-15 ng/mL Hepatic dose • Adult: PO (Child-Pugh A) Afinitor: 7.5 mg/day; (Child-Pugh B) Afinitor: 5 mg/day, Zortress: 0.75 mg/day divided q12hr; (Child-Pugh C) Afinitor: 2.5 mg/day
Source page 535
Available forms: Tablets 0.25, 0.5, 0.75 mg (Zortess); 2.5, 5, 7.5, 10 mg (Afinitor); tablets for oral suspension 2, 3, 5 mg (Afinitor Disperg)
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Administer: Follow procedure for proper handling of antineoplastics • Swallow tablets whole with a full glass of water; do not chew, crush, or break • Afinitor: take at same time of day; if unable to swallow, consistently with or without food, disperse in 30 mL of water • Zortress: must take consistently with/ without food, give at same time of day q12hr with cycloSPORINE • Store protected from light at room temperature Afinitor adjustments for toxicity Noninfectious pneumonitis • Grade 1: asymptomatic with radio- graphic findings only: no dosage change • Grade 2: symptomatic but no interfer- ence with activities of daily living (ADLs): consider withholding therapy, resume Afinitor at a lower dosage when symptoms improve to ≤grade 1; discontinue Afinitor if symptoms do not improve within 4 wk • Grade 3: symptomatic and interfering with ADL and oxygen therapy indicated: hold therapy; consider resuming Afinitor at a lower dosage when symptoms im- prove to ≤grade 1; consider discontinuing Afinitor if grade 3 toxicity recurs • Grade 4: life-threatening and ventila- tor support indicated: discontinue therapy Stomatitis • Grade 1: minimum symptoms and nor- mal diet: no dosage adjustment required • Grade 2: symptomatic but can eat and swallow modified diet: hold therapy until symptoms improve to ≤grade 1 and re- sume Afinitor at the same dosage; if grade 2 toxicity recurs, hold therapy and resume Afinitor at a lower dosage when symptoms improve to ≤grade 1 • Grade 3: symptomatic and unable to adequately eat or hydrate orally: hold therapy; resume Afinitor at a lower dos- age when symptoms improve to ≤grade 1 • Grade 4: symptomatic and life-threat- ening: discontinue therapy Other nonhematologic toxicity (excluding metabolic events) • Grade 1: No dosage adjustment re- quired if toxicity is tolerable • Grade 2: No dosage adjustment re- quired if toxicity is tolerable; if toxicity is intolerable, hold therapy until symp- toms improve to ≤grade 1 and resume Afinitor at the same dosage; if grade 2 toxicity recurs, hold therapy and re- sume Afinitor at a lower dosage when symptoms improve to ≤grade 1 • Grade 3: Hold therapy; consider re- suming Afinitor at a lower dosage when symptoms improve to ≤grade 1; if grade 3 toxicity recurs, consider discontinuing therapy • Grade 4: Discontinue Afinitor therapy Metabolic events (hyperglycemia, dyslipidemia) • Grade 1 or 2: No dose adjustment re- quired • Grade 3: Temporarily withhold ther- apy; resume Afinitor at a lower dosage • Grade 4: Discontinue Afinitor therapy • Afinitor Disperz (oral suspension): wear gloves when preparing, use 10- mL syringe and place dose in syringe, do not crush, break, using 5-mL water and 4-mL air draw into syringe with dose, wait a few minutes until in sus- pension after use, use same amount of water and air, swirl, give contents
Source pages 535, 536
Extracted information for everolimus only.
Assess: • Lipid profile: cholesterol, triglycer- ides, lipid-lowering agent may be needed; blood glucose
Source page 537
Evaluate: • Therapeutic response: decreased spread of tumor; prevention of transplant E rejection
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CLINICAL CONSIDERATIONS
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Patient and caregiver information:
Source page 537
Extracted information for everolimus only.
PHARMACOKINETICS Rapidly, well absorbed; peak 1-2 hr; protein binding 74%; extensively metabolized by CYP3A4 enzyme system, P-gp; half-life 30 hr; reduced by high- fat meal; excreted in feces (80%), urine (5%)
Source page 536
Filter the extracted dose blocks for this individual drug.
Prophylaxis (Zortress)
• Adult/adolescent/child: 4.5 mg/m2 daily, then titrate to a target trough of 5-15 ng/mL Hepatic dose
Candidate age grouping · source page 535