• Assess for symptoms of noninfectious pneumonitis (hypoxia, pleural effusion, cough, dyspnea) during therapy. If symptoms are mild, therapy may continue. If Grade 2 pneumonitis occurs: hold therapy until Grade 0–1; reinitiate everolimus at a 50% dose. Permanently discontinue if does not resolve or improve to Grade 1 within 4 wk. If Grade 3 pneumonitis occurs: hold therapy until Grade 0–1; resume at 50% of previous dose. Change to every other day if dose is lower than lowest available strength. Permanently discontinue if Grade 3 pneumonitis recurs. If Grade 4 pneumonitis occurs: permanently discontinue.
• Assess for mouth ulcers, stomatitis, or oral mucositis; usually occurs within first 8 wk of therapy. Begin dexamethasone alcohol-free oral solution as a swish and spit mouthwash when starting therapy to reduce incidence and severity of stomatitis. Topical treatments may be used; avoid peroxide-containing mouthwashes and antifungals unless fungal infection has been diagnosed. If stomatitis Grade 2 occurs: hold therapy until Grade 0–1; resume at previous dose. If Grade 2 recurs, withhold until Grade 0–1; resume at 50% dose. Change to every other day if dose is lower than lowest available strength. If Grade 3 stomatitis occurs: hold therapy until Grade 0–1; hold until Grade 0–1; resume at 50% of previous dose. Change to every other day if dose is lower than lowest available strength. If Grade 4 stomatitis occurs: discontinue permanently.
• Assess for signs and symptoms of systemic fungal infections (fever, malaise, weight loss, sweats, cough, dyspnea, pulmonary infiltrates, serious systemic illness with or without concomitant shock). Withhold therapy until infection has been diagnosed and adequately treated.
• Monitor for signs and symptoms of hypersensitivity reactions (anaphylaxis, dyspnea, flushing, chest pain, angioedema) during therapy. Permanently discontinue therapy if severe reactions occur.

Lab Test Considerations:

• Verify negative pregnancy test before starting therapy.
  • Monitor renal function prior to and periodically during therapy. May cause ↑ BUN, serum creatinine, and proteinuria.
  • Monitor fasting serum glucose and lipid profile prior to and periodically during therapy. May cause ↑ cholesterol, triglycerides, glucose. Attempt to achieve optimal glucose and lipid control prior to therapy. If Grade 3 metabolic events (hyperglycemia, dyslipidemia) occur: hold until improvement to Grade 0, 1, or 2. Resume at 50% of previous dose. Change to every other day if dose is lower than lowest available strength.
  • Monitor CBC prior to and every 6 mo for 1st yr of therapy and annually thereafter; may cause ↓ hemoglobin, lymphocytes, neutrophils, and platelets. If Grade 2 thrombocytopenia occurs: hold dose until Grade 0–1; resume at same dose. If Grade 3 or 4 thrombocytopenia occurs: hold until improvement to Grade 0, 1, or 2. Resume at 50% of previous dose. Change to every other day if dose is lower than lowest available strength. If Grade 3 neutropenia occurs: hold dose until Grade 0–1; resume at same dose. If Grade 4 neutropenia occurs: hold until improvement to Grade 0, 1, or 2. Resume at 50% of previous dose. Change to every other day if dose is lower than lowest available strength. If Grade 3 febrile neutropenia occurs: hold until improvement to Grade 0, 1, or 2 and no fever. Resume at 50% of previous dose. Change to every other day if dose is lower than lowest available strength. If Grade 4 febrile neutropenia occurs: discontinue permanently.
  • May cause ↑ AST, ALT, phosphate, and bilirubin.
  • Afinitor: Monitor Afinitor trough levels 2 wk after initiation of therapy, a change in dose, a change in coadministration of CYP3A4 and/or P-gp inducers or inhibitors, change in hepatic function, or change in dose form between everolimus tablets and Disperz. Once at a stable dose, monitor trough concentrations every 3–6 mo in patients with changing body surface area or every 6–12 mo in patients with stable body surface area for duration of treatment. Therapeutic blood concentrations are 5–15 ng/mL (Afinitor). If trough concentration is <5 ng/mL, ↑ daily dose by 2.5 mg in patients taking tablets and 2 mg for Disperz. If trough concentration is >15 ng/mL, ↓ daily dose by 2.5 mg in patients taking tablets and 2 mg for Disperz. If dose ↓ is required with lowest dose, administer every other day. Do not combine dose forms to achieve dose.

  • Zortress

    Therapeutic blood concentrations are 3–8 ng/mL via the LCMSMS assay (Zortress). Base dose adjustments of Zortress on trough concentrations obtained 4 or 5 days after a previous dosing change. Adjust dose if trough concentration is <3 ng/mL by doubling dose using available tablet strengths (0.25 mg, 0.5 mg or 0.75 mg). If trough concentration is >8 ng/mL on 2 consecutive measures, ↓ dose of Zortress by 0.25 mg twice daily.