a-VEL-ue-mab

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies

• Metastatic Merkel cell carcinoma (MCC).
• Maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.
• Locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 mo of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
• Advanced renal cell carcinoma (RCC) as first-line therapy (in combination with axitinib).

• Binds to programmed death ligand 1 (PD-L1) to prevent its interaction with the programmed cell death-1 (PD-1) and B7.1 (or CD80) receptors, which activates the antitumor immune response.

• Decreased spread of MCC.
• Decreased spread of and improved survival in urothelial carcinoma.
• Improved progression-free survival in RCC.

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Primarily eliminated via proteolytic degradation.

Half-life: 6.1 days.

(plasma concentrations)

Contraindicated in:

• OB: Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

• Diabetes, hypertension, and/or dyslipidemia
• Rep: Women of reproductive potential
• Pedi: Children <12 yr (safety and effectiveness not established).

CV: MYOCARDITIS, HF, MI, hypertension, peripheral edema, pericarditis, vasculitis.

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, pruritus, rash.

EENT: iritis, uveitis.

Endo: ADRENAL INSUFFICIENCY, hypothyroidism, hyperthyroidism, hypoparathyroidism, hypophysitis, type 1 diabetes.

F and E: hyponatremia, hyperkalemia.

GI: COLITIS, HEPATITIS, abdominal pain, constipation, ↓appetite, diarrhea, ↑lipase, ↑liver enzymes, nausea, vomiting, gastritis, ↑ amylase, pancreatitis.

GU: urinary tract infection, nephritis.

Hemat: anemia, lymphopenia, thrombocytopenia, hemolytic anemia, neutropenia.

Metab: ↓weight.

MS: RHABDOMYOLYSIS, pain, myositis.

Neuro: autoimmune neuropathy, Guillain-Barré syndrome, myasthenic syndrome, myelitis , ENCEPHALITIS, MENINGITIS, dizziness, headache.

Resp: PNEUMONITIS, cough, dyspnea, fever.

Misc: infusion-related reactions, fatigue.

Drug-Drug:

• None reported.

MCC

• IV (Adults and Children 12 yr): 800 mg every 2 wk until disease progression or unacceptable toxicity.

Urothelial Carcinoma and RCC

• IV (Adults): 800 mg every 2 wk until disease progression or unacceptable toxicity.

• Solution for injection: 20 mg/mL;

• Monitor for other immune-mediated reactions (including but not limited to myocarditis, myositis, psoriasis, arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barré syndrome, bullous dermatitis, - pancreatitis, rhabdomyolysis, myasthenia gravis, histiocytic necrotizing lymphadenitis, demyelination, vasculitis, hemolytic anemia, hypophysitis, iritis, and encephalitis). May occur during or after last dose of avelumab. Interrupt or discontinue avelumab depending on severity and administer systemic corticosteroid therapy (1–2 mg/kg/day prednisone or equivalent until improved to Grade 1. Upon improvement, initiate corticosteroid taper and continue taper over at least 1 mo.
• Monitor for signs and symptoms of pneumonitis (new or worsening cough, chest pain, shortness of breath) during therapy. Evaluate with x-ray. Administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent, followed by a corticosteroid taper. For Grade 2 pneumonitis: hold avelumab and resume with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. For Grade 3 or 4 or recurrent Grade 2 pneumonitis: permanently discontinue avelumab.
• Assess for signs and symptoms of colitis (diarrhea, severe abdominal pain, bloody or tarry stools) periodically during therapy. If symptoms occur administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent, followed by a corticosteroid taper. If Grade 2 or 3 diarrhea or colitis occurs: hold avelumab and resume with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. If Grade 4 diarrhea or colitis occurs: permanently discontinue avelumab.
• Monitor for signs and symptoms of hypophysitis (headache, photophobia, visual field defects) during therapy. May cause hypopituitarism. Begin hormone replacement therapy. Hold or permanently discontinue avelumab based on severity.
• Assess for skin reactions including Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) (prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash) during therapy. Treat mild to moderate non-exfoliative rashes with topical emollients and/or topical corticosteroids. If SJS, TEN, or DRESS is suspected, hold avelumab; if confirmed, permanently discontinue avelumab.
• Monitor for signs and symptoms of neurologic toxicity (headache, neck stiffness, change in consciousness, weakness) periodically during therapy. If Grade 2 symptoms occur, hold avelumab. If Grade 3 or 4 symptoms occur, discontinue avelumab permanently.
• Monitor for signs and symptoms of infusion-related reactions (fever, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, urticaria) during infusion. For Grade 1 or 2 infusion-related reactions: interrupt or slow rate of infusion. For severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions: stop infusion and permanently discontinue avelumab.
• Monitor for signs and symptoms of cardiovascular events during therapy. Assess left ventricular ejection fraction at baseline and periodically during therapy. Manage cardiovascular risk factors (hypertension, diabetes, dyslipidemia). Discontinue avelumab for Grade 2, 3, or 4 cardiovascular events.

• May cause hepatitis; monitor liver function tests prior to and periodically during therapy. For monotherapy:If levels increase: administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent, followed by a corticosteroid taper. For hepatitis with no tumor involvement of the liver:If AST or ALT ↑ >3 times to <8 times (ULN) or total bilirubin ↑ >1.5 times to <3 times ULN: hold avelumab and resume with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. If AST or ALT >8 times ULN or total bilirubin >3 times ULN: discontinue avelumab permanently. For hepatitis with tumor involvement of the liver: If baseline AST or ALT >1 to 3 times ULN and increases to >5 to 10 times ULN or if baseline AST or ALT >3 to 5 times ULN and increases to >8 to 10 times ULN: hold avelumab. If AST or ALT >10 times ULN or if total bilirubin >3 times ULN: permanently discontinue avelumab. For combination therapy with axitinib:If ALT or AST 3 times ULN but <10 times ULN without concurrent total bilirubin 2 times ULN: hold both avelumab and axitinib until recover to Grades 0–1. Consider rechallenge avelumab or axitinib or sequential rechallenge with both avelumab and axitinib after recovery. If ALT or AST 10 times ULN or >3 times ULN with concurrent total bilirubin 2 times ULN: Permanently discontinue both avelumab and axitinib.
  • Monitor for signs and symptoms of adrenal insufficiency, including but not limited to hypothyroidism, hyperthyroidism, adrenal insufficiency, and hyperglycemia during and after treatment. Administer corticosteroids as appropriate, followed by a corticosteroid taper. If Grade 3 or 4 endocrinopathies occur: hold avelumab until clinically stable or permanently discontinue base on severity, treat low levels, and resume with complete or partial resolution (Grade 0 to 1) after corticosteroid taper.
  • May cause nephritis; monitor for ↑ serum creatinine prior to and periodically during therapy. Administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent, followed by a corticosteroid taper. If serum creatinine >1.5 times ULN and <6 times ULN: hold avelumab and resume with complete or partial resolution (Grade 0 to 1) of nephritis and renal dysfunction after corticosteroid taper. If serum creatinine >6 times ULN: permanently discontinue avelumab.

IV Administration:

• Premedicate with an antihistamine and acetaminophen prior to the first 4 infusions. May be administered for subsequent doses based on presence and severity of prior infusion reactions.
  • Solution is clear and colorless to slightly yellow; do not use solutions that are cloudy, discolored, or contain particulate matter.
    Diluent: Withdraw avelumab from vial and inject into 250 mL bag of 0.9% NaCl or 0.45% NaCl. Invert bag gently to mix without foaming or excessive shearing. Discard partially used vials.Store at room temperature and protect from light for up to 4 hrs from dilution or refrigerate for up to 24 hrs. Allow to come to room temperature before infusing. Do not freeze or shake diluted solution.
  • Rate: Infuse over 60 min through a 0.2 micron sterile, non-pyrogenic, low protein binding in-line filter.
  • Y-Site Incompatibility: Do not administer other medications through same IV line.

• Explain purpose of avelumab to patient and family and inform of potential adverse reactions.
• Instruct patient to notify health care professional immediately is signs and symptoms of infusion reactions occur.
• Advise patient to notify health are professional immediately if signs and symptoms of pneumonitis; hepatitis (jaundice, severe nausea or vomiting, pain on right side of abdomen, lethargy, or easy bruising or bleeding); colitis; adrenal insufficiency (hypotension, weight loss, weakness, nausea, vomiting, anorexia, lethargy, confusion, restlessness); hypothyroidism (intolerance to cold, constipation, dry skin, headache, listlessness, tiredness, or weakness); hyperthyroidism (headache, nervousness, diarrhea, excessive sweating, heat intolerance, chest pain, increased pulse rate, palpitations, weight loss >2 lb/wk); diabetes mellitus (confusion, drowsiness; flushed, dry skin; fruit-like breath odor; rapid, deep breathing, polyuria; loss of appetite; unusual thirst); nephritis (decreased urine output, blood in urine, swelling in ankles, loss of appetite), skin reactions (rash, itching, rash with tiny spots or bumps, reddening of skin, blisters, peeling); or cardiovascular events (new or worsening chest discomfort, pain or pressure; swelling in feet or ankles; shortness of breath; nausea or vomiting; weight gain; pain or discomfort in arms, back, neck, or jaw, cold sweat; lightheadedness or dizziness) occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, herbal products.
• Rep: Advise females of reproductive potential to use effective contraception and avoid breast feeding during and for at least 1 month after last dose of avelumab.

• Decreased spread of MCC.
• Decreased spread of and improved survival in urothelial carcinoma.
• Improved progression-free survival in RCC.

Bavencio

• Risk for infection (Adverse Reactions).
• Diarrhea (Adverse Reactions).

NDC Code^*

• 44087- EMD Serono, Inc.
  • 44087-3535- BAVENCIO
    • 44087-3535-1- 1 VIAL, SINGLE-DOSE in 1 CARTON (44087-3535-1) > 10 mL in 1 VIAL, SINGLE-DOSE