programmed death ligand 1 (PD-L1) inhibitors
- Metastatic Merkel cell carcinoma (MCC).
- 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.
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 and urothelial carcinoma.
Absorption: IV administration results in complete bioavailability.
Distribution: Minimally distributed to tissues.
Metabolism and Excretion: Primarily eliminated via proteolytic degradation.
Half-life: 6.1 days
TIME/ACTION PROFILE (plasma concentrations)
- OB: May cause fetal harm in pregnancy;
- Lactation: Avoid breast feeding.
Use Cautiously in:
- Rep: Women of reproductive potential;
- Pedi: Children <12 yr (safety and effectiveness not established).
Adverse Reactions/Side Effects
CNS: dizziness, headache
CV: hypertension, peripheral edema
Derm: pruritus, rash
Endo: adrenal insufficiency, hyperglycemia, hyperthyroidism, hypothyroidism, type 1 diabetes mellitus
F and E: hyponatremia, hyperkalemia
GI: COLITIS, HEPATITIS, abdominal pain, constipation, ↓ appetite, diarrhea, ↑ lipase, ↑ liver enzymes, nausea, vomiting, ↑ amylase
GU: renal impairment, urinary tract infection
Hemat: anemia, lymphopenia, thrombocytopenia, neutropenia
Metabolic: ↓ weight
Resp: PNEUMONITIS, cough, dyspnea, fever
Misc: INFUSION-RELATED REACTIONS, fatigue
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
IV (Adults and Children ≥12 yr): 800 mg every 2 wk until disease progression or unacceptable toxicity.
IV (Adults): 800 mg every 2 wk until disease progression or unacceptable toxicity.
Solution for IV infusion (must be diluted): 20 mg/mL
- 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: withhold 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: withhold avelumab and resume with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. If Grade 4 diarrhea or colitis or recurrent Grade 3 diarrhea or colitis occurs: permanently discontinue avelumab.
- 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, Stevens Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN), pancreatitis, rhabdomyolysis, myasthenia gravis, histiocytic necrotizing lymphadenitis, demyelination, vasculitis, hemolytic anemia, hypophysitis, iritis, and encephalitis). If moderate or severe clinical signs or symptoms or Grade 3 or 4 endocrinopathies occur: withhold avelumab and resume with complete or partial resolution (Grade 0 to 1) of other immune-mediated adverse reactions after corticosteroid taper. For life-threatening adverse reaction (excluding endocrinopathies), recurrent severe immune-mediated adverse reaction, requirement for 10 mg per day or more prednisone or equivalent for more than 12 wks, persistent Grade 2 or 3 immune-mediate adverse reactions lasting 12 weeks or longer: permanently discontinue avelumab.
- Monitor for signs and symptoms of infusion-related reactions (pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, urticaria) during infusion. For mild or moderate 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.
Lab Test Considerations:
May cause hepatitis; monitor liver function tests prior to and periodically during therapy. If ↑ levels: administer corticosteroids (initial dose of 1 to 2 mg/kg/day prednisone or equivalent, followed by a corticosteroid taper. If AST or ALT ↑ >3 times to < 5 times upper limit of normal or total bilirubin ↑ >1.5 times to <3 times upper limit of normal: withhold avelumab and resume with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. If AST or ALT >5 times ULN or total bilirubin >3 times the upper limit of normal: discontinue avelumab permanently.
- 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: withhold avelumab, 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: withhold 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.
- 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; 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.
- 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), rash; or infusion-related reactions 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.
- 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 and urothelial carcinoma.
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