durvalumab

General

Pronunciation:
dur-val-ue-mab

Trade Name(s)

  • Imfinzi

Ther. Class.
antineoplastics

Pharm. Class.
monoclonal antibodies
programmed death ligand 1 (PD-L1) inhibitors

Indications

  • 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.
  • Unresectable, stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed with concurrent platinum-containing chemotherapy and radiation.

Action

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

Therapeutic Effect(s):

  • Decreased spread of urothelial carcinoma.
  • Decreased spread of NSCLC with improved progression-free survival.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism and Excretion: Unknown.

Half-life: 18 days.

TIME/ACTION PROFILE (blood levels)

ROUTEONSETPEAKDURATION
IVunknownunknownunknown

Contraindication/Precautions

Contraindicated in:

  • OB: May cause fetal harm; avoid pregnancy;
  • Lactation: Avoid breast feeding.

Use Cautiously in:

  • Rep: Woman of reproductive potential;
  • Pedi: Safety and effectiveness not established.

Adverse Reactions/Side Effects

CV: peripheral edema

Derm: STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, pruritus, rash, bullous dermatitis

Endo: hyperglycemia, hypothyroidism, adrenal insufficiency, hyperthyroidism, hypophysitis, type 1 diabetes mellitus

F and E: hyperkalemia, hypocalcemia, hyponatremia, hypercalcemia, hypermagnesemia, hypokalemia

GI: COLITIS/DIARRHEA, HEPATITIS, abdominal pain, constipation, ↓ appetite, nausea, ↑ liver enzymes

GU: acute kidney injury, glomerulonephritis, ↑ serum creatinine, renal failure

Hemat: NEUTROPENIA, lymphopenia, anemia

Metabolic: hypoalbuminemia

MS: pain

Resp: PNEUMONITIS, cough, dyspnea

Misc: INFECTION, INFUSION-RELATED REACTIONS, fatigue, fever

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None known.

Route/Dosage

Urothelial Carcinoma

IV (Adults) 10 mg/kg every 2 wk until disease progression or unacceptable toxicity.

NSCLC

IV (Adults) 10 mg/kg every 2 wk until disease progression, unacceptable toxicity, or a maximum of 12 mo.

Availability

Solution for IV infusion (requires dilution): 50 mg/mL

Assessment

  • Monitor for signs and symptoms of pneumonitis (new or worsening cough, chest pain, shortness of breath). For Grade 2: administer corticosteroids, prednisone 1 to 2 mg per kg per day or equivalent. For Grade 3 or 4: Administer prednisone 1 to 4 mg per kg per day or equivalent, followed by taper. Interrupt or permanently discontinue durvalumab based on the severity.
  • Assess for signs and symptoms of colitis (diarrhea, severe abdominal pain, bloody or tarry stools) periodically during therapy. Initiate prednisone 1–2 mg/kg/day or equivalent, for moderate (Grade 2) or severe (Grade 3-4) colitis, followed by taper. If Grade 2 diarrhea or colitis occurs: withhold dose until Grade 1 or resolved and corticosteroid dose ≤ prednisone 10 mg per day (or equivalent). If Grade 3 or 4 diarrhea or colitis occurs: permanently discontinue durvalumab.
  • Monitor for signs and symptoms of adrenal insufficiency, diabetes, and hypophysitis periodically during therapy. Initiate prednisone 1 to 2 mg per kg per day or equivalent, for moderate (Grade 2) or severe (Grade 3-4) symptoms, followed by taper. If Grade 2–4 symptoms occur: withhold durvalumab until clinically stable.
  • Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Initiate prednisone 1–2 mg/kg/day or equivalent, for moderate (Grade 2) or severe (Grade 3-4) skin reaction, followed by taper. If Grade 2 symptoms occur for >1 week or Grade 3: withhold dose until Grade 1 or resolved and corticosteroid dose ≤ prednisone 10 mg per day (or equivalent). If Grade 4 symptoms occur: discontinue durvalumab permanently.
  • Monitor for signs and symptoms of infection (fever, cough, frequent urination, pain with urination, flu-like symptoms) prior to and periodically during therapy. If Grade 3 or 4 infection occurs: withhold dose until clinically stable.
  • Monitor for signs and symptoms of infusion-related reactions (pyrexia, chills, flushing, itching or rash, dizziness, dyspnea, wheezing, back pain, neck pain, feeling faint, facial swelling) during infusion. For Grade 1 or 2 infusion-related reactions: interrupt or slow rate of infusion. For Grade 3 or 4 infusion-related reactions: stop infusion and permanently discontinue durvalumab.
  • Monitor for other immune-mediated reactions (aseptic meningitis, hemolytic anemia, immune thrombocytopenic purpura, myocarditis, myositis, and ocular inflammatory toxicity, including uveitis, keratitis). For Grade 2 immune-mediated adverse reactions: exclude other causes and initiate corticosteroids as indicated. For severe (Grade 3 or 4) adverse reactions: administer corticosteroids, prednisone 1 to 4 mg per kg per day or equivalent, followed by taper. Interrupt or permanently discontinue durvalumab for severe reaction.

Lab Test Considerations:

May cause immune-mediated hepatitis. Monitor for signs and symptoms of hepatitis. For ALT or AST >3 but ≤8 times upper limit of normal (ULN) or total bilirubin >1.5 but ≤5 times the ULN: withhold dose until Grade 1 or resolved and corticosteroid dose ≤ prednisone 10 mg per day (or equivalent). For ALT or AST >8 times ULN or total bilirubin >5 times ULN or concurrent ALT or AST >3 times ULN and total bilirubin >2 times ULN with no other cause: permanently discontinue durvalumab.

  • Monitor serum thyroid prior to and periodically during therapy.
  • Monitor blood glucose periodically during therapy.
  • Monitor renal function prior to and periodically during therapy. Initiate prednisone 1–2 mg/kg/day or equivalent, for moderate (Grade 2) or severe (Grade 3-4) nephritis, followed by taper. For creatinine >1.5 to 3 times ULN: withhold dose until Grade 1 or resolved and corticosteroid dose ≤ prednisone 10 mg per day (or equivalent). For creatinine >3 times ULN: permanently discontinue durvalumab.
  • May cause hypocalcemia, hyponatremia, and hyperkalemia.

Potential Diagnoses

Implementation

IV Administration

  • Intermittent Infusion: Diluent: Dilute with 0.9% NaCl or D5W. Invert gently to mix; do not shake. Solution is clear to opalescent, colorless to slightly yellow. Do not administer solutions that are cloudy, discolored, or contain particulate matter. Concentration: 1 mg/mL to 15 mg/mL. Administer immediately after preparation. May be stored up to 24 hrs if refrigerated or up to 4 hr at room temperature. Do not freeze.
  • Rate:Administer over 60 min through a sterile, low-protein binding 0.2 or 0.22 micron in-line filter.

Patient/Family Teaching

  • Explain purpose of durvalumab 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 (prolonged or unusual headache, feeling cold, extreme tiredness, constipation, weight gain or weight loss, deepening voice, dizziness or fainting, urinating more often than usual, feeling more hungry or thirsty than usual, nausea or vomiting, hair loss, abdominal pain, changes in mood or behavior, decreased sex drive, irritability, forgetfulness); nephritis (decreased urine output, blood in urine, swelling in ankles, loss of appetite), rash, itching, or skin blistering; or infusion-related reactions occur.
  • Advise patient to inform health care professional if other signs and symptoms (neck stiffness; fatigue; excessive bleeding or bruising; confusion; muscle weakness or pain; fever; blurry vision, double vision, or other vision problem; chest pain, shortness of breath, irregular heartbeat; eye pain or redness; changes in mood or behavior) occur.
  • Rep: Advise females of reproductive potential to use effective contraception and avoid breast feeding during and for at least 3 months after last dose of durvalumab.

Evaluation/Desired Outcomes

  • Decreased spread of urothelial carcinoma.
  • Decreased spread of NSCLC with improved progression-free survival.
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