Names and pronunciation
(dur-val′-yoo-mab) Imfinzi
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Drug reference
(dur-val′-yoo-mab) Imfinzi
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Func. class.: Antineoplastic monoclo- nal antibody
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ACTION: A human IgG1 kappa (IgG1k) monoclonal antibody, pro- duced in Chinese hamster ovary; inhib- its programmed death ligand interactions
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USES: For the treatment of locally advanced non-small cell lung cancer (NSCLC); extensive stage small cell lung cancer in combination with eto- poside and either CARBOplatin or CISplatin
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CONTRAINDICATIONS: Preg- nancy, hypersensitivity Precautions: Adrenal insufficiency, aseptic meningitis, autoimmune dis- ease, breastfeeding, colitis, contracep- tion requirements, Crohn’s disease, dia- betes mellitus, diarrhea, hemolytic anemia, hepatic disease, hepatitis, hy- pophysitis, hypopituitarism, IBS, infu- sion-related reactions, keratitis, myo- carditis, organ transplant, pneumonitis, pulmonary disease, reproductive risk, serious rash, SLE, thyroid disease, ul- cerative colitis, uveitis
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SIDE EFFECTS CNS: Fatigue, fever GI: Nausea, diarrhea, constipation, anorexia, abdominal pain, colitis HEMA: Anemia, hemolytic anemia, lymphopenia RESP: Cough, dyspnea META: Hyponatremia, hyperbilirubine- mia, hypercalcemia, hypermagnesium, hypoalbuminemia ENDO: Hyperglycemia, hyperthyroidism, hypothyroidism MISC: Infection, peripheral edema, mus- culoskeletal pain, rash, antibody formation, aseptic meningitis, dehydration, infusion reactions, keratitis, myocarditis, uveitis
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INTERACTIONS • None known Drug/Lab Test Increase: LFTs, blood glucose, serum creatinine/BUN, thyroid function tests Decrease: thyroid function tests
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DOSAGE AND ROUTES Consolidation treatment of locally advanced or unresectable non– small-cell lung cancer (NSCLC) • Adult: IV INF 10 mg/kg, beginning 1-42 days after the last radiation dose, q2wk until disease progression or unacceptable toxicity, for up to 12 mo Extensive small cell lung cancer • Adult >30 kg: IV INF 1500 mg prior to chemotherapy on same day; q3wk × 4 cycles, then 1500 mg q4wk (single agent) Adult <30 kg: IV INF 20 mg/kg be- fore chemotherapy on the same day q3wk × 4 cycles, then q4wk (single agent) Renal dose • Mild to moderate renal impairment (CCr ≥30 mL/min): no change • Severe renal impairment (CCr 15- 29 mL/min): unknown
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Available forms: Powder for injection 120 mg/2.4 mL, 500 mg/10 mL
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Administer: IV route • Follow cytotoxic handling procedures • Visually inspect for particulate matter and discoloration, product should be clear to opalescent, colorless to slightly yellow, free from particles. Discard if so- lution is cloudy or discolored or if parti- cles are observed • Do not shake Preparation: • Withdraw the required volume of drug and transfer into an IV container contain- ing 0.9% sodium chloride injection or 5% dextrose injection to prepare an infusion with a final concentration ranging from 1 mg/mL to 15 mg/mL • Mix diluted solution by gentle inver- sion. Do not shake • Discard partially used or empty vials of durvalumab Storage of diluted solution: • Does not contain a preservative; give immediately after preparation • If storage of diluted solution is neces- sary, the total time from vial puncture to the start of administration should be <24 hr if refrigerated 36°F-46°F (2°C-8°C), or <4 hr at room temperature up to 77°F (up to 25°C). Do not freeze IV Infusion: • Give diluted over 60 min through an IV line using a low protein-binding 0.2- or 0.22-micron in-line filter • Do not admix or give other products through the same line
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Assess: • Monitor baseline and periodically blood glucose, LFTs, serum creatinine/BUN • Serious infection: may be fatal; mon- itor for signs and symptoms of infection; use prophylactic anti-infectives as ap- propriate. • Pregnancy/breastfeeding: product can cause fetal harm; females of repro- ductive potential should avoid becoming pregnant during and for 3 mo after final dose; obtain a pregnancy test prior to starting product; do not breastfeed during and for at least 3 mo after last dose • Immune-mediated pneumonitis or interstitial lung disease (ILD): may be fatal; monitor for signs or symptoms (new or worsening chest pain or shortness of breath) of pneumonitis. If pneumonitis is suspected, obtain a chest x-ray; an interruption or discontinuation of therapy and treatment with high-dose corticoste- roids (followed by a steroid taper) may be necessary. The median time to onset of immune-mediated pneumonitis was 55.5 days (range, 24 to 423 days) • Immune-mediated hepatitis: may be fatal; monitor for abnormal liver tests prior to each cycle of treatment; interruption or discontinuation of therapy may be needed with high-dose corticosteroids (followed D by a steroid taper). The median time to onset of immune-mediated hepatitis was 51.5 days (range, 15 to 312 days) • Diarrhea and immune-mediated coli- tis: monitor for signs and symptoms of colitis (diarrhea or severe abdominal pain). Treatment with antidiarrheal agents and high-dose corticosteroids (followed by a steroid taper), along with an interruption or discontinuation of therapy, may be nec- essary. The median time to onset of im- mune-mediated colitis was 73 days (range, 13 to 345 days). Use with caution in those with inflammatory bowel disease such as ulcerative colitis or Crohn’s disease • Thyroid disease/disorders (hypothy- roidism/hyperthyroidism): monitor thy- roid function tests (TFTs) at baseline and periodically during treatment. Asymptomatic patients with abnormal TFTs can receive treatment; manage these patients with hormone replace- ment and symptomatic management as needed. The median time to onset of hypothyroidism was 42 days (range, 15 to 239 days), and the median time to first onset of hyperthyroidism was 43 days (range, 14-71 days) • Immune-mediated adrenal insuffi- ciency and hypophysitis/hypopituita- rism: monitor for signs and symptoms of adrenal insufficiency (hypotension, de- creased cortisol level, fatigue, weakness, and weight loss) and hypophysitis (de- creased pituitary hormone levels, pitu- itary gland inflammation, severe intracta- ble headache, and vision impairment) during and after treatment. An interrup- tion of therapy, treatment with high-dose corticosteroids, and hormone replace- ment may be necessary • Immune-mediated nephritis: moni- tor renal function at baseline and prior to each cycle of treatment. No initial dose adjustment is recommended in patients with renal dysfunction; use with caution in patients with renal dis- ease or renal impairment. If immune- mediated nephritis occurs, an interrup- tion or discontinuation of therapy may be needed with treatment with high- dose corticosteroids • Immune-mediated reactions (aseptic meningitis, hemolytic anemia, immune thrombocytopenic purpura, myocarditis, myositis) and ocular inflammatory tox- icity (uveitis and keratitis): monitor for signs and symptoms of immune-mediated reactions; confirm etiology or exclude other causes. Therapy may need to be temporarily withheld or permanently dis- continued; administer corticosteroids as needed • Severe infusion-related reactions: monitor signs and symptoms of an infu- sion-related reaction. Interrupt or slow the rate of infusion in those with mild or moderate infusion reactions. Perma- nently discontinue in those with grade 3 or 4 infusion reactions
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Evaluate: • Therapeutic response: lack of disease progression
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To report adverse reactions immedi- ately; to report diarrhea, hepatic, flu-like symptoms, cough, trouble breathing, rash • About reason for treatment, expected results • Pregnancy/breastfeeding: to notify provider if pregnancy is planned or sus- pected; to use effective contraception during treatment and for 3 mo after discontinuing treatment; do not breast- feed during or for 3 mo after final dose
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PHARMACOKINETICS Steady state 16 wk, half-life 17 days
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• Adult: IV INF 10 mg/kg, beginning 1-42 days after the last radiation dose, q2wk until disease progression or unacceptable toxicity, for up to 12 mo Extensive small cell lung cancer
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• Adult >30 kg: IV INF 1500 mg prior to chemotherapy on same day; q3wk × 4 cycles, then 1500 mg q4wk (single agent) Adult <30 kg: IV INF 20 mg/kg be- fore chemotherapy on the same day q3wk × 4 cycles, then q4wk (single agent) Renal dose
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