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Durvalumab Instructions
Generic name: durvalumab
Trade name: Imfinzi
All names: durvalumab , durvalumab , durvalumab, Imfinzi, durvalumab
Indications:
For the treatment of patients with locally advanced or metastatic urothelial carcinoma:
-Disease progression during or after platinum-based chemotherapy
-Disease progression within 12 months after neoadjuvant or adjuvant platinum-based chemotherapy
For patients with unresectable stage III non-small cell lung cancer (NSCLC) whose disease has not progressed after concurrent platinum-based chemotherapy and radiochemotherapy
Usage and dosage:
Common dosage for adult urothelial carcinoma: 10 mg/kg IV (intravenous) over 60 minutes every 2 weeks until disease progression or unacceptable toxicity
Usual dosage for the treatment of non-small cell lung cancer in adults: 10 mg/kg IV (intravenous) over 60 minutes every 2 weeks until disease progression, unacceptable toxicity, or up to 12 months.
Administer intravenous infusion over 60 minutes through a sterile, low protein-binding 0.2 or 0.22 micron in-line filter.
Do not administer medications through the same intravenous line.
Adverse reactions:
>10%:
Cardiovascular: peripheral edema (15%)
Central nervous system: fatigue (34% to 39%)
Dermatology: dermatitis (≤26%), rash (≤26%; including immune-mediated rash), pruritus (12%)
Endocrinology and metabolism: hyperglycemia (52%) %), hypocalcemia (46%), hyponatremia (33%), hyperkalemia (32%), elevated gamma-glutamyl transferase (24%), hypothyroidism (11% to 12%)
Gastrointestinal tract: constipation (21%), decreased appetite (19%), colitis (18%), diarrhea (18%), nausea (16%), abdominal pain (10% to 14%)
Secretion Genitourinary tract infections (15%)
Hematology and neoplasms: lymphopenia (43%; grade 3/4: 11%)
Liver: elevated serum ALT (39%), elevated serum AST (36%), hepatitis (12%)
Infections: Infection (38% to 56%)
Neuromuscular and skeletal: musculoskeletal pain (24%)
Respiratory system: cough (≤40%), productive cough (≤40%), pneumonia (≤34%), radiation pneumonitis (≤34%), upper respiratory tract infection (26%), pneumonia (17%), dyspnea (≤13%), dyspnea on exertion (≤ not more than 13%)
Others: Fever (≤15%; including tumor-related fever)
1% - 10%:
Central nervous system: speech disorder (<10%)
Dermatology: night sweats (<10%)
Endocrinology and metabolism: hyperthyroidism (7%), hypermagnesemia (grade 3/4: 4%), dehydration (grade 3/4: ≥3%), hypercalcemia (grade 3/4: 3%), hypoalbuminemia (grade 3/4: 1%), hypokalemia (grade 3/4) : 1%)
Genitourinary system: dysuria (<10%)
Hematology and tumors: anemia (grade 3/4: 8%), neutropenia (grade 3/4: 1%)
Liver: elevated serum alkaline phosphatase (3/4: 4%), hyperbilirubinemia (3/4: 1%)
Immunity: antibody development (3%)
Infection : Increased susceptibility (<10%)
Kidney: Nephritis (6%; immune mediated), increased serum creatinine (Grade 3/4: 1%)
Other: Infusion-related reactions (2%)
Undefined frequency:
Endocrine metabolism: Hypophysitis
Liver: Liver injury
Infection: Sepsis
Kidney: Acute renal failure
<1 %:
Adrenocortical insufficiency, aseptic meningitis (immune mediated), hemolytic anemia (immune mediated), immune thrombocytopenia, myocarditis (immune mediated), myositis (immune mediated), ocular toxicity (immune mediated, including uveitis and keratitis), pituitary insufficiency, thyroiditis, type 1 diabetes, vitiligo
Contraindications:
Hypersensitivity to durvalumab or any component of the formulation
Precautions:
Adrenal Insufficiency: Immune-related adrenal insufficiency has been reported with durvalumab. Monitor for clinical signs/symptoms of adrenal insufficiency. If grade 2 or higher adrenal insufficiency occurs, administer systemic corticosteroids and hormone replacement therapy as clinically indicated; interrupt durvalumab therapy (based on severity).
Skin Toxicity: Durvalumab causes immune-mediated rash. Bullous dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis syndrome have been reported with other anti-PD-L1 monoclonal antibodies. Monitor for cutaneous viral signs/symptoms and use systemic corticosteroids and then taper for grade 2 rash or dermatitis lasting more than 1 week, or severe grade 3 or 4 rash/dermatitis. Treatment interruption or discontinuation may be required (depending on severity).
Diabetes: Immune-related type 1 diabetes occurred in patients treated with durvalumab. The median time to onset was 1.4 months. Monitor blood glucose and clinical signs of diabetes. Initiate insulin therapy for type 1 diabetes and interrupt durvalumab therapy (based on severity) until clinical stability.
Gastrointestinal Toxicity: Immune-mediated enteritis or diarrhea occurred in patients receiving durvalumab. Grade 3 and 4 diarrhea or colitis have been reported. Median time to onset was 1.4 months (range: 1 day to 14 months). Monitor for signs and symptoms of colitis or diarrhea and manage with treatment interruption or discontinuation and systemic corticosteroids. In clinical studies, systemic corticosteroids, including high-dose corticosteroids, and other immunosuppressants (eg, infliximab, mycophenolate mofetil) have been indicated in some patients (rarely). Approximately three-quarters of patients experience immune-mediated diarrhea/colitis.
Hepatotoxicity: Immune-mediated hepatitis has occurred (some fatal) in patients receiving durvalumab. The median time to onset was 1 month (range: 1 day to 14 months). Monitor for signs/symptoms of hepatitis (including abnormal liver function tests) during treatment with durvalumab and after discontinuation of durvalumab. Treat grade 2 or higher immune-mediated hepatitis with systemic corticosteroids and interrupt or discontinue treatment. In clinical studies, some patients with immune hepatitis have been treated with high-dose corticosteroids; mycophenolate mofetil has been used (rarely) to treat immune hepatitis. About half of patients experience immune-mediated hepatitis. Grade 3 or 4 elevations in ALT (alanine aminotransferase), AST (aspartate aminotransferase), and/or total bilirubin have been reported.
Hypophysitis/Hypopituitarism: Immune-related hypophysitis/hypopituitarism occurred in patients treated with durvalumab. Monitor for clinical signs of hypophysitis or hypopituitarism. If grade 2 or higher hypophysitis occurs, use corticosteroids and hormone replacement therapy as indicated; interrupt durvalumab (based on severity). Hypopituitarism causes adrenal insufficiency and (rarely) diabetes insipidus.
Infections: Infections occur in nearly half of patients receiving durvalumab (some fatal). The most common grade 3 or 4 infections were urinary tract infection (urothelial carcinoma study) and pneumonia (non-small cell lung cancer study). The overall incidence of infection in the NSCLC study was higher than in patients in other studies in which radiation therapy was often not administered immediately before durvalumab. Monitor for signs/symptoms of infection; use anti-infective medications if infection is suspected or confirmed. Defer treatment for grade 3 or 4 infections.
Infusion Reactions: Infusion reactions, including serious or life-threatening infusion-related reactions, have been observed with durvalumab. Monitor for signs/symptoms of infusion reactions. For mild or moderate infusion reactions, interrupt or slow down the infusion rate (consider both preoperative and subsequent infusions). For Grade 3 or 4 infusion reactions, permanently discontinue durvalumab.
Nephrotoxicity: Durvalumab causes immune-mediated nephritis (including fatal cases). Monitor renal function before initiating treatment and periodically during durvalumab treatment. Nephritis may require systemic corticosteroids and treatment interruption or discontinuation. Nephritis disappears in about 50% of patients. The median onset time is 2 months (1 day to 14 months).
Pulmonary Toxicity: Immune-mediated pneumonitis or interstitial lung disease has occurred in patients receiving durvalumab, including fatal cases. The median time to onset is 2 months (range: 1 day to 19 months), and the median time to response is 2 to 5 months (range: 19 months)
In one study of non-small cell lung cancer, patients who completed final chemotherapy within 42 days before starting durvalumab had higher rates of pneumonia, including radiation pneumonitis, than patients in other studies who typically did not receive radiation therapy immediately before durvalumab. Monitor for signs/symptoms of pneumonia; evaluate suspected pneumonia with imaging and treat with systemic corticosteroids and durvalumab with or without interruption; some patients receive infliximab. In clinical studies, approximately half of patients experienced immune-mediated pneumonitis.
Thyroid Disorders: Immune-related thyroid disease has occurred in patients receiving durvalumab. Monitor thyroid function at baseline and periodically during treatment; monitor for clinical signs of thyroid disease. Hypothyroidism, hyperthyroidism, and thyroiditis (including grade 3 thyroiditis) have occurred in clinical trials. There are patients who have thyroiditis or hyperthyroidism before hypothyroidism. Treat hypothyroidism with hormone replacement while continuing durvalumab. Initiate appropriate medical management of hyperthyroidism; withhold durvalumab (based on severity). Hyperthyroidism is treated with beta-blockers and/or sulfamides in some patients.
Ocular Toxicity: Ocular inflammatory reactions including uveitis and keratitis. If uveitis occurs concurrently with other immune-mediated reactions, evaluate for Koyanagi-Harada syndrome; treatment with systemic steroids may be necessary to reduce the risk of permanent vision loss.
Other immune-mediated toxicities: Other immune-related adverse reactions that have been (rarely) associated with durvalumab include aseptic meningitis, hemolytic anemia, immune thrombocytopenia (formerly known as immune thrombocytopenic purpura), myocarditis, and myositis. These immune-mediated toxicities usually occur during treatment but may occur after discontinuation of treatment. For suspected grade 2 immune-mediated reactions, exclude other causes and initiate systemic corticosteroids as clinically indicated. Treat with systemic corticosteroids for grade 3 or 4 immune-mediated reactions. Treatment may need to be interrupted or discontinued. Other immune-mediated reactions have also been reported with other anti-PD-L1 monoclonal antibodies, including pancreatitis, systemic inflammatory response syndrome, rhabdomyolysis, myasthenia gravis, histiocytic necrotizing lymphadenitis, demyelination, vasculitis, hemolytic anemia, iritis, encephalitis, facial and abducens neuroparesis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, and Vogt-Koyanagi-Harada syndrome.
Females of reproductive potential should use effective contraception during treatment and for at least 3 months after the last dose of durvalumab.
Storage:
Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze.
Protect vial from light (keep in original packaging). Don't shake.
Diluted Solution
Diluted infusion solutions should be used immediately after preparation.
If not administering immediately, refrigerate at 2°C to 8°C (36°F to 46°F) for 24 hours (from vial puncture to administration) or at room temperature for 8 hours (not to exceed 25°C [77°F]) (Note: Prior to August 2019, the manufacturer's label stated storage time at room temperature of 4 hours)
Do not freeze or shake diluted solutions.
Mechanism of action:
Dervalumab is a human immunoglobulin G1-kappa monoclonal antibody that blocks programmed cell death ligand 1 (PD-L1) that binds to PD-1 and CD80 (B7.1); PD-L1 blockade can lead to increased T cell activation, allowing T cells to kill tumor cells. PD-L1 is an immune checkpoint protein expressed on tumor cells and tumor infiltrating cells. It downregulates anti-tumor T cell function by binding to PD-1 and B7.1; blocking the interaction between PD-1 and B7.1 restores anti-tumor T cell function.