Attention Pharmacist: Dispense the accompanying Medication Guide to each patient. Page 6of 56 The recommended dose of IMFINZI depends on the indication. Additional efficacy outcome measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR), per RECIST v1.1. Selective, high affinity antibody that blocks PD-L1 binding to PD-1 and CD80, allowing T cells to recognize and kill tumor cells. Withhold or permanently discontinue Imfinzi based on the severity, Imfinzi can cause immune-mediated hypophysitis. Events resolved in 12 of the 19 patients and resulted in permanent discontinuation of Imfinzi in 4 patients. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%) and COPD (1.1%). Among the 1889 patients, 38% were exposed for 6 months or more and 18% were exposed for 12 months or more. This cohort consisted of 182 patients with locally advanced or metastatic urothelial carcinoma who had progressed while on or after a platinum-based therapy, including those who progressed within 12 months of receiving therapy in a neo-adjuvant or adjuvant setting. The OS results are summarized in Table 8 and Figure 2. Immune-mediated rash or dermatitis occurred in 1.6% (30/1889) of patients receiving Imfinzi, including Grade 3 (0.4%) adverse reactions. he world has finally taken a major step in ending the COVID-19 pandemic — a vaccine has been approved and there are at least two more that appear to be at least 90 percent effective in additi… The data described in the Warnings and Precautions section reflect exposure to Imfinzi in 1889 patients from the PACIFIC study (a randomized, placebo-controlled study that enrolled 475 patients with Stage III NSCLC), Study 1108 (an open-label, single-arm, multicohort study that enrolled 970 patients with advanced solid tumors), and an additional open-label, single arm trial that enrolled 444 patients with metastatic lung cancer, an indication for which durvalumab is not approved. Events resolved in 15 of the 28 patients and resulted in permanent discontinuation in 5 patients. Table 6 summarizes the laboratory abnormalities that occurred in at least 20% of patients treated with Imfinzi plus chemotherapy. Durvalumab (Imfinzi) These drugs have also been shown to be helpful in treating different types of cancer, and are being studied for use against others. Urothelial Carcinoma The recommended dose of IMFINZI … These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Imfinzi can cause immune-mediated hypophysitis. The study excluded patients who had disease progression following chemoradiation, with active or prior autoimmune disease within 2 years of initiation of the study or with medical conditions that required systemic immunosuppression [see Clinical Studies (14.2)]. Of 201 patients in the CASPIAN study who received Imfinzi 1500 mg every 3 weeks in combination with chemotherapy for four doses followed by Imfinzi 1500 mg every 4 weeks no patients tested positive for treatment-emergent ADA. No dose reduction for Imfinzi is recommended. The safety of Imfinzi in patients with Stage III NSCLC who completed concurrent platinum-based chemoradiotherapy within 42 days prior to initiation of study drug was evaluated in the PACIFIC study, a multicenter, randomized, double-blind, placebo-controlled study. Human immunoglobulin G1 (IgG1) is known to cross the placental barrier; therefore, durvalumab has the potential to be transmitted from the mother to the developing fetus. By binding to its receptors, PD-L1 reduces cytotoxic T-cell activity, proliferation, and cytokine production. The pre-specified interim analysis of PFS based on 371 events (81% of total planned events) demonstrated a statistically significant improvement in PFS in patients randomized to Imfinzi compared to placebo. Withhold or permanently discontinue Imfinzi depending on severity, Imfinzi can cause immune-mediated thyroid disorders. Events resolved in 20 of the 27 patients. The median duration of exposure to Imfinzi was 10 months (range: 0.2 to 12.6). Table 4 summarizes the laboratory abnormalities that occurred in at least 20% of patients treated with Imfinzi. In Patients Who Received Recent Prior Radiation. This patient required long-term insulin therapy and Imfinzi was permanently discontinued. Systemic corticosteroids were required in all patients with immune-mediated colitis, while 2 patients (2/31) required other immunosuppressants (e.g., infliximab, mycophenolate). Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Imfinzi is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who:This indication is approved under accelerated approval based on tumor response rate and duration of response. © AstraZeneca 2021, MEDICATION GUIDE In animal models, inhibition of PD-L1/PD-1 signaling increased the severity of some infections and enhanced inflammatory responses. Eligible patients had WHO Performance Status of 0 or 1 and were suitable to receive a platinum-based chemotherapy regimen as first-line treatment for SCLC. There are no data on the use of IMFINZI in pregnant women. Withhold or permanently discontinue Imfinzi depending on severity, Imfinzi can cause primary or secondary adrenal insufficiency. This patient-friendly article is about chemotherapy drug, Durvalumab also known by its trade name Imfinzi; it is used in treating urothelial carcinoma (bladder cancer) and stage III non-small … Inactive ingredients: L-histidine, L-histidine hydrochloride monohydrate, α,α-trehalose dihydrate, polysorbate 80, water for injection, USP. Exfoliative dermatitis, including Stevens Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 blocking antibodies. Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including: Problems can also happen in other organs and tissues. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. … 1 Francis Crick Ave. Various grades of visual impairment to include blindness can occur. Exfoliative dermatitis, including Stevens Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 blocking antibodies. Randomization was stratified by sex, age (< 65 years vs. ≥ 65 years), and smoking history (smoker vs. non-smoker). There are no data on the use of IMFINZI in pregnant … Imfinzi is a prescription medicine used to treat adults with: It is not known if Imfinzi is safe and effective in children. Advise pregnant women of the potential risk to a fetus. Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses, without inducing antibody dependent cell-mediated cytotoxicity (ADCC). ATC Classification . If you would like more information about Imfinzi, talk with your healthcare provider. Based on its mechanism of action, fetal exposure to durvalumab mal also increase the risk of developing immune-mediated disorders or altering the normal immune response. Revised: 02/2021. PD-L1 and PD-1 knockout mice have also shown decreased survival following infection with lymphocytic choriomeningitis virus. The FDA approval of Imfinzi for non-small cell lung cancer was based on the PACIFIC study in 713 patients with unresectable Stage 3 NSCLC who completed at least 2 cycles of concurrent platinum-based chemotherapy and radiation before starting study drug. Durvalumab is a programmed cell death ligand 1 (PD-L1) blocking antibody. Imfinzi is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. Mechanism of Action of Remdesivir. Imfinzi is specifically indicated as a 1st-line treatment for adult patients with extensive-stage small cell lung cancer in combination with standard-of-care chemotherapies, etoposide and either carboplatin or cisplatin (platinum-etoposide). Discard unused portion. The study population characteristics were: median age of 63 years (range: 28 to 82); 40% age 65 or older; 70% male; 84% White, 15% Asian, and 0.9% Black; 65% WHO/ECOG PS of 1; and 93% were former/current smokers. What are the possible side effects of Imfinzi? In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Of 2280 patients who received Imfinzi 10 mg/kg every 2 weeks or 20 mg/kg every 4 weeks as a single-agent, 69 patients (3%) tested positive for treatment-emergent anti-drug antibodies (ADA) and 12 (0.5%) tested positive for neutralizing antibodies. Imfinzi can cause immune-mediated thyroid disorders. Detailed clinical and laboratory monitoring guidelines for early detection of adverse reactions of IMFINZI and recommended management are described in the full prescribing information (link below). For more information, call 1-800-236-9933 or go to www.Imfinzi.com, This Medication Guide has been approved by the U.S. Food and Drug Administration. A total of 25% of the patients received cisplatin and 74% of the patients received carboplatin. In lactating cynomolgus monkeys, durvalumab was present in breast milk at about 0.15% of maternal serum concentrations after administration of durvalumab from the confirmation of pregnancy through delivery at exposure levels approximately 6 to 20 times higher than those observed at the recommended clinical dose of 10 mg/kg (based on AUC). Thyroiditis can present with or without endocrinopathy. In general, withhold Imfinzi for severe (Grade 3) immune-mediated adverse reactions. Patients were randomized 2:1 to receive Imfinzi 10 mg/kg or placebo intravenously every 2 weeks for up to 12 months or until unacceptable toxicity or confirmed RECIST v1.1-defined progression. Withhold or permanently discontinue Imfinzi depending on severity [see Dosage and Administration (2.2)]. Durvalumab was present in the milk of lactating cynomolgus monkeys and was associated with premature neonatal death (see Data). Systemic corticosteroids were required in 3 patients (3/7) with immune-mediated thyroiditis, while 5 patients (5/7) required endocrine therapy. Monitor for signs and symptoms of infusion-related reactions. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. The data described in this section reflect exposure to Imfinzi in patients with Stage III NSCLC enrolled in the PACIFIC study and in patients with ES-SCLC enrolled in the CASPIAN study. Imfinzi (durvalumab) is a programmed death-ligand 1 (PD-L1) blocking antibody. In the exploratory subgroup analyses of OS based on the planned platinum chemotherapy received at cycle 1, the HR was 0.70 (95% CI 0.55, 0.89) in patients who received carboplatin, and the HR was 0.88 (95% CI 0.55, 1.41) in patients who received cisplatin. No overall differences in safety or effectiveness were observed between patients 65 years or older and younger patients. A total of 713 patients were randomized: 476 patients to the Imfinzi arm and 237 to the placebo arm. Adrenal insufficiency did not lead to permanent discontinuation of Imfinzi in any patients. Respiratory, Thoracic, and Mediastinal Disorders. Patients with asymptomatic or treated brain metastases were eligible. There is no information regarding the presence of durvalumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Imfinzi (durvalumab) Injection for intravenous use is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution, free from visible particles. Dosage Form: injection, solution. These include pneumonitis, hepatotoxicity, neurotoxicity, sepsis, diabetic ketoacidosis and pancytopenia (1 patient each). Withhold or permanently discontinue Imfinzi depending on severity [see Dosage and Administration (2.2)]. These complications can be serious and can lead to death. See prescribing information. The recommended dose is 10 mg/kg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. Dosage modifications for Imfinzi for adverse reactions that require management different from these general guidelines are summarized in Table 2. The recommended dosages for Imfinzi as a single agent and Imfinzi in combination with chemotherapy are presented in Table 1 [see Clinical Studies (14)]. Adverse effects associated with the use of Imfinzi may include, but are not limited to, the following: Adverse effects associated with the use of Imfinzi for non-small cell lung cancer (NSCLC) include : Imfinzi (durvalumab) is a programmed death-ligand 1 (PD-L1) blocking antibody. Systemic corticosteroids were required in all patients with immune-mediated hepatitis, while 1 patient (1/19) required use of mycophenolate with high-dose steroids. Design, CMS, Hosting & Web Development :: ePublishing, Data Integrity for GCP Professionals: Core Requirements, Expectations and Challenges, MAGI's Clinical Research vConference — Spring 2021, Regenerative Medicine: Steps to Accelerate Development, Clinical Trial Agreements: A Guide to Key Words and Phrases, Mid-Study Updates Delay Trials At Least a Month, CSDD Report Finds, Real-Time Data Helped Sponsors Respond to Sites’ Needs During the Pandemic, Increasing Protocol Complexity Requires Adapting Quality Metrics Tools, Ask the Experts: Participant Reimbursement, Compensation and Incentives. Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody. Based on its mechanism of action and data from animal studies, Imfinzi can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. The PACIFIC study did not include sufficient numbers of patients aged 75 years and over to determine whether they respond differently from younger patients. Withhold or discontinue Imfinzi based on the severity, Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis, Imfinzi can cause immune-mediated rash or dermatitis. Because of the potential for adverse reactions in breastfed infants, advise women not to breastfeed during treatment with Imfinzi and for at least 3 months after the last dose. Follow patients closely for evidence of transplant-related complications and intervene promptly. Based on the modeling of pharmacokinetic data and exposure relationships for safety, there are no anticipated clinically meaningful differences in efficacy and safety for the doses of 1500 mg every 4 weeks compared to 10 mg/kg every 2 weeks in patients weighing > 30 kg with NSCLC. The median time for PFS was 16.8 months for 476 patients receiving Imfinzi compared with 5.6 months for 237 patients receiving placebo. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Grade 3 immune-mediated type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving Imfinzi. Withhold or permanently discontinue Imfinzi based on the severity [see Dosage and Administration (2.2)]. Imfinzi was tested against placebo. L01XC28 - durvalumab ; Belongs to the class of … Interrupt, slow the rate of, or permanently discontinue Imfinzi based on the severity [see Dosage and Administration (2.2)]. There are no data on the use of IMFINZI in pregnant women. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies. Hypothyroidism can follow hyperthyroidism. Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection. Kaplan-Meier Curves of Overall Survival in the CASPIAN Study. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.
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