Imfinzi Special Precautions

Traceability: In order to improve the traceability of biological medicinal products, the tradename and the batch number of the administered product should be clearly recorded.
Immune-mediated pneumonitis: Immune-mediated pneumonitis or interstitial lung disease, defined as requiring use of systemic corticosteroids and with no clear alternate aetiology, occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions).
Pneumonitis and radiation pneumonitis: Radiated pneumonitis is frequently observed in patients receiving radiation therapy to the lung and the clinical presentation of pneumonitis and radiation pneumonitis is very similar. In the PACIFIC Study, in patients who had completed treatment with at least 2 cycles of concurrent chemoradiation within 1 to 42 days prior to initiation of the trial, pneumonitis or radiation pneumonitis occurred in 161 (33.9%) patients in the IMFINZI-treated group and 58 (24.8%) in the placebo group, including Grade 3 (3.4% vs 3.0%) and Grade 5 (1.1% vs 1.7%).
Patients should be monitored for signs and symptoms of pneumonitis. Suspected pneumonitis should be confirmed with radiographic imaging and other infectious and disease-related aetiologies excluded, and managed as recommended in Dosage & Administration.
Immune-mediated hepatitis: Immune-mediated hepatitis, defined as requiring use of systemic corticosteroids and with no clear alternate aetiology, occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Monitor alanine aminotransferase, aspartate aminotransferase, total bilirubin, and alkaline phosphatase levels prior to initiation of treatment and prior to each subsequent infusion. Additional monitoring is to be considered based on clinical evaluation Immune-mediated hepatitis should be managed as recommended in Dosage & Administration.
Immune-mediated colitis: Immune-mediated colitis or diarrhoea, defined as requiring use of systemic corticosteroids and with no clear alternate aetiology, occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Adverse drug reactions of intestinal perforation and large intestine perforation were reported in patients receiving IMFINZI in combination with tremelimumab. Patients should be monitored for signs and symptoms of colitis/diarrhoea and intestinal perforation and managed as recommended in Dosage & Administration.
Immune-mediated endocrinopathies: Immune-mediated hypothyroidism/hyperthyroidism/thyroiditis: Immune-mediated hypothyroidism, hyperthyroidism, or thyroiditis occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab, and hypothyroidism may follow hyperthyroidism (see Adverse Reactions). Patients should be monitored for abnormal thyroid function tests prior to and periodically during treatment as indicated based on clinical evaluation. Immune-mediated hypothyroidism, hyperthyroidism, and thyroiditis should be managed as recommended in Dosage & Administration.
Immune-mediated adrenal insufficiency: Immune-mediated adrenal insufficiency occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Patients should be monitored for clinical signs and symptoms of adrenal insufficiency. For symptomatic adrenal insufficiency, patients should be managed as recommended in Dosage & Administration.
Immune-mediated type 1 diabetes mellitus, which can first present as diabetic ketoacidosis that can be fatal if not detected early, occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Patients should be monitored for clinical signs and symptoms of type 1 diabetes mellitus. For symptomatic type 1 diabetes mellitus, patients should be managed as recommended in Dosage & Administration.
Immune-mediated hypophysitis/hypopituitarism: Immune-mediated hypophysitis/hypopituitarism occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Patients should be monitored for clinical signs and symptoms of hypophysitis. For symptomatic hypophysitis or hypopituitarism, patients should be managed as recommended in Dosage & Administration.
Immune-mediated nephritis: Immune-mediated nephritis, defined as requiring use of systemic corticosteroids and with no clear alternate aetiology, occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Patients should be monitored for abnormal renal function tests prior to and periodically during treatment with IMFINZI or IMFINZI in combination with tremelimumab and managed as recommended in Dosage & Administration.
Immune-mediated rash: Immune-mediated rash or dermatitis (including pemphigoid), defined as requiring use of systemic corticosteroids and with no clear alternate aetiology, occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab see Adverse Reactions. Events of Stevens-Johnson Syndrome (SJS) or toxic epidermal necrolysis have been reported in patients treated with PD-1 inhibitors. Patients should be monitored for signs and symptoms of rash or dermatitis and managed as recommended in Dosage & Administration.
Immune-mediated myocarditis: Immune-mediated myocarditis, which can be fatal, occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Patients should be monitored for signs and symptoms of immune-mediated myocarditis and managed as recommended in Dosage & Administration.
Immune-mediated pancreatitis: Immune-mediated pancreatitis, occurred in patients receiving IMFINZI in combination with tremelimumab and chemotherapy (see Adverse Reactions). Patients should be monitored for signs and symptoms of immune-mediated pancreatitis and managed as recommended in Dosage & Administration.
Other immune mediated adverse reactions: Given the mechanism of action of IMFINZI or IMFINZI in combination with tremelimumab, other potential immune-mediated adverse reactions may occur. The following immune-related adverse reactions have been observed in patients treated with IMFINZI monotherapy or IMFINZI in combination with tremelimumab: myasthenia gravis, myositis, polymyositis, meningitis, Guillain-Barré syndrome, immune thrombocytopenia and pancreatitis (see Adverse Reactions). Events of pancreatitis have been reported in patients in the clinical study programme. Patients should be monitored for signs and symptoms and managed as recommended in Dosage & Administration.
Infusion-related reactions: Patients should be monitored for signs and symptoms of infusion-related reactions. Severe infusion related reactions have been reported in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Infusion-related reactions should be managed as recommended in Dosage & Administration.
Disease-specific precaution (BTC): Cholangitis and biliary tract infections: Cholangitis and biliary tract infections are not uncommon in patients with advanced BTC. Cholangitis events were reported in TOPAZ-1 in both treatment groups (14.5% [IMFINZI + chemotherapy] vs. 8.2% [placebo + chemotherapy]); these were mostly in association with biliary stents and were not immune-mediated in aetiology. Patients with BTC (especially those with biliary stents) should be closely monitored for development of cholangitis or biliary tract infections before initiation of treatment and, regularly, thereafter.
Metastatic NSCLC: Limited data are available in elderly patients (≥75 years) treated with IMFINZI in combination with tremelimumab and platinum-based chemotherapy (see Adverse Reactions and Pharmacology: Pharmacodynamics under Actions). Careful consideration of the potential benefit/risk of this regimen on an individual basis is recommended.
Patients excluded from clinical trials: Patients with the following were excluded from clinical trials: a baseline ECOG performance score ≥2; active or prior documented autoimmune disease within 2 years of initiation of the study; a history of immunodeficiency; a history of severe immune-mediated adverse reactions; medical conditions that required systemic immunosuppression, except physiological dose of systemic corticosteroids (≤10 mg/day prednisone or equivalent); uncontrolled intercurrent illnesses; active tuberculosis or hepatitis B or C or HIV infection or patients receiving live attenuated vaccine within 30 days before or after the start of IMFINZI. In the absence of data, durvalumab should be used with caution in these populations after careful consideration of the potential benefit/risk on an individual basis. The safety of concurrent prophylactic cranial irradiation (PCI) with IMFINZI in patients with ES-SCLC is unknown.
For more information on exclusion criteria for each specific study see Pharmacology: Pharmacodynamics under Actions.
Effects on ability to drive and use machines: Based on its pharmacodynamic properties, durvalumab is unlikely to affect the ability to drive and use machines. However, if patients experience adverse reactions affecting their ability to concentrate and react, they should be advised to use caution when driving or operating machinery.