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Zynyz is a brand name for Retifanlimab. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Squamous cell carcinoma of the anal canal (SCAC) ZYNYZ is indicated in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with metastatic or with inoperable locally recurrent squamous cell carcinoma of the anal canal (SCAC). Merkel cell carcinoma (MCC) ZYNYZ is indicated as…
Verbatim from this product's EMA label. Tap a section to expand.
Treatment should be initiated and supervised by a physician experienced in the treatment of cancer. Posology Squamous cell carcinoma of the anal canal (SCAC) The recommended dose is 500 mg retifanlimab every 4 weeks administered as an intravenous infusion over 30 minutes, in combination with carboplatin and paclitaxel for 6 cycles followed by retifanlimab 500 mg as monotherapy every 4 weeks for all cycles thereafter.
Treatment should continue until disease progression or unacceptable toxicity for up to 1 year. 3 For the dosing and administration of carboplatin and paclitaxel, including recommended patient management, refer to the respective Summary of Product Characteristics (SmPC).
Merkel cell carcinoma (MCC) The recommended dose is 500 mg retifanlimab every 4 weeks administered as an intravenous infusion over 30 minutes. Treatment should continue until disease progression or unacceptable toxicity for up to 2 years.
Dose modifications Dose escalation or reduction of retifanlimab is not indicated. 8).
Table 1:
Recommended dose modifications for ZYNYZ Adverse reaction Severitya Dose modification Pneumonitis Grade 2 Withhold until adverse reactions recover to Grades 0-1. Grades 3 or 4 Permanently discontinue. Colitis Grades 2 or 3 Withhold until adverse reactions recover to Grades 0-1.
Recurrent Grade 3 or Grade 4 Permanently discontinue. 5 and up to 3 times ULN Withhold until adverse reactions recover to Grades 0-1. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids.
Grade 4 with AST or ALT increases to more than 8 times ULN OR TB greater than 3 times ULN Permanently discontinue. 5 but no more than 3 times ULN Withhold until adverse reactions recover to Grades 0-1. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids.
Grade 4 with AST or ALT increase to more than 10 times ULN OR TB greater than 3 times ULN Permanently discontinue. Endocrinopathies • Adrenal insufficiency • Hypothyroidism • Hyperthyroidism • Type 1 diabetes mellitus • Hyperglycaemia • Hypophysitis Grade 2 adrenal insufficiency Withhold until adverse reactions recover to Grades 0-1 or otherwise clinically stable.
Summary of the safety profile Immune-related adverse reactions occurred with retifanlimab. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of retifanlimab (see “Description of selected adverse reactions” below).
The safety of retifanlimab as monotherapy has been evaluated in 452 patients with advanced solid malignancies who received the recommended 500 mg every 4 weeks dose, including 107 patients with metastatic or recurrent locally advanced MCC.
4 months (range, 1 day – 27 months). 6%). 7% of patients; most serious adverse reactions were immune-related adverse reactions. ZYNYZ was permanently discontinued due to adverse reactions in 8% of patients; most of them were immune-related events.
The safety of retifanlimab in combination with carboplatin and paclitaxel has been evaluated in 154 patients with metastatic or with inoperable locally recurrent SCAC. 6 months). 4%). 6% of patients; most serious adverse reactions were immune-related adverse reactions.
8% of patients; most of them were immune-related events. Tabulated list of adverse reactions Adverse reactions reported in the pooled dataset for patients treated with ZYNYZ monotherapy (N = 452) and in combination with carboplatin and paclitaxel (N = 154) are presented in Table 2.
These reactions are presented by system organ class and by frequency. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); and not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing incidence. 11 Table 2: Adverse reactions in patients treated with retifanlimab Retifanlimab monotherapy (N = 452) Retifanlimab in combination with carboplatin and paclitaxel (N = 154) System organ class Frequency of all grades Frequency of grades 3-4 Frequency of all grades Frequency of grades 3-4 Blood and lymphatic system disorders Very common Anaemiaa Common Anaemiaa Very common Lymphopeniab Neutropeniac Very common Neutropeniac Common Lymphopeniab Endocrine disorders Common Hypothyroidism, Hyperthyroidism Uncommon Adrenal insufficiency Thyroiditisd Hypophysitis Type 1 diabetes mellituse Uncommon Adrenal insufficiency Hypophysitis Type 1 diabetes mellituse Very common Hypothyroidism Common Adrenal insufficiency Hyperthyroidism Hypophysitis Hyperglycaemia Uncommon Autoimmune thyroiditis Secondary adrenocortical insufficiency Common Adrenal insufficiency Uncommon Hypothyroidism Hyperthyroidism Secondary adrenocortical insufficiency Metabolism and nutrition disorders Very common Decreased appetite Uncommon Decreased appetite Common Hyponatraemia Common Hyponatraemia Nervous system disorders Common Paraesthesia Uncommon Polyneuropathyf Radiculopathy Vocal cord paralysis Uncommon Polyneuropathyf Radiculopathy Very common Peripheral sensory neuropathy Common Peripheral motor neuropathy Peripheral sensorimotor neuropathy Common Peripheral sensorimotor neuropathy Eye disorders Uncommon Uveitisg Keratitis Uncommon Uveitisg Cardiac disorders Uncommon Pericarditis Myocarditis Uncommon Myocarditis Respiratory, thoracic and mediastinal disorders Common Pneumonitish Uncommon Pneumonitish 12 Retifanlimab monotherapy (N = 452) Retifanlimab in combination with carboplatin and paclitaxel (N = 154) Gastrointestinal disorders Very common Diarrhoea Nausea Constipation Common Colitisi Uncommon Pancreatitis Uncommon Diarrhoea Pancreatitis Colitisi Very common Colitisj Common Stomatitis Common Colitisj Hepatobiliary disorders Common Hepatocellular injury Hepatitisk Uncommon Hyperbilirubinaemia Cholangitis Uncommon Hepatitisk Hepatocellular injury Cholangitis Hyperbilirubinaemia Common Hepatitisl Uncommon Immune-mediated cholangitis Common Hepatitisl Uncommon Immune-mediated cholangitis Skin and subcutaneous skin disorders Very common Rashm Pruritus Common Rashm Very common Pruritus Rashn Common Rashn Uncommon Pruritus Musculoskeletal and connective tissue disorders Very common Arthralgia Uncommon Arthritiso Myositis Eosinophilic fasciitis Polymyalgia rheumatica Uncommon Arthralgia Arthritiso Myositis Eosinophilic fasciitis Common Arthritis Renal and urinary disorders Common Acute kidney injury Renal failure Uncommon Tubulointerstitial nephritis Uncommon Acute kidney injury Tubulointerstitial nephritis General disorders and administration site conditions Very common Fatiguep Pyrexia Common Fatiguep Uncommon Pyrexia Very common Asthenia Common Asthenia Investigations Common Transaminases increasedq Blood creatinine increased Amylase increased Lipase increased Blood bilirubin increased Common Transaminases increasedq Uncommon Blood bilirubin increased Lipase increased Very common Alanine aminotransferase increased Common Aspartate aminotransferase increased Common Alanine aminotransferase increased Aspartate aminotransferase increased Lipase increased 13 Retifanlimab monotherapy (N = 452) Retifanlimab in combination with carboplatin and paclitaxel (N = 154) Blood thyroid stimulating hormone increased Uncommon Blood thyroid stimulating hormone decreased Blood creatinine increased Amylase increased Lipase increased Blood creatinine increased Amylase increased Uncommon Blood creatinine increased […]
Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Immune-related adverse reactions Immune-related adverse reactions, which may be severe or fatal, can occur in patients treated with retifanlimab.
Immune-related adverse reactions can occur in any organ or tissue and may affect more than one body system simultaneously. While immune-related adverse reactions usually occur during treatment, symptoms can also manifest after discontinuation.
Important immune-related adverse reactions listed in this section are not inclusive of all possible immune-related reactions. Early identification and management of immune-related adverse reactions is essential to ensure safe use of retifanlimab.
Patients should be monitored for symptoms and signs of immune-related adverse reactions. Blood chemistries, including liver tests and thyroid function tests, should be evaluated at start of treatment and periodically during treatment.
For suspected immune-related adverse reactions, adequate evaluation including specialty consultation should be ensured to confirm aetiology or exclude other causes. Based on the severity of the adverse reaction, treatment with retifanlimab should be withheld or permanently discontinued and corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) or other appropriate therapy administered.
Upon improvement to Grade ≤ 1, corticosteroid taper should be initiated and continued for at least 1 month (see Table 1). In patients with pre-existing autoimmune disease (AID), data from observational studies suggest that the risk of immune-mediated adverse reactions following immune-checkpoint inhibitor therapy may be increased as compared with the risk in patients without pre-existing AID.
In addition, flares of the underlying AID were frequent, but the majority were mild and manageable. However, data specific to retifanlimab are scarce. 8). Patients should be monitored for signs and symptoms of pneumonitis. Suspected pneumonitis should be confirmed with radiographic imaging and other causes excluded.
1.
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Grades 3 or 4 adrenal insufficiency Withhold until adverse reactions recover to Grades 0-1. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to 4 Adverse reaction Severitya Dose modification reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids.
Grades 3 or 4 hypothyroidism Withhold until adverse reactions recover to Grades 0-1 or is otherwise clinically stable. Grades 3 or 4 hyperthyroidism Withhold until adverse reactions recover to Grades 0-1 or is otherwise clinically stable.
Grades 3 or 4 type 1 diabetes mellitus (or hyperglycaemia) Withhold until adverse reactions recover to Grades 0-1 or is otherwise clinically stable. Grade 2 hypophysitis (asymptomatic) Withhold until adverse reactions recover to Grades 0-1.
May restart after controlled by hormone replacement therapy. , headaches, visual disturbances) Withhold until adverse reactions recover to Grades 0-1. May restart after controlled by hormone replacement therapy, if indicated and steroid taper is complete.
Grade 3 or 4 hypophysitis (symptomatic) Withhold until adverse reactions recover to Grades 0-1. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids.
Nephritis with renal dysfunction Grade 2 increased blood creatinine Withhold until adverse reactions recover to Grades 0-1. b Skin reactions Grade 3 or suspected SJS or suspected TEN Persistent Grade 2 (≥ 2 weeks) Withhold until adverse reactions recover to Grades 0-1.
Grade 4 or confirmed SJS or confirmed TEN Permanently discontinue. Myocarditis Confirmed Grades 2, 3 or 4 Permanently discontinue. Other immune-related adverse reactions (including myositis, encephalitis, demyelinating neuropathy, Guillain Barré syndrome, sarcoidosis, autoimmune haemolytic anaemia, pancreatitis, uveitis, diabetic ketoacidosis, arthralgia) Grade 3 Withhold until adverse reactions recover to Grades 0-1.
Grade 4 Permanently discontinue. 5 Adverse reaction Severitya Dose modification Persistent Grade 2 or 3 immune-related adverse reactions (excluding endocrinopathies) Grade 2 or 3 (≥ 12 weeks after last dose) Recurrent Grade 3 or 4 Recurrent Grade 2 pneumonitis Permanently discontinue.
Infusion-related reactions Grade 1 Interrupt or slow the rate of infusion.
Grade 2 First occurrence:
Interrupt infusion and resume at 50% of the original rate if symptoms resolve within 1 hour.
Subsequent occurrences:
Permanently discontinue after recommended prophylaxis. Grade 3 Permanently discontinue. If rapidly responsive to symptomatic management and/or to brief interruption of infusion, retifanlimab does not need to be permanently discontinued.
Grade 4 Permanently discontinue. AST = aspartate aminotransferase; ALT = alanine aminotransferase; ULN = upper limit of normal; TB = total bilirubin; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis. a Toxicity graded per National […]
Patients should be managed with retifanlimab treatment modifications and corticosteroids (see Table 1). 8). Patients should be monitored for signs and symptoms of colitis and managed with retifanlimab treatment modifications, anti-diarrhoeal agents and corticosteroids (see Table 1).
8). Patients should be monitored for abnormal liver tests prior to and periodically during treatment as indicated based on clinical evaluation and managed with retifanlimab treatment modifications and corticosteroids (see Table 1). For Grade 1 hepatitis, liver chemistry monitoring should be increased to twice per week until liver chemistry tests return to baseline.
8). Patients should be monitored for abnormal thyroid function tests prior to and periodically during treatment and for cortisol, as indicated based on symptoms and/or falling thyroid-stimulating hormone. Hypothyroidism and hyperthyroidism Immune-related hypothyroidism and hyperthyroidism (including thyroiditis) have been reported in patients receiving retifanlimab.
Immune-related hypothyroidism and hyperthyroidism (including thyroiditis) should be managed with retifanlimab treatment modifications as recommended in Table 1. 8). Patients should be monitored for signs and symptoms of hypophysitis and managed with retifanlimab treatment modifications, corticosteroids and hormone replacement, as clinically indicated (see Table 1).
Adrenal insufficiency Immune-related adrenal insufficiency has been reported in patients receiving retifanlimab. Patients should be monitored for clinical signs and symptoms of adrenal insufficiency and managed with corticosteroids and hormone replacement, as clinically indicated (see Table 1).
8). Patients should be monitored for hyperglycaemia and signs and symptoms of diabetes as indicated based on clinical evaluation and managed with oral anti-hyperglycaemics or insulin and retifanlimab treatment modifications (see Table 1).
8). 2). 8). Events of Stevens-Johnson syndrome have been reported in patients treated with PD-1 inhibitors. Patients should be monitored for signs and symptoms of skin reactions. Immune-related skin reactions should be managed as recommended in Table 1.
Caution should be used when considering the use of retifanlimab in a patient who has previously experienced a severe or life-threatening skin adverse reaction on prior treatment with other checkpoint inhibitors. 8 Other immune-related adverse reactions Clinically significant, immune-related adverse reactions were reported in patients treated with retifanlimab in clinical studies including: […]