Loading…
Opdualag is a brand name for Relatlimab. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Opdualag is indicated for the first-line treatment of advanced (unresectable or metastatic) melanoma in adults and adolescents 12 years of age and older with tumour cell PD-L1 expression < 1%.
Verbatim from this product's EMA label. Tap a section to expand.
Treatment must be initiated and supervised by physicians experienced in the treatment of cancer. Patients treated with Opdualag must be given the patient card and be informed about the risks of Opdualag (see also package leaflet). 1).
Posology The recommended dose for adults and adolescents 12 years of age and older is 480 mg nivolumab and 160 mg relatlimab every 4 weeks administered as an intravenous infusion over 30 minutes. 2). Treatment with Opdualag should be continued as long as clinical benefit is observed or until treatment is no longer tolerated by the patient.
Dose escalation or reduction is not recommended. Dosing delay or discontinuation may be required based on individual safety and tolerability. Guidelines for permanent discontinuation or withholding of doses are described in Table 1. 4.
5 and up to 3 times ULN Withhold dose(s) until laboratory values return to baseline and management with corticosteroids, if needed, is complete AST or ALT increases to more than 5 times ULN regardless of baseline. or Total bilirubin increases to more than 3 times ULN or Concurrent AST or ALT increase to more than 3 times ULN and total bilirubin increase to more than 2 times ULN Permanently discontinue treatment Immune-related nephritis and renal dysfunction Grade 2 or 3 creatinine elevation Withhold dose(s) until creatinine returns to baseline and management with corticosteroids is complete Grade 4 creatinine elevation Permanently discontinue treatment Immune-related endocrinopathies Symptomatic Grade 2 or 3 hypothyroidism, hyperthyroidism, hypophysitis Grade 2 adrenal insufficiency Grade 3 diabetes Withhold dose(s) until symptoms resolve and management with corticosteroids (if needed for symptoms of acute inflammation) is complete.
0 (NCI-CTCAE v5). 4. b The safety of re-initiating Opdualag in patients previously experiencing immune-related myocarditis is not known. c Presenting as an overlap of either two or all three conditions. The most severe CTCAE grade from the individual events should be considered to assess the recommended treatment modification for Opdualag.
Special populations Paediatric population The safety and efficacy of Opdualag in children below 12 years of age have not been established. 2). 2). 2). Data from patients with severe renal impairment are too limited to draw conclusions on this population.
Summary of the safety profile Nivolumab in combination with relatlimab is associated with immune-related adverse reactions (see “Description of selected adverse reactions” below). 4. The most common adverse reactions are fatigue (44%), musculoskeletal pain (34%), rash (30%), diarrhoea (30%), arthralgia (29%), pruritus (28%), headache (21%), nausea (21%), cough (18%), hypothyroidism (18%), decreased appetite (16%), abdominal pain (16%), vitiligo (14%), urinary tract infection (14%), pyrexia (13%), constipation (13%), upper respiratory tract infection (12%), dyspnoea (12%), vomiting (12%), dizziness (10%), and oedema (10%).
1%). Incidences of Grade 3-5 adverse reactions in patients with advanced (unresectable or metastatic) melanoma were 47% for nivolumab in combination with relatlimab and 38% for nivolumab treated patients. Tabulated summary of adverse reactions The safety of nivolumab in combination with relatlimab has been evaluated in 355 patients with advanced (unresectable or metastatic) melanoma (study CA224047).
94 months, are presented in Table 2. The frequencies included above and in Table 2 are based on all-cause adverse event frequencies. 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 the order of decreasing seriousness.
Table 2:
Adverse reactions in clinical studies Infections and infestations Very common urinary tract infection, upper respiratory tract infection Common folliculitis Blood and lymphatic system disorders Very common anaemiaa, lymphopaeniaa, leucopaeniaa, neutropaeniaa Common thrombocytopaeniaa, eosinophilia Uncommon haemolytic anaemia Endocrine disorders Very common hypothyroidism Common adrenal insufficiency, hypophysitis, hyperthyroidism, thyroiditis Uncommon hypopituitarism, hypogonadism Metabolism and nutrition disorders Very common decreased appetite Common diabetes mellitus, hypoglycaemiaa, weight decreased, hyperuricaemia, hypoalbuminaemia, dehydration Psychiatric disorders Common confusional state Nervous system disorders Very common dizziness, headache Common peripheral neuropathy, dysgeusia Uncommon encephalitis, Guillain-Barré syndrome, optic neuritis, myasthenia gravis, Myocarditis- Myositis-Myasthenia Gravis Overlap Syndromec Eye disorders Common uveitis, visual impairment, dry eye, increased lacrimation Uncommon Vogt-Koyanagi-Harada disease, ocular hyperaemia Cardiac disorders Common myocarditis Uncommon pericardial effusion Vascular disorders Common phlebitis Respiratory, thoracic and mediastinal disorders Very common dyspnoea, cough Common pneumonitisb, pleural effusion, nasal congestion Uncommon asthma Gastrointestinal disorders Very common diarrhoea, vomiting, nausea, abdominal pain, constipation Common colitis, pancreatitis, gastritis, dysphagia, stomatitis, dry mouth Uncommon oesophagitis Rare pancreatic exocrine insufficiency Not known coeliac disease Hepatobiliary disorders Common hepatitis Uncommon cholangitis 12 Skin and subcutaneous tissue disorders Very common rash, vitiligo, pruritus Common alopecia, lichenoid keratosis, psoriasis, urticaria, photosensitivity reaction, dry skin Uncommon pemphigoid Musculoskeletal and connective tissue disorders Very common musculoskeletal pain, arthralgia Common arthritis, muscle spasms, muscular weakness Uncommon myositis, Sjogren’s Syndrome, polymyalgia rheumatica, rheumatoid arthritis, systemic lupus erythematosus Renal and urinary disorders Common renal failure, proteinuria Uncommon nephritis Reproductive system and breast disorders Uncommon azoospermia General disorders and administration site conditions Very common oedema, fatigue, pyrexia Common influenza-like illness, chills Rare serositis Investigations Very common increased ASTa, increased ALTa, hyponatraemiaa, increased creatininea, increased alkaline phosphatasea, hypocalcaemiaa, hypomagnesaemiaa, hyperkalaemiaa, hypercalcaemiaa, hypokalaemiaa, hypernatraemiaa, increased bilirubina Common hypermagnesaemiaa, troponin increased, gamma-glutamyl transferase increased, blood lactate dehydrogenase increased, lipase increased, amylase increased, c-reactive protein increased Uncommon red blood cell sedimentation rate increased Injury, poisoning and procedural complications Common infusion-related reaction a Frequencies of laboratory terms reflect the proportion of patients who experienced a worsening from baseline in laboratory measurements.
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. Assessment of PD-L1 status When assessing the PD-L1 status of the tumour, it is important that a well-validated and robust methodology is used.
2). Immune-related adverse reactions affecting more than one body system can occur simultaneously. Patients should be monitored continuously (at least up to 5 months after the last dose) as an adverse reaction with Opdualag may occur at any time during or after discontinuation of therapy.
For suspected immune-related adverse reactions, adequate evaluation should be performed to confirm aetiology or exclude other causes. Based on the severity of the adverse reaction, Opdualag should be withheld and corticosteroids administered.
If immunosuppression with corticosteroids is used to treat an adverse reaction, a taper of at least 1 month duration should be initiated upon improvement. Rapid tapering may lead to worsening or recurrence of the adverse reaction. Non-corticosteroid immunosuppressive therapy should be added if there is worsening or no improvement despite corticosteroid use.
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 the combination of nivolumab and relatlimab are scarce. Opdualag should not be resumed while the patient is receiving immunosuppressive doses of corticosteroids or other immunosuppressive therapy.
Prophylactic antibiotics may be used to prevent opportunistic infections in patients receiving immunosuppressive therapy. Opdualag must be permanently discontinued for any severe immune-related adverse reaction that recurs and for any life-threatening immune-related adverse reaction.
1.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Know a brand we are missing in European Union? Suggest a brand →
Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
2). Data from patients with severe hepatic impairment are too limited to draw conclusions on this population. Method of administration Opdualag is for intravenous use only. It is to be administered as an intravenous infusion over a period of 30 minutes.
Opdualag must not be administered as an intravenous push or bolus injection. 9%) solution for injection or glucose 50 mg/mL (5%) solution for […]
b Fatal case has been reported in the clinical study. 4). 1% of patients. 8%. 28% of patients. 4). 0+). 7% of patients and required high […]
8). g. focal ground glass opacities, patchy infiltrates), dyspnoea, and hypoxia. Infectious and disease-related aetiologies should be ruled out. For Grade 3 or 4 pneumonitis, Opdualag must be permanently discontinued, and corticosteroids should be initiated at a dose of 2 to 4 mg/kg/day methylprednisolone equivalents.
For Grade 2 (symptomatic) pneumonitis, Opdualag should be withheld and corticosteroids initiated at a dose of 1 mg/kg/day methylprednisolone equivalents. Upon improvement, Opdualag may be resumed after corticosteroid taper. If worsening or no improvement occurs despite initiation of 6 corticosteroids, corticosteroid dose should be increased to 2 to 4 mg/kg/day methylprednisolone equivalents, and Opdualag must be permanently discontinued.
8). Patients should be monitored for diarrhoea and additional symptoms of colitis, such as abdominal pain and mucus and/or blood in stool. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-related colitis.
Infectious and other aetiologies of diarrhoea should be ruled out, therefore appropriate laboratory tests and additional examinations must be performed. If diagnosis of corticosteroid-refractory immune-related colitis is confirmed, addition of an alternative immunosuppressive agent to the corticosteroid therapy, or replacement of the corticosteroid therapy should be considered.
For Grade 4 diarrhoea or colitis, Opdualag must be permanently discontinued, and corticosteroids should be initiated at a dose of 1 to 2 mg/kg/day methylprednisolone equivalents. Opdualag should be withheld for Grade 3 diarrhoea or colitis, and corticosteroids initiated at a dose of 1 to 2 mg/kg/day methylprednisolone equivalents.
Upon improvement, Opdualag may be resumed after corticosteroid taper. If worsening or no improvement occurs despite initiation of corticosteroids, Opdualag must be permanently discontinued. For Grade 2 diarrhoea or colitis, Opdualag should be withheld.
5 to 1 mg/kg/day methylprednisolone equivalents. Upon improvement, Opdualag may be resumed after corticosteroid taper, if needed. If worsening or no improvement occurs despite initiation of corticosteroids, corticosteroid dose should be increased to 1 to 2 mg/kg/day methylprednisolone equivalents, and Opdualag must be permanently discontinued.
8). Patients should be monitored for signs and symptoms of hepatitis such as transaminase and total bilirubin elevations. Infectious and disease-related aetiologies should be ruled out. For AST or ALT increases to more than 5 times ULN regardless of baseline, total bilirubin increases to more than 3 times ULN, or concurrent AST or ALT increase to more than 3 times ULN and total bilirubin increase to more than 2 times ULN, Opdualag must be permanently discontinued, and corticosteroids should be initiated at a dose of 1 to 2 mg/kg/day methylprednisolone equivalents.
5 and up to 3 times ULN, Opdualag […]