Opdualag

/ BMS

Treatment must be initiated and supervised by physicians experienced in the treatment of cancer.
The recommended dose for adults and pediatric patients 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. This dose is established for pediatric patients 12 years of age and older weighing at least 30 kg.
Treatment 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.
See prescribing information for full details.

Unresectable or metastatic melanoma, for adult and pediatric patients 12 years of age or older.

Hypersensitivity to the active substances or to any of the excipients.

Immune-related adverse reactions
Immune-related adverse reactions can occur with nivolumab in combination with relatlimab which require appropriate management, including initiation of corticosteroids and treatment modifications.
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 this medical product may occur at any time during or after discontinuation of therapy.
This medical product should not be resumed while the patient is receiving immunosuppressive doses of corticosteroids or other immunosuppressive therapy.
This medical product must be permanently discontinued for any severe immune-related adverse reaction that recurs and for any life-threatening immune-related adverse reaction.
Thyroid dysfunction
For symptomatic hypothyroidism, this medical product should be withheld, and thyroid hormone replacement should be initiated as needed. For symptomatic hyperthyroidism, this medical product should be withheld and antithyroid treatment should be initiated as needed. Upon improvement, this medical product may be resumed after corticosteroid taper, if needed. Monitoring of thyroid function should continue to ensure appropriate hormone replacement is utilised. This medical product must be permanently discontinued for life-threatening (Grade 4) hyperthyroidism or hypothyroidism.
Adrenal insufficiency
This medical product must be permanently discontinued for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency. For symptomatic Grade 2 adrenal insufficiency, this medical product should be withheld, and physiologic corticosteroid replacement should be initiated as needed. Monitoring of adrenal function and hormone levels should continue to ensure appropriate corticosteroid replacement is utilised.
Hypophysitis
This medical product must be permanently discontinued for life-threatening (Grade 4) hypophysitis. For symptomatic Grade 2 or 3 hypophysitis, this medical product should be withheld. Upon improvement, this medical product may be resumed after corticosteroid taper, if needed. Monitoring of pituitary function and hormone levels should continue to ensure appropriate hormone replacement is utilised.
Diabetes mellitus
For symptomatic diabetes, this medical product should be withheld, and insulin replacement should be initiated as needed. Monitoring of blood sugar should continue to ensure appropriate insulin replacement is utilised.
Other important warnings and precautions, including class effects
Solid organ transplant rejection has been reported in the post-marketing setting in patients treated with PD-1 inhibitors. Treatment with nivolumab in combination with relatlimab may increase the risk of rejection in solid organ transplant recipients. The benefit of treatment with nivolumab in combination with relatlimab versus the risk of possible organ rejection should be considered in these patients.
Haemophagocytic lymphohistiocytosis (HLH) has been observed with nivolumab as monotherapy, nivolumab in combination with relatlimab and nivolumab in combination with other agents with a fatal event reported with nivolumab in combination with relatlimab. Caution should be taken when administering nivolumab in combination with relatlimab. If HLH is confirmed, administration of nivolumab in combination with relatlimab should be discontinued and treatment for HLH initiated.
GVHD: Treatment with nivolumab in combination with relatlimab may increase the risk of severe GVHD and death in patients who have had prior allogeneic HSCT, mainly in those with prior history of GVHD. The benefit of treatment with nivolumab in combination with relatlimab versus the possible risk should be considered in these patients.
Infusion reactions
Severe infusion reactions have been reported in clinical studies of nivolumab in combination with relatlimab. In case of a severe or life-threatening infusion reaction, infusion must be discontinued and appropriate medical therapy administered. Patients with mild or moderate infusion reaction may receive this medical product with close monitoring and preventative treatment according to local guidelines for prophylaxis of infusion reactions.
See prescribing information for full details.

Very common: urinary tract infection, anaemia, lymphopaenia, neutropaenia, leucopaenia, hypothyroidism, decreased appetite, headache, dyspnoea, cough, diarrhoea, vomiting, nausea, abdominal pain, constipation, rash, vitiligo, pruritus, musculoskeletal pain, arthralgia, fatigue, pyrexia, increased AST, increased ALT, hyponatraemia, increased creatinine, increased alkaline phosphatase, hyperkalaemia, hypocalcaemia, hypomagnesaemia, hypercalcaemia, hypokalaemia
Common: upper respiratory tract infection, thrombocytopaeniaa, eosinophilia, adrenal insufficiency, hypophysitis, hyperthyroidism, thyroiditis, diabetes mellitus, hypoglycaemia, weight decreased, hyperuricaemia, hypoalbuminaemia, dehydration, confusional state, peripheral neuropathy, dizziness, dysgeusia, uveitis, visual impairment, dry eye, increased lacrimation, myocarditis, phlebitis, pneumonitis, nasal congestion, colitis, pancreatitis, gastritis, dysphagia, stomatitis, dry mouth, hepatitis, alopecia, lichenoid keratosis, photosensitivity reaction, dry skin, arthritis, muscle spasms, muscular weakness, renal failure, proteinuria, oedema, influenza-like illness, chills, increased bilirubina, hypernatraemiaa, hypermagnesaemiaa, troponin increased, gamma-glutamyl transferase increased, blood lactate dehydrogenase increased, lipase increased, amylase increased, infusion-related reaction.
See prescribing information for full details.

Nivolumab and relatlimab are both human monoclonal antibodies and as such, no interaction studies have been conducted. As monoclonal antibodies are not metabolised by cytochrome P450 (CYP) enzymes or other active substances metabolising enzymes, inhibition or induction of these enzymes by co-administered medicinal products is not anticipated to affect the pharmacokinetics of relatlimab or nivolumab.
Systemic immunosuppression
The use of systemic corticosteroids and other immunosuppressants at baseline, before starting nivolumab in combination with relatlimab, should be avoided because of their potential interference with the pharmacodynamic activity. However, systemic corticosteroids and other immunosuppressants can be used after starting nivolumab in combination with relatlimab to treat immune-related adverse reactions.

Pregnancy: There is a limited amount of data from the use of nivolumab in combination with relatlimab in pregnant women. Human IgG4 is known to cross the placental barrier and nivolumab and relatlimab are an IgG4; therefore, nivolumab and relatlimab have the potential to be transmitted from the mother to the developing foetus. This medical product is not recommended during pregnancy and in women of childbearing potential not using effective contraception unless the clinical benefit outweighs the potential risk. Effective contraception should be used for at least 5 months following the last dose of Opdualag.
Lactation: It is unknown whether nivolumab and/or relatlimab are excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which is decreasing to low concentrations soon afterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. Afterwards, this medical product could be used during breast-feeding if clinically needed.

In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted immediately.