Drug Action
Nivolumab is a human immunoglobulin G4 monoclonal antibody, which binds to the programmed death-1 (PD-1) receptor thereby potentiating an immune response to tumour cells.
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Drug reference
Nivolumab is a human immunoglobulin G4 monoclonal antibody, which binds to the programmed death-1 (PD-1) receptor thereby potentiating an immune response to tumour cells.
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Melanoma (in combination with ipilimumab) (specialist use only) | Advanced renal cell carcinoma (in combination with ipilimumab) (specialist use only) ▶BY INTRAVENOUS INFUSION ▶Adult: (consult product literature) Melanoma (as monotherapy) (specialist use only) | Advanced renal cell carcinoma (as monotherapy) (specialist use only) ▶BY INTRAVENOUS INFUSION ▶Adult: 240 mg every 2 weeks, alternatively 480 mg every 4 weeks, consult product literature for information on dose adjustments based on individual patient safety and tolerability Non-small cell lung cancer (as monotherapy) (specialist use only) | Urothelial carcinoma (as monotherapy) (specialist use only) | Squamous cell cancer of the head and neck (as monotherapy) (specialist use only) | Classical Hodgkin lymphoma (as monotherapy) (specialist use only) ▶BY INTRAVENOUS INFUSION ▶Adult: 240 mg every 2 weeks, consult product literature for information on dose adjustments based on individual patient safety and tolerability Adjuvant treatment of melanoma (as monotherapy) (specialist use only) ▶BY INTRAVENOUS INFUSION ▶Adult: 3 mg/kg every 2 weeks, consult product literature for information on dose adjustments based on individual patient safety and tolerability
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May increase risk of severe graft-versus-host reaction in patients who have had prior haematopoietic stem cell transplant (particularly in those with a prior history). patients may need pre-medication to minimise the development of infusion-related reactions
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NICE decisions ▶Nivolumab for treating advanced (unresectable or metastatic) melanoma (February 2016) NICE TA384 Nivolumab (Opdivo ®) as monotherapy is recommended, within its marketing authorisation, as a treatment option for advanced (unresectable or metastatic) melanoma in adults. www.nice.org.uk/guidance/ta384 ▶Nivolumab in combination with ipilimumab for treating advanced melanoma (July 2016) NICE TA400 Nivolumab (Opdivo ®) in combination with ipilimumab is recommended, within its marketing authorisation, as a treatment option for advanced (unresectable or metastatic) melanoma in adults, only if the manufacturer provides ipilimumab with the discount agreed in the patient access scheme. www.nice.org.uk/guidance/ta400 ▶Nivolumab for adjuvant treatment of completely resected melanoma with lymph node involvement or metastatic disease (January 2019) NICE TA558 Nivolumab (Opdivo ®) is recommended for use within the Cancer Drugs Fund as an option for the adjuvant treatment of completely resected melanoma in adults with lymph node involvement or metastatic disease. It is recommended only if the conditions in the managed access agreement are followed. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta558 ▶Nivolumab for previously treated advanced renal cell carcinoma (updated November 2017) NICE TA417 Nivolumab (Opdivo ®) is recommended, within its marketing authorisation, as an option for previously treated advanced renal cell carcinoma in adults, when the manufacturer provides nivolumab in line with the commercial access agreement with NHS England. www.nice.org.uk/guidance/ta417 ▶Nivolumab with ipilimumab for untreated advanced renal cell carcinoma (May 2019) NICE TA581 Nivolumab (Opdivo ®) with ipilimumab is recommended for use within the Cancer Drugs Fund as an option for adults with untreated advanced renal cell carcinoma that is intermediate- or poor-risk as defined in the International Metastatic Renal Cell Carcinoma Database Consortium criteria. It is recommended only if the conditions in the managed access agreement for nivolumab with ipilimumab are followed. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta581 ▶Nivolumab for treating relapsed or refractory classical Hodgkin lymphoma (updated November 2017) NICE TA462 Nivolumab (Opdivo ®) is recommended, within its marketing authorisation, as an option for treating relapsed or refractory classical Hodgkin lymphoma in adults after autologous stem cell transplant and treatment with brentuximab vedotin, when the manufacturer provides nivolumab in line with the commercial access agreement with NHS England. www.nice.org.uk/guidance/ta462 ▶Nivolumab for previously treated squamous non-small-cell lung cancer (November 2017) NICE TA483 Nivolumab (Opdivo ®) is recommended for use within the Cancer Drugs Fund as an option for treating locally advanced or metastatic squamous non-small-cell lung cancer in adults after chemotherapy, only if: . nivolumab is stopped at 2 years of uninterrupted treatment, or earlier in the event of disease progression, and . the conditions in the managed access agreement are followed. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta483 ▶Nivolumab for previously treated non-squamous non-small- cell lung cancer (November 2017) NICE TA484 Nivolumab (Opdivo ®) is recommended for use within the Cancer Drugs Fund as an option for treating locally advanced or metastatic non-squamous non-small-cell lung cancer in adults after chemotherapy, only if: . their tumours are PD-L1 positive, and . nivolumab is stopped at 2 years of uninterrupted treatment, or earlier in the event of disease progression, and . the conditions in the managed access agreement are followed. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta484 ▶Nivolumab for treating squamous cell carcinoma of the head and neck after platinum-based chemotherapy (November 2017) NICE TA490 Nivolumab (Opdivo ®) is recommended for use within the Cancer Drugs Fund as an option for treating squamous cell carcinoma of the head and neck in adults whose disease has progressed on platinum-based chemotherapy, only if: . the disease has progressed within 6 months of having chemotherapy, and . nivolumab is stopped at 2 years of uninterrupted treatment, or earlier in the event of disease progression, and . the conditions in the managed access agreement are followed. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta490 ▶Nivolumab for treating locally advanced unresectable or metastatic urothelial cancer after platinum-containing chemotherapy (July 2018) NICE TA530 Nivolumab (Opdivo ®) is not recommended, within its marketing authorisation, for treating locally advanced unresectable or metastatic urothelial carcinoma in adults who have had platinum-containing therapy. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta530 Scottish Medicines Consortium (SMC) decisions SMC No. 1144/16 The Scottish Medicines Consortium has advised (July 2016) that nivolumab (Opdivo ®) is accepted for use within NHS Scotland for the treatment of locally advanced or metastatic squamous non-small cell lung cancer after prior chemotherapy in adults. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower. SMC No. 1180/16 The Scottish Medicines Consortium has advised (October 2016) that nivolumab (Opdivo ®) is accepted for restricted use within NHS Scotland for the treatment of locally advanced or metastatic non-squamous non-small cell lung cancer after prior chemotherapy in adults, subject to a two-year clinical stopping rule. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower. SMC No. 1120/16 The Scottish Medicines Consortium has advised (August 2016) that nivolumab (Opdivo ®) is accepted for restricted use within NHS Scotland as monotherapy for the treatment of advanced (unresectable or metastatic) melanoma in adults previously untreated with ipilimumab. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower. SMC No. 1187/16 The Scottish Medicines Consortium has advised (November 2016) that nivolumab (Opdivo ®) is accepted for restricted use within NHS Scotland in combination with ipilimumab for the first-line treatment of advanced (unresectable or metastatic) melanoma in adults. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower. SMC No. SMC2112 The Scottish Medicines Consortium has advised (December 2018) that nivolumab (Opdivo ®) is accepted for use within NHS Scotland as monotherapy for the adjuvant treatment of adults with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower. SMC No. 1188/16 The Scottish Medicines Consortium has advised (June 2017) that nivolumab (Opdivo ®) is accepted for use within NHS Scotland as monotherapy for treating adults with advanced renal cell carcinoma after prior therapy. The advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower. SMC No. SMC2153 The Scottish Medicines Consortium has advised (June 2019) that nivolumab (Opdivo ®) is accepted for use within NHS Scotland in combination with ipilimumab for the first-line treatment of adults with intermediate/poor-risk advanced renal cell carcinoma. SMC No. 1240/17 The Scottish Medicines Consortium has advised (July 2017) that nivolumab (Opdivo ®) is accepted for use within NHS Scotland for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma after autologous stem cell transplant and treatment with brentuximab vedotin. This advice is contingent upon the continuing Immune system and malignant disease availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower. SMC No. 1261/17 The Scottish Medicines Consortium has advised (September 2017) that nivolumab (Opdivo ®) is accepted for restricted use within NHS Scotland as monotherapy, for the treatment of squamous cell cancer of the head and neck in adults progressing on or after platinum-based therapy. Treatment with nivolumab is subject to a two year clinical stopping rule. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower. SMC No. 1285/18 The Scottish Medicines Consortium has advised (January 2018) that nivolumab (Opdivo ®) is not recommended for use within NHS Scotland as monotherapy for the treatment of locally advanced unresectable or metastatic urothelial carcinoma in adults after failure of prior platinum-containing therapy, as the economic case was not demonstrated.
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MHRA/CHM ADVICE: NIVOLUMAB (OPDIVO ®): REPORTS OF ORGAN TRANSPLANT REJECTION (JULY 2017) A European review of worldwide data concluded that nivolumab may increase the risk of rejection in organ transplant recipients. The MHRA recommends considering the benefit of treatment with nivolumab versus the risk of possible organ transplant rejection for each patient. MHRA/CHM ADVICE: NIVOLUMAB (OPDIVO ®): REPORTS OF CYTOMEGALOVIRUS (CMV) GASTROINTESTINAL INFECTION OR REACTIVATION (OCTOBER 2019) A European review of worldwide data identified cases suggestive of gastrointestinal CMV infection or reactivation in nivolumab-treated patients, including fatal cases. Patients should be advised to contact their healthcare professional immediately at the onset of symptoms of colitis. Possible causes, including infections, should be investigated; a stool infection work-up should be Immune system and malignant disease performed and patients screened for CMV. For patients with corticosteroid-refractory immune-related colitis, use of an additional immunosuppressive agent should only be considered if other causes are excluded using viral PCR on biopsy, and eliminating other viral, bacterial, and parasitic causes.
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→Appendix 1: monoclonal antibodies
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▶Common or very common Abdominal pain. alopecia. anaemia. appetite decreased. arthralgia. constipation. cough. decreased leucocytes. diarrhoea. dizziness. dry mouth. dyspnoea. electrolyte imbalance. fatigue. fever. gastrointestinal disorders. haemolytic anaemia. headache . hyperglycaemia. hypersensitivity. hypertension. hyperthyroidism. hypoglycaemia. hypothyroidism. increased risk of infection. infusion related reaction. musculoskeletal discomfort. myalgia. nausea. nerve disorders. neutropenia. oedema. pain. respiratory disorders. skin reactions. stomatitis. thrombocytopenia. vomiting. weight decreased ▶Uncommon Adrenal insufficiency. arrhythmias. arthritis. cardiac inflammation. chest pain. connective tissue disorders. dehydration. diabetes mellitus. dry eye. eosinophilia. eye inflammation. hepatic disorders. hypophysitis. hypopituitarism. metabolic acidosis. nephritis tubulointerstitial. pancreatitis. paresis. pericardial disorders. renal impairment. thyroiditis. vision blurred ▶Rare or very rare Demyelination. diabetic ketoacidosis. histiocytic necrotising lymphadenitis. myasthenic syndrome. myopathy. severe cutaneous adverse reactions (SCARs). vasculitis ▶Frequency not known Cytomegalovirus infection reactivation. hypoparathyroidism. meningitis aseptic. sarcoidosis. solid organ transplant rejection. tumour lysis syndrome SIDE-EFFECTS, FURTHER INFORMATION Immune-related reactions Manufacturer advises that most immune- related adverse reactions improved or resolved with appropriate management, including initiation of corticosteroids and treatment modifications—consult product literature for further information. Infusion-related reactions Manufacturer advises that patients with mild or moderate infusion reactions may continue treatment with close monitoring and use of pre- medication according to local guidelines; discontinue treatment if severe infusion reactions occur.
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Manufacturer advises effective contraception required during treatment and for at least 5 months after treatment in women of childbearing potential.
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Manufacturer advises avoid unless potential benefit outweighs risk—toxicity in animal studies.
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Manufacturer advises avoid—no information available.
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Manufacturer advises caution in moderate to severe impairment (limited information available).
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Manufacturer advises monitor for signs and symptoms of infusion- and immune- related reactions, cardiac and pulmonary reactions, and electrolyte disturbances before and periodically during treatment. Patients should be monitored for adverse Immune system and malignant disease reactions for at least 5 months after the last dose.
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Manufacturer advises for intermittent intravenous infusion, give undiluted or dilute to a concentration of not less than 1 mg/mL with Glucose 5% or Sodium Chloride 0.9%; give over 30 or 60 minutes (depending on dose—consult product literature) through an in-line filter (pore size 0.2–1.2 micron). l HANDLING AND STORAGE Manufacturer advises store in a refrigerator (2–8 °C)—consult product literature for storage conditions after preparation of the infusion.
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There can be variation in the licensing of different medicines containing the same drug. Solution for infusion CAUTIONARY AND ADVISORY LABELS 3 ELECTROLYTES: May contain Sodium ▶Opdivo (Bristol-Myers Squibb Pharmaceuticals Ltd) A Nivolumab 10 mg per 1 ml Opdivo 40mg/4ml concentrate for solution for infusion vials | 1 vial P £439.00 (Hospital only) Opdivo 100mg/10ml concentrate for solution for infusion vials | 1 vial P £1,097.00 (Hospital only) Opdivo 240mg/24ml concentrate for solution for infusion vials | 1 vial P £2,633.00 (Hospital only) eiiii F 903
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Patients should be provided with a patient alert card with each prescription.
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(consult product literature)
First-line fragment. Read the complete Indications and Dose section above.
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240 mg every 2 weeks, alternatively 480 mg
First-line fragment. Read the complete Indications and Dose section above.
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240 mg every 2 weeks, consult product literature
First-line fragment. Read the complete Indications and Dose section above.
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3 mg/kg every 2 weeks, consult product
First-line fragment. Read the complete Indications and Dose section above.
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