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Nivolumab parenteral

Updated 2 Feb 2023 | Nivolumab

Presentation

Infusions of nivolumab.

Drugs List

  • nivolumab 100mg/10ml concentrate for solution for infusion
  • nivolumab 120mg/12ml concentrate for solution for infusion
  • nivolumab 240mg/24ml concentrate for solution for infusion
  • nivolumab 40mg/4ml concentrate for solution for infusion
  • OPDIVO 100mg/10ml concentrate for solution for infusion
  • OPDIVO 120mg/12ml concentrate for solution for infusion
  • OPDIVO 240mg/24ml concentrate for solution for infusion
  • OPDIVO 40mg/4ml concentrate for solution for infusion
  • Therapeutic Indications

    Uses

    Advanced renal cell carcinoma
    Carcinoma - upper gastro-intestinal tract
    Locally advanced/metastatic Non-Small Cell Lung Cancer (NSCLC)
    Malignant melanoma
    Malignant pleural mesothelioma
    Relapsed/refractory classical Hodgkin lymphoma (cHL) after ASCT
    Squamous cell carcinoma of head and neck
    Treatment of advanced colorectal cancer combined with other cytotoxics
    Urothelial carcinoma: Treatment

    Advanced metastatic or unresectable melanoma in adults as monotherapy or in combination with ipilimumab.

    Adjuvant treatment of melanoma in adults with lymph node involvement or metastatic disease who have undergone complete resection.

    Locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) after prior chemotherapy treatment.

    As monotherapy for advanced renal cell carcinoma (RCC) after prior chemotherapy treatment. In combination with ipilimumab as first line treatment of adult patients with intermediate to poor risk advanced renal cell carcinoma.
    Relapsed or refractory classical Hodgkin's lymphoma (cHL) after autologous stem cell transplant (ASCT) and treatment with brentuximab vedotin.

    Squamous cell cancer of the head and neck in adults progressing on or after platinum-based therapy. Locally advanced unresectable or metastatic urothelial carcinoma in adults after failure of prior platinum-containing therapy.

    As monotherapy for the treatment of adults with unresectable, advanced, recurrent or metastatic oesophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum-based combination chemotherapy.

    As monotherapy for the adjuvant treatment of adults with completely resected oesophageal or gastro-oesophageal junction cancer and residual pathologic disease following prior neoadjuvant chemoradiotherapy.

    In combination with fluoropyrimidine- and platinum-based combination chemotherapy for the first-line treatment of adults with HER2-negative, advanced or metastatic gastric, gastro-oesophageal junction or oesophageal adenocarcinoma with PD-L1 expression and a combined positive score (CPS) equal or more than 5.

    First-line treatment of metastatic non-small cell lung cancer in adults in combination with ipilimumab and 2 cycles of platinum-based chemotherapy where tumours have no sensiting EGFR mutation or ALK translocation.

    Unresectable, malignant, pleural mesothelioma in adults as the first-line treatment in combination with ipilimumab.

    In combination with ipilimumab for the treatment of adults with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer after prior fluoropyrimidine-based combination chemotherapy.

    In combination with cabozantinib as first line treatment of adult patients with advanced cell carcinoma.

    Dosage

    Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

    Doses may vary significantly if this agent is used as monotherapy or different combinations.

    Adults

    Monotherapy

    Melanoma (advanced or adjuvant treatment); Renal cell carcinoma (RCC)
    240mg intravenously every 2 weeks over 30 minutes or 480mg intravenously every 4 weeks over 60 minutes.

    Oesophageal or gastro-oesophageal junction cancer (OC or GEJC) - adjuvant treatment
    240mg intravenously every 2 weeks over 30 minutes or 480mg intravenously every 4 weeks over 30 minutes for the first 16 weeks, followed by 480mg every 4 weeks over 30minutes.

    Non-small cell lung cancer (NSCLC); Classical Hodgkin lymphoma (cHL); Squamous cell cancer of the head and neck (SCCHN); Urothelial carcinoma; Oesophageal squamous cell carcinoma (OSCC)
    240mg intravenously every 2 weeks over 30 minutes.

    In melanoma, RCC, OC or GEJC patients who need to be switched from 240mg every 2 weeks schedule to the 480mg every 4 weeks schedule, the first 480mg dose should be administered 2 weeks after the last 240mg dose.
    In melanoma or RCC patients who need to be switched from the 480mg every 4 weeks schedule to the 240mg every 2 weeks schedule, the first 240mg dose should be administered 4 weeks after the last 480mg dose.

    Combination therapy with ipilimumab

    Melanoma
    1mg/kg intravenously in combination with 3mg/kg ipilimumab every 3 weeks for the first 4 doses followed by nivolumab monotherapy administered intravenously at 240mg every 2 weeks or at 480mg every 4 weeks.
    The administration of the first dose of nivolumab in the monotherapy phase should occur 3 weeks after the last dose of the combination of nivolumab and ipilimumab if using 240mg every 2 weeks or 6 weeks after the last dose of the combination of nivolumab and ipilimumab if using 480mg every 4 weeks.

    Malignant pleural mesothelioma
    360mg intravenously over 30minutes every 3 weeks for up to 24 months in patients without disease progression.

    Renal cell carcinoma (RCC) and dMMR or MSI-H colorectal cancer
    3mg/kg intravenously in combination with 1mg/kg ipilimumab every 3 weeks for the first 4 doses followed by nivolumab monotherapy administered intravenously at 240mg every 2 weeks or at 480mg every 4 weeks (RCC only).
    The administration of the first dose of nivolumab in the monotherapy phase should occur 3 weeks after the last dose of the combination of nivolumab and ipilimumab if using 240mg every 2 weeks or 6 weeks after the last dose of the combination of nivolumab and ipilimumab if using 480mg every 4 weeks (RCC only).

    Combination therapy with cabozantinib

    Renal cell carcinoma
    240mg intravenously every 2 weeks or 480mg intravenously every 4 weeks.

    Combination therapy with ipilimumab and chemotherapy

    Non-small cell lung cancer
    360mg intravenously over 30 minutes every 3 weeks in combination with 1mg/kg ipilimumab administered intravenously over 30 minutes every 6 weeks, and platinum-based chemotherapy administered every 3 weeks.
    After completion of 2 cycles of chemotherapy 360mg of nivolumab intravenously every 3 weeks in combination with 1mg/kg ipilimumab every 6 weeks should be administered.
    Treatment can be continued until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

    Combination with chemotherapy

    Gastro, gastro-oesophageal junction or oesophageal adenocarcinoma
    360mg intravenously over 30 minutes in combination with fluoropyrimidine- and platinum-based chemotherapy administered every 3 weeks or 240mg intravenously over 30 minutes in combination with fluoropyrimidine- and platinum-based chemotherapy administered every 2 weeks.
    Treatment can be continued until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

    Administration

    For intravenous infusion over 30 or 60 minutes depending on the dose.

    Contraindications

    Children under 18 years
    Breastfeeding
    Pregnancy

    Precautions and Warnings

    Autoimmune disease
    History of progenitor cell transplantation
    Immunosuppression
    Patients over 75 years
    Performance status of ECOG greater than or equal to 2
    Restricted sodium intake
    Solid organ transplant recipients
    Central nervous system metastasis
    Cerebral metastases
    Dehydration
    History of severe cutaneous adverse reactions
    Interstitial lung disease
    Moderate hepatic impairment
    Severe renal impairment

    Sodium content of formulation may be significant
    Advise ability to drive/operate machinery may be affected by side effects
    Consider use of corticosteroids if adverse reactions occur
    Maintain adequate hydration of patient prior / during treatment
    Risk of serious transplant-related complications
    Treatment to be initiated and supervised by a specialist
    Consult local policy on the safe use of anti-cancer drugs
    Record name and batch number of administered product
    Staff: Not to be handled by pregnant staff
    Monitor cardiac function prior to, during and following up from treatment
    Monitor renal and hepatic function before and during treatment
    Monitor serum electrolytes before and during treatment
    Monitor thyroid function prior to and periodically during treatment
    Monitor and manage cytomegalovirus reactivation during treatment
    Monitor closely for skin reactions
    Monitor for adverse reactions during and for 5 months after last dose
    Monitor for signs and symptoms of colitis
    Monitor for signs and symptoms of pneumonitis
    Monitor for signs of dehydration
    Monitor for signs of immune related hepatitis
    Monitor patients for endocrinopathies
    Monitor patients for signs of tumour lysis syndrome
    Monitor pulmonary function regularly
    Perform stool infection workup & screen for CMV if diarrhoea/colitis occurs
    Advise patient to report any new or worsening respiratory symptoms
    Advise patients to report signs of diarrhoea and stomatitis
    Discontinue if grade 3 or greater elevations in transaminase / bilirubin
    Discontinue if haemophagocytic lymphohistiocytosis (HLH) is suspected
    Discontinue treatment if grade 3 colitis occurs in combination therapy
    Discontinue treatment if grade 3 diarrhoea occurs in combination therapy
    Discontinue treatment if grade 3 or 4 adrenal insufficiency occurs
    Discontinue treatment if severe cardiac adverse reactions occur
    Discontinue treatment if Stevens-Johnson Syndrome suspected
    Discontinue treatment if toxic epidermal necrolysis is suspected
    Suspend treatment if grade 2 adrenal insufficiency occurs
    Suspend treatment if grade 2 elevations in transaminase or bilirubin
    Suspend treatment if grade 2 or 3 colitis occurs in monotherapy
    Suspend treatment if grade 2 or 3 creatinine elevations
    Suspend treatment if grade 2 or 3 diarrhoea occurs in monotherapy
    Suspend treatment if grade 2 or 3 endocrinopathies occur
    Suspend treatment if grade 3 or worse skin reaction occurs
    Consider discontinuing if pulmonary adverse events suspected/confirmed
    Discontinue if grade 3 myocarditis occurs
    Discontinue if grade 3 or greater adverse reaction that recurs/persists
    Discontinue if grade 4 toxicity occurs
    Discontinue if severe immune reaction recurs or is life threatening
    Discontinue permanently if life threatening infusion reactions occur
    Discontinue treatment if grade 3 or greater pneumonitis occurs
    Suspend treatment if grade 2 myocarditis occurs
    Suspend treatment if grade 2 pneumonitis occurs
    Suspend treatment if grade 3 diabetes occurs
    Suspend treatment if grade 3 or greater adverse reaction occurs
    Female: Contraception required during & for at least 5 months after therapy
    Advise patients to report skin rash
    Remind patient of importance of carrying Alert Card with them at all times

    Patients receiving immunosuppressant corticosteroid doses, or other immunosuppressive agents, should not receive nivolumab concurrently.

    The delayed onset of nivolumab should be considered before initiating in patients with rapidly progressing disease.

    The treatment with nivolumab or nivolumab in combination with ipilimumab for clinically stable patients should be continued in presence of initial evidence of disease progression (an initial transient increase in tumor size, small new lesions within the first few months followed by tumour shrinkage) until disease progression is confirmed.

    If an endocrinopathy is considered immune related, treatment should be suspended and thyroid hormone replacement therapy/antithyroid therapy should be initiated as necessary, along with corticosteroids. If symptoms resolve, resume nivolumab (as combination or monotherapy) after corticosteroid taper.

    Caution should be used when considering nivolumab treatment in patients who have previously experienced severe/ life threatening skin reactions with other immune-stimulatory anticancer treatments.

    Patients who have previously been exposed to nivolumab are at increased risk of acute graft-versus-host-disease (aGVHD) and transplant related mortality when receiving allogeneic haematopoietic stem cell transplant (HSCT).

    The maximum treatment duration with nivolumab as adjuvant therapy is 12 months.

    Tumour expression of programmed cell death ligand 1 (PD-L1) should be confirmed by a validated test when selecting patients for nivolumab treatment following the specified indication.

    In patients with primitive peritoneal, pericardial, testis, or tunica vaginalis mesothelioma, carcinoma of the nasopharynx or salivary gland and apparent tumour invasion in organs located adjacent to the oesophagus, stage IV resectable oesophageal or gastro-oesophageal junction cancer nivolumab should be used with caution due to the absence of data.

    If nivolumab is used during second phase of treatment (nivolumab monotherapy) following combination treatment and Grade 3 diarrhoea or colitis occurs then the treatment should be permanently discontinued.

    When suspending treatment due to adverse reactions corticosteroid should be initiated according to the local guidelines. Treatment should be resumed at the normal dose once symptoms have resolved and corticosteroid taper.

    For the immune-related adverse reactions permanently discontinue treatment if Grade 4 or reccurent Grade 3 reaction occurs or persistent Grade 2 or 3 reaction occurs despite treatment modification.

    Combination treatment with cabozantinib in renal cell carcinoma
    If ALT or AST are more than 3 times ULN but equal or less than 10 times ULN without concurrent total bilirubin equal or more than 2 times ULN, both nivolumab and cabozantinib should be withheld until adverse reactions recover to Grade 0 or 1. Corticosteroid therapy may be initiated. Rechallenge with a single medicine or both medicines may be considered.
    If ALT or AST is more than 10 times ULN or more than 3 times ULN with concurrent total bilirubin equal or more than 2 times ULN nivolumab and cabozantinib should be permanently discontinued and corticosteroid therapy may be initiated.

    Adjuvant treatment of melanoma
    There is no information about adjuvant treatment of melanoma in the presence of the following risk factors.
    Patients with prior therapy for melanoma (except surgery, adjuvant radiotherapy after neurosurgical resection for lesions of the central nervous system and prior adjuvant interferon completed equal to or 6 months prior to treatment). Patients treated with anti-PD1, anti-PDL1, anti-PDL2 anti-CD137 or anti CTLA-4 antibody (including any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways).

    Pregnancy and Lactation

    Pregnancy

    Nivolumab is contraindicated during pregnancy.

    The manufacturer recommends that nivolumab is not used during pregnancy. Human IgG4 is known to cross the placenta, so transfer of nivolumab to the developing foetus cannot be excluded. Animal studies have shown embryofoetal toxicity. At the time of writing, there is no data on the use of nivolumab in human pregnancy.

    Lactation

    Nivolumab is contraindicated during breastfeeding.

    The manufacturer recommends a decision must be made whether to discontinue breastfeeding or nivolumab therapy, weighing the benefits for the child and the mother. At the time of writing, it is unknown whether nivolumab is excreted in human breast milk. As other antibodies can be secreted in milk, a risk to neonates cannot be excluded. The high molecular weight of nivolumab may limit the amount of the drug present in milk, and then is likely to be destroyed in the infant's gastrointestinal tract.

    Side Effects

    Abdominal pain
    Acute adrenal insufficiency
    Alopecia
    Altered thyroid hormone levels
    Anaemia
    Arrhythmias
    Arthralgia
    Arthritis
    Aseptic meningitis
    Atrial fibrillation
    Blurred vision
    Bronchitis
    Chest pain
    Colitis
    Constipation
    Cough
    Cytomegalovirus infection
    Decreased appetite
    Dehydration
    Demyelinating disorders
    Diabetes mellitus
    Diarrhoea
    Dizziness
    Dry mouth
    Dry skin
    Duodenal ulcer
    Duodenitis
    Dyspnoea
    Electrolyte disturbances
    Elevated amylase levels
    Elevated serum lipase
    Encephalitis
    Eosinophilia
    Erythema
    Erythema multiforme
    Fatigue
    Gastritis
    Gastro-intestinal perforation
    Guillain-Barre syndrome
    Haemophagocytic lymphohistiocytosis
    Headache
    Hepatitis
    Hyperglycaemia
    Hypersensitivity reactions including anaphylaxis
    Hypertension
    Hypokalaemia
    Hypoparathyroidism
    Hypophysitis
    Immune reaction
    Increase in alkaline phosphatase
    Increase in serum ALT/AST
    Infusion-related symptoms
    Ketoacidosis
    Leucopenia
    Lymphadenitis
    Lymphopenia
    Musculoskeletal pain
    Myasthenia gravis-like syndrome
    Myocarditis
    Myopathy
    Nausea
    Nephritis
    Neuropathy
    Neutropenia
    Oedema
    Pain
    Pancreatitis
    Pericardial disorders
    Pituitary disorder
    Pneumonitis
    Polymyalgia rheumatica
    Polyneuropathy
    Pruritus
    Psoriasis
    Pulmonary embolism
    Pulmonary infiltration
    Pyrexia
    Rash
    Renal failure
    Rosacea
    Sarcoidosis
    Serum bilirubin increased
    Serum creatinine increased
    Sjogren's syndrome
    Solid organ graft rejection
    Spondyloarthropathy
    Stevens-Johnson syndrome
    Stomatitis
    Tachycardia
    Thrombocytopenia
    Thyroiditis
    Toxic epidermal necrolysis
    Tumour lysis syndrome
    Upper respiratory tract infection
    Urticaria
    Uveitis
    Vasculitis
    Vitiligo
    Vomiting
    Weight loss

    Overdosage

    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

    Further Information

    Last Full Review Date: September 2019

    Reference Sources

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at: https://ncbi.nlm.nih.gov/books/NBK501922/
    Nivolumab Last revised: 19 April 2021
    Last accessed: 31 March 2022

    Summary of Product Characteristics: Opdivo 10mg/ml concentrate for solution for infusion. Bristol-Myers Squibb Pharma. Revised March 2022.

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