- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Infusions of nivolumab.
Advanced renal cell carcinoma
Carcinoma - upper gastro-intestinal tract
Locally advanced/metastatic Non-Small Cell Lung Cancer (NSCLC)
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.
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.
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
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.
For intravenous infusion over 30 or 60 minutes depending on the dose.
Children under 18 years
Precautions and Warnings
History of progenitor cell transplantation
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
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
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.
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.
Acute adrenal insufficiency
Altered thyroid hormone levels
Elevated amylase levels
Elevated serum lipase
Hypersensitivity reactions including anaphylaxis
Increase in alkaline phosphatase
Increase in serum ALT/AST
Myasthenia gravis-like syndrome
Serum bilirubin increased
Serum creatinine increased
Solid organ graft rejection
Toxic epidermal necrolysis
Tumour lysis syndrome
Upper respiratory tract infection
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 ).
Last Full Review Date: September 2019
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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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.