Boxed Warnings
Warning: immune-related adverse reactions with Opdivo and ipilimumab combination therapy. Immune-related adverse reactions are seen more frequently, and are more severe, with Opdivo and ipilimumab combination therapy than with Opdivo or ipilimumab monotherapy.
Immune-related adverse reactions can involve any organ system. The majority of these initially manifest during treatment; however, a minority can occur weeks to months after discontinuation. Some immune-related adverse reactions can be permanent (such as thyroid dysfunction and diabetes mellitus). Life-threatening or fatal immune-related adverse reactions that have occurred include colitis, intestinal perforation, hepatitis, pneumonitis, hypophysitis, adrenal insufficiency, toxic epidermal necrolysis, myocarditis, encephalitis and myasthenia gravis (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).
Early diagnosis and appropriate management are essential to minimise life-threatening complications (see Section 4.2 Dose and Method of Administration). Monitoring at least prior to each dose is recommended. Advise patients of the importance of immediately reporting possible symptoms.
Physicians should consult the ipilimumab product information prior to initiation of Opdivo in combination with ipilimumab. The combination of Opdivo and ipilimumab should be administered and monitored under the supervision of physicians experienced with the use of immunotherapy in the treatment of cancer.
1 Name of Medicine
Nivolumab.
2 Qualitative and Quantitative Composition
10 mg/mL concentrate solution for infusion.
Each 1 mL of concentrate contains 10 mg of nivolumab.
One 10 mL vial contains 40 mg of nivolumab in 4 mL.
One 10 mL vial contains 100 mg of nivolumab in 10 mL.
One 25 mL vial contains 240 mg of nivolumab in 24 mL.
Opdivo (nivolumab (rch)) is a fully human anti-PD-1 monoclonal antibody (IgG4) produced in mammalian (Chinese hamster ovary) cells by recombinant DNA technology.
Excipient with known effect. Each 1 mL of concentrate contains 0.1 mmol (or 2.5 mg) sodium.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
Concentrate for solution for infusion.
Clear to opalescent, colourless to pale yellow liquid that may contain few light particles. The solution has a pH of approximately 6.0 and an osmolarity of approximately 340 mOsm/kg.
4 Clinical Particulars
4.9 Overdose
There is no information on overdosage with Opdivo.
In case of overdosage, patients must be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).
5 Pharmacological Properties
5.3 Preclinical Safety Data
The effects of Opdivo on prenatal and postnatal development were evaluated in monkeys that received Opdivo at 10 and 50 mg/kg twice weekly from the onset of organogenesis in the first trimester through delivery, at exposure levels 8 and 35 times, respectively, those observed at the clinical dose of 3 mg/kg of Opdivo (based on AUC). There was a dose-dependent increase in foetal losses and increased neonatal mortality mainly in the 3rd trimester of pregnancy and after birth.
The remaining offspring of Opdivo-treated females survived to scheduled termination, with no treatment-related clinical signs, alterations to normal development, organ-weight effects, or gross and microscopic pathology changes. Results for growth indices, as well as teratogenic, neurobehavioral, immunological and clinical pathology parameters throughout the 6-month postnatal period were comparable to the control group.
Genotoxicity. Studies to evaluate the genotoxic potential of Opdivo have not been performed.
Carcinogenicity. Studies to evaluate the carcinogenic potential of Opdivo have not been performed.
6 Pharmaceutical Particulars
6.7 Physicochemical Properties
CAS number. CAS: 946414-94-4.
7 Medicine Schedule (Poisons Standard)
Schedule 4 - Prescription Only Medicine.
Summary Table of Changes
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