OPDIVO
Safety Information1
Clinical use:
Efficacy and safety not established in pediatric patients.
Most serious warnings and precautions:
Severe/fatal immune-mediated adverse reactions
(imARs): OPDIVO as monotherapy or in combination
with YERVOY (ipilimumab) can
cause severe and
fatal immune-mediated adverse reactions, including
pneumonitis, interstitial lung disease, encephalitis,
myocarditis,
Stevens-Johnson syndrome (SJS), toxic
epidermal necrolysis (TEN) and autoimmune
hemolytic anemia. Immune-mediated adverse
reactions may involve any organ system. Onset may
occur during treatment or months after the last
dose. Early diagnosis and
appropriate management
are essential to minimize potential life-threatening
complications. Monitor patients for signs and
symptoms of imARs and appropriately manage with
treatment modifications. Permanently discontinue
for any severe imARs that
recur
and for any life-threatening imARs.
When OPDIVO is administered in combination with cabozantinib, refer to the product monograph for cabozantinib prior to initiation of treatment.
Administration: Administer OPDIVO under the
supervision of physicians experienced in the
treatment of cancer.
Allogeneic hematopoietic stem
cell transplantation (HSCT): Complications, including
fatal events, occurred in patients who received
allogeneic HSCT after OPDIVO. Preliminary results
from the follow-up of patients undergoing
allogeneic HSCT after previous exposure to
nivolumab showed a higher than expected number
of cases of acute graft-versus-host disease (GVHD)
and transplant-related mortality.
Complications may
occur despite intervening therapy between PD-1
blockade and allogeneic HSCT. Follow patients
closely for early
evidence of transplant-related
complications such as hyperacute GVHD, severe
(Grades 3 to 4) acute GVHD, steroid-requiring febrile
syndrome, hepatic venoocclusive disease (VOD), and
other immune-mediated adverse reactions, and
intervene promptly.
Multiple myeloma: Increased mortality in patients
with multiple myeloma [not an approved indication]
when OPDIVO is added to a
thalidomide analogue
and dexamethasone. Treatment of patients with
multiple myeloma with a PD-1 blocking antibody in
combination
with a thalidomide analogue plus
dexamethasone is not recommended outside of
controlled clinical trials.
Other relevant warnings and precautions:
- imARs have occurred at higher frequencies when
OPDIVO was administered in combination with
YERVOY vs. OPDIVO alone - Severe cases of these imARs have been observed,
including fatal cases. Monitor patients for signs
and symptoms of: - Cardiac adverse events and pulmonary embolism
with combination therapy - Endocrinopathies, including hypothyroidism,
hyperthyroidism, hypoparathyroidism, adrenal
insufficiency, hypophysitis, diabetes
mellitus,
and diabetic ketoacidosis - Diarrhea, additional symptoms of colitis, and
cytomegalovirus (CMV) infection/reactivation - Hepatotoxicity, including hepatitis
- Pneumonitis or interstitial lung disease
- Nephrotoxicity, including nephritis and renal
failure - Rash, Stevens-Johnson syndrome, toxic
epidermal necrolysis - Encephalitis
- Aplastic anemia
- Autoimmune hemolytic anemia
- Myotoxicity (myositis, myocarditis, and
rhabdomyolysis) - Other imARs, including solid organ transplant
rejection and rapid-onset and severe
graft-versus-host disease (GVHD) - Infusion reaction
- Patients on controlled sodium diet
- Haemophagocytic lymphohistiocytosis (HLH)
- Effective contraception in women of reproductive
potential - In the absence of data, OPDIVO in combination with chemotherapy should be used with caution in the HER2 negative subpopulations (baseline ECOG performance score ≥ 2 or had untreated CNS metastases) after careful consideration of the potential benefits on an individual basis as these subpopulations were not part of the clinical trial in GC, GEJC or EAC
- Pregnancy and nursing women
- Has not been studied in patients with moderate
or severe hepatic or severe renal impairment - Hepatotoxicity: Opdivo in combination with
cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to OPDIVO alone - Higher discontinuation rate due to AEs in patients >75 years of age:
- mNSCL: >75 OPDIVO + ipilimumab = 29% vs. 18% for all patients, OPDIVO + ipilimumab + chemo 7% vs. 9.1% for all patients
- MPM: 67% for patients >75 vs. 51% for patients <75 and 30% vs. 27% for serious AEs
For more information:
Please consult the OPDIVO Product Monograph at
https://www.bms.com/assets/bms/ca/documents
/productmonograph/OPDIVO_EN_PM.pdf for important information relating to adverse reactions, drug interactions, and dosing, which have not been discussed in this piece.
The Product Monograph is also available by calling
us at: 1-866-463-6267.
References
- OPDIVO Product Monograph. Bristol-Myers Squibb Canada Co.
- YERVOY Product Monograph. Bristol-Myers Squibb Canada Co.