Anti-PD-1 and PD-L1 monoclonal antibodies (immune checkpoint inhibitors)
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Opdivo Dosage

Drug Detail:Opdivo (Nivolumab [ nye-vol-ue-mab ])

Generic Name: NIVOLUMAB 10mg in 1mL

Dosage Form: injection

Drug Class: Anti-PD-1 and PD-L1 monoclonal antibodies (immune checkpoint inhibitors)

Contents
Uses Warnings Before Taking Dosage Side effects Interactions FAQ

Patient Selection

Select patients with metastatic NSCLC for treatment with OPDIVO in combination with ipilimumab based on PD-L1 expression [see Clinical Studies (14.4)].

Information on FDA-approved tests for the determination of PD-L1 expression in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

Recommended Dosage

The recommended dosages of OPDIVO as a single agent are presented in Table 1.

Table 1: Recommended Dosages for OPDIVO as a Single Agent
* 30-minute intravenous infusion.

Indication

Recommended OPDIVO Dosage

Duration of Therapy

Metastatic non-small cell lung cancer

240 mg every 2 weeks*

or

480 mg every 4 weeks*

Until disease progression or unacceptable toxicity

Advanced renal cell carcinoma

Classical Hodgkin lymphoma

Squamous cell carcinoma of the head and neck

​Locally advanced or metastatic urothelial carcinoma

Esophageal squamous cell carcinoma

​Unresectable or metastatic melanoma

​Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more:

​240 mg every 2 weeks*

​ or

​480 mg every 4 weeks*

​Until disease progression or unacceptable toxicity

​Pediatric patients age 12 years and older and weighing less than 40 kg:

​3 mg/kg every 2 weeks*

​or

​6 mg/kg every 4 weeks*

Adjuvant treatment of melanoma

240 mg every 2 weeks*

or

480 mg every 4 weeks*

Until disease recurrence or unacceptable toxicity for up to 1 year

​Adjuvant treatment of urothelial carcinoma (UC)

Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer

Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more:

240 mg every 2 weeks*

or

480 mg every 4 weeks*

Until disease progression or unacceptable toxicity

Pediatric patients age 12 years and older and weighing less than 40 kg:

3 mg/kg every 2 weeks*

​Adjuvant treatment of resected esophageal or gastroesophageal junction cancer

​240 mg every 2 weeks*

​or

​480 mg every 4 weeks*

​Until disease progression or unacceptable toxicity for a total treatment duration of 1 year

The recommended dosages of OPDIVO in combination with other therapeutic agents are presented in Table 2. Refer to the respective Prescribing Information for each therapeutic agent administered in combination with OPDIVO for the recommended dosage information, as appropriate.

Table 2: Recommended Dosages of OPDIVO in Combination with Other Therapeutic Agents
* 30-minute intravenous infusion on the same day.

Indication

Recommended OPDIVO Dosage

Duration of Therapy

Unresectable or metastatic melanoma

1 mg/kg every 3 weeks*

with ipilimumab 3 mg/kg intravenously*

In combination with ipilimumab for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier

​Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more:

240 mg every 2 weeks*

or

480 mg every 4 weeks*

After completing 4 doses of combination therapy, administer as single agent until disease progression or unacceptable toxicity

​Pediatric patients age 12 years and older and weighing less than 40 kg:
3 mg/kg every 2 weeks*

​or

​6 mg/kg every 4 weeks*

​Neoadjuvant treatment of resectable non-small cell lung cancer

​360 mg every 3 weeks*

​with platinum-doublet chemotherapy on the same day every 3 weeks

​In combination with platinum-doublet chemotherapy for 3 cycles

Metastatic non-small cell lung cancer expressing PD-L1

360 mg every 3 weeks*

with ipilimumab 1 mg/kg every 6 weeks*

In combination with ipilimumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression

Metastatic or recurrent non-small cell lung cancer

360 mg every 3 weeks*

with ipilimumab 1 mg/kg every 6 weeks*

and histology-based platinum

doublet chemotherapy every 3 weeks

In combination with ipilimumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression

2 cycles of histology-based platinum-doublet chemotherapy

Malignant pleural mesothelioma

360 mg every 3 weeks*

with ipilimumab 1 mg/kg every 6 weeks*

In combination with ipilimumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression

Advanced renal cell carcinoma

3 mg/kg every 3 weeks*

with ipilimumab 1 mg/kg intravenously*

In combination with ipilimumab
for 4 doses

240 mg every 2 weeks*

or

480 mg every 4 weeks*

Administer OPDIVO in combination with cabozantinib 40 mg orally once daily without food

OPDIVO: Until disease progression, unacceptable toxicity, or up to 2 years

Cabozantinib: Until disease progression or unacceptable toxicity

240 mg every 2 weeks*

or

480 mg every 4 weeks*

After completing 4 doses of combination therapy with ipilimumab, administer as single agent until disease progression or unacceptable toxicity

Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer

3 mg/kg every 3 weeks*

with ipilimumab 1 mg/kg intravenously*

In combination with ipilimumab
for 4 doses

Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more:

240 mg every 2 weeks*

or

480 mg every 4 weeks*

After completing 4 doses of combination therapy, administer as single agent until disease progression or unacceptable toxicity

Pediatric patients age 12 years and older and weighing less than 40 kg:

3 mg/kg every 2 weeks*

Hepatocellular carcinoma

1 mg/kg every 3 weeks*

with ipilimumab 3 mg/kg intravenously*

In combination with ipilimumab
for 4 doses

240 mg every 2 weeks*

or

480 mg every 4 weeks*

After completing 4 doses of combination therapy, administer as single agent until disease progression or unacceptable toxicity

​Esophageal squamous cell carcinoma

​240 mg every 2 weeks*

​or

​480 mg every 4 weeks*

​Administer OPDIVO in combination with fluoropyrimidine- and platinum-containing chemotherapy

​OPDIVO: Until disease progression, unacceptable toxicity, or up to 2 years

​Chemotherapy: Until disease progression or unacceptable toxicity

​3 mg/kg every 2 weeks*

​or

​360 mg every 3 weeks*

​with ipilimumab 1 mg/kg every 6 weeks*

​In combination with ipilimumab until disease progression, unacceptable toxicity, or up to 2 years

​Gastric cancer, Gastroesophageal junction cancer, and Esophageal adenocarcinoma

​240 mg every 2 weeks*

​with fluoropyrimidine- and platinum-containing chemotherapy every 2 weeks

​or

​360 mg every 3 weeks*

​with fluoropyrimidine- and platinum-containing chemotherapy every 3 weeks

​Until disease progression, unacceptable toxicity, or up to 2 years

Dose Modifications

No dose reduction for OPDIVO is recommended. In general, withhold OPDIVO for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue OPDIVO for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating steroids.

Dosage modifications for OPDIVO or OPDIVO in combination for adverse reactions that require management different from these general guidelines are summarized in Table 3 and Table 4.

When OPDIVO is administered in combination with ipilimumab, withhold or permanently discontinue both ipilimumab and OPDIVO for an adverse reaction meeting these dose modification guidelines.

Table 3: Recommended Dosage Modifications for Adverse Reactions
a Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids.
b If AST and ALT are less than or equal to ULN at baseline, withhold or permanently discontinue OPDIVO based on recommendations for hepatitis with no liver involvement.
c Depending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement. Resume once acute symptoms have resolved.
ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal

Adverse Reaction

Severity

Dosage Modification

Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1)]

Pneumonitis

Grade 2

Withholda

Grades 3 or 4

Permanently discontinue

Colitis

For colitis in patients treated with combination therapy with ipilimumab, see Table 4.

Grade 2 or 3

Withholda

Grade 4

Permanently discontinue

Hepatitis with no tumor involvement of the liver

For liver enzyme elevations in patients treated with combination therapy with ipilimumab, see Table 4.

AST/ALT increases to >3 and ≤8 times ULN

or

Total bilirubin increases to >1.5 and ≤3 times ULN.

Withholda

AST or ALT increases to >8 times ULN

or

Total bilirubin increases to >3 times ULN.

Permanently discontinue

Hepatitis with tumor involvement of the liverb

For liver enzyme elevations in patients treated with combination therapy with ipilimumab, see Table 4.

Baseline AST/ALT is >1 and ≤3 times ULN and increases to >5 and ≤10 times ULN

or

Baseline AST/ALT is >3 and ≤5 times ULN and increases to >8 and ≤10 times ULN.

Withholda

AST/ALT increases to >10 times ULN

or

Total bilirubin increases to >3 times ULN.

Permanently discontinue

Endocrinopathiesc

Grade 3 or 4

Withhold until clinically stable or permanently discontinue depending on severity

Nephritis with Renal Dysfunction

Grade 2 or 3 increased blood creatinine

Withholda

Grade 4 increased blood creatinine

Permanently discontinue

Exfoliative Dermatologic Conditions

Suspected SJS, TEN, or DRESS

Withhold

Confirmed SJS, TEN, or DRESS

Permanently discontinue

Myocarditis

Grades 2, 3, or 4

Permanently discontinue

Neurological Toxicities

Grade 2

Withholda

Grade 3 or 4

Permanently discontinue

Other Adverse Reactions

Infusion-Related Reactions

[see Warnings and Precautions (5.2)]

Grade 1 or 2

Interrupt or slow the rate of infusion

Grade 3 or 4

Permanently discontinue
Table 4: Recommended Dosage Modifications for Adverse Reactions in Patients Treated with Combination Therapy
a Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids​.
 b If AST and ALT are less than or equal to ULN at baseline, withhold or permanently discontinue OPDIVO in combination with ipilimumab based on recommendations for hepatitis with no liver involvement.​
c Consider corticosteroid therapy for hepatic adverse reactions if OPDIVO is withheld or discontinued when administered in combination with cabozantinib.
d After recovery, rechallenge with one or both of OPDIVO and cabozantinib may be considered. If rechallenging with cabozantinib with or without OPDIVO, refer to cabozantinib Prescribing Information.

Treatment

Adverse Reaction

Severity

Dosage Modification

OPDIVO in combination with ipilimumab

Colitis

Grade 2

Withholda

Grade 3 or 4

Permanently discontinue

Hepatitis with no tumor involvement of the liver

or

Hepatitis with tumor involvement of the liver/non-HCC

AST/ALT increases to >3 times ULN and ≤5 times ULN

or

Total bilirubin increases to ≥1.5 and ≤3 times ULN.

Withholda

AST or ALT >5 times ULN or

Total bilirubin >3 times ULN.

Permanently discontinue

Hepatitis with tumor involvement of the liverb/HCC

Baseline AST/ALT is >1 and ≤3 times ULN and increases to >5 and ≤10 times ULN

or

Baseline AST/ALT is >3 and ≤5 times ULN and increases to >8 and ≤10 times ULN.

Withholda

AST/ALT increases to >10 times ULN

or

Total bilirubin increases to >3 times ULN.

Permanently discontinue

OPDIVO in combination with cabozantinib

Liver enzyme elevations

ALT or AST >3 times ULN but ≤10 times ULN with concurrent total bilirubin <2 times ULN

Withholdc both OPDIVO and cabozantinib until adverse reactions recoverd to Grades 0-1

ALT or AST >10 times ULN

or >3 times ULN with concurrent total bilirubin ≥2 times ULN

Permanently discontinuec both OPDIVO and cabozantinib

Preparation and Administration

Visually inspect for particulate matter and discoloration. OPDIVO is a clear to opalescent, colorless to pale-yellow solution. Discard if cloudy, discolored, or contains extraneous particulate matter other than a few translucent-to-white, proteinaceous particles. Do not shake.

Preparation

•
Withdraw the required volume of OPDIVO and transfer into an intravenous container.
•
Dilute OPDIVO with either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to prepare an infusion with a final concentration ranging from 1 mg/mL to 10 mg/mL. The total volume of infusion must not exceed 160 mL.
• For adult and pediatric patients with body weight 40 kg or greater, do not exceed a total volume of infusion of 160 mL.
• For adult and pediatric patients with body weight less than 40 kg, do not exceed a total volume of infusion of 4 mL/kg of body weight.
•
Mix diluted solution by gentle inversion. Do not shake.
•
Discard partially used vials or empty vials of OPDIVO.
•
The product does not contain a preservative.

•
After preparation, store the diluted solution either:
• at room temperature and room light for no more than 8 hours from the time of preparation to end of the infusion. Discard diluted solution if not used within 8 hours from the time of preparation; or
• under refrigeration at 2°C to 8°C (36°F to 46°F) and protected from light for no more than 7 days from the time of preparation to end of infusion. Discard diluted solution if not used within 7 days from the time of preparation.
•
Do not freeze.

Administration

•
Administer the infusion, after dilution, over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low protein binding in-line filter (pore size of 0.2 micrometer to 1.2 micrometer).
•
Administer OPDIVO in combination with other therapeutic agents as follows:
o
With ipilimumab: administer OPDIVO first followed by ipilimumab on the same day.
o
With platinum-doublet chemotherapy: administer OPDIVO first followed by platinum-doublet chemotherapy on the same day
o
With ipilimumab and platinum-doublet chemotherapy: administer OPDIVO first followed by ipilimumab and then platinum-doublet chemotherapy on the same day.
o
With fluoropyrimidine- and platinum-containing chemotherapy: administer OPDIVO first followed by fluoropyrimidine- and platinum-containing chemotherapy on the same day.
•
Use separate infusion bags and filters for each infusion.
•
Flush the intravenous line at end of infusion.
•
Do not co-administer other drugs through the same intravenous line.
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