Nivolumab (Monograph)

Brand names: Opdivo, Opdivo Qvantig
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Jul 10, 2025. Written by ASHP.

Introduction

Nivolumab, a fully human anti-programmed-death receptor-1 (anti-PD-1) monoclonal antibody, is an antineoplastic agent.

Nivolumab and hyaluronidase-nvhy (nivolumab/hyaluronidase-nvhy) is a fixed combination of nivolumab (an anti-PD-1 monoclonal antibody) and hyaluronidase (an endoglycosidase).

Uses for Nivolumab

Melanoma

Nivolumab (Opdivo) is used as monotherapy or in combination with ipilimumab for the treatment of unresectable or metastatic melanoma in adults and pediatric patients ≥12 years of age (designated an orphan drug by FDA for this use).

Nivolumab/hyaluronidase-nvhy (Opdivo Qvantig) is used as monotherapy (or following combination treatment with IV nivolumab and ipilimumab) for the treatment of unresectable or metastatic melanoma in adults; not indicated for use in combination with ipilimumab.

Used as adjuvant therapy for stage IIB, IIC, III, or IV melanoma in adults (both products) or pediatric patients ≥12 years (Opdivo only) following complete resection.

Non-small Cell Lung Cancer (NSCLC)

Nivolumab and nivolumab/hyaluronidase-nvhy are used in combination with platinum doublet chemotherapy for the treatment of adults with resectable (node-positive or tumors ≥4 cm) NSCLC in the neoadjuvant setting.

Nivolumab and nivolumab/hyaluronidase-nvhy are used for the treatment of adults with resectable NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, for neoadjuvant treatment in combination with platinum doublet chemotherapy followed by single-agent nivolumab/hyaluronidase-nvhy as adjuvant treatment after surgery.

Nivolumab is used in combination with ipilimumab for the first-line treatment of adults with metastatic NSCLC expressing programmed-death ligand-1 (PD-L1; i.e., tumor proportion score ≥1%), with no EGFR or ALK genomic aberrations; FDA-approved diagnostic test required to confirm presence of high PD-L1 expression prior to initiation.

Nivolumab is used in combination with ipilimumab and 2 cycles of platinum doublet chemotherapy for the first-line treatment of adults with metastatic or recurrent NSCLC with no EGFR or ALK genomic aberrations.

Nivolumab/hyaluronidase-nvhy is not indicated in combination with ipilimumab for treatment of metastatic NSCLC.

Nivolumab and nivolumab/hyaluronidase-nvhy are used for the treatment of adults with metastatic NSCLC that has progressed during or following therapy with platinum-based chemotherapy and, in patients with EGFR mutation- or ALK-positive tumors, therapy with an FDA-labeled EGFR or ALK inhibitor.

Malignant Pleural Mesothelioma

Nivolumab is used in combination with ipilimumab for first-line treatment of unresectable MPM in adults; (designated an orphan drug by FDA for this use).

Renal Cell Carcinoma

Nivolumab and nivolumab/hyaluronidase-nvhy are used as monotherapy for the treatment of adults with advanced renal cell carcinoma previously treated with antiangiogenic therapy.

Nivolumab is used in combination with ipilimumab for the treatment of intermediate- or poor-risk, previously untreated, advanced renal cell carcinoma in adults; nivolumab/hyaluronidase-nvhy is used for this indication after initial treatment with IV nivolumab plus ipilimumab. Nivolumab/hyaluronidase-nvhy not indicated in combination with ipilimumab for treatment of renal cell carcinoma.

Nivolumab and nivolumab/hyaluronidase-nvhy are used in combination with cabozantinib as first-line treatment of adults with advanced renal cell carcinoma.

Hodgkin Lymphoma

Nivolumab is used for treatment of classical Hodgkin lymphoma (cHL) that has relapsed or progressed following autologous stem cell transplantation and subsequent therapy with brentuximab vedotin or following failure of ≥3 systemic therapies (including autologous stem cell transplantation) (designated an orphan drug by FDA for this cancer).

Accelerated approval based on objective response rate. Continued approval may be contingent on verification and description of clinical benefit in confirmatory studies.

Squamous Cell Carcinoma of the Head and Neck

Nivolumab and nivolumab/hyaluronidase-nvhy are used for treatment of adults with metastatic or recurrent squamous cell carcinoma of the head and neck that has progressed during or following therapy with platinum-based chemotherapy.

Urothelial Carcinoma

Nivolumab and nivolumab/hyaluronidase-nvhy are used for adjuvant treatment of adults with urothelial carcinoma who are at high risk of recurrence following radical resection.

Nivolumab and nivolumab/hyaluronidase-nvhy are used in combination with cisplatin and gemcitabine for first-line treatment of adults with unresectable or metastatic urothelial carcinoma.

Nivolumab and nivolumab/hyaluronidase-nvhy are used for treatment of adults with locally advanced or metastatic urothelial carcinoma that has progressed during or following platinum-containing therapy or within 12 months of platinum-containing therapy in the neoadjuvant or adjuvant setting.

Colorectal Cancer

Nivolumab is used as a single agent or in combination with ipilimumab for the treatment of patients ≥12 years of age with metastatic colorectal cancer with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR) that has progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing therapy. Accelerated approval based on objective response rate and duration of response. Continued approval may be contingent on verification and description of clinical benefit in confirmatory studies.

Nivolumab/hyaluronidase-nvhy is used as a single agent, or as a single agent following combination therapy with IV nivolumab plus ipilimumab, for the treatment of adults with metastatic colorectal cancer with MSI-H or dMMR that has progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing therapy. Accelerated approval based on objective response rate and duration of response. Continued approval may be contingent on verification and description of clinical benefit in confirmatory studies. Nivolumab/hyaluronidase-nvhy not indicated in combination with ipilimumab for treatment of colorectal cancer.

Hepatocellular Carcinoma

Nivolumab is used in combination with ipilimumab for treatment of hepatocellular carcinoma in adults previously treated with sorafenib; (designated an orphan drug by FDA for this cancer). Accelerated approval based on objective response rate and duration of response. Continued approval may be contingent on verification and description of clinical benefit in confirmatory studies.

Nivolumab/hyaluronidase-nvhy is used as a single agent for treatment of hepatocellular carcinoma in adults previously treated with sorafenib and following treatment with IV nivolumab plus ipilimumab. Accelerated approval based on objective response rate and duration of response. Continued approval may be contingent on verification and description of clinical benefit in confirmatory studies.

Esophageal Cancer

Nivolumab and nivolumab/hyaluronidase-nvhy are used for treatment of completely resected esophageal or gastroesophageal junction cancer in adults who have received neoadjuvant chemoradiotherapy and have residual pathologic disease; (designated an orphan drug by FDA for this cancer).

Nivolumab and nivolumab/hyaluronidase-nvhy are used in combination with fluoropyrimidine- and platinum-containing chemotherapy as first-line treatment of adults with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) (designated an orphan drug by FDA for this cancer).

Nivolumab is used in combination with ipilimumab as first-line treatment of adults with unresectable advanced or metastatic ESCC; (designated an orphan drug by FDA for this cancer). Nivolumab/hyaluronidase-nvhy not indicated in combination with ipilimumab for treatment of unresectable advanced or metastatic ESCC.

Nivolumab and nivolumab/hyaluronidase-nvhy are used after prior treatment with fluoropyrimidine- and platinum-containing chemotherapy for treatment of adults with unresectable advanced, recurrent, or metastatic ESCC; (designated an orphan drug by FDA for this cancer).

Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma

Nivolumab and nivolumab/hyaluronidase-nvhy are used in combination with fluoropyrimidine- and platinum-containing chemotherapy for the treatment of adults with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma; (designated an orphan drug by FDA for this cancer).

Nivolumab Dosage and Administration

General

Pretreatment Screening

Verify pregnancy status in females of reproductive potential.
Assess liver enzymes, serum creatinine, and thyroid function at baseline.
Assess liver enzymes in patients initiating combination therapy with nivolumab or nivolumab/hyaluronidase-nvhy and cabozantinib.
An FDA-approved diagnostic test is required to confirm the presence of high programmed-death ligand-1 (PD-L1) expression (i.e., tumor proportion score ≥1%) prior to initiating nivolumab (Opdivo) for the first-line treatment of adults with metastatic non-small cell lung cancer (NSCLC) expressing PD-L1, with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic aberrations.

Patient Monitoring

Monitor patients receiving IV nivolumab (Opdivo) for signs and symptoms of infusion-related reactions.
Periodically assess liver enzymes, serum creatinine, and thyroid function.
Periodically monitor liver enzymes in patients receiving combination therapy with nivolumab or nivolumab/hyaluronidase-nvhy and cabozantinib.
Monitor closely during treatment for signs and symptoms of potential clinical manifestations of underlying immune-mediated adverse effects.
Monitor for manifestations of hypophysitis during treatment.
Monitor for manifestations of diabetes mellitus (e.g., hyperglycemia) during treatment.
Monitor closely for early manifestations of stem cell transplantation-related immune-mediated complications.

Dispensing and Administration Precautions

To prevent medication errors, check the vial labels to ensure that the correct drug (Opdivo Qvantig for subcutaneous use or Opdivo for IV use) is being prepared and administered.

Other General Considerations

Nivolumab/hyaluronidase-nvhy (Opdivo Qvantig) is not indicated for use in combination with ipilimumab.

Administration

Nivolumab (Opdivo) is administered by IV infusion only, after dilution; available as a 10 mg/mL single-dose vial.

The fixed combination of nivolumab and hyaluronidase-nvhy (Opdivo Qvantig) is administered by sub-Q injection; available as a single-dose vial that contains 600 mg of nivolumab and 10,000 units of hyaluronidase per 5 mL (120 mg/2000 units per mL).

IV Administration

Administer nivolumab (Opdivo) by IV infusion.

Dilute nivolumab injection to an appropriate concentration for IV infusion over 30 minutes.

Do not infuse simultaneously through the same IV line with other drugs. When administered in combination with other agents, infuse nivolumab first; follow with ipilimumab, then chemotherapy (as appropriate).

Administer using a sterile, nonpyrogenic, low-protein-binding 0.2- to 1.2-μm inline filter. Use separate infusion bags and filters for each infusion and flush the IV line at the end of infusion.

Dilution

Dilute appropriate dose in a sufficient volume of 0.9% sodium chloride or 5% dextrose injection to a final concentration of 1–10 mg/mL. Total volume of infusion solution must not exceed 160 mL; in adults and pediatric patients weighing <40 kg, do not exceed 4 mL per kg.

Mix the diluted solution by gentle inversion; do not shake.

Discard any partially used vials.

Rate of Administration

Administer by IV infusion over 30 minutes.

Sub-Q Administration

Healthcare professionals should administer nivolumab/hyaluronidase-nvhy (Opdivo Qvantig) by sub-Q injection using a 23–25G (3/8–5/8”) hypodermic injection needle or sub-Q administration set (e.g., winged/butterfly). Do not administer IV. No incompatibilities observed between nivolumab/hyaluronidase-nvhy and polypropylene and polycarbonate syringes, or polyethylene, polyurethane, polyvinyl chloride, and fluorinated ethylene propylene subcutaneous administration sets.

To prepare, remove vials from refrigeration and allow to come to room temperature. Do not dilute. Use a syringe and transfer needle to withdraw from vial(s) into a single syringe; do not shake. Select appropriate syringe label from product packaging to match prescribed dose and apply to syringe. Discard any partially used or empty vials.

Once withdrawn into the syringe, use immediately. If not used immediately, attach a tip cap to the syringe before storing it. To avoid clogging of the needle, do not attach injection needle until immediately prior to administration.

Inject into sub-Q tissue of 1 of the 4 quadrants of the abdomen, or in the thigh, over 3–5 minutes. Do not inject into red, bruised, or tender areas or into areas with moles or scars. If administration is interrupted, continue administration at the same site or an alternate site. Rotate sites with each injection. Do not administer other sub-Q medications at the same site.

Dosage

Pediatric Patients

Pediatric dosing information applies to nivolumab (Opdivo) only; nivolumab/hyaluronidase (Opdivo Qvantig) is not currently approved for use in pediatric patients.

Melanoma

Monotherapy for Unresectable or Metastatic Melanoma

Pediatric patients ≥12 years of age weighing ≥40 kg: 240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Pediatric patients ≥12 years of age weighing <40 kg: 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Combination Therapy for Unresectable or Metastatic Melanoma

Pediatric patients ≥12 years of age: 1 mg/kg every 3 weeks for 4 doses (use in combination with ipilimumab 3 mg/kg), followed by single-agent nivolumab based on weight:

≥40 kg: 240 mg every 2 weeks or 480 mg every 4 weeks

<40 kg: 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks

Continue therapy until disease progression or unacceptable toxicity occurs.

Adjuvant Therapy for Stage IIB, IIC, III, or IV Metastatic Melanoma

Pediatric patients ≥12 years of age weighing ≥40 kg: 240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy for up to 1 year or until disease recurrence or unacceptable toxicity occurs.

Pediatric patients ≥12 years of age weighing <40 kg: 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks. Continue therapy for up to 1 year or until disease recurrence or unacceptable toxicity occurs.

Colorectal Cancer

Monotherapy for Metastatic Colorectal Cancer with MSI-H or dMMR

Pediatric patients ≥12 years of age weighing ≥40 kg: 240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Pediatric patients ≥12 years of age weighing <40 kg: 3 mg/kg every 2 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Combination Therapy for Metastatic Colorectal Cancer with MSI-H or dMMR

Pediatric patients ≥12 years of age: 3 mg/kg every 3 weeks for 4 doses (use in combination with ipilimumab 1 mg/kg) followed by single-agent nivolumab based on weight:

≥40 kg: 240 mg every 2 weeks or 480 mg every 4 weeks

<40 kg: 3 mg/kg every 2 weeks

Continue therapy until disease progression or unacceptable toxicity occurs.

Adults

Melanoma

Monotherapy for Unresectable or Metastatic Melanoma

IV (Opdivo)

240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

600 mg nivolumab/10,000 units hyaluronidase every 2 weeks or 1200 mg nivolumab/20,000 units hyaluronidase every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Combination Therapy for Unresectable or Metastatic Melanoma

IV (Opdivo)

1 mg/kg every 3 weeks (use in combination with ipilimumab 3 mg/kg) for up to 4 doses or until unacceptable toxicity occurs, followed by single-agent nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

Following combination therapy with IV nivolumab (Opdivo) plus ipilimumab: 600 mg nivolumab/10,000 units hyaluronidase every 2 weeks or 1200 mg nivolumab/20,000 units hyaluronidase every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Adjuvant Therapy for Stage IIB, IIC, III, or IV Metastatic Melanoma

IV (Opdivo)

240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy for up to 1 year or until disease recurrence or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

600 mg nivolumab/10,000 units hyaluronidase every 2 weeks or 1200 mg nivolumab/20,000 units hyaluronidase every 4 weeks. Continue therapy for up to 1 year or until disease recurrence or unacceptable toxicity occurs.

NSCLC

Monotherapy for Metastatic NSCLC

IV (Opdivo)

240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy until disease recurrence or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

600 mg nivolumab/10,000 units hyaluronidase every 2 weeks or 1200 mg nivolumab/20,000 units hyaluronidase every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Combination Therapy for Neoadjuvant/Adjuvant Treatment of Resectable NSCLC

IV (Opdivo)

Neoadjuvant therapy: 360 mg in combination with platinum doublet chemotherapy every 3 weeks on the same day; continue for 3 cycles. Nivolumab should be administered before chemotherapy.

Neoadjuvant therapy followed by single-agent adjuvant therapy: 360 mg in combination with platinum doublet chemotherapy every 3 weeks on the same day; continue for 4 cycles. After surgery, monotherapy with nivolumab 480 mg every 4 weeks for up to 13 cycles (1 year) or until disease recurrence or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantiq)

Neoadjuvant therapy: 900 mg nivolumab/15,000 units hyaluronidase in combination with platinum doublet chemotherapy every 3 weeks on the same day; continue for 3 cycles.

Neoadjuvant therapy followed by single-agent adjuvant therapy: 900 mg nivolumab/15,000 units hyaluronidase in combination with platinum doublet chemotherapy every 3 weeks on the same day; continue for 3 cycles. After surgery, monotherapy with 1200 mg nivolumab/20,000 units hyaluronidase every 4 weeks for up to 13 cycles (1 year) or until disease recurrence or unacceptable toxicity occurs.

Combination Therapy for Metastatic NSCLC

IV (Opdivo)

Combination with ipilimumab, PD-L1 ≥1%: 360 mg every 3 weeks (use in combination with ipilimumab 1 mg/kg every 6 weeks) for up to 2 years or until disease progression or unacceptable toxicity occurs.

Combination with ipilimumab and platinum doublet chemotherapy: 360 mg every 3 weeks (use in combination with ipilimumab 1 mg/kg every 6 weeks and 2 cycles of platinum doublet chemotherapy) for 2 cycles. Continue therapy with nivolumab plus ipilimumab for up to 2 years or until disease progression or unacceptable toxicity occurs.

Malignant Pleural Mesothelioma

IV (Opdivo)

360 mg every 3 weeks (use in combination with ipilimumab 1 mg/kg every 6 weeks) for up to 2 years or until disease progression or unacceptable toxicity occurs.

Renal Cell Carcinoma

Monotherapy for Advanced Renal Cell Carcinoma

IV (Opdivo)

240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

600 mg nivolumab/10,000 units hyaluronidase every 2 weeks or 1200 mg nivolumab/20,000 units hyaluronidase every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Combination Therapy with Ipilimumab for Intermediate- or Poor-risk Advanced Renal Cell Carcinoma

IV (Opdivo)

3 mg/kg every 3 weeks for 4 doses (use in combination with ipilimumab 1 mg/kg) followed by single-agent nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

Combination Therapy with Cabozantinib for Advanced Renal Cell Carcinoma

IV (Opdivo)

240 mg every 2 weeks or 480 mg every 4 weeks (use in combination with oral cabozantinib 40 mg once daily without food). Continue therapy for up to 2 years or until disease progression or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

600 mg nivolumab/10,000 units hyaluronidase every 2 weeks or 1200 mg nivolumab/20,000 units hyaluronidase every 4 weeks (use in combination with oral cabozantinib 40 mg once daily without food). Continue therapy for up to 2 years or until disease recurrence or unacceptable toxicity occurs.

Hodgkin Lymphoma

IV (Opdivo)

240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Squamous Cell Carcinoma of the Head and Neck

IV (Opdivo)

240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

600 mg nivolumab/10,000 units hyaluronidase every 2 weeks or 1200 mg nivolumab/20,000 units hyaluronidase every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Urothelial Carcinoma

Monotherapy for Locally Advanced or Metastatic Urothelial Carcinoma

IV (Opdivo)

240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

600 mg nivolumab/10,000 units hyaluronidase every 2 weeks or 1200 mg nivolumab/20,000 units hyaluronidase every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Adjuvant Treatment of Urothelial Carcinoma

IV (Opdivo)

240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy for up to 1 year or until disease recurrence or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

Combination Therapy for Unresectable or Metastatic Urothelial Carcinoma

IV (Opdivo)

360 mg every 3 weeks (use in combination with cisplatin and gemcitabine on the same day every 3 weeks). Continue for up to 6 cycles, then administer nivolumab monotherapy with 240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy for up to 2 years from the first dose or until disease progression or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

900 mg nivolumab/15,000 units hyaluronidase every 3 weeks (use in combination with cisplatin and gemcitabine every 3 weeks on the same day). Continue for up to 6 cycles, then administer monotherapy with 600 mg nivolumab/10,000 units hyaluronidase every 2 weeks or 1200 mg nivolumab/20,000 units hyaluronidase every 4 weeks. Continue therapy for up to 2 years or until disease progression or unacceptable toxicity occurs.

Colorectal Cancer

Monotherapy for Metastatic Colorectal Cancer with MSI-H or dMMR

IV (Opdivo)

240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

600 mg nivolumab/10,000 units hyaluronidase every 2 weeks or 1200 mg nivolumab/20,000 units hyaluronidase every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Combination Therapy for Metastatic Colorectal Cancer with MSI-H or dMMR

IV (Opdivo)

Hepatocellular Carcinoma

IV (Opdivo)

1 mg/kg every 3 weeks (use in combination with ipilimumab 3 mg/kg) for 4 doses. Then, administer monotherapy with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

Esophageal Cancer

Monotherapy for ESCC

IV (Opdivo)

240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

600 mg nivolumab/10,000 units hyaluronidase every 2 weeks or 1200 mg nivolumab/20,000 units hyaluronidase every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Monotherapy for Adjuvant Treatment of Resected Esophageal Cancer

IV (Opdivo)

240 mg every 2 weeks or 480 mg every 4 weeks. Continue therapy for up to 1 year or until disease progression or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

600 mg nivolumab/10,000 units hyaluronidase every 2 weeks or 1200 mg nivolumab/20,000 units hyaluronidase every 4 weeks. Continue therapy for up to 1 year or until disease progression or unacceptable toxicity occurs.

Combination Therapy with Fluropyrimidine- and Platinum-Containing Chemotherapy for ESCC

IV (Opdivo)

240 mg every 2 weeks or 480 mg every 4 weeks (use in combination with fluoropyrimidine- and platinum-containing chemotherapy). Continue nivolumab for up to 2 years or until disease progression or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

600 mg nivolumab/10,000 units hyaluronidase every 2 weeks or 1200 mg nivolumab/20,000 units hyaluronidase every 4 weeks (use in combination with fluoropyrimidine- and platinum-containing chemotherapy). Continue therapy for up to 2 years or until disease progression or unacceptable toxicity occurs.

Combination Therapy with Ipilimumab for ESCC

IV (Opdivo)

3 mg/kg every 2 weeks or 360 mg every 3 weeks (use in combination with ipilimumab 1 mg/kg every 6 weeks). Continue combination therapy for up to 2 years or until disease progression or unacceptable toxicity occurs.

Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma

IV (Opdivo)

240 mg every 2 weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy every 2 weeks or 360 mg every 3 weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy every 3 weeks. Continue therapy for up to 2 years or until disease progression or unacceptable toxicity occurs.

Sub-Q (Opdivo Qvantig)

600 mg nivolumab/10,000 units hyaluronidase every 2 weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy every 2 weeks or 900 mg nivolumab/15,000 units hyaluronidase every 3 weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy every 3 weeks. Continue therapy for up to 2 years or until disease progression or unacceptable toxicity occurs.

Therapy Interruption for Toxicity

No dosage reduction recommended if immune-mediated adverse effects occur; instead, temporary or permanent discontinuance may be required.

Withhold therapy in patients experiencing any grade 3 (severe) immune-mediated adverse effects. If withheld, resume therapy once toxicity resolves to grade 0 or 1 after corticosteroid taper (except endocrinopathy).

Permanently discontinue if resolution does not occur within 12 weeks of the last dose, or there is an inability to reduce prednisone (or equivalent) to a dose of ≤10 mg within 12 weeks of initiation. Permanently discontinue therapy in patients experiencing any life- threatening or grade 4 immune-mediated adverse effect, patients with recurrent grade 3 immune-mediated adverse effects requiring systemic immunosuppression, and those requiring a corticosteroid dosage of ≥10 mg of prednisone daily (or equivalent) for >12 weeks.

When nivolumab is administered in combination with ipilimumab, withhold or permanently discontinue both agents for an adverse reaction meeting the dosage modification guidance below.

Immune-mediated Pneumonitis

If grade 2 immune-mediated pneumonitis occurs, interrupt therapy until toxicity resolves to grade 0 or 1.

If grade 3 or 4 immune-mediated pneumonitis occurs, permanently discontinue drug.

Immune-mediated Colitis

If grade 2 or 3 immune-mediated colitis occurs in patients receiving monotherapy, interrupt therapy until toxicity resolves to grade 0 or 1. If grade 4 immune-mediated colitis occurs in patients receiving monotherapy, permanently discontinue therapy.

If grade 2 immune-mediated colitis occurs in patients receiving nivolumab in combination with ipilimumab, interrupt therapy until toxicity resolves to grade 0 or 1.

If grade 3 or 4 immune-mediated colitis occurs in patients receiving nivolumab in combination with ipilimumab, permanently discontinue drug.

Immune-mediated Hepatic Effects - Monotherapy

For ALT or AST concentrations exceeding the ULN at baseline or for ALT or AST concentrations >3 to 8 times the ULN or total bilirubin concentrations >1.5 to 3 times the ULN in patients without tumor involvement of the liver, interrupt therapy until toxicity resolves to grade 0 or 1. For ALT or AST concentrations >8 times the ULN or total bilirubin concentrations >3 times the ULN (in patients without tumor involvement of the liver) permanently discontinue drug.

For ALT or AST concentrations >5 to 10 times the ULN in patients with tumor involvement of the liver and baseline ALT or AST concentrations exceeding the ULN but not >3 times the ULN, interrupt therapy until toxicity resolves to grade 0 or 1. For ALT or AST concentrations >8 to 10 times the ULN in patients with tumor involvement of the liver and baseline ALT or AST concentrations >3 to 5 times the ULN, interrupt therapy until toxicity resolves to grade 0 or 1.

For ALT or AST concentrations >10 times the ULN or total bilirubin concentrations >3 times the ULN in patients with tumor involvement of the liver, permanently discontinue drug.

Immune-mediated Hepatic Effects - Combination Therapy

For patients taking nivolumab (Opdivo) plus ipilimumab 1) without tumor involvement of the liver; 2) with tumor involvement of the liver that is not hepatocellular carcinoma (HCC); or 3) with tumor involvement of the liver or HCC and baseline ALT or AST at or below the ULN who have ALT or AST elevations >3 but <5 times the ULN or total bilirubin concentrations >1.5 but <3 times the ULN and baseline ALT and AST concentrations within normal limits, interrupt therapy until the toxicity resolves to grade 0 or 1. For ALT or AST elevations >5 times the ULN or total bilirubin concentrations >3 times the ULN in such patients, permanently discontinue combination therapy with nivolumab (Opdivo) plus ipilimumab.

For patients taking nivolumab (Opdivo) plus ipilimumab with tumor involvement of the liver or HCC who have ALT or AST elevations >5 times but <10 times the ULN and baseline ALT or AST concentrations >1 but <3 times the ULN, interrupt combination therapy until the toxicity resolves to grade 0 or 1. For such patients with ALT or AST elevations >8 times the ULN but <10 times the ULN and baseline ALT or AST concentrations >3 times but <5 times the ULN, interrupt therapy until the toxicity resolves to grade 0 or 1. If the ALT or AST increases to >10 times the ULN or the total bilirubin increases >3 times the ULN in such patients, permanently discontinue combination therapy.

For patients receiving nivolumab or nivolumab/hyaluronidase-nvhy plus cabozantinib who have ALT or AST elevations >3 but <10 times the ULN and concurrent total bilirubin <2 times the ULN, withhold both agents until the toxicity resolves to grade 0 or 1. Consider corticosteroid therapy for hepatic adverse reactions if nivolumab is withheld when administered in combination with cabozantinib. After recovery, rechallenge with one or both agents may be considered; if rechallenging with cabozantinib with or without nivolumab, refer to the cabozantinib prescribing information.

For patients receiving nivolumab or nivolumab/hyaluronidase-nvhy plus cabozantinib who have ALT or AST elevations >10 times the ULN or >3 times the ULN with concurrent total bilirubin ≥2 times the ULN, permanently discontinue both agents. Consider corticosteroid therapy for hepatic adverse reactions if nivolumab is discontinued when administered in combination with cabozantinib.

Immune-mediated Endocrinopathies

If grade 3 or 4 immune-mediated endocrinopathies occur, interrupt therapy until the patient is clinically stable; consider therapy discontinuation depending on severity. Consider withholding therapy for grade 2 endocrinopathies until symptom improvement occurs with hormone replacement. Resume therapy once acute symptoms have resolved.

Immune-mediated Nephritis with Renal Dysfunction

For grade 2 or 3 Scr elevations, interrupt therapy until toxicity resolves to grade 0 or 1.

For grade 4 Scr elevations, permanently discontinue drug.

Immune-mediated Exfoliative Dermatologic Conditions

If Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug rash with eosinophilia and systemic symptoms (DRESS) is suspected, interrupt therapy until toxicity resolves to grade 0 or 1.

If Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS is confirmed, permanently discontinue drug.

Immune-mediated Myocarditis

If grade 2, 3, or 4 myocarditis occurs, permanently discontinue drug.

Immune-mediated Neurological Toxicities

If grade 2 neurological toxicities occur, interrupt therapy until toxicity resolves to grade 0 or 1.

If grade 3 or 4 neurological toxicity occurs, permanently discontinue drug.

Infusion-related Reactions

If grade 1 or 2 infusion-related reactions occur, interrupt infusion or reduce infusion rate.

If grade 3 or 4 infusion-related reactions occur, permanently discontinue drug.

Special Populations

Hepatic Impairment

Nivolumab, mild or moderate preexisting hepatic impairment: No dosage adjustment required.

Nivolumab, severe preexisting hepatic impairment: Not studied; no dosage recommendations at this time.

Nivolumab/hyaluronidase-nvhy: no specific dosage recommendations.

Renal Impairment

Nivolumab, mild, moderate, or severe preexisting renal impairment: No dosage adjustment required.

Nivolumab/hyaluronidase-nvhy: no specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations at this time.

Cautions for Nivolumab

Contraindications

None.

Warnings/Precautions

Severe and Fatal Immune-mediated Adverse Reactions

Severe or fatal immune-mediated adverse reactions can occur in any organ system or tissue; generally occur during therapy, but can manifest after discontinuation.

Monitor patients closely for clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue nivolumab depending on severity. In general, if nivolumab requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to grade 1 or less. Upon improvement to grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Certain reactions, such as endocrinopathies and dermatologic reactions, do not necessarily require systemic steroids.

Immune-mediated Pneumonitis

Immune-mediated pneumonitis reported, with higher reported incidence in patients who have previously received thoracic radiation.

Withhold or permanently discontinue treatment depending on severity.

Immune-mediated Colitis

Immune-mediated colitis reported; diarrhea is a commonly reported symptom of immune-mediated colitis.

Withhold or permanently discontinue treatment depending on severity.

Immune-mediated Hepatitis and Hepatotoxicity

Immune-mediated hepatitis reported, which is defined as requiring use of corticosteroids and with no clear alternate etiology.

Perform liver function tests prior to initiation of therapy and periodically during therapy.

Withhold or permanently discontinue treatment depending on severity.

Immune-mediated Endocrinopathies

Immune-mediated endocrinopathies (e.g., hypophysitis, hypothyroidism, hyperthyroidism, adrenal insufficiency, diabetes mellitus, diabetic ketoacidosis) reported.

Hypophysitis

Monitor for manifestations of hypophysitis.

If indicated, initiate hormone replacement therapy. Withhold or permanently discontinue treatment depending on severity.

Adrenal Insufficiency

Monitor for manifestations of adrenal insufficiency.

If grade 2 or greater immune-mediated adrenal insufficiency occurs, initiate symptomatic treatment (including hormone replacement therapy) as clinically indicated. Withhold treatment depending on severity.

Thyroid Dysfunction

Immune-mediated thyroid disorders, including thyroiditis (with or without endocrinopathy), hyperthyroidism, and hypothyroidism, reported.

Evaluate thyroid function prior to initiation of therapy and periodically during therapy.

Initiate thyroid hormone replacement therapy or medical management as clinically indicated.

Diabetes

Monitor for hyperglycemia and other signs of diabetes. Initiate treatment with insulin as clinically indicated. Withhold treatment depending on severity.

Immune-mediated Nephritis with Renal Dysfunction

Immune-mediated nephritis, defined as requiring use of steroids and with no clear alternate etiology, reported.

Evaluate renal function prior to initiation of therapy and periodically during therapy.

Withhold or permanently discontinue treatment depending on severity.

Immune-mediated Dermatologic Adverse Reactions

Immune-mediated rash or dermatitis, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms (DRESS), reported.

Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue treatment depending on severity.

Other Immune-mediated Adverse Reactions

Numerous other immune-mediated cardiac/vascular, CNS, ocular, GI, musculoskeletal/connective tissue, endocrine, and hematologic/immune adverse reactions reported, sometimes severe or fatal .

Withhold or permanently discontinue treatment depending on severity.

Infusion-related Reactions

Infusion-related reactions, sometimes severe, reported with infusion of IV nivolumab (Opdivo).

Frequency of infusion-related reactions not substantially different following 30- or 60- minute IV infusion.

Depending on severity of infusion-related reaction, interrupt infusion, reduce infusion rate, or permanently discontinue nivolumab.

Complications of Allogeneic Stem Cell Transplantation

Complications (i.e., hyperacute, acute, or chronic graft-versus-host disease [GVHD]; febrile syndrome requiring systemic corticosteroid therapy; hepatic veno-occlusive disease following allogeneic stem cell transplantation with a reduced-intensity conditioning regimen) may occur in patients undergoing allogeneic stem cell transplantation before or after therapy with anti-PD-1 monoclonal antibodies, including nivolumab. Complications may occur despite other intervening therapy between nivolumab administration and transplantation.

Consider potential benefits and risks of anti-PD-1 monoclonal antibody therapy administered either before or after allogeneic stem cell transplantation. Closely monitor for early manifestations of stem cell transplantation-related complications and manage promptly if they occur.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm. In animal reproduction studies, administration of nivolumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in increased abortion and premature infant death. Effects may be greater during the second and third trimesters of pregnancy.

Verify pregnancy status in females of reproductive potential prior to initiating therapy. Women of childbearing potential should use an effective contraceptive method while receiving the drug and for ≥5 months after the last dose. If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.

Increased Mortality in Patients with Multiple Myeloma when Nivolumab Is Added to a Thalidomide Analogue and Dexamethasone

Increased mortality reported in patients with multiple myeloma receiving an anti-PD-1 monoclonal antibody, including nivolumab, in combination with an immunomodulatory agent (i.e., lenalidomide, pomalidomide) and dexamethasone; nivolumab is not currently FDA-labeled for use in patients with multiple myeloma.

Use of an anti-PD-1 or anti-programmed-death ligand-1 (anti-PD-L1) antibody in combination with a thalidomide analog and dexamethasone in patients with multiple myeloma is not recommended outside of a controlled clinical trial.

Immunogenicity

Potential for immunogenicity. Development of binding antibodies and neutralizing antibodies to nivolumab reported.

Effects on safety (including infusion-related reactions) or efficacy not observed.

Effects on pharmacokinetics of the drug not observed in patients receiving single- agent nivolumab; however, clearance of nivolumab increased by 20% in presence of anti-nivolumab antibodies in patients receiving nivolumab in combination with ipilimumab.

Specific Populations

Pregnancy

May cause fetal harm. Verify pregnancy status in females of reproductive potential prior to initiation.

Lactation

Not known whether nivolumab or hyaluronidase is distributed into milk; effects on breast-fed child and milk production also not known. Because of potential for serious adverse reactions in the breast-fed child, avoid breast-feeding during treatment and for 5 months after the last dose.

Females and Males of Reproductive Potential

May cause fetal harm. Verify pregnancy status in females of reproductive potential prior to initiation. Advise such females to use effective contraception during treatment and for 5 months after the last dose.

Pediatric Use

Nivolumab/hyaluronidase-nvhy (Opdivo Qvantig): Safety and efficacy not established in pediatric patients.

Nivolumab (Opdivo): Safety and efficacy not established in pediatric patients <18 years of age with NSCLC, malignant pleural mesothelioma, renal cell carcinoma, cHL, squamous cell carcinoma of the head and neck, urothelial carcinoma, hepatocellular carcinoma, esophageal cancer, gastric cancer, gastroesophageal cancer, and esophageal adenocarcinoma.

Safety and efficacy of nivolumab have been established in pediatric patients ≥12 years of age for the following indications: as monotherapy or in combination with ipilimumab for the treatment of unresectable or metastatic melanoma; as a single agent for the adjuvant treatment of completely resected stage IIB, IIC, III, or IV melanoma; and as a single agent or in combination with ipilimumab for treatment of MSI-H or dMMR metastatic colorectal cancer. Use of nivolumab for these indications supported by evidence from adequate and well-controlled studies in adults and additional pharmacokinetic data in pediatric patients. Exposure to nivolumab is similar in pediatric patients ≥12 years of age and adults, and the courses of melanoma and MSI-H or dMMR colorectal cancer are similar enough in pediatric patients ≥12 years of age and adults to allow extrapolation of safety and efficacy. Safety and efficacy of nivolumab for these indications not established in pediatric patients <12 years of age.

Geriatric Use

Nivolumab monotherapy: Insufficient experience in some studies in patients with cHL, squamous cell carcinoma of the head and neck, or MSI-H or dMMR metastatic colorectal cancer to determine whether patients ≥65 years of age respond differently than younger adults; however, no overall differences in safety or efficacy compared with younger adults observed in other studies in patients with melanoma, NSCLC, renal cell carcinoma, urothelial carcinoma, esophageal squamous cell carcinoma (ESCC), and esophageal or gastroesophageal junction cancer. In clinical trials evaluating monotherapy with nivolumab/hyaluronidase-nvhy (Opdivo Qvantig), no overall differences in safety or efficacy were observed between geriatric patients and younger adults.

Nivolumab in combination with ipilimumab: geriatric patients included in trials for melanoma, NSCLC, malignant pleural mesothelioma (MPM), advanced renal cell carcinoma, and ESCC with no overall differences in safety and efficacy compared with younger adults; however, patients ≥75 years of age experienced higher rates of serious adverse reactions and/or discontinuation due to adverse reactions in some trials. Clinical studies of patients with hepatocellular carcinoma receiving this combination did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger adults.

Nivolumab in combination with platinum-containing chemotherapy: no overall differences in safety and efficacy compared with younger adults.

Nivolumab in combination with ipilimumab and platinum doublet chemotherapy for treatment of NSCLC: No overall differences in safety compared with younger adults; however, patients ≥75 years of age experienced higher rates of discontinuation due to adverse reactions.

Nivolumab in combination with cabozantinib for treatment of renal cell carcinoma: no overall differences in safety and efficacy compared with younger adults.

Hepatic Impairment

Clearance not affected by mild or moderate hepatic impairment. Not studied in patients with severe hepatic impairment.

Renal Impairment

Clearance not affected by mild, moderate, or severe renal impairment.

Common Adverse Effects

Nivolumab (Opdivo) monotherapy (incidence ≥20%): fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, pyrexia, headache, abdominal pain, vomiting, and urinary tract infection.

Nivolumab/hyaluronidase-nvhy (Opdivo Qvantig) monotherapy for treatment of renal cell carcinoma (incidence ≥10%): musculoskeletal pain, fatigue, pruritus, rash, hypothyroidism, diarrhea, cough, and abdominal pain.

Nivolumab in combination with ipilimumab (incidence ≥20%): fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, hypothyroidism, constipation, decreased weight, and dizziness.

Nivolumab in combination with platinum doublet chemotherapy (incidence ≥20%): nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy.

Nivolumab in combination with ipilimumab and platinum doublet chemotherapy (incidence ≥20%): fatigue, musculoskeletal pain, nausea, diarrhea, rash, decreased appetite, constipation, and pruritus.

Nivolumab in combination with cabozantinib (incidence ≥20%): diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysesthesia syndrome, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

Nivolumab in combination with fluoropyrimidine- and platinum-containing chemotherapy (incidence ≥20%): nausea, peripheral neuropathy, decreased appetite, fatigue, constipation, stomatitis, diarrhea, vomiting, abdominal pain, and musculoskeletal pain.

Drug Interactions

No formal drug interaction studies to date.

Specific Drugs

Drug

Interaction

Ipilimumab

Nivolumab 1 mg/kg every 3 weeks and ipilimumab 3 mg/kg every 3 weeks: No effect on ipilimumab clearance; nivolumab clearance increased by 29%

Nivolumab 3 mg/kg every 3 weeks and ipilimumab 1 mg/kg every 3 weeks: No effect on clearance of either drug

Nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks: Ipilimumab clearance increased by 30%; no effect on nivolumab clearance.

Nivolumab 360 mg every 3 weeks and ipilimumab 1 mg/kg every 6 weeks plus chemotherapy: Ipilimumab clearance increased by 22%; no effect on nivolumab clearance.

Nivolumab Pharmacokinetics

Absorption

Bioavailability

Steady-state concentrations achieved within 12 weeks.

Exposure is dose proportional over the dosage range of 0.1–10 mg/kg every 2 weeks; systemic accumulation is 3.7-fold when administered every 2 weeks.

When coformulated with hyaluronidase, geometric mean bioavailability of nivolumab is 74% and peak concentrations occurred around 6 days.

Predicted exposure following 30-minute IV infusion is comparable to that observed following 60-minute IV infusion.

Distribution

Extent

Not known whether nivolumab is distributed into human milk.

Elimination

Half-life

Approximately 25 days.

Special Populations

Mild hepatic impairment (total bilirubin concentration not exceeding the ULN with AST concentration exceeding the ULN, or total bilirubin concentration >1 to 1.5 times the ULN with any AST concentration) or moderate hepatic impairment (total bilirubin concentration >1.5 to 3 times the ULN with any AST concentration) does not affect clearance. Data not available for severe hepatic impairment (total bilirubin concentration >3 times the ULN with any AST concentration).

Mild, moderate, or severe renal impairment (estimated GFR ≥15 mL/minute per 1.73 m²) does not affect clearance.

Age, body weight, gender, race, baseline LDH, programmed death ligand 1 (PD-L1) expression, solid tumor type, and tumor burden do not have meaningful effects on clearance of nivolumab.

When coformulated with hyaluronidase, body weight, sex, estimated GFR, and performance status do not have meaningful effects on clearance of nivolumab.

In patients with metastatic tumors, clearance decreases by about 25% from baseline to steady state; not considered clinically important. In patients with completely resected melanoma, clearance does not decrease over time but is 24% lower than the steady-state clearance in patients with metastatic melanoma.

Stability

Storage

Parenteral

Injection

2–8°C. Do not freeze; protect from light by storing in original package. Discard unused solution after initial entry into vial.

Diluted solution may be stored at room temperature for up to 8 hours from time of preparation to end of infusion or at 2–8°C for up to 7 days from time of preparation to end of infusion. Do not freeze.

Injection, for sub-Q use

2–8°C. Do not freeze; protect from light by storing in original package. Discard unused solution after initial entry into vial.

After withdrawal from the vial into a syringe, syringe may be stored under refrigeration (2–8°C), protected from light for up to 48 hours (do not freeze) or at room temperature (20–25°C) for up to 8 hours. Protection from light not required when syringe is stored at room temperature. Discard if storage time exceeds these limits.

Actions

IgG₄ kappa immunoglobulin that is selective for PD-1, an immune-checkpoint receptor expressed on activated T-cells, monocytes, B-cells, natural killer (NK) T-cells, and dendritic cells.
Overexpression of PD-1 ligands on surface of tumor cells results in activation of PD-1 activity and suppression of cytotoxic T-cell activity.
Blocks interaction between PD-1 and its ligands, resulting in enhanced immune response, including enhanced antitumor immune response.
Enhanced T-cell function, including enhanced antitumor immune response, demonstrated when combined with an anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) antibody (i.e., ipilimumab) compared with either drug alone.
Hyaluronidase depolymerizes hyaluronan within the sub-Q tissue to cause a temporary increase in tissue permeability; coadministered with other sub-Q agents to increase dispersion and absorption of the coadministered drug.

Advice to Patients

Advise patients to read the manufacturer’s medication guide before beginning treatment and each time nivolumab is administered.
Risk of immune-mediated pneumonitis. Inform clinician immediately if new or worsening cough, chest pain, or shortness of breath occurs.
Risk of immune-mediated colitis. Inform clinician immediately if diarrhea, severe abdominal pain, or changes in stool occur.
Risk of immune-mediated hepatitis. Inform clinician immediately if signs and symptoms of liver damage (e.g., jaundice, severe nausea or vomiting, abdominal pain [particularly in the right upper quadrant], lethargy, easy bruising or bleeding, lack of appetite, dark urine, drowsiness) occur.
Risk of immune-mediated endocrine effects. Inform clinician immediately if manifestations of hypophysitis, hyperthyroidism, hypothyroidism, adrenal insufficiency, or diabetes mellitus occur.
Risk of immune-mediated nephritis or renal dysfunction. Inform clinician immediately if signs and symptoms of nephritis (e.g., decreased urine output, hematuria, peripheral edema, lack of appetite) occur.
Risk of immune-mediated skin adverse reactions. Inform clinician immediately if a rash develops.
Risk of infusion-related reactions. Inform clinician immediately if signs and symptoms of such reactions, including dizziness, chills, fever, breathing difficulty, pruritus, flushing, and feeling of faintness, occur.
Risk of allogeneic stem cell transplantation-related complications.
Risk of solid organ transplant rejection and other transplant (including corneal graft) rejection. Advise patients to inform their clinician immediately if signs and symptoms of transplant rejection occur.
Risk of other immune-mediated adverse reactions involving any organ system. Advise patients to inform their clinician immediately for any new or worsening signs or symptoms.
Risk of fetal harm. Advise women of childbearing potential that they should use an effective method of contraception while receiving nivolumab and for at least 5 months after the last dose of the drug. Stress importance of women informing clinicians if they are or plan to become pregnant. If pregnancy occurs, advise pregnant women of potential risk to the fetus.
Advise women to avoid breast-feeding while receiving nivolumab therapy and for 5 months after the last dose.
Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., autoimmune disorders, history of organ transplantation, liver damage, pulmonary disorders).
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Nivolumab
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IV infusion only	40 mg/4 mL (10 mg/mL)	Opdivo	Bristol-Myers Squibb
		100 mg/10 mL (10 mg/mL)	Opdivo	Bristol-Myers Squibb
		120 mg/12 mL (10 mg/mL)	Opdivo	Bristol-Myers Squibb
		240 mg/24 mL (10 mg/mL)	Opdivo	Bristol-Myers Squibb