Nivolumab

Indications

Nivolumab is used for: Advanced renal cell carcinoma, Locally advanced non-small cell lung carcinoma, Locally advanced squamous cell carcinoma of the head and neck, Locally advanced urothelial carcinoma, Metastatic melanoma, Metastatic non-small cell lung carcinoma, Metastatic squamous , cell carcinoma of the head and neck, Metastatic urothelial carcinoma, Refractory classical Hodgkin lymphoma, Relapsed classical Hodgkin lymphoma, Metastatic colorectal cancer, Hepatocellular carcinoma, Metastatic melanoma.

Adult Dose

Intravenous Advanced renal cell carcinoma, Locally advanced non-small cell lung carcinoma, Locally advanced squamous cell carcinoma of the head and neck, Locally advanced urothelial carcinoma, Metastatic melanoma, Metastatic non-small cell lung carcinoma, Metastatic squamous cell carcinoma of the head and neck, Metastatic urothelial carcinoma, Refractory classical Hodgkin lymphoma, Relapsed classical Hodgkin lymphoma Adult: 3 mg/kg, given via infusion over 60 minutes, every 2 weeks. Continued until disease progression or unacceptable toxicity. Metastatic colorectal cancer Adult: 240 mg, given via infusion over 60 minutes, every 2 weeks or 480 mg for every 4 weeks. Continued until disease progression or unacceptable toxicity. Child: >12 years Same as adult dose. Hepatocellular carcinoma Adult: 240 mg, given via infusion over 60 minutes, every 2 weeks or 480 mg for every 4 weeks. Continued until disease progression or unacceptable toxicity. Metastatic melanoma Adult: In combination with ipilimumab: 1 mg/kg, given via infusion over 60 minutes, every 3 weeks for 4 doses, followed by ipilimumab. Thereafter, 3 mg/kg over 60 minutes, every 2 weeks, as monotherapy Continued until disease progression or unacceptable toxicity.

Child Dose

Intravenous Metastatic colorectal cancer Child: >12 years 240 mg, given via infusion over 60 minutes, every 2 weeks or 480 mg for every 4 weeks. Continued until disease progression or unacceptable toxicity.

Renal Dose

Administration

IV Preparation Admixture Withdraw required volume for calculated dose and transfer to an IV container Dilute with either 0.9% NaCl or D5W to a final concentration ranging from 1-10 mg/mL Total volume of infusion must not exceed 160 mL Mix diluted solution by gentle inversion; do NOT shake Discard partially used vials or empty vials IV Administration Infuse IV over 30-60 min in an IV line containing a sterile, nonpyrogenic, low protein-binding inline filter (pore size of 0.2-1.2 microns) For adult and pediatric patients (<40 kg): Total volume of infusion must not exceed 4 mL/kg of body weigh Do not co-administer other drugs through the same IV line When administered in combination with ipilimumab, infuse nivolumab first followed by ipilimumab on the same day; use separate infusion bags and filters for each infusion Flush the IV line at end of infusion

Contra Indications

Precautions

Patient with history or concurrent active brain metastases or active auto-immune disease, ocular/uveal melanoma, symptomatic interstitial lung disease, poor prognosis or aggressive disease, and medical conditions requiring systemic immunosuppression. Patient with carcinoma of the nasopharynx or salivary gland when used for the treatment of head and neck cancer. Patient who received hematopoietic stem cell transplant. Moderate to severe hepatic impairment. Children. Pregnancy and lactation. Lactation Unknown if distributed in human breast milk; advise women to discontinue breastfeeding during treatment

Pregnancy-Lactation

Interactions

Potentially Fatal: Decreased therapeutic effect with immunosuppressants.

Adverse Effects

Side effects of Nivolumab : >10% (All grades) Melanoma Increased AST (28%) Hyponatremia (25%) Increased alkaline phosphatase (22%) Rash (21%) Pruritus (19%) Cough (17%) Increased ALT (16%) Hyperkalemia (15%) URTI (11%) NSCLC Fatigue (50%) Lymphopenia (47%) Dyspnea, hyponatremia (38%) Musculoskeletal pain (36%) Cough (32%) Nausea (29%) Increases creatinine (22%) Hypercalcemia, hypokalemia, hypomagnesemia (20%) Vomiting, asthenia (19%) Hypocalcemia, hyperkalemia, diarrhea (18%) Edema, pyrexia (17%) Abdominal pain, rash, increased AST (16%) Increased alkaline phosphatase, thrombocytopenia (14%) Chest pain, arthralgia, decreased appetite and weight (13%) Increased ALT (12%) 1-10% (all grades) Melanoma Peripheral edema (10%) NSCLC Pneumonia (10%) Pain (10%) 1-10% (grades 3-4) Melanoma Hyponatremia (5%) Increased AST (2.4%) Increased alkaline phosphatase (2.4%) Hyperkalemia (2%) Increased ALT (1.6%) NSCLC Dyspnea (9%) Fatigue (7%) Musculoskeletal pain (6%) Pneumonia (5%) Decreased appetite (2.6%) Pain (2.6%) Nausea (1.7%) Abdominal pain (1.7%) Asthenia (1.7%) Edema (1.7%) Cough (1.7%)

Mechanism of Action

Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody which binds to negative immunoregulatory protein programmed death-1 (PD-1) receptor. This results in the activation of immune response to tumour cells.