Nivomab IV Infusion 40 mg/4 ml

Uses

Nivomab IV Infusion 40 mg/4 ml is a programmed death receptor-1 (PD-1)-blocking antibody used for the treatment of:

Melanoma:

• patients with unresectable or metastatic melanoma, as a single agent or in combination with ipilimumab.
• patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection, in the adjuvant setting.

• adult patients with metastatic non-small cell lung cancer expressing PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, as first-line treatment in combination with ipilimumab.
• adult patients with metastatic or recurrent non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations as first-line treatment, in combination with ipilimumab and 2 cycles of platinum doublet chemotherapy.
• patients with metastatic non-small cell lung cancer and progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Nivomab IV Infusion 40 mg/4 ml.

• patients with intermediate or poor risk advanced renal cell carcinoma, as a first-line treatment in combination with ipilimumab.
• patients with advanced renal cell carcinoma, as a first-line treatment in combination with cabozantinib.
• patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.

• autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin, or
• 3 or more lines of systemic therapy that includes autologous HSCT.

• patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma in combination with fluoropyrimidine- and platinum-containing chemotherapy.
• This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
• Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analog plus dexamethasone is not recommended outside of controlled clinical trials.

Nivomab IV Infusion 40 mg/4 ml is also used to associated treatment for these conditions: Advanced Renal Cell Cancer, Classical Hodgkin's Lymphoma, Hepatocellular Carcinoma, Low Risk Advanced Renal Cell Cancer, Melanomas, Metastatic Colorectal Cancer (MCRC), Metastatic Melanoma, Metastatic Non-Small Cell Lung Cancer, Metastatic Small Cell Lung Cancer, Metastatic Squamous Cell Carcinoma of the Head and Neck, Metastatic Urothelial Carcinoma (UC), Recurrent Head and Neck Squamous Cell Carcinoma, Unresectable Melanoma, Intermediate risk Advanced Renal Cell Cancer, Locally advanced Urothelial Carcinoma, Complete resection

How Nivomab IV Infusion 40 mg/4 ml works

The ligands PD-L1 and PD-L2 bind to the PD-1 receptor on T-cells, inhibiting the action of these cells. Tumor cells express PD-L1 and PD-L2. Nivomab IV Infusion 40 mg/4 ml binds to PD-1, preventing PD-L1 and PD-L2 from inhibiting the action of T-cells, restoring a patient's tumor-specific T-cell response.

Dosage

Nivomab IV Infusion 40 mg/4 ml dosage

Administer by intravenous infusion based upon recommended infusion rate for each indication.

Unresectable or metastatic melanoma:

• 240 mg every 2 weeks or 480 mg every 4 weeks.
• 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every 3 weeks for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks.

• 3 mg/kg every 2 weeks with ipilimumab 1 mg/kg every 6 weeks.
• 360 mg every 3 weeks with ipilimumab 1 mg/kg every 6 weeks and 2 cycles of platinum-doublet chemotherapy.
• 240 mg every 2 weeks or 480 mg every 4 weeks.

• 3 mg/kg followed by ipilimumab 1 mg/kg on the same day every 3 weeks for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks.
• 240 mg every 2 weeks or 480 mg every 4 weeks administered in combination with cabozantinib 40 mg once daily without food.
• 240 mg every 2 weeks or 480 mg every 4 weeks.

• Adult and pediatric patients ≥40 kg: 240 mg every 2 weeks or 480 mg every 4 weeks.
• Pediatric patients <40 kg: 3 mg/kg every 2 weeks.
• Adult and pediatric patients ≥40 kg: 3 mg/kg followed by ipilimumab 1 mg/kg on the same day every 3 weeks for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks.

• 240 mg every 2 weeks or 480 mg every 4 weeks.
• 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every 3 weeks for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks.

• 360 mg every 3 weeks with fluoropyrimidine- and platinum-containing chemotherapy every 3 weeks.
• 240 mg every 2 weeks with fluoropyrimidine- and platinum-containing chemotherapy every 2 weeks.

Side Effects

Most common adverse reactions (incidence ≥20%) in patients were:

• As a single agent: fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, pyrexia, headache, abdominal pain, and vomiting.
• In combination with ipilimumab: fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, hypothyroidism, decreased weight, and dizziness.
• In combination with ipilimumab and platinum-doublet chemotherapy: fatigue, musculoskeletal pain, nausea, diarrhea, rash, decreased appetite, constipation, and pruritus.
• In combination with cabozantinib: diarrhea, fatigue, hepatotoxicity, palmar-plantar
  erythrodysaesthesia syndrome, stomatitis, rash, hypertension, hypothyroidism,
  musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough,
  and upper respiratory tract infection.
• In combination with fluoropyrimidine- and platinum-containing chemotherapy: peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation, and musculoskeletal pain.

Toxicity

Data regarding overdoses of nivolumab are not readily available. Common adverse effects include Rash, pruritus, cough, upper respiratory tract infection, and peripheral edema.

Precaution

Immune-Mediated Adverse Reactions:

• Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis and hepatotoxicity, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, and immune-mediated nephritis and renal dysfunction.
• Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.
• Withhold or permanently discontinue based on severity and type of reaction.

Food Interaction

Nivomab IV Infusion 40 mg/4 ml Hypertension interaction

[Major] The use of monoclonal antibodies administered via IV infusion may cause serious infusion reactions, including bronchospasm, hypoxia, dyspnea, fluctuations in blood pressure, laryngeal edema and pulmonary edema.

Caution should be taken in patients with a history of cardiopulmonary disease as they may require additional post-infusion medications to manage respiratory complications.

It is recommended to administer required intravenous hydration and premedication with antihistamines, analgesics, and antipyretics before administration.

Monitor closely for signs and symptoms of infusion reactions during and for at least 4 hours following completion of each infusion in a setting where cardiopulmonary resuscitation medication and equipment are available.

Immediately interrupt or permanently discontinue treatment and institute supportive management for severe or prolonged infusion reactions as appropriate.

Nivomab IV Infusion 40 mg/4 ml Disease Interaction

Major: infections, infusion reactions, tumor lysis syndromeModerate: colitis, diabetes, hepatic impairment, neurologic disorders, pneumonitis, renal dysfunction, thyroid disease, myasthenia gravis

Volume of Distribution

The volume of distribution at steady state when a dose of 10 mg/kg of nivolumab is administered is reported to be 91.1 mL/kg. At doses ranging from 0.1 to 20 mg/kg the volume of distribution is reported to be 8L.

Elimination Route

Pharmacokinetic studies have suggested that nivolumab presents linear pharmacokinetics with a dose-proportional increase in peak concentration and AUC. The time to peak plasma concentration ranges between 1-4 hours. The absorption pharmacokinetic properties respective to the administration of a dose of 10 mg/kg are reported to be Cmax, Tmax and AUC of 242 µg/kg, 2.99 hours and 68100 µg*h/mL respectively.

Half Life

The serum half life of nivolumab is approximately 20 days with an elimination half life of 26.7 days.

Clearance

The estimated clearance rate of nivolumab is 9.4 mL/h. The clearance rate seems to be increased according to body weight.

Elimination Route

There have not been studies regarding the specific route of elimination of nivolumab.

Pregnancy & Breastfeeding use

Pregnancy: Based on data from animal studies and its mechanism of action, Nivomab IV Infusion 40 mg/4 ml can cause fetal harm when administered to a pregnant woman. 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. Human IgG4 is known to cross the placental barrier and nivolumab is an immunoglobulin G4 (IgG4); therefore, nivolumab has the potential to be transmitted from the mother to the developing fetus. The effects of Nivomab IV Infusion 40 mg/4 ml are likely to be greater during the second and third trimesters of pregnancy. There are no available data on Nivomab IV Infusion 40 mg/4 ml use in pregnant women to evaluate a drug-associated risk. Advise pregnant women of the potential risk to a fetus.

Lactation: There are no data on the presence of nivolumab in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for 5 months after the last dose of nivolumab.

Contraindication

None

Storage Condition

Store under refrigeration at 2°C to 8°C. Protect from light by storing in the original package until time of use. Do not freeze or shake.

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