Opdivo

What is Opdivo?

Opdivo is a prescription medicine used to treat skin cancer

• people with a type of skin cancer called melanoma:
  • Opdivo may be used alone or in combination with ipilimumab to treat melanoma that has spread or cannot be removed by surgery (advanced melanoma), or
  • Opdivo may be used alone to help prevent melanoma from coming back after it and lymph nodes that contain cancer have been removed by surgery.
• people with a type of advanced stage lung cancer called non-small cell lung cancer (NSCLC).
  • Opdivo may be used in combination with ipilimumab as your first treatment for NSCLC:
    • when your lung cancer has spread to other parts of your body (metastatic), and
    • your tumors are positive for PD-L1, but do not have an abnormal EGFR or ALK gene.
  • Opdivo may be used in combination with ipilimumab and 2 cycles of chemotherapy that contains platinum and another chemotherapy medicine, as the first treatment of your NSCLC when your lung cancer:
    • has spread or grown, or comes back, and
    • your tumor does not have an abnormal EGFR or ALK gene.
  • Opdivo may be used when your lung cancer:
    • has spread or grown, and
    • you have tried chemotherapy that contains platinum, and it did not work or is no longer working.
    • If your tumor has an abnormal EGFR or ALK gene, you should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.
• adults with a type of cancer that affects the lining of the lungs and chest wall called malignant pleural mesothelioma.
  • Opdivo may be used in combination with ipilimumab as your first treatment for malignant pleural mesothelioma that cannot be removed by surgery.
• people with kidney cancer (renal cell carcinoma).
  • Opdivo may be used in combination with ipilimumab in certain people when their cancer has spread (advanced RCC), and you have not already had treatment for your advanced RCC.
  • Opdivo may be used in combination with cabozantinib when your cancer has spread (advanced RCC), and you have not already had treatment for your advanced RCC.
  • Opdivo may be used alone when your cancer has spread or grown after treatment with other cancer medicines.
• adults with a type of blood cancer called classical Hodgkin lymphoma.
  • Opdivo may be used if:
    • your cancer has come back or spread after a type of stem cell transplant that uses your own stem cells (autologous), and
    • you used the medicine brentuximab vedotin before or after your stem cell transplant, or
    • you received at least 3 kinds of treatment including a stem cell transplant that uses your own stem cells (autologous).
• people with head and neck cancer (squamous cell carcinoma).
  • Opdivo may be used when your head and neck cancer:
    • has come back or spread, and
    • you have tried chemotherapy that contains platinum and it did not work or is no longer working.
• people with bladder cancer (urothelial carcinoma).
  • Opdivo may be used when your bladder cancer:
    • has spread or grown, and
    • you have tried chemotherapy that contains platinum, and it did not work or is no longer working.
• adults and children 12 years of age and older, with a type of colon or rectal cancer (colorectal cancer).
  • Opdivo may be used alone or in combination with ipilimumab when your colon or rectal cancer:
    • has spread to other parts of the body (metastatic),
    • is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), and
    • you have tried treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, and it did not work or is no longer working.
• people with liver cancer (hepatocellular carcinoma).
  • Opdivo may be used alone or in combination with ipilimumab if you have previously received treatment with sorafenib.
• people with cancer of the tube that connects your throat to your stomach (esophageal cancer).
  • Opdivo may be used when your esophageal cancer:
    • is a type called squamous cell carcinoma, and
    • cannot be removed with surgery, and
    • has come back or spread to other parts of the body after you have received chemotherapy that contains fluoropyrimidine and platinum.

It is not known if Opdivo is safe and effective when used:

• in children younger than 12 years of age with MSI-H or dMMR metastatic colorectal cancer, or
• in children younger than 18 years of age for the treatment of any other cancers.

Description

Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody. Nivolumab is an IgG4 kappa immunoglobulin that has a calculated molecular mass of 146 kDa. It is expressed in a recombinant Chinese Hamster Ovary (CHO) cell line.

OPDIVO is a sterile, preservative-free, non-pyrogenic, clear to opalescent, colorless to pale-yellow liquid that may contain light (few) particles.

OPDIVO (nivolumab) injection for intravenous use is supplied in single-dose vials. Each mL of OPDIVO solution contains nivolumab 10 mg, mannitol (30 mg), pentetic acid (0.008 mg), polysorbate 80 (0.2 mg), sodium chloride (2.92 mg), sodium citrate dihydrate (5.88 mg), and Water for Injection, USP. May contain hydrochloric acid and/or sodium hydroxide to adjust pH to 6.

Mechanism of Action

Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.

Combined nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) mediated inhibition results in enhanced T-cell function that is greater than the effects of either antibody alone, and results in improved anti-tumor responses in metastatic melanoma and advanced RCC. In murine syngeneic tumor models, dual blockade of PD-1 and CTLA-4 resulted in increased anti-tumor activity.

What is the most important information I should know about Opdivo?

Opdivo is a medicine that may treat certain cancers by working with your immune system. Opdivo can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or can lead to death. These problems may happen anytime during treatment or even after your treatment has ended. You may have more than one of these problems at the same time. Some of these problems may happen more often when Opdivo is used in combination with another therapy.

Call or see your healthcare provider right away if you develop any new or worse signs or symptoms, including:

Lung problems.

• new or worsening cough
• shortness of breath
• chest pain

Intestinal problems.

• diarrhea (loose stools) or more frequent bowel movements than usual
• stools that are black, tarry, sticky, or have blood or mucus
• severe stomach-area (abdominal) pain or tenderness

Liver problems.

• yellowing of your skin or the whites of your eyes
• severe nausea or vomiting
• pain on the right side of your stomach area (abdomen)
• dark urine (tea colored)
• bleeding or bruising more easily than normal

Hormone gland problems.

• headaches that will not go away or unusual headaches
• eye sensitivity to light
• eye problems
• rapid heart beat
• increased sweating
• extreme tiredness
• weight gain or weight loss
• feeling more hungry or thirsty than usual
• urinating more often than usual
• hair loss
• feeling cold
• constipation
• your voice gets deeper
• dizziness or fainting
• changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness

Kidney problems.

• decrease in your amount of urine
• blood in your urine
• swelling of your ankles
• loss of appetite

Skin problems.

• rash
• itching
• skin blistering or peeling
• painful sore or ulcers in mouth or nose, throat, or genital area

Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with Opdivo . Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include:

• Chest pain, irregular heartbeat, shortness of breath or swelling of ankles
• Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
• Double vision, blurry vision, sensitivity to light, eye pain, changes in eye sight
• Persistent or severe muscle pain or weakness, muscle cramps
• Low red blood cells, bruising

Getting medical treatment right away may help keep these problems from becoming more serious.

Your healthcare provider will check you for these problems during treatment with Opdivo . Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with Opdivo, if you have severe side effects.

What should I tell my healthcare provider before using Opdivo?

Before receiving Opdivo, tell your healthcare provider about all of your medical conditions, including if you:

• have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
• have received an organ transplant
• have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
• have received radiation treatment to your chest area in the past and have received other medicines that are like Opdivo
• have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
• are pregnant or plan to become pregnant. Opdivo can harm your unborn baby.
  Females who are able to become pregnant:
  • Your healthcare provider should do a pregnancy test before you start receiving Opdivo.
  • You should use an effective method of birth control during and for at least 5 months after the last dose of Opdivo. Talk to your healthcare provider about birth control methods that you can use during this time.
  • Tell your healthcare provider right away if you become pregnant during treatment with Opdivo.
• are breastfeeding or plan to breastfeed. It is not known if Opdivo passes into your breast milk. Do not breastfeed during treatment with Opdivo.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I use Opdivo?

• Your healthcare provider will give you Opdivo into your vein through an intravenous (IV) line over 30 minutes.
• When Opdivo is used alone, it is usually given every 2 weeks or 4 weeks depending on the dose you are receiving.
• When Opdivo is used in combination with ipilimumab (except for treating NSCLC), Opdivo is usually given every 3 weeks, for a total of 4 doses. Ipilimumab will be given on the same day. After that, Opdivo will be given alone every 2 weeks or 4 weeks depending on the dose you are receiving.
• For NSCLC that has spread to other parts of your body, when Opdivo is used in combination with ipilimumab, Opdivo is given either every 2 weeks or every 3 weeks, and ipilimumab is given every 6 weeks for up to 2 years. Your healthcare provider will determine if you will also need to receive chemotherapy every 3 weeks for 2 cycles.
• For malignant pleural mesothelioma, Opdivo is given every 3 weeks and ipilimumab is given every 6 weeks for up to 2 years.
• For RCC, when used in combination with cabozantinib, Opdivo is usually given every 2 weeks or 4 weeks depending on the dose you are receiving. Cabozantinib is given once daily by mouth.
• Your healthcare provider will decide how many treatments you need.
• Your healthcare provider will do blood tests to check you for side effects.
• If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.

What are the possible side effects of Opdivo?

Opdivo can cause serious side effects, including:

• See “What is the most important information I should know about Opdivo?”
• Severe infusion reactions. Tell your healthcare provider or nurse right away if you get these symptoms during an infusion of Opdivo:
  • chills or shaking
  • itching or rash
  • flushing
  • shortness of breath or wheezing
  • dizziness
  • feel like passing out
  • fever
  • back or neck pain
• Complications of stem cell transplant that uses donor stem cells (allogeneic). These complications can be severe and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with Opdivo. Your healthcare provider will monitor you for signs of complications if you have an allogeneic stem cell transplant.

The most common side effects of Opdivo when used alone include:

• feeling tired
• rash
• pain in muscles, bones, and joints
• itchy skin
• diarrhea
• nausea
• weakness
• cough
• vomiting
• shortness of breath
• constipation
• decreased appetite
• back pain
• upper respiratory tract infection
• fever
• headache
• stomach-area (abdominal) pain

The most common side effects of Opdivo when used in combination with ipilimumab include:

• feeling tired
• diarrhea
• rash
• itching
• nausea
• pain in muscles, bones, and joints
• fever
• cough
• decreased appetite
• vomiting
• stomach-area (abdominal) pain
• shortness of breath
• upper respiratory tract infection
• headache
• low thyroid hormone levels (hypothyroidism)
• decreased weight
• dizziness

The most common side effects of Opdivo when used in combination with ipilimumab and chemotherapy include:

• feeling tired
• pain in muscles, bones, and joints
• nausea
• diarrhea
• rash
• decreased appetite
• constipation
• itching

The most common side effects of Opdivo when used in combination with cabozantinib include:

• diarrhea
• feeling tired or weak
• liver problems. See “What is the most important information I should know about Opdivo?”
• rash, redness, pain, swelling or blisters on the palms of your hands or soles of your feet
• mouth sores
• rash
• high blood pressure
• low thyroid hormone levels
• pain in muscles, bones, and joints
• decreased appetite
• nausea
• change in the sense of taste
• stomach-area (abdominal) pain
• cough
• upper respiratory tract infection

These are not all the possible side effects of Opdivo.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Opdivo

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. If you would like more information about Opdivo, talk with your healthcare provider. You can ask your healthcare provider for information about Opdivo that is written for health professionals.

What are the ingredients in Opdivo?

Active ingredient: nivolumab

Inactive ingredients: mannitol, pentetic acid, polysorbate 80, sodium chloride, sodium citrate dihydrate, and Water for Injection. May contain hydrochloric acid and/or sodium hydroxide.

Label

OPDIVO 40 MG/4 ML REPRESENTATIVE PACKAGING

• See How Supplied section for a complete list of available packages of OPDIVO.
• NDC 0003-3772-11
  Rx only
• Opdivo®
  (nivolumab)
  injection
• 40 mg/4 mL
  (10 mg/mL)
• For intravenous Infusion Only
  Single-dose vial; Discard unused portion.
  Please provide enclosed Medication Guide to the patient.
• Bristol Myers Squibb

OPDIVO 100 MG/10 ML REPRESENTATIVE PACKAGING

• NDC 0003-3774-12
  Rx only
• Opdivo®
  (nivolumab)
  injection
• 100 mg/10 mL
  (10 mg/mL)
• For Intravenous Infusion Only
  Single-dose vial; Discard unused portion.
  Please provide enclosed Medication Guide to the patient.
• Bristol Myers Squibb

OPDIVO 120 MG/12 ML REPRESENTATIVE PACKAGING

• NDC 0003-3756-14
  Rx only
• Opdivo®
  (nivolumab)
  injection
• 120 mg/12 mL
  (10 mg/mL)
• For Intravenous Infusion Only
  Single-dose vial; Discard unused portion.
  Please provide enclosed Medication Guide to the patient.
• Bristol Myers Squibb

OPDIVO 240 MG/24 ML REPRESENTATIVE PACKAGING

• NDC 0003-3734-13
  Rx only
• Opdivo®
  (nivolumab)
  injection
• 240 mg/24 mL
  (10 mg/mL)
• For Intravenous Infusion Only
  Single-dose vial; Discard unused portion.
  Please provide enclosed Medication Guide to the patient.
• Bristol Myers Squibb

SRC: NLM .