Ipilimumab

Ipilimumab is a prescription medication indicated for the treatment of:

• Unresectable or metastatic melanoma
• Advanced Renal Cell Carcinoma (RCC)
• Unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC)
• Unresectable or metastatic hepatocellular carcinoma (HCC)
• Non-Small Cell Lung Cancer (NSCLC)
• Unresectable Malignant Pleural Mesothelioma
• Unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC)

Ipilimumab is available under the following different brand names: Yervoy.

Adult and pediatric dosage
Injectable solution, single dose

• 5 mg/mL (10 mL, 40 mL)

Melanoma
Adult dosage

• Unresectable or metastatic melanoma
  • Single agent
    • 3 mg/kg IV every 3 weeks for a maximum of 4 doses
  • Combination with nivolumab
    • 3 mg/kg IV every 3 weeks plus nivolumab 1 mg/kg IV every 3 weeks for a maximum of 4 doses or unacceptable toxicity, whichever occurs earlier
    • Continue single-agent nivolumab until disease progression or unacceptable toxicity; refer to nivolumab prescribing information for single-agent nivolumab dosing
• Adjuvant therapy
  • 3 mg/kg IV every 3 weeks for up to 4 doses, followed by 3 mg/kg IV every 12 weeks for up to 4 additional doses

Pediatric dosage

• Unresectable or metastatic melanoma
  • Single agent
    • 3 mg/kg IV every 3 weeks for a maximum of 4 doses
  • Combination with nivolumab
    • 3 mg/kg IV every 3 weeks PLUS nivolumab 1 mg/kg IV every 3 weeks for a maximum of 4 doses or unacceptable toxicity, whichever occurs earlier
    • Continue single-agent nivolumab until disease progression or unacceptable toxicity

Renal cell carcinoma
Adult dosage

• Ipilimumab 1 mg/kg IV every 3 weeks following nivolumab on the same day for 4 doses
• After completing 4 doses of combination therapy, continue nivolumab as a single agent until intolerable toxicity or disease progression

Colorectal cancer (CRC)
Adult dosage

• 1 mg/kg IV every 3 weeks plus nivolumab 240 mg IV every 3 weeks for a maximum of 4 doses

Pediatric dosage

• Children weighing 40 kg and more: 1 mg/kg IV every 3 weeks plus nivolumab 240 mg IV every 3 weeks for 4 doses
• Children weighing less than 40 kg: 1 mg/kg IV every 3 weeks plus nivolumab 3 mg/kg IV every 3 weeks for 4 doses

Hepatocellular carcinoma (HCC)
Adult dosage

• 3 mg/kg IV every 3 weeks plus nivolumab 1 mg/kg IV every 3 weeks for a maximum of 4 doses

Non-small cell lung cancer
Adult dosage

• Patient selection
  • Select patients based on PD-L1 expression
  • Information on FDA-approved tests is available at: https://www.fda.gov/CompanionDiagnostics
• Combination with nivolumab
  • Nivolumab 360 mg IV every 3 weeks, plus
  • Ipilimumab 1 mg/kg IV every 6 weeks
  • Continue until disease progression, unacceptable toxicity, or for up to 2 years in patients without disease progression
• Combination with nivolumab and platinum-based chemotherapy
  • Nivolumab 360 mg IV every 3 weeks, plus
  • Ipilimumab 1 mg/kg IV every 6 weeks, plus
  • Histology-based platinum doublet chemotherapy every 3 weeks for 2 cycles
  • Continue until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression

Malignant pleural mesothelioma
Adult dosage

• Ipilimumab 1 mg/kg IV every 6 weeks, plus
• Nivolumab 360 mg IV every 3 weeks
• Continue in combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression

Esophageal Cancer
Adult dosage

• 1 mg/kg IV every 6 weeks plus nivolumab 3 mg/kg IV every 2 weeks or 360 mg IV every 3 weeks
• Continue until disease progression, unacceptable toxicity, or up to 2 years

Dosage Considerations – Should be Given as Follows: 
See “Dosages

Common side effects of Ipilimumab include:

• tiredness
• diarrhea 
• itching (pruritus) 
• rash
• nausea 
• vomiting
• headache
• weight loss  
• fever 
• decreased appetite
• sleeplessness, wakefulness
• pain in muscles, bones, and joints
• cough
• upper respiratory tract infection
• abdominal pain
• hypothyroidism
• constipation
• decreased weight
• dizziness

Serious side effects of Ipilimumab include:

• lung problems causing symptoms like cough
• intestinal problems causing symptoms like diarrhea, black or tarry stools, and severe abdominal pain
• liver problems causing symptoms like yellowing of the skin and white of the eyes, dark urine, severe nausea and vomiting, bleeding or bruising more than normal, pain on the right side of the abdomen
• hormone gland problems causing symptoms like unusual headaches, eye problems, sensitivity to light, rapid heartbeat, 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, voice getting deeper, dizziness or fainting, changes in mood or behavior, such as decreased sex drive, irritability or forgetfulness
• kidney problems causing symptoms like decrease in urine output, blood in the urine, swelling of the ankles, loss of appetite
• skin problems causing symptoms like rash, itching, skin blistering or peeling, swollen lymph nodes, painful sores or ulcers in the mouth, nose, throat, or genital area, and fever
• severe infusion reactions causing chills or shaking, itching or rash, flushing, or wheezing, dizziness, fainting, fever, and back or neck pain
• risk of organ or tissue transplant rejection
• complications of stem cell transplant that uses donor stem cells

Rare side effects of Ipilimumab include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Visit the RxList Drug Interaction Checker for any drug interactions. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ipilimumab?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ipilimumab?”

Cautions

Immune-mediated adverse reactions

• Severe and fatal immune-mediated reactions reported
• May occur in any organ system or tissue and at any time after starting therapy, including after discontinuation
• Institute medical management promptly; consult specialists as appropriate
• Hold or permanently discontinue based on severity
• Administer systemic corticosteroids (e.g., 1-2 mg/kg/day prednisone or equivalent) until improvement to Grade of 1 and less, then taper corticosteroids over at least 1 month
• Other systemic immunosuppressants may be required if reactions are not controlled with corticosteroids

Immune-mediated colitis

• Frequently associated with diarrhea
• Cytomegalovirus (CMV) infection/reactivation reported with corticosteroid-refractory immune-mediated colitis
• For corticosteroid-refractory colitis, consider repeating infectious workups to exclude alternative etiologies

Immune-mediated hepatitis

• Evaluate liver enzymes at baseline and before each dose

Immune-mediated dermatologic reactions

• Bullous and exfoliative dermatitis may occur (.eg, Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis)
• Treat mild to moderate no exfoliative rashes with topical emollients and/or topical corticosteroids
• Hold or permanently discontinue depending on severity

Immune-mediated endocrinopathies

• Immune-mediated adrenal insufficiency, Cushing’s syndrome, hypophysitis, thyroiditis, hyperthyroidism, hypothyroidism, and type 1 diabetes mellitus were reported
• Hypophysitis can cause hypopituitarism
• Initiate symptomatic treatment (e.g., hormone replacement, insulin) as clinically indicated
• Evaluate thyroid function and adrenocorticotropic hormone (ACTH) level at baseline and before each dose

Immune-mediated pneumonitis

• Severe or life-threatening pneumonitis may occur

Immune-mediated nephritis

• May occur with renal dysfunction
• Evaluate renal function (e.g., serum creatinine) at baseline and before each dose

Infusion-related reactions

• Severe infusion-related reactions reported
• Monitor for signs and symptoms
• Interrupt, reduce the rate, or permanently discontinue based on severity

Complications of allogeneic HSCT

• Fatal or serious graft-versus-host-disease (GVHD) can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a CTLA-4 receptor blocking antibody
• Complications may occur despite intervening therapy between CTLA-4 receptor blockade and allogeneic HSCT
• Follow patients closely for evidence of GVHD and intervene promptly; consider the benefits versus risks of treatment with a CTLA-4 receptor blocking antibody after allogeneic HSCT

Risks associated when administered with nivolumab

• Indicated for use in combination with nivolumab for specific cancer types
• Refer to the nivolumab prescribing information for additional risk information that applies to combination therapy

Embryo-fetal toxicity

• Fetal harm may occur if used during pregnancy
• Advise pregnant patients of the potential risk to the fetus
• Effective contraception recommended during and after therapy in females of reproductive potential

Pregnancy and Lactation

• Based on findings from animal studies and its mechanism of action, it may cause fetal harm when administered to pregnant women
• There is insufficient human data for drug exposure in pregnant women
• Advise pregnant women of the potential risk to a fetus
• Human IgG1 is known to cross the placental barrier, and Ipilimumab is an IgG1; therefore, Ipilimumab has the potential to be transmitted from the mother to the developing fetus
• Verify pregnancy status in females of reproductive potential before initiation
• Report pregnancies to Bristol-Myers Squibb at 1-844-593-7869

Contraception

• Women of reproductive potential: Use effective contraception during treatment and for 3 months following the last dose

Lactation

• Unknown whether distributed in human breast milk
• Advise women to discontinue breastfeeding during treatment and for 3 months after the last dose
• In monkeys, Ipilimumab was present in milk
• There are no data to assess the effects on milk production