ipilimumab

REMS

Unresectable/metastatic melanoma (as monotherapy or in combination with nivolumab).
Adjuvant treatment of cutaneous melanoma with pathologic involvement of regional lymph nodes >1 mm in patients who have undergone complete resection, including total lymphadenectomy
Previously untreated, advanced renal cell carcinoma in patients who are at intermediate or poor risk (in combination with nivolumab).
Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
Hepatocellular carcinoma in patients who have been previously treated with sorafenib (in combination with nivolumab).
First-line treatment of metastatic non–small-cell lung cancer (NSCLC) in patients whose tumors express PD-L1(≥1%) and have no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations (in combination with nivolumab).
First-line treatment of metastatic or recurrent NSCLC in patients whose tumors have no EGFR or ALK genomic tumor aberrations (in combination with nivolumab and two cycles of platinum-based chemotherapy).
First-line treatment of unresectable malignant pleural mesothelioma (in combination with nivolumab).
First-line treatment of unresectable advanced or metastatic esophageal squamous cell carcinoma (in combination with nivolumab).

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Lactation: Lactation.

Use Cautiously in:

Patients undergoing allogeneic hematopoietic stem cell transplantation (↑ risk of graft-versus-host disease
OB: Use only if potential maternal benefit justifies potential risk to the fetus
Rep: Women of reproductive potential
Pedi: Children <12 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

CV: MYOCARDITIS, pericarditis, vasculitis.

Derm: pruritus, rash, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN).

EENT: hearing loss, immune-mediated iritis, immune-mediated uveitis.

Endo: immune-mediated hypothyroidism, IMMUNE-MEDIATED ADRENAL INSUFFICIENCY, immune-mediated hyperthyroidism, immune-mediated hypoparathyroidism, immune-mediated hypophysitis, immune-mediated type 1 diabetes.

GI: diarrhea, immune-mediated colitis, immune-mediated gastritis, IMMUNE-MEDIATED HEPATITIS, immune-mediated pancreatitis.

GU: immune-mediated nephritis.

Hemat: immune-mediated hemolytic anemia.

MS: immune-mediated myositis, IMMUNE-MEDIATED RHABDOMYOLYSIS.

Neuro: fatigue, Guillain-Barré syndrome, autoimmune neuropathy, IMMUNE-MEDIATED ENCEPHALITIS, IMMUNE-MEDIATED MENINGITIS, immune-mediated myasthenic syndrome, immune-mediated myelitis.

Resp: IMMUNE-MEDIATED PNEUMONITIS.

Misc: INFUSION REACTIONS.

Interactions ⬆ ⬇

Drug-Drug:

Concurrent use with vemurafenib may ↑ risk of hepatic dysfunction.

Availability ⬆ ⬇

Solution for injection: 5 mg/mL;

Route/Dosage ⬆ ⬇

Unresectable/Metastatic Melanoma

IV (Adults and Children ≥12 yr): As monotherapy: 3 mg/kg every 3 wk for up to 4 doses. In combination with nivolumab: 3 mg/kg every 3 wk for up to 4 doses or unacceptable toxicity (administer after nivolumab on same day); after completing 4 doses of the combination, give nivolumab alone until disease progression or unacceptable toxicity.

Adjuvant Treatment of Melanoma

IV (Adults and Children ≥12 yr): 10 mg/kg every 3 wk for up to 4 doses, then 10 mg/kg every 12 wk for up to 3 yr.

Advanced Renal Cell Carcinoma

IV (Adults): 1 mg/kg every 3 wk for up to 4 doses (administer after nivolumab on same day); after completing 4 doses of the combination, give nivolumab alone until disease progression or unacceptable toxicity.

Colorectal Cancer

IV (Adults): 1 mg/kg every 3 wk for 4 doses (administer after nivolumab on same day); after completing 4 doses of the combination, give nivolumab alone until disease progression or unacceptable toxicity.

Hepatocellular Carcinoma

IV (Adults): 3 mg/kg every 3 wk for 4 doses (administer after nivolumab on same day); after completing 4 doses of the combination, give nivolumab alone until disease progression or unacceptable toxicity.

Metastatic or Recurrent Non–Small-Cell Lung Cancer

IV (Adults): 1 mg/kg every 6 wk until disease progression, unacceptable toxicity or for up to 2 yr (if no disease progression) (administer after nivolumab, but before platinum-based chemotherapy [if being given] on same day).

Malignant Pleural Mesothelioma

IV (Adults): 1 mg/kg every 6 wk until disease progression, unacceptable toxicity or for up to 2 yr (if no disease progression) (administer after nivolumab on same day).

Esophageal Squamous Cell Carcinoma

IV (Adults): 1 mg/kg every 6 wk until disease progression, unacceptable toxicity or for up to 2 yr (administer after nivolumab on same day).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and prevents it from binding to CD80/CD86 ligands. CTLA-4 is a negative regulator of T-cell activation; binding results in augmented T-cell activation and proliferation as well as enhanced T-cell responsiveness.

Therapeutic Effects:

↓ spread or recurrence of melanoma and improved survival.
Improved survival with renal cell carcinoma, NSCLC, malignant pleural mesothelioma, and esophageal squamous cell carcinoma.
↓ progression of MSI-H or dMMR metastatic colorectal cancer.
↓ progression of hepatocellular carcinoma.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Crosses the placenta.

Metabolism/Excretion: Unknown.

Half-life: 14.7 days.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

Patient/Family Teaching ⬆ ⬇

Explain purpose and potential adverse effects of ipilimumab to patient.
Inform patient of the risk of immune-mediated reactions due to T-cell activation and proliferation. Advise patients these may be severe and fatal. Instruct patient to notify health care professional immediately if signs and symptoms occur.
Instruct patient to read the Medication Guide before starting therapy and with each Rx refill in case of changes.
Advise patient to notify health care professional if signs and symptoms of colitis (diarrhea; black, tarry, sticky, bloody, or mucus in stools; severe abdominal pain or tenderness), hepatitis (yellowing of skin or the whites of eyes, severe nausea or vomiting, pain on right side of abdomen), skin reactions (rash, itching, skin blistering or peeling, painful sores in mouth or nose, throat, or genital area), endocrinopathies (persistent or unusual headache, eye sensitivity to light, eye problems, 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, deepening of voice, dizziness or fainting, changes in mood or behavior, decreased sex drive, irritability, or forgetfulness), pneumonitis (new or worsening cough, shortness of breath, chest pain), nephritis (decrease in amount of urine, blood in urine, swelling of ankles, loss of appetite), or eye problems (blurry vision, double vision, or other vision problems, eye pain or redness) occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, herbal products.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during and for 3 mo following last dose. Women must choose to discontinue breast feeding or ipilimumab. Advise female patients to notify health care professional if pregnancy is planned or suspected. Encourage women who become pregnant during therapy to contact Bristol-Myers Squibb by calling 1-844-593-7869.

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Indications ⬇