ipilimumab (Rx)

Brand and Other Names:Yervoy
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution, single-dose

  • 5mg/mL (10mL, 40mL)

Melanoma

Unresectable or metastatic melanoma

  • Indicated for treatment of unresectable or metastatic melanoma in adults and children aged ≥12 yr
  • 3 mg/kg IV q3Week for a maximum of 4 doses  

Cutaneous Melanoma

  • Indicated for adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes >1 mm who have undergone complete resection, including total lymphadenectomy
  • 10 mg/kg IV q3Week for 4 doses followed by 10 mg/kg q12Week for up to 3 yr  

Renal Cell Carcinoma

Indicated in combination with nivolumab for patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma

Ipilimumab1 mg/kg IV q3Weeks 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

Also see nivolumab drug monograph for dose and continuation as monotherapy

Microsatellite Instability-High or Mismatch Repair Deficient Metastatic Colorectal Cancer

Indicated in combination with nivolumab for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan

Ipilimumab 3 mg/kg IV immediately following nivolumab 1 mg/kg IV on the same day, q3Weeks for 4 doses  

After completing 4 doses of combination therapy, continue nivolumab as a single-agent until intolerable toxicity or disease progression

Also see nivolumab drug monograph for dose and continuation as monotherapy

Hepatocellular Carcinoma

Indicated in combination with nivolumab for hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib

Ipilimumab 3 mg/kg IV immediately following nivolumab 1 mg/kg IV on the same day, q3Weeks for 4 doses  

After completing 4 doses of combination therapy, continue nivolumab as a single-agent until intolerable toxicity or disease progression

Also see nivolumab drug monograph for dose and continuation as monotherapy

Non-small Cell Lung Cancer

Combination with nivolumab

  • Indicated in combination with nivolumab for first-line treatment of metastatic non-small cell lung cancer (NSCLC) in adults whose tumors express PD-L1 (≥1%) with no EGFR or ALK genomic tumor aberrations
  • Nivolumab 3 mg/kg IV q2Weeks, plus  
  • Ipilimumab 1 mg/kg IV q6Weeks
  • Continue until disease progression, unacceptable toxicity, or for up to 2 years in patients without disease progression

Combination with nivolumab and platinum-based chemotherapy

  • Indicated in combination with nivolumab and 2 cycles of platinum-doublet chemotherapy, for first-line treatment of metastatic or recurrent NSCLC in adults with no EGFR or ALK genomic tumor aberrations
  • Nivolumab 360 mg/kg IV q3Weeks, PLUS  
  • Ipilimumab 1 mg/kg IV q6Weeks, PLUS
  • Histology-based platinum doublet chemotherapy q3Weeks for 2 cycles
  • Continue until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression

Malignant Pleural Mesothelioma

Indicated in combination with nivolumab for patients with unresectable malignant pleural mesothelioma, as first-line treatment

Ipilimumab 1 mg/kg IV q6Weeks, PLUS

Nivolumab 360 mg IV q3Weeks

Continue in combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression

Dosage Modifications

Note: No dose reduction is recommended for adverse reactions

When in combination with nivolumab, withhold or permanently discontinue ipilimumab and nivolumab for toxicity

Renal impairment

  • All severities: No dosage adjustment required

Hepatic impairment

  • Mild (TB >1 to 1.5x ULN or AST >ULN): No dose adjustment required
  • Moderate-to-severe (TB >1.5x ULN and any AST): Not studied; caution advised

Interrupt or slow rate of infusion

  • Grade 1 or 2 infusion-related reactions

Withhold

  • Resume once complete or partial resolution (Grade 0 or 1) after corticosteroid taper
    • Grade 2 colitis or diarrhea
    • Grade 2 pneumonitis
    • Grade 2 or 3 increased blood creatinine nephritis with renal dysfunction
    • Grade 2 neurological toxicities
    • Grade 2 myocarditis
  • Resume when acute symptoms have resolved
    • Grade 2 to 4 hypophysitis
  • Resume when AST/ALT returns to baseline
    • Hepatitis (AST or ALT >3x to <5x ULN or total bilirubin >1.5x to <3x ULN)

Withhold until specialist assessment

  • Grade 2 exfoliative or bullous dermatologic conditions

Withhold if not clinically stable

  • Grade 2 to 4 endocrinopathies

Permanently discontinue

  • Grade 3 or 4 colitis or diarrhea
  • Hepatitis (AST or ALT >5x ULN or total bilirubin >3x ULN)
  • Grade 3 or 4 exfoliative or bullous dermatologic conditions
  • Grade 3 or 4 pneumonitis
  • Grade 4 increased blood creatinine
  • Grade 3 or 4 myocarditis
  • Grade 2 to 4 ophthalmologic that does not improve to Grade 1 within 2 weeks while receiving topical therapy or that requires systemic treatment
  • Grade 3 or 4 neurological toxicities if signs of encephalitis or respiratory insufficiency due to neurological toxicity regardless of grade
  • Grade 3 or 4 infusion-related reactions

Dosing Considerations

Patient selection

Orphan Designations

Small cell lung cancer

Orphan sponsor

  • Bristol-Myers Squibb Company; 5 Research Parkway; Wallingford, Connecticut 06492

Dosage Forms & Strengths

injectable solution, single-dose

  • 5mg/mL (10mL, 40mL)

Malignant Melanoma

Indicated for treatment of unresectable or metastatic melanoma in adults and adolescents aged ≥12 yr

<12 years: Safety and efficacy not established

≥12 years: 3 mg/kg IV q3Week for a maximum of 4 doses  

Microsatellite Instability-High or Mismatch Repair Deficient Metastatic Colorectal Cancer

Indicated in combination with nivolumab for patients aged ≥12 years with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan

<12 years: Safety and efficacy not established

≥12 years: 1 mg/kg IV q3Weeks following nivolumab on the same day; repeat for up to 4 doses or until intolerable toxicity or disease progression  

Also see nivolumab drug monograph for dose and continuation as monotherapy

Dosage Modifications

Renal impairment

  • All severities: No dosage adjustment required

Hepatic impairment

  • Mild (TB >1 to 1.5 x ULN or AST >ULN): No dose adjustment required
  • Moderate-to-severe (TB >1.5 x ULN and any AST): Not studied; caution advised

Interrupt or slow rate of infusion

  • Grade 1 or 2 infusion-related reactions

Withhold

  • Resume in patients with complete or partial resolution (Grade 0 or 1) after corticosteroid taper
    • Grade 2 colitis or diarrhea
    • Grade 2 pneumonitis
    • Grade 2 or 3 increased blood creatinine nephritis with renal dysfunction
    • Grade 2 neurological toxicities
    • Grade 2 myocarditis
  • Resume when acute symptoms have resolved
    • Grade 2 to 4 hypophysitis
  • Resume when AST/ALT returns to baseline
    • Hepatitis (AST or ALT >3x to <5x ULN or total bilirubin >1.5x to <3x ULN)

Withhold until specialist assessment

  • Grade 2 exfoliative or bullous dermatologic conditions

Withhold if not clinically stable

  • Grade 2 to 4 endocrinopathies

Permanently discontinue

  • Grade 3 or 4 colitis or diarrhea
  • Hepatitis (AST or ALT >5x ULN or total bilirubin >3x ULN)
  • Grade 3 or 4 exfoliative or bullous dermatologic conditions
  • Grade 3 or 4 pneumonitis
  • Grade 4 increased blood creatinine
  • Grade 3 or 4 myocarditis
  • Grade 2 to 4 ophthalmologic that does not improve to Grade 1 within 2 weeks while receiving topical therapy or that requires systemic treatment
  • Grade 3 or 4 neurological toxicities if signs of encephalitis or respiratory insufficiency due to neurological toxicity regardless of grade
  • Grade 3 or 4 infusion-related reactions
Next:

Interactions

Interaction Checker

and ipilimumab

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Dermatitis immune-mediated manifestations (up to 70%)

            Fatigue (41%)

            Diarrhea (32%)

            Pruritus (31%)

            Rash (29%)

            1-10%

            Colitis (8%)

            Immune-mediated enterocolitis (7%)

            Immune-mediated hepatitis (2%)

            Endocrinopathies (1.8%) including adrenal insufficiency, hypogonadism, and hypothyroidism

            <1%

            Neurologic immune-mediated manifestations (eg, Guillain-Barre, peripheral motor neuropathy)

            Ocular immune-mediated manifestations (eg, uveitis, iritis)

            Nephrotic immune-mediated manifestations (nephritis)

            Pulmonary immune-mediated manifestations (pneumonitis)

            Other immune-mediated adverse reactions (<1%) include nephritis, pneumonitis, meningitis, pericarditis, uveitis, iritis, and hemolytic anemia

            Meningitis

            Pericarditis

            Myocarditis

            Angiopathy

            Temporal arteritis

            Vasculitis

            Polymyalgia rheumatica

            Conjunctivitis

            Blepharitis

            Episcleritis

            Scleritis

            Leukocytoclastic vasculitis

            Erythema multiforme

            Psoriasis

            Pancreatitis

            Arthritis

            Autoimmune thyroiditis

            Postmarketing Reports

            Skin and subcutaneous tissue disorders: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)

            Blood and lymphatic system disorders: Hemophagocytic lymphohistiocytosis (HLH)

            Immune System: Graft-versus-host disease, solid organ transplant rejection

            Previous
            Next:

            Warnings

            Contraindications

            None

            Cautions

            Severe infusion-related reactions can occur; discontinue in patients with severe or life-threatening infusion reactions

            Fatal or serious graft-versus-host disease (GVHD) can occur in patients who receive a CTLA-4 receptor blocking antibody either before or after allogeneic hematopoietic stem cell transplantation (HSCT); closely monitor for evidence of GVHD and intervene promptly; consider benefit versus risks of treatment with a CTLA-4 receptor blocking antibody after allogeneic HSCT

            May cause fetal harm when administered to pregnant females

            When used in combination with nivolumab, refer to nivolumab prescribing information for additional risk information that applies to the combination use treatment

            Immune-mediated adverse reactions

            • Owing to the mechanism of action that blocks T-cell inhibitory signal via CTLA-4 pathway, thereby removing inhibition of the immune response to potential immune-mediated adverse reactions
            • Immune-mediated adverse reactions (eg, diarrhea/colitis, hepatitis, dermatologic adverse reactions, endocrinopathies, pneumonitis, immune-mediated nephritis with renal dysfunction), which may be severe or fatal, can occur in any organ system or tissue
            • May occur at any time after initiating therapy
            • Immune-mediated adverse reactions usually manifest during treatment, but can also manifest after discontinuation
            • Early detection and management are essential to ensure safe use
            • Monitor for signs and symptoms of underlying immune-mediated adverse reactions
            • Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose
            • Institute medical management promptly, including specialty consultation as appropriate
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            Based on findings from animal studies and its mechanism of action, may cause fetal harm when administered to pregnant females

            There is insufficient human data for drug exposure in pregnant females

            Advise pregnant females 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 prior to initiation

            Report pregnancies to Bristol-Myers Squibb at 1-844-593-7869

            Contraception

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

            Animal data

            • Administration of ipilimumab to cynomolgus monkeys from onset of organogenesis through delivery resulted in higher incidences of abortion, stillbirth, premature delivery (with corresponding lower birth weight), and higher incidences of infant mortality in a dose-related manner

            • Effects of ipilimumab are likely to be greater during second and third trimesters of pregnancy

            Lactation

            Unknown whether distributed in human breast milk

            Advise women to discontinue breastfeeding during treatment and for 3 months after last dose

            In monkeys, ipilimumab was present in milk

            There are no data to assess the effects on milk production

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Recombinant, human cytotoxic T-lymphocyte antigen 4 (CTLA-4) - blocking antibody

            CTLA-4 is a negative regulator of T-cell activation; ipilimumab binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86

            Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation

            Proposed mechanism of action is indirect, possibly through inhibition of CTLA-4 signaling, which can in turn reduce T-regulatory cell function and may contribute to a general increase in T cell responsiveness, including the anti-tumor immune response

            IgG1 kappa immunoglobulin with an approximate molecular weight of 148 kd; produced in mammalian (Chinese hamster ovary) cell culture

            Absorption

            Minimum plasma concentration: 19.4 mcg/mL (steady-state)

            Distribution

            Vd: 7.21 L (steady-state)

            Elimination

            Half-life (terminal): 15.4 days

            Clearance: 16.8 mL/hr

            When administered in combination with nivolumab, ipilimumab clearance was unchanged in presence of antiipilimumab antibodies and the CL of nivolumab increased by 20% in the presence of antinivolumab antibodies

            Previous
            Next:

            Administration

            IV Incompatibilities

            Do not coadminister with other drugs through same IV line

            IV Compatibilities

            0.9% NaCl

            Dextrose 5% (D5W)

            IV Preparation

            Do not shake vial

            Allow vials to stand at room temperature for ~5 minutes

            Withdraw required volume and transfer into an IV bag

            Dilute with 0.9% NaCl or D5W to prepare a diluted solution with a final concentration ranging from 1-2 mg/mL

            Mix diluted solution by gentle inversion

            Discard partially used or empty vials

            IV Administration

            Do not mix with, or administer as an infusion with, other medicinal products

            Flush the IV line with 0.9% NaCl or D5W after each dose

            Infusion rate

            • Melanoma: Infuse over 90 minutes
            • Renal cell carcinoma, MSI-H dMMR, hepatocellular carcinoma, NSCLC, malignant pleural mesothelioma: Infuse over 30 minutes
            • Infuse through an IV line containing a sterile, nonpyrogenic, low-protein-binding in-line filter

            Administration with nivolumab

            • When administered in combination with nivolumab, infuse nivolumab first followed by ipilimumab on the same day
            • Use separate infusion bags and filters for each infusion

            Storage

            Unopened vials

            • Store refrigerated at 2-8°C (36-46°F)
            • Do not freeze
            • Protect vials from light

            Diluted solution

            • Store the diluted solution refrigerated (2-8°C; 36-46°F) or at room temperature (20-25°C; 68-77°F) for up to 24 hr
            • Discard partially used vials or empty vials
            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.