Ipilimumab
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From MedlinePlus, U.S. National Library of Medicine
CTLA-4-directed Blocking Antibody
Dosing in kidney impairment
Severe and Fatal Immune-Mediated Adverse Reactions : Immune-mediated adverse reactions (IMAR) can occur in any organ system or tissue, including the following: immune-mediated colitis, immune-mediated hepatitis, immune-mediated dermatologic adverse reactions, immune-mediated endocrinopathies, immune-mediated pneumonitis, and immune-mediated nephritis with renal dysfunction, and can occur at any time during treatment or after discontinuation.
Immune-Mediated Endocrinopathies YERVOY 3 mg/kg as a Single Agent Grade 2-5 immune-mediated endocrinopathies occurred in 4% (21/511) of patients who received YERVOY 3 mg/kg as a single agent. Severe to life-threatening (Grade 3-4) endocrinopathies occurred in 9 patients (1.8%). All 9 of these patients had hypopituitarism with some patients having additional concomitant endocrinopathies, such as adrenal insufficiency, hypogonadism, and hypothyroidism.
Six of the 9 patients were hospitalized for severe endocrinopathies. Moderate (Grade 2) endocrinopathy occurred in 12 patients (2.3%), including hypothyroidism, adrenal insufficiency, hypopituitarism, hyperthyroidism and Cushing’s syndrome. Of the 21 patients with moderate to life-threatening endocrinopathy, 17 required long-term hormone replacement therapy, including adrenal hormones (n=10) and thyroid hormones (n=13).
Adrenal Insufficiency: Adrenal insufficiency occurred in 7% (48/666) of patients who received YERVOY 1 mg/kg with nivolumab for the treatment of RCC or mCRC, including Grade 4 (0.3%), Grade 3 (2.5%), and Grade 2 (4.1%). Adrenal insufficiency led to permanent discontinuation of YERVOY with nivolumab in 1.2% and withholding of YERVOY with nivolumab in 2.1% of patients.
Approximately 94% of patients with adrenal insufficiency received hormone replacement therapy. Systemic corticosteroids were required in 94% (45/48) of patients with adrenal insufficiency. Adrenal insufficiency resolved in 29% of the 48 patients. Of the 14 patients in whom YERVOY or nivolumab was withheld for adrenal insufficiency, 11 received additional treatment after symptom improvement; of these, 2 had recurrence of adrenal insufficiency.
Adrenal Insufficiency: Adrenal insufficiency occurred in 8% (35/456) of patients with melanoma or HCC receiving YERVOY 3 mg/kg with nivolumab 1 mg/kg every 3 weeks, including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of YERVOY with nivolumab in 0.4% of patients and withholding of treatment in 2.0% of patients.
| * Refer to the Prescribing Information for the agents administered in combination with YERVOY for recommended dosing information, as appropriate. † Refer to the Prescribing Information for nivolumab for dosage information after completing use in combination with YERVOY. | ||
| Indication | Recommended YERVOY Dosage | Duration of Therapy |
| Unresectable or metastatic melanoma | 3 mg/kg every 3 weekswith nivolumab 1 mg/kg | In combination with nivolumab for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier.After completing 4 doses of combination therapy, administer nivolumab as a single agent until disease progression or unacceptable toxicity.† |
| Advanced renal cell carcinoma | 1 mg/kg every 3 weekswith nivolumab 3 mg/kg | In combination with nivolumab for a maximum of 4 doses.After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.† |
| Microsatellite instability-high (MSI‑H) or mismatch repair deficient (dMMR) metastatic colorectal cancer | Adult patients and pediatric patients age 12 years and older and weighing 40 kg or more:1 mg/kg every 3 weekswith nivolumab 240 mg | In combination with nivolumab for a maximum of 4 doses.†After completing 4 doses of combination therapy, administer nivolumab as single agent until disease progression, unacceptable toxicity, or up to 2 years.† |
| Pediatric patients age 12 years and older and weighing less than 40 kg: 1 mg/kg every 3 weeks with nivolumab 3 mg/kg | ||
| Hepatocellular carcinoma | 3 mg/kg every 3 weekswith nivolumab 1 mg/kg | In combination with nivolumab for a maximum of 4 doses.After completing a maximum of 4 doses of combination therapy, administer nivolumab as single agent until disease progression or unacceptable toxicity.† |
| Metastatic non-small cell lung cancer expressing PD‑L1 | 1 mg/kg every 6 weekswith nivolumab 360 mg every 3 weeks | In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.† |
| Metastatic or recurrent non-small cell lung cancer | 1 mg/kg every 6 weekswith nivolumab 360 mg every 3 weeksand histology-based platinum‑doubletchemotherapy every 3 weeks | In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.† |
| 2 cycles of histology-based platinum-doublet chemotherapy | ||
| Malignant pleural mesothelioma | 1 mg/kg every 6 weekswith nivolumab 360 mg every 3 weeks | In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.† |
| Esophageal squamous cell carcinoma | 1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks or 360 mg every 3 weeks | In combination with nivolumab until disease progression, unacceptable toxicity, or up to 2 years. |
| ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit of normal * Based on Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 a Resume in patients with complete or partial resolution (Grade 0 or 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids. b If AST/ALT are less than or equal to ULN at baseline, withhold or permanently discontinue YERVOY based on recommendations for hepatitis with no liver involvement. c This guidance is only applicable to HCC patients who are being treated with YERVOY in combination with nivolumab. d Depending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement. Resume once acute symptoms have resolved. | ||
| Adverse Reaction | Severity* | Dosage Modifications |
| Immune-Mediated Adverse Reactions [See Warnings and Precautions (5.1)] | ||
| Colitis | Grade 2 | Withholda |
| Grade 3 or 4 | Permanently discontinue | |
| Hepatitis with no tumor involvement of the liveror Hepatitis with tumor involvement of the liver/non-HCC | AST or ALT increases to more than 3 times and up to 5 times the ULNor Total bilirubin increases to more than 1.5 times and up to 3 times the ULN | Withholda |
| AST or ALT more than 5 times the ULN or Total bilirubin more than 3 times the ULN | Permanently discontinue | |
| Hepatitis with tumor involvement of the liverb/HCCc | Baseline AST/ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULNorBaseline AST/ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN. | Withholda |
| AST/ALT increases to more than 10 times ULNorTotal bilirubin increases to more than 3 times ULN. | Permanently discontinue | |
| Exfoliative Dermatologic Conditions | Suspected SJS, TEN, or DRESS | Withhold |
| Confirmed SJS, TEN, or DRESS | Permanently discontinue | |
| Endocrinopathiesd | Grades 3 or 4 | Withhold until clinically stable or permanently discontinue depending on severity |
| Pneumonitis | Grade 2 | Withholda |
| Grade 3 or 4 | Permanently discontinue | |
| Nephritis with Renal Dysfunction | Grade 2 or 3 increased blood creatinine | Withholda |
| Grade 4 increased blood creatinine | Permanently discontinue | |
| Neurological Toxicities | Grade 2 | Withholda |
| Grade 3 or 4 | Permanently discontinue | |
| Myocarditis | Grade 2, 3 or 4 | Permanently discontinue |
| Ophthalmologic | Grade 2, 3, or 4 that does not improve to Grade 1 within 2 weeks while receiving topical therapy or that requires systemic treatment | Permanently discontinue |
| Other Adverse Reactions | ||
| Infusion-Related Reactions [see Warnings and Precautions (5.2)] | Grade 1 or 2 | Interrupt or slow the rate of infusion |
| Grade 3 or 4 | Permanently discontinue | |
Preparation and administration
Prepare this dose
Your numbers for ipilimumab. Take vial strength, diluent, and limits from the label below.
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Preparation and Administration
Do not shake product.
Visually inspect for particulate matter and discoloration prior to administration. Discard vial if solution is cloudy, there is pronounced discoloration (solution may have pale-yellow color), or there is foreign particulate matter other than translucent-to-white, amorphous particles. Preparation of Solution
Allow the vial(s) to stand at room temperature for approximately 5 minutes prior to preparation of infusion.
Withdraw the required volume of YERVOY and transfer into an intravenous bag.
Dilute with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to a final concentration ranging from 1 mg/mL to 2 mg/mL . Mix diluted solution by gentle inversion.
After preparation, store the diluted solution either refrigerated at 2°C to 8°C (36°F to 46°F) or at room temperature of 20°C to 25°C (68°F to 77°F) for no more than 24 hours from the time of preparation to the time of infusion.
Discard partially used or empty vials of YERVOY. Administration
Do not co-administer other drugs through the same intravenous line.
Flush the intravenous line with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP after each dose.
Administer diluted YERVOY solution by intravenous infusion over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low-protein-binding in-line filter.
When administered in combination with nivolumab, infuse nivolumab first followed by YERVOY on the same day.
When administered with nivolumab and platinum-doublet chemotherapy, infuse nivolumab first followed by YERVOY and then platinum-doublet chemotherapy on the same day.
Use separate infusion bags and filters for each infusion.
| ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit of normal * Based on Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 a Resume in patients with complete or partial resolution (Grade 0 or 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids. b If AST/ALT are less than or equal to ULN at baseline, withhold or permanently discontinue YERVOY based on recommendations for hepatitis with no liver involvement. c This guidance is only applicable to HCC patients who are being treated with YERVOY in combination with nivolumab. d Depending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement. Resume once acute symptoms have resolved. | ||
| Adverse Reaction | Severity* | Dosage Modifications |
| Immune-Mediated Adverse Reactions [See Warnings and Precautions (5.1)] | ||
| Colitis | Grade 2 | Withholda |
| Grade 3 or 4 | Permanently discontinue | |
| Hepatitis with no tumor involvement of the liveror Hepatitis with tumor involvement of the liver/non-HCC | AST or ALT increases to more than 3 times and up to 5 times the ULNor Total bilirubin increases to more than 1.5 times and up to 3 times the ULN | Withholda |
| AST or ALT more than 5 times the ULN or Total bilirubin more than 3 times the ULN | Permanently discontinue | |
| Hepatitis with tumor involvement of the liverb/HCCc | Baseline AST/ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULNorBaseline AST/ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN. | Withholda |
| AST/ALT increases to more than 10 times ULNorTotal bilirubin increases to more than 3 times ULN. | Permanently discontinue | |
| Exfoliative Dermatologic Conditions | Suspected SJS, TEN, or DRESS | Withhold |
| Confirmed SJS, TEN, or DRESS | Permanently discontinue | |
| Endocrinopathiesd | Grades 3 or 4 | Withhold until clinically stable or permanently discontinue depending on severity |
| Pneumonitis | Grade 2 | Withholda |
| Grade 3 or 4 | Permanently discontinue | |
| Nephritis with Renal Dysfunction | Grade 2 or 3 increased blood creatinine | Withholda |
| Grade 4 increased blood creatinine | Permanently discontinue | |
| Neurological Toxicities | Grade 2 | Withholda |
| Grade 3 or 4 | Permanently discontinue | |
| Myocarditis | Grade 2, 3 or 4 | Permanently discontinue |
| Ophthalmologic | Grade 2, 3, or 4 that does not improve to Grade 1 within 2 weeks while receiving topical therapy or that requires systemic treatment | Permanently discontinue |
| Other Adverse Reactions | ||
| Infusion-Related Reactions [see Warnings and Precautions (5.2)] | Grade 1 or 2 | Interrupt or slow the rate of infusion |
| Grade 3 or 4 | Permanently discontinue | |
Contraindications
None. • None. (4)
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , YERVOY can cause fetal harm when administered to a pregnant woman. There is insufficient human data for YERVOY exposure in pregnant women. In animal reproduction studies, administration of ipilimumab to cynomolgus monkeys from the 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 (see Data ) .
The effects of ipilimumab are likely to be greater during the second and third trimesters of pregnancy. 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. Advise pregnant women of the potential risk to a fetus. Report pregnancies to Bristol-Myers Squibb at 1-844-593-7869. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data In a combined study of embryo-fetal and peri-postnatal development, pregnant cynomolgus monkeys received ipilimumab every 3 weeks from the onset of organogenesis in the first trimester through parturition. No treatment-related adverse effects on reproduction were detected during the first two trimesters of pregnancy. Beginning in the third trimester, administration of ipilimumab at doses resulting in exposures approximately 2.6 to 7.2 times the human exposure at a dose of 3 mg/kg resulted in dose-related increases in abortion, stillbirth, premature delivery (with corresponding lower birth weight), and an increased incidence of infant mortality.
In addition, developmental abnormalities were identified in the urogenital system of 2 infant monkeys exposed in utero to 30 mg/kg of ipilimumab (7.2 times the humans exposure based on area under the curve at a dose of 3 mg/kg). One female infant monkey had unilateral renal agenesis of the left kidney and ureter, and 1 male infant monkey had an imperforate urethra with associated urinary obstruction and subcutaneous scrotal edema. Genetically engineered mice heterozygous for CTLA-4 (CTLA-4+/−), the target for ipilimumab, appeared healthy and gave birth to healthy CTLA-4+/− heterozygous offspring.
Mated CTLA-4+/− heterozygous mice also produced offspring deficient in CTLA-4 (homozygous negative, CTLA-4−/−). The CTLA-4−/− homozygous negative…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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