Class: Monoclonal antibody
- Injection, solution, concentrate 5 mg/mL
Ipilimumab binds to cytotoxic T lymphocyte antigen 4 (CTLA-4), blocking the interaction between CTLA-4 with its ligand, leading to augmentation of T-cell activation and proliferation.
C min is 21.8 mcg/mL. Steady state is reached by the third dose.
V ss is 7.21 L.
Terminal half-life is 14.7 days. Cl is 15.3 mL/h.
Special PopulationsRenal Function Impairment
CrCl at baseline did not have a clinically important effect in patients with CrCl 29 mL/min or more.Hepatic Function Impairment
Baseline AST, total bilirubin, and ALT did not affect pharmacokinetics in patients with varying degrees of hepatic impairment.Elderly
Age had no clinically meaningful effect on Cl of ipilimumab.Gender
Gender had no clinically meaningful effect on Cl of ipilimumab.Body weight
Cl increased with increasing body weight.
Indications and Usage
Treatment of unresectable or metastatic melanoma.
None well documented.
Dosage and AdministrationMelanoma
IV 3 mg/kg over 90 min every 3 wk for a total of 4 doses.Dose modification
Withhold dose for moderate immune-mediated adverse reactions or for symptomatic endocrinopathy. For patients with complete or partial resolution of adverse reactions (grade 0 to 1), and who are receiving less than prednisone 7.5 mg or equivalent per day, resume at a dosage of 3 mg/kg every 3 wk until administration of all 4 planned doses or 16 wk from first dose, whichever occurs earlier.Discontinuation
Permanently discontinue for any of the following: persistent moderate adverse reactions or inability to reduce corticosteroid dosage to prednisone 7.5 mg or equivalent per day; failure to complete full treatment course within 16 wk from administration of first dose; severe or life-threatening reactions, including: colitis with abdominal pain, fever, ileus, or peritoneal signs; increase in stool frequency (7 or more over baseline), stool incontinence, need for IV hydration for more than 24 h, or GI hemorrhage and perforation; AST or ALT more than 5 times ULN or total bilirubin more than 3 times the ULN; Stevens-Johnson syndrome, TEN, or rash complicated by full thickness dermal ulceration; necrotic, bullous, or hemorrhagic manifestations; severe motor or sensory neuropathy, Guillain-Barré syndrome, or myasthenia gravis; severe immune-mediated reactions involving any organ system (nephritis, pneumonitis, pancreatitis, noninfectious myocarditis); or immune-mediated ocular disease unresponsive to topical immunosuppressive therapy.
- Administer by IV infusion over 90 min through an IV line containing sterile, nonpyrogenic, low protein-binding in-line filter.
- Do not shake. Allow vials to stand at room temperature for 5 min prior to infusion preparation.
- Withdraw required volume of ipilimumab and transfer to an IV bag. Dilute with sodium chloride 0.9% injection or dextrose 5% injection to a final concentration ranging from 1 to 2 mg/mL. Mix by gentle inversion.
- Do not mix or administer as an infusion with other medicinal products.
- Flush IV line with sodium chloride 0.9% injection or dextrose 5% injection after each dose.
Store vials under refrigeration (36° to 46°F). Do not freeze. Protect from light. Store diluted solution for no more than 24 h under refrigeration (36° to 46°F) or at room temperature (68° to 77°F). Discard partially used or empty vials.
None well documented.
Pruritus (31%); rash (29%); immune-mediated dermatitis, urticaria (2%).
Diarrhea (32%); colitis (8%); immune-mediated enterocolitis (7%); immune-mediated hepatotoxicity (1%).
Fatigue (41%); immune-mediated hypopituitarism, immune-mediated endocrinopathy (4%); eosinophilia, nephritis (1%); immune-mediated neuropathy (1%).
WarningsImmune-mediated adverse reactions
Ipilimumab can result in severe and fatal immune-mediated adverse reactions due to T-cell activation and proliferation. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including TEN), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of ipilimumab. Permanently discontinue ipilimumab and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions. Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinology, and evaluate clinical chemistries, including LFTs and thyroid function tests at baseline and before each dose.
Monitor for enterocolitis, bowel perforation, dermatitis, motor or sensory neuropathy, hypophysitis, adrenal insufficiency, and hyper- or hypothyroidism. Monitor LFTs and assess patients for hepatotoxicity. Monitor thyroid function tests and clinical chemistries before each dose and as clinically indicated.
Category C . May cause fetal harm. Human IgG1 is known to cross the placenta and ipilimumab is an IgG1; therefore, ipilimumab has the potential to be transmitted to a developing fetus.
Undetermined. Lactating women should not breast-feed.
Safety and efficacy have not been established.
Development of antibodies may occur.
No information available.
- Advise patients to read the Medication Guide before each infusion.
- Inform patients of the potential risk of immune-mediated adverse reactions, including intestinal perforation, hepatitis leading to liver failure, dermatologic reactions, neuropathy, and inflammation of glands and eyes.
- Advise women that ipilimumab may cause fetal harm.
- Advise breast-feeding women not to breast-feed while taking ipilimumab.
Copyright © 2009 Wolters Kluwer Health.