Ipilimumab

Indications

Ipilimumab is used for: Metastatic melanoma, Renal Cell Carcinoma

Adult Dose

Intravenous Metastatic melanoma Adult: 3 mg/kg via infusion over 90 minutes every 3 weeks for a total of 4 doses. In case of toxicity, doses may be delayed, but all treatment must be given within 16 weeks of 1st dose. Melanoma Adult: As adjuvant therapy in patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of >1 mm who have undergone complete resection: 10 mg/kg via infusion over 90 minutes every 3 weeks for a total of 4 doses then, 10 mg/kg every 12 weeks for up to 3 years or until documented disease recurrence or unacceptable toxicity. In case of toxicity, omit dose/s. Renal Cell Carcinoma Indicated in combination with nivolumab for patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma 1 mg/kg IV infused over 30 min immediately following nivolumab on the same day; repeat q3Weeks for up to 4 doses or until intolerable toxicity or disease progression

Child Dose

Intravenous Metastatic melanoma Child: >12 years: 3 mg/kg via infusion over 90 minutes every 3 weeks for a total of 4 doses. In case of toxicity, doses may be delayed, but all treatment must be given within 16 weeks of 1st dose.

Renal Dose

Administration

V Preparation 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 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. Administer diluted solution over 90 minutes (melanoma) or 30 minutes (renal cell carcinoma) 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

Contra Indications

No known contraindications

Precautions

May cause immune-mediated adverse reactions including enterocolitis, hepatitis, dermatitis, neuropathies, endocrinopathies, ocular, and other significant or severe immune-mediated manifestations; may require initiation of systemic corticosteroids at a dose of 1 to 2 mg/kg/day of prednisone or equivalent Monitor patients for signs or symptoms of ocular toxicity, which may include blurred vision and reduced visual acuity; immune-mediated ocular toxicity may be associated with retinal detachment or permanent vision loss; administer corticosteroid eye drops to patients who develop uveitis, iritis, or episcleritis; permanently discontinue therapy for immune-mediated ocular disease that is unresponsive to local immunosuppressive therapy; if uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt Koyanagi-Harada-like syndrome, which has been observed in patients receiving drug and may require treatment with systemic steroids to reduce the risk of permanent vision loss Withhold dose for moderate immune-mediated adverse reactions until return to baseline, improvement to mild severity, or complete resolution, and patient is receiving <7.5 mg/day prednisone or equivalent Administer systemic high-dose corticosteroids for severe, persistent, or recurring immune-mediated reactions Evaluate liver function tests before each dose; permanently discontinue with Grade 3-4 hepatotoxicity Monitor thyroid function tests and clinical chemistries prior to each dose Evaluate at each visit for signs and symptoms of endocrinopathy and institute hormone replacement therapy as needed Patient with history of autoimmune disease. Children. Pregnancy and lactation. Lactation Unknown whether distributed in human breast milk Advise women to discontinue nursing during treatment and for 3 months after the final dose There are no data to assess the effects on milk production

Pregnancy-Lactation

Pregnancy Based on data from animal studies and its mechanism of action, can cause fetal harm when administered to a pregnant woman Advise females of reproductive potential to use effective contraception during treatment and for 3 months after the last dose 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 Animal studies 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 The effects are likely to be greater during the second and third trimesters of pregnancy Lactation Unknown whether distributed in human breast milk Advise women to discontinue nursing during treatment and for 3 months after the final dose In monkeys, ipilimumab was present in milk There are no data to assess the effects on milk production

Interactions

May increase hepatotoxicity of vemurafenib.

Adverse Effects

Side effects of Ipilimumab : >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

Mechanism of Action

Ipilimumab, an antineoplastic drug, is a recombinant, fully human monoclonal antibody. It inhibits cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), a down-regulator of T-cell activation pathways, thereby prolonging T-cell activation and proliferation and enhancing anti-tumour immune response. It may also decrease T-regulatory cell function and increase T cell responsiveness.