Ipilimumab: Indication, Dosage, Side Effect, Precaution

Generic Medicine Info Patient Medicine Information

This information is not country-specific. Please refer to the Myanmar prescribing information.

Generic Medicine Info

Indications and Dosage

Intravenous
Cutaneous melanoma

Adult: Adjuvant treatment in patients with pathologic involvement of regional lymph nodes of >1 mm who have undergone complete resection, including total lymphadenectomy: As monotherapy: 10 mg/kg every 3 weeks for up to 4 doses, followed by 10 mg/kg every 12 weeks for up to 3 years. Doses are given via infusion over 90 minutes. Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guidelines).

Intravenous
Metastatic melanoma, Unresectable melanoma

Adult: As monotherapy: 3 mg/kg every 3 weeks via infusion over 30 minutes for a total of 4 doses. In combination with nivolumab: 3 mg/kg every 3 weeks via infusion over 30 minutes for up to 4 doses or until unacceptable toxicity; followed by nivolumab monotherapy until disease progression or unacceptable toxicity (refer to specific product information of nivolumab for dosage recommendations). Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guidelines).
Child: As monotherapy: ≥12 years Same as adult dose. Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guidelines).

Intravenous
Advanced renal cell carcinoma

Adult: As 1st-line treatment of intermediate- or poor-risk cases: In combination with nivolumab: 1 mg/kg every 3 weeks via infusion over 30 minutes for up to 4 doses; followed by nivolumab monotherapy until disease progression or unacceptable toxicity (refer to specific product information of nivolumab for dosage recommendations). Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guidelines).

Intravenous
Hepatocellular carcinoma

Adult: For patients who have been previously treated with sorafenib: In combination with nivolumab: 3 mg/kg every 3 weeks via infusion over 30 minutes for 4 doses; followed by nivolumab monotherapy until disease progression or unacceptable toxicity (refer to specific product information of nivolumab for dosage recommendations). Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guidelines).

Intravenous
Unresectable malignant pleural mesothelioma

Adult: As 1st-line treatment: In combination with nivolumab: 1 mg/kg every 6 weeks via infusion over 30 minutes until disease progression, unacceptable toxicity, or for up to 2 years in patients without disease progression. Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guidelines).

Intravenous
Microsatellite instability-high metastatic colorectal cancer

Adult: For the treatment of cases that have progressed after therapy with fluoropyrimidine, oxaliplatin, and irinotecan: In combination with nivolumab: 1 mg/kg every 3 weeks via infusion over 30 minutes for 4 doses; followed by nivolumab monotherapy until disease progression or unacceptable toxicity (refer to specific product information of nivolumab for dosage recommendations). Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guidelines).
Child: ≥12 years Same as adult dose. Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guidelines).

Intravenous
PD-L1 expression in metastatic non-small cell lung carcinoma

Adult: As 1st-line treatment in patients whose tumours express PD-L1 (≥1%) as determined by an approved test, with no EGFR or ALK genomic tumour aberrations: In combination with nivolumab: 1 mg/kg every 6 weeks via infusion over 30 minutes until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression. Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guidelines).

Intravenous
Metastatic non-small cell lung carcinoma

Adult: As 1st-line treatment in patients whose tumours have no sensitising epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation: In combination with nivolumab and 2 cycles of platinum-based chemotherapy: 1 mg/kg every 6 weeks via infusion over 30 minutes until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression. Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guidelines).

Reconstitution

IV infusion: Allow the vial(s) to sit at room temperature for approx 5 minutes prior to infusion preparation. Dilute the required volume with 0.9% NaCl solution for injection or 5% dextrose in water to make a final concentration between 1-4 mg/mL. Mix by gentle inversion; do not shake. When given in combination with nivolumab, infuse the nivolumab dose 1st, followed by the ipilimumab dose on the same day. When administered in combination with nivolumab and platinum-based chemotherapy, infuse the nivolumab dose 1st, followed by the ipilimumab dose, and then the platinum-based chemotherapy dose all on the same day. Use separate infusion bags and filters for each infusion.

Contraindications

Severe active autoimmune disease where further immune activation is potentially imminently life-threatening. Lactation.

Special Precautions

Patient with chronic infections, history of recurring infections, or underlying conditions predisposing to development of infection; well-controlled myasthenia gravis, history of severe skin adverse reactions on a prior cancer immune stimulatory therapy; active or history of brain metastases, leptomeningeal metastases, history of autoimmune disease, interstitial lung disease, conditions requiring systemic immunosuppression; primitive peritoneal, pericardial, testis or tunica vaginalis mesothelioma; transaminase levels ≥5 times upper limit of normal (ULN) or bilirubin levels >3 times the ULN at baseline. Patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT). Children. Pregnancy.

Adverse Reactions

Significant: Cardiac and pulmonary events including pulmonary embolism; severe diarrhoea, immune-mediated nephritis with renal dysfunction, other immune-mediated endocrinopathies (e.g. thyroiditis, Cushing syndrome, Graves ophthalmopathy), peripheral motor neuropathy, sensory neuropathy, cystitis noninfective, immune-mediated rash and dermatitis, severe infusion-related reactions. Rarely, immune-mediated blepharitis, iritis, episcleritis, orbital myositis, scleritis, conjunctivitis, and uveitis; Vogt-Koyanagi-Harada syndrome, serous retinal detachment, neurosensory hypoacusis, myelitis and demyelination, nerve paresis, motor dysfunction, angiopathy, temporal arteritis, vasculitis, polymyalgia rheumatica, histiocytic necrotising lymphadenitis (Kikuchi lymphadenitis), psoriasis, sarcoidosis.
Blood and lymphatic system disorders: Anaemia, lymphopenia, febrile neutropenia, eosinophilia, leucopenia, thrombocytopenia.
Cardiac disorders: Tachycardia, chest pain.
Eye disorders: Blurred vision, eye pain, dry eye.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, constipation, GERD, abdominal pain, mucosal or gastrointestinal haemorrhage, stomatitis, pancreatitis.
General disorders and administration site conditions: Fatigue, lethargy, chills, pyrexia, asthenia, oedema, influenza-like illness, oedema, inj site reactions.
Hepatobiliary disorders: Abnormal hepatic function.
Immune system disorders: Hypersensitivity reaction.
Investigations: Decreased weight; increased ALT, AST, blood alkaline phosphatase, blood bilirubin, serum lipase, serum amylase, serum creatinine, and TSH.
Metabolism and nutrition disorders: Decreased appetite, dehydration, hypo- or hyperkalaemia, hypo- or hypercalcaemia, hypo- or hypermagnesaemia, hypo- or hypernatraemia, hypo- or hyperglycaemia.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, muscle spasm, musculoskeletal pain.
Neoplasms benign, malignant and unspecified: Tumour pain.
Nervous system disorders: Dizziness, headache, peripheral neuropathy.
Psychiatric disorders: Confusional state, insomnia.
Renal and urinary disorders: Renal failure including acute kidney injury.
Respiratory, thoracic and mediastinal disorders: Dyspnoea, cough, upper respiratory tract infection, pneumonia.
Skin and subcutaneous tissue disorders: Pruritus, erythema, vitiligo, urticaria, eczema, dry skin, alopecia, night sweats.
Vascular disorders: Hypotension, flushing, hot flush.
Potentially Fatal: Severe immune-mediated reactions which may involve any organ system (e.g. gastrointestinal perforation, colitis, pneumonitis, hepatitis, hepatic failure, bullous or exfoliative dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms [DRESS]; endocrinopathies such as adrenal insufficiency, type 1 diabetes mellitus, diabetic ketoacidosis, hypophysitis, hyperthyroidism, hypothyroidism, hypogonadism, hypopituitarism); haemophagocytic lymphohistiocytosis (HLH), gastrointestinal cytomegalovirus (CMV) infection or reactivation (in patients with corticosteroid-refractory immune-related colitis); serious graft-vs-host disease (GVHD), particularly in patients receiving ipilimumab before or after allogeneic HSCT. Rarely, immune-mediated autoimmune neuropathy, meningitis, Guillain-Barre syndrome, myasthenic syndrome or myasthenia gravis, encephalitis, pericarditis, myositis, myocarditis, rhabdomyolysis, and solid organ transplant rejection.

Pregnancy Category (US FDA)

IV/Parenteral: C

Patient Counseling Information

This drug may cause tiredness, if affected, do not drive or operate machinery.

Monitoring Parameters

Confirm pregnancy status before therapy initiation in females of reproductive potential. Select patients for treatment based on the PD-L1 expression status as clinically indicated. Obtain LFTs at baseline, prior to each dose, and periodically thereafter (monitor more frequently if hepatotoxicity develops); serum chemistries, electrolytes, and ACTH before each dose and regularly during therapy; serum creatinine at baseline and periodically thereafter; TSH, free T₄, and morning cortisol levels at baseline, prior to dose, and as clinically indicated. Monitor for signs and symptoms of cardiac and pulmonary events, infusion reactions, and immune-mediated reactions, including adrenal insufficiency, hypophysitis, thyroid disorders, colitis, motor or sensory neuropathy, dermatologic toxicity, pneumonitis, and hepatitis. Assess for ocular toxicity at baseline, then at 4-8 weeks with further evaluation as clinically necessary. Closely check for evidence of GVHD in patients receiving ipilimumab before or after allogeneic HSCT.

Drug Interactions

Increased risk of hepatotoxicity (e.g. elevated transaminases) with vemurafenib. Systemic corticosteroids given prior to ipilimumab dose may interfere with the efficacy of ipilimumab; after starting ipilimumab therapy, systemic corticosteroids may be given for immune-related reactions. May increase the risk of gastrointestinal haemorrhage with anticoagulants.

Action

Description: Ipilimumab is a recombinant, fully human monoclonal antibody antineoplastic agent. It binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a down-regulator of T-cell activation pathways, thereby inhibiting the interaction of CTLA-4 with its ligands. This activity enhances T-cell activation and proliferation, including the number of reactive T-effector cells which mobilise to provide a direct T-cell immune attack against tumour cells. The inhibition of CTLA-4 may also decrease T- regulatory cell function resulting in increased T-cell responsiveness, including anti-tumour immune response.
Pharmacokinetics:
Excretion: Terminal elimination half-life: 15.4 days.

Storage

Store between 2-8°C. Do not freeze. Protect from light. Diluted solutions for infusion are stable for up to 24 hours when stored between 2-8°C or 20-25°C.

MIMS Class

Cancer Immunotherapy

ATC Classification

L01FX04 - ipilimumab ; Belongs to the class of other monoclonal antibodies and antibody drug conjugates. Used in the treatment of cancer.

References

Anon. Ipilimumab. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 07/06/2022.

Anon. Ipilimumab. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/06/2022.

Bristol-Myers Squibb (NZ) Limited. Yervoy 5 mg per 1 mL Concentrate Solution for Infusion data sheet 27 January 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 07/06/2022.

Buckingham R (ed). Ipilimumab. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/06/2022.

Joint Formulary Committee. Ipilimumab. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/06/2022.

Yervoy 5 mg/mL Concentrate for Solution for Infusion (Bristol-Myers Squibb Pharma EEIG). MHRA. https://products.mhra.gov.uk. Accessed 07/06/2022.

Yervoy Injection (E.R. Squibb & Sons, L.L.C.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 07/06/2022.

Disclaimer: This information is independently developed by MIMS based on Ipilimumab from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2024 MIMS. All rights reserved. Powered by MIMS.com