Belinostat


Concise Prescribing Info
Indications/Uses
Relapsed or refractory peripheral T-cell lymphoma.
Dosage/Direction for Use
Adult : IV 1,000 mg/m2 once daily over 30 minutes on days 1-5 every 21 days until disease progression or unacceptable toxicity. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Dosage Details
Intravenous
Peripheral T-Cell lymphoma
Adult: In relapsed or refractory cases: 1,000 mg/m2 once daily via infusion over 30 minutes on days 1-5 every 21 days until disease progression or unacceptable toxicity. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Special Patient Group
Obese patients: Same as adult dose. Utilise patient’s actual body weight for calculation of dosage.

Pharmacogenomics:

Belinostat is primarily metabolised by UGT1A1. Genetic polymorphism on UGT1A1 gene such as UGT1A1*28 allele may affect the pharmacokinetics of belinostat. Patients who are homozygous to UGT1A1*28 allele may have reduced enzyme activity resulting in decreased clearance of belinostat. The prevalence of this polymorphism is estimated in 20% of black population, 10% of white population, and 2% of the Asian population.

Patient homozygous to UGT1A1*28 allele
Recommendation: Reduce initial dose to 750 mg/m2.
Reconstitution
Reconstitute vial labelled as containing 500 mg with 9 mL sterile water for inj to provide a solution containing 50 mg/mL. IV infusion: Further dilute appropriate dose with 250 mL of NaCl 0.9% solution.
Contraindications
Active infections. Pregnancy.
Special Precautions
Patient with history of extensive or intensive chemotherapy, advanced disease and/or high tumour burden. Patient with known UGT1A1*28 allele. Obese individuals. Hepatic impairment. Lactation.
Adverse Reactions
Significant: Thrombocytopenia, leukopenia, anaemia; nausea, vomiting, diarrhoea; LFT abnormalities; tumour lysis syndrome.
Cardiac disorders: Dyspnoea.
Gastrointestinal disorders: Constipation, abdominal pain.
General disorders and administration site conditions: Fatigue, fever, phlebitis, inj site pain.
Investigations: Prolonged QT interval on ECG, increased lactate dehydrogenase.
Metabolism and nutrition disorders: Peripheral oedema, hypokalaemia, decreased appetite.
Musculoskeletal and connective tissue disorders: Chills.
Nervous system disorders: Headache, dizziness.
Respiratory, thoracic and mediastinal disorders: Cough.
Skin and subcutaneous tissue disorders: Rash, pruritus.
Vascular disorders: Hypotension.
Potentially Fatal: Hepatotoxicity; serious infections (e.g. pneumonia, sepsis).
MonitoringParameters
Monitor CBC with platelets and differential at baseline and weekly thereafter; serum chemistries, electrolytes, LFT, kidney function at baseline and before each cycle. Monitor for signs and symptoms of gastrointestinal toxicity, tumour lysis syndrome, bleeding and infection.
Drug Interactions
Increased serum concentration with atazanavir. May diminish therapeutic effect of BCG vaccine. May enhance neutropenic effect of deferiprone. May enhance adverse/toxic effect of clozapine.
Action
Description: Belinostat, a histone deacetylase (HDAC) inhibitor, catalyses acetyl group removal from protein lysine residues leading to accumulation of acetyl groups which results to tumour cell cycle arrest and apoptosis. It has preferential cytotoxicity to tumour cells than normal healthy cells.
Pharmacokinetics:
Distribution: Volume of distribution: Approx 114 L/m2. Plasma protein binding: Approx 93-96%.
Metabolism: Metabolised in the liver primarily by UGT1A1, also by CYP2A6, CYP2C9 and CYP3A4 into amide and acid metabolites.
Excretion: Via urine (84.8% ± 9.8% as metabolites; 2% as unchanged drug); faeces (9.7 ± 6.5%). Elimination half-life: 1.1 hours.
Chemical Structure

Chemical Structure Image
Belinostat

Source: National Center for Biotechnology Information. PubChem Database. Belinostat, CID=6918638, https://pubchem.ncbi.nlm.nih.gov/compound/Belinostat (accessed on Jan. 21, 2020)

Storage
Store between 20-25°C.
This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
ATC Classification
L01XX49 - belinostat ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.
References
Annotation of FDA Label for Belinostat and UGT1A1. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org/. Accessed 12/11/2019.

Anon. Belinostat. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 12/11/2019.

Beleodaq for Inj (Spectrum Pharmaceuticals, Inc.). U.S. FDA. https://www.fda.gov/. Accessed 15/11/2019.

Beleodaq Injection, Powder, Lyophilized for Solution (Acrotech Biopharma LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 12/11/2019.

Buckingham R (ed). Belinostat. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 12/11/2019.

Disclaimer: This information is independently developed by MIMS based on Belinostat 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 © 2020 MIMS. All rights reserved. Powered by MIMS.com
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