Belinostat

Patients taking UGT1A1 inhibitors: Avoid use if possible. Reduce belinostat dose by 25% if receiving a dose of 1,000 mg/m² or 750 mg/m². If receiving 500 mg/m², discontinue belinostat during UGT1A1 inhibitor use.

Pharmacogenomics:

Belinostat is metabolised primarily by UGT1A1 enzymes. Genetic polymorphism of UGT1A1 gene such as the UGT1A1*28 allele may result in decreased UGT1A1 enzyme activity. The prevalence of individuals with UGT1A1*28 homozygous allele is approx 20% in the black population, 10% in the white population, and 2% in the Asian population. Reduced function alleles other than UGT1A1*28 may also be present in certain populations.

Patients homozygous to UGT1A1*28 allele
Individuals who are homozygous to UGT1A1*28 allele may have reduced enzyme activity, resulting in higher systemic belinostat concentration and increased risk of adverse reaction. The US Food and Drug Administration (US FDA) drug labelling recommends decreasing the initial dose to 750 mg/m² to reduce dose-limiting toxicities.

CrCl (mL/min)	Dosage
<30	Avoid use.
30-<60	Reduce dose to 500 mg/m2 once daily on Days 1-5 of a 21-day cycle.

Moderate (total bilirubin >1.5-3 times ULN and any AST): Reduce dose to 500 mg/m² once daily on Days 1-5 of a 21-day cycle. Severe (total bilirubin >3 times ULN and any AST): Avoid use.

Reconstitute vial labelled as containing 500 mg with 9 mL of sterile water for inj to make a final concentration of 50 mg/mL. Swirl until no visible particles are in the reconstituted solution. Withdraw the required volume for the dose and further dilute in 250 mL of NaCl 0.9% solution.

Patient with history of extensive or intensive chemotherapy. Patients homozygous to UGT1A1*28 allele. Renal and hepatic impairment. Pregnancy and lactation. Concomitant use with UGT1A1 inhibitors.

Significant: Bone marrow suppression (e.g. thrombocytopenia, leucopenia, neutropenia, lymphopenia, anaemia), gastrointestinal toxicity (e.g. nausea, vomiting, diarrhoea), LFT abnormalities, tumour lysis syndrome.
Gastrointestinal disorders: Abdominal pain, constipation.
General disorders and administration site conditions: Peripheral oedema, pain at inj site, chills, fatigue, fever.
Investigations: Prolonged QT interval; increased LDH, serum creatinine.
Metabolism and nutrition disorders: Hypokalaemia, decreased appetite.
Nervous system disorders: Headache, dizziness.
Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea.
Skin and subcutaneous tissue disorders: Pruritus, rash.
Vascular disorders: Hypotension, phlebitis.
Potentially Fatal: Hepatotoxicity, serious infections (e.g. pneumonia, sepsis).

IV: D

Women of childbearing potential must use proven birth control methods during and 6 months after treatment. Men with female partners of childbearing potential must use proven birth control methods during and 3 months after treatment. Do not breastfeed during therapy and for 2 weeks after treatment.

Evaluate pregnancy status in women of childbearing potential before treatment initiation. Monitor CBC with platelets and differential at baseline and weekly during therapy; serum chemistries (e.g. kidney function, LFTs) at baseline and before each cycle. Monitor for signs and symptoms of gastrointestinal toxicity, tumour lysis syndrome, hepatotoxicity, and infection.

Increased systemic exposure and increased risk of adverse reactions with UGT1A1 inhibitors.

Description:
Mechanism of Action: Belinostat is a histone deacetylase inhibitor. It catalyses acetyl group removal from protein lysine residues, leading to the accumulation of acetyl groups, resulting in cell cycle arrest and apoptosis. In addition, it has preferential cytotoxicity toward tumour cells than normal cells.
Pharmacokinetics:
Distribution: Volume of distribution: Approx 114 L/m². Plasma protein binding: Approx 93-96%.
Metabolism: Metabolised in the liver mainly by UGT1A1 and also by CYP2A6, CYP2C9 and CYP3A4 enzymes into amide and acid metabolites.
Excretion: Via urine (84.8% ± 9.8% mainly as metabolites; <2% as unchanged drug); faeces (9.7% ± 6.5%). Elimination half-life: 1.1 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 6918638, Belinostat. https://pubchem.ncbi.nlm.nih.gov/compound/Belinostat. Accessed Mar. 26, 2025.

Intact vial: Store between 15-30°C. Reconstituted solution: Store between 15-25°C for 12 hours. Diluted solution for infusion: Store between 15-25°C for up to 36 hours. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.

Hóa trị gây độc tế bào

L01XH04 - belinostat ; Belongs to the class of histone deacetylase (HDAC) inhibitors. Used in the treatment of cancer.

Annotation of FDA Label for Belinostat and UGT1A1. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 03/03/2025.

Beleodaq Injection, Powder, Lyophilized, for Solution (Acrotech Biopharma Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 03/03/2025.

Belinostat. UpToDate Lexidrug, AHFS DI (Adult and Pediatric) Online. American Society of Health-System Pharmacists, Inc. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 03/03/2025.

Belinostat. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 03/03/2025.

Brayfield A, Cadart C (eds). Belinostat. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/03/2025.

UGT1A1 - Belinostat. UpToDate Lexidrug, Pharmacogenomics Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 03/03/2025.