Belinostat: Indication, Dosage, Side Effect, Precaution

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

Generic Medicine Info

Indications and Dosage

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).

Pregnancy Category (US FDA)

IV: D

Monitoring Parameters

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:
Mechanism of Action: 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

Storage

Store between 20-25°C.
This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.

MIMS Class

Cytotoxic Chemotherapy

ATC Classification

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

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