Beleodaq (belinostat)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Belinostat, a histone deacetylase (HDAC) inhibitor, is an antineoplastic agent.
Belinostat, a histone deacetylase (HDAC) inhibitor, is an antineoplastic agent. HDAC enzymes catalyze the removal of acetyl groups from the lysine residues of proteins, including histones and transcription factors. Overexpression of HDAC enzymes or aberrant recruitment of HDAC enzymes to oncogenic transcription factors causing hypoacetylation of core nucleosomal histones has been observed in some cancer cells.
Hypoacetylation of histones is associated with a condensed chromatin structure and repression of gene transcription. Inhibition of HDAC activity allows for the accumulation of acetyl groups on the histone lysine residues, resulting in an open chromatin structure and transcriptional activation. In vitro, belinostat causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells.
Belinostat inhibits the enzymatic activity of histone deacetylases and exhibits cytotoxic activity and induces apoptosis in various tumor cell lines at nanomolar concentrations.
Belinostat is metabolized principally (80-90%) by uridine diphosphate-glucuronosyltransferase (UGT) 1A1; the drug also is metabolized by cytochrome P-450 (CYP) isoenzymes 2A6, 2C9, and 3A4 to form the metabolites belinostat amide and belinostat acid. Other metabolites of the drug include methyl belinostat and 3-(anilinosulfonyl)-benzenecarboxylic acid (3-ASBA); the enzymes responsible for the formation of these metabolites have not been determined. Belinostat is a likely substrate, but an unlikely inhibitor, of P-glycoprotein (P-gp).
The main circulating metabolites are excreted in urine, with 2 metabolites predominating (3-ASBA and belinostat glucuronide, which account for 4.61 and 30.5%, respectively, of an administered dose); only a small portion (less than 2%) of a dose is excreted in urine as unchanged drug. Belinostat is 92.9-95.8% bound to plasma proteins. Following administration of belinostat (150-1200 mg/m2), the elimination half-life of the drug was 1.1 hours.
In patients with genetic polymorphisms associated with reduced UGT1A1 activity (e.g., individuals who are homozygous for the UGT1A1*28 allele), clearance of belinostat may be reduced and dosage adjustment may be required. (See Reduced Uridine Diphosphate-glucuronosyltransferase (UGT) 1A1 Activity under Dosage: Dosage Modification, in Dosage and Administration.)
USES: Belinostat is used to treat a certain type of cancer (peripheral T-cell lymphoma - PTCL). Belinostat works by slowing or stopping the growth of cancer cells.
Generic name: belinostat
Pronunciation: (be-LIN-oh-stat)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Beleodaq
Indications
The following indications are listed for Beleodaq:
- Peripheral T-Cell Lymphoma
Dosing
No dosing information is available for this tab.
Belinostat is administered by IV infusion over 30 minutes. If infusion site reactions (e.g., pain) occur, the infusion time may be extended to 45 minutes.
Prior to administration, commercially available belinostat powder for injection must be reconstituted and diluted using proper aseptic technique. The lyophilized powder is reconstituted by adding 9 mL of sterile water for injection to a vial labeled as containing 500 mg of the drug to provide a solution containing 50 mg/mL. The vial should be swirled until complete dissolution of the powder occurs. The solution should be inspected visually for particulate matter and discoloration prior to dilution and administration. The reconstituted belinostat solution may be stored at 15-25degreesC for up to 12 hours.
For preparation of the final diluted belinostat solution for infusion, the required dose of reconstituted belinostat solution should be injected into an infusion bag containing 250 mL of 0.9% sodium chloride injection. The final diluted solution may be stored at 15-25degreesC for up to 36 hours (including infusion time). Belinostat should be administered through a 0.22-mcm inline filter.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Belinostat is metabolized principally (80-90%) by uridine diphosphate-glucuronosyltransferase (UGT) 1A1. In vitro studies indicate that belinostat and its metabolites, including belinostat glucuronide, belinostat amide, and methyl belinostat, are inhibitors of cytochrome P-450 (CYP) isoenzymes 2C8 and 2C9; other metabolites, including 3-(anilinosulfonyl)-benzenecarboxylic acid (3-ASBA) and belinostat acid, are inhibitors of CYP2C8 in vitro.
Belinostat is a likely substrate, but an unlikely inhibitor, of P-glycoprotein (P-gp).
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
The manufacturer states there are no known contraindications to the use of belinostat.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in 10% or more of patients receiving belinostat include nausea, fatigue, pyrexia, vomiting, constipation, diarrhea, dyspnea, rash, peripheral edema, cough, pruritus, chills, decreased appetite, headache, infusion site pain, prolonged QT interval, abdominal pain, hypotension, phlebitis, and dizziness. Laboratory abnormalities reported in 10% or more of patients receiving belinostat include anemia, thrombocytopenia, elevated serum LDH concentrations, and hypokalemia.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of belinostat have not been established in pediatric patients.
Category D. (See Users Guide and see Fetal/Neonatal Morbidity and Mortality under Cautions: Warnings/Precautions.)
It is not known whether belinostat is distributed into milk in humans; because of the potential for serious adverse reactions to belinostat in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
In the principal efficacy study evaluating belinostat in patients with PTCL, 48% of patients were 65 years of age or older and 10% were 75 years of age or older. In patients with PTCL, the overall response rate was 36% in those 65 years of age and older compared with 16% in those younger than 65 years of age. No meaningful differences in overall response rate were observed between patients 75 years of age and older and those younger than 75 years of age. No clinically important differences in safety were observed between geriatric patients and younger adults. (See Dosage and Administration: Special Populations.)
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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