belinostat (Rx)

Brand and Other Names:Beleodaq
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • 500mg/vial

Peripherial T-Cell Lymphoma

Histone deacetylase (HDAC) inhibitor indicated for relapsed or refractory peripheral T-cell lymphoma

1000 mg/m² IV qDay on days 1-5 of a 21-day cycle  

Infuse IV over 30 minutes

Cycles can be repeated every 21 days until disease progression or unacceptable toxicity

Dosage Modifications

ANC should be ≥1.0 x 10^9/L and the platelet count should be ≥50 x 10^9/L prior to the start of each cycle and prior to resuming treatment following toxicity

Discontinue with recurrent ANC nadirs <0.5 x 10^9/L and/or recurrent platelet count nadirs <25 x 10^9/L after 2 dosage reductions

Other toxicities must be ≤grade 2 prior to re-treatment

Monitoring

  • Monitor complete blood cell counts at baseline and weekly
  • Perform serum chemistry tests, including renal and hepatic functions, prior to the start of the first dose of each cycle

Hematologic toxicities

  • Platelet count ≥25 x 10^9/L and nadir ANC ≥0.5 x 10^9/L: No change
  • Nadir ANC <0.5 x 10^9/L (any platelet count): Decrease dose by 25% (750 mg/m²)
  • Platelet count <25 x 10^9/L (any nadir ANC): Decrease dose by 25% (750 mg/m²)

Non-hematologic toxicities

  • Grade 3 or 4 adverse reaction: Decrease dose by 25% (750 mg/m²)
  • Grade 3 or 4 nausea/vomiting/diarrhea >7 days: Decrease dose by 25% (750 mg/m²)
  • Recurrence of Grade 3 or 4 adverse reaction after 2 dosage reductions: Discontinue

Reduced UGT1A1 activity

  • Patients known to be homozygous for the UGT1A1*28 allele: Reduce starting dose to 750 mg/m²

Renal or hepatic impairment

  • Metabolized in the liver and hepatic impairment is expected to increase systemic exposure; patients with moderate-to-severe hepatic impairment were excluded from clinical trials
  • CrCl >39 mL/min: No dosage adjustment required
  • CrCl ≤39 mL/min: Insufficient dose to recommend dosage modification

Dosing Considerations

Indication approved under accelerated approval based on tumor response rate and duration of response

An improvement in survival or disease-related symptoms has not been established

Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial

Safety and efficacy not established

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Interactions

Interaction Checker

and belinostat

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    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            All toxicity grades

            Nausea (42%)

            Fatigue (37%)

            Pyrexia (35%)

            Anemia (32%)

            Vomiting (29%)

            Constipation (23%)

            Diarrhea (23%)

            Dyspnea (22%)

            Rash (20%)

            Peripheral edema (20%)

            Cough (19%)

            Thrombocytopenia (16%)

            Pruritus (16%)

            Chills (16%)

            Increased blood lactate dehydrogenase (16%)

            Decrease appetite (15%)

            Headache (15%)

            Infusion site pain (14%)

            Hypokalemia (12%)

            Prolonged QT (11%)

            Abdominal pain (11%)

            1-10%

            Hypotension (10%)

            Phlebitis (10%)

            Dizziness (10%)

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            Warnings

            Contraindications

            None

            Cautions

            Thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia may occur; monitor blood cell counts and modify dosage for hematologic toxicities (see Dosage Modifications)

            Serious and fatal infections (eg, pneumonia and sepsis) reported; do not administer if patient has an active infection

            May cause hepatic toxicity and liver function test abnormalities; monitor liver function tests before treatment and before each treatment cycle; omit or modify dosage for hepatic toxicities (see Dosage Modifications)

            Tumor lysis syndrome reported; monitor patients with advanced stage disease and/or high tumor burden and take appropriate precautions

            Nausea, vomiting, and diarrhea commonly occur and may require the use of antiemetic and antidiarrheal medications

            Can cause fetal harm when administered to a pregnant woman; advise women of potential harm to the fetus and to avoid pregnancy

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            Pregnancy & Lactation

            Pregnancy

            Based on mechanism of action, drug can cause teratogenicity and/or embryo-fetal lethality because it is genotoxic and targets actively dividing cells

            There are no available data on drug use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes; no animal reproduction studies conducted; advise pregnant women of potential risk to fetus

            Pregnancy testing is recommended for females of reproductive potential prior to initiating therapy

            Based on findings from animal studies, drug may impair male fertility; reversibility of effect on fertility is unknown

            Contraception

            • Females: Drug can cause embryo-fetal harm when administered to a pregnant woman; advise females of reproductive potential to use effective contraception during treatment with drug and for 6 months after last dose
            • Males: Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after last dose

            Lactation

            There are no data on presence of drug in human milk, effects on breastfed child, or on milk production; because of potential for serious adverse reactions in breastfed child, advise patients that breastfeeding is not recommended during treatment with and for 2 weeks after last dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Histone deacetylase (HDAC) inhibitor; HDACs catalyze the removal of acetyl groups from the lysine residues of histones and some nonhistone proteins

            In vitro, belinostat caused the accumulation of acetylated histones and other proteins, inducing cell cycle arrest and/or apoptosis of some transformed cells; shows preferential cytotoxicity towards tumor cells compared with normal cells

            Distribution

            Protein bound: 92.9-95.8%

            Limited tissue distribution

            Metabolism

            Primarily by UGT1A1 (80-90%); also CYP2A6, CYP2C9, CYP3A4

            Elimination

            Half-life: 1.1 hr

            Plasma clearance: 124 mL/min

            Excretion: 40% urine (as metabolites); <2% urine (unchanged)

            Pharmacogenomics

            UGT1A1 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity (eg, UGT1A1*28 polymorphism) ~20% of the black population, 10% of the white population, and 2% of the Asian population are homozygous for the UGT1A1*28 allele

            Because belinostat is primarily (80-90%) metabolized by UGT1A1, the clearance of belinostat could be decreased in patients with reduced UGT1A1 activity (eg, patients with UGT1A1*28 allele)

            Reduce initial dose in patients known to be homozygous for the UGT1A1*28 allele (see Dosage Modifications)

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            Administration

            IV Preparation

            Aseptically reconstitute each vial by adding 9 mL of sterile water for injection; resulting concentration is 50 mg/mL

            Swirl vial contents until there are no visible particles in the resulting solution

            Further dilute by withdrawing volume needed for the required dosage from reconstituted vial and transfer to a 250-mL infusion bag of 0.9 % NaCl

            Visually inspect the solution for particulate matter; do not use if cloudiness or particulates are observed

            IV Administration

            Connect the infusion bag containing drug solution to an infusion set with a 0.22-micron in-line filter for administration

            Infuse IV over 30 minutes

            May extend infusion time to 45 minutes if infusion site pain or other symptoms attributed to the infusion occur

            Cytotoxic agent; follow special handling and disposal procedures for antineoplastic drugs

            Storage

            Unreconstituted vials: Store at room temperature 20-25°C (68-77°F); excursions are permitted between 15-30°C (59-86°F); retain in original package until use

            Reconstituted vial: May store at ambient temperature (15-25°C; 59-77°F) for up to 12 hr

            Infusion bag with dose: May be stored at ambient room temperature (15-25°C; 59-77°F) for up to 36 hr, including infusion time

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.