Beleodaq

Name: Beleodaq

Beleodaq Interactions

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Other drugs may interact with belinostat, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Manufacturer

  • Spectrum Pharmaceuticals, Inc.

Beleodaq and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Beleodaq crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Beleodaq.

Dosing & Uses

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

What should I discuss with my healthcare provider before receiving belinostat?

You should not use belinostat if you are allergic to it, or if you have:

  • an active infection.

To make sure belinostat is safe for you, tell your doctor if you have:

  • liver disease;

  • kidney disease; or

  • if you have received high-dose or intensive chemotherapy in the past.

Do not use belinostat if you are pregnant. It could harm the unborn baby. Use effective birth control to prevent pregnancy, and tell your doctor if you become pregnant during treatment.

It is not known whether belinostat passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Beleodaq Pharmacokinetics

Distribution

Extent

Not known whether belinostat is distributed into milk.1

Plasma Protein Binding

92.9–95.8%.1

Special Populations

Systemic exposure not affected by Clcr >39 mL/minute.1

Elimination

Metabolism

Extensively metabolized in the liver, principally (80–90%) by UGT1A1.1 Also metabolized to belinostat amide and belinostat acid by CYP2A6, 2C9, and 3A4; enzymes responsible for conversion to methyl belinostat and 3-ASBA not determined to date.1

Elimination Route

Main circulating metabolites are excreted in urine; 2 metabolites (3-ASBA and belinostat glucuronide) predominate (4.61 and 30.5% of dose, respectively).1

Minimally (<2%) excreted in urine as unchanged drug.1

Half-life

1.1 hours (over dosage range of 150–1200 mg/m2).1

Special Populations

In patients with genetic polymorphisms associated with reduced UGT1A1 activity (e.g., individuals homozygous for the UGT1A1*28 allele), clearance may be reduced.1

Actions

  • Inhibits enzymatic activity of histone deacetylases and exhibits cytotoxic activity and induces apoptosis in various tumor cell lines at nanomolar concentrations;1 5 9 HDAC enzymes catalyze the removal of acetyl groups from the lysine residues of proteins, including histones and transcription factors.1 5 6 7 8

  • Overexpression of HDAC enzymes or aberrant recruitment of HDAC enzymes to oncogenic transcription factors causing hypoacetylation of core nucleosomal histones observed in some cancer cells.7 8

  • Hypoacetylation of histones is associated with a condensed chromatin structure and repression of gene transcription.6 7 8

  • Inhibition of HDAC activity allows for accumulation of acetyl groups on the histone lysine residues, resulting in an open chromatin structure and transcriptional activation.7 8

  • In vitro, causes accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells.1

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Belinostat

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion

500 mg

Beleodaq

Spectrum

Uses of Beleodaq

  • It is used to treat T-cell lymphoma.

What are some things I need to know or do while I take Beleodaq?

  • Tell all of your health care providers that you take Beleodaq. This includes your doctors, nurses, pharmacists, and dentists.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
  • You may have more of a chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu. Some infections have been very bad and even deadly.
  • If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.
  • Use birth control that you can trust to prevent pregnancy while taking this medicine.
  • This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking Beleodaq, call your doctor right away.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

What happens if I overdose?

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Beleodaq side effects

Get emergency medical help if you have any signs of an allergic reaction to Beleodaq: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • severe or continued vomiting or diarrhea;

  • fever, chills, flu symptoms, swollen gums, painful mouth sores, pain when swallowing, skin sores;

  • stabbing chest pain, wheezing, trouble breathing, cough with yellow or green mucus;

  • pain or burning when you urinate;

  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

  • liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

  • signs of tumor cell breakdown--lower back pain, blood in your urine, little or no urinating; numbness or tingly feeling around your mouth; muscle weakness or tightness; fast or slow heart rate, weak pulse, feeling short of breath; confusion, fainting.

Common Beleodaq side effects may include:

  • nausea, vomiting;

  • fever;

  • tired feeling; or

  • anemia (low red blood cells)--pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Renal Dose Adjustments

Data not available

Other Comments

Administration advice:
-Preparation, handling, and disposal of this drug should be performed in a manner consistent with safe procedures for cytotoxic agents.

Reconstitution/preparation techniques:
-The manufacturer product information should be consulted.

Monitoring:
-Monitor for thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia during therapy; modify treatment as necessary.
-Perform liver function tests before treatment and before the start of each treatment cycle. Modify, interrupt, or discontinue treatment as necessary.
-Monitor patients with advanced stage disease and/or high tumor burden; take proper precautions and treat as appropriate.

Patient advice:
-Treatment can lower blood counts, lower resistance to infection, and cause liver problems. Contact your doctor immediately if you experience significant fatigue, unusual bleeding or bruising, fever, or yellowing of the skin/whites of the eyes.
-Fetal harm may occur with this drug; avoid pregnancy during treatment. If pregnancy occurs, contact your doctor immediately.
-Nausea, vomiting, and diarrhea are common with this drug. Contact your doctor for help in treating these side effects.

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