belinostat

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Primarily metabolized by the liver via the UGT1A1 enzyme system with minor metabolism by other systems; <2% excreted unchanged in urine.

Half-Life: 1.1 hr.

Time/Action Profile ⬆ ⬇

(response)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	12 mo

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Severe renal impairment;
Severe hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Advanced stage disease/large tumor burden (↑ risk of tumor lysis syndrome);
Patients who are homozygous for UGT1A1*28 allele (↓ dose);
Moderate renal impairment (↓ dose);
Moderate hepatic impairment (↓ dose);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, peripheral edema, phlebitis

Derm: pruritus, rash

F and E: hypokalemia

GI: nausea, vomiting, abdominal pain, constipation, diarrhea, HEPATOTOXICITY

GU: ↓fertility (men), ↑serum creatinine

Hemat: leukopenia, ANEMIA, THROMBOCYTOPENIA

Local: infusion site pain

Metab: ↓appetite

Neuro: fatigue, dizziness, headache

Resp: cough

Misc: chills, tumor lysis syndrome, fever, INFECTION

Interactions ⬆ ⬇

Drug-drug:

UGT1A1 inhibitors, including atazanvir , may ↑ levels and risk of toxicity; avoid concurrent use. If concurrent use unavoidable, ↓ belinostat dose.

Route/Dosage ⬆ ⬇

IV (Adults ): 1000 mg/m²once daily on Days 1–5 of a 21-day cycle. Cycles may be repeated until disease progression or unacceptable toxicity. Patients homozygous for UGT1A1*28 allele: 750 mg/m² on Days 1–5 of a 21-day cycle. Cycle may be repeated until disease progression or unacceptable toxicity. Concurrent use of UGT1A1 inhibitor: ↓belinostat dose by 25%.

Renal Impairment

IV (Adults ): CCr 30–<60 mL/min: 500 mg/m²once daily on Days 1–5 of a 21-day cycle. Cycles may be repeated until disease progression or unacceptable toxicity.

Hepatic Impairment

IV (Adults ): Moderate hepatic impairment (total bilirubin >1.5–3 times upper limit of normal and any AST level): 500 mg/m²once daily on Days 1–5 of a 21-day cycle. Cycles may be repeated until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Lyophilized powder for injection: 500 mg/vial

Assessment ⬆ ⬇

Monitor for signs and symptoms of infections (fever, chills, dyspnea, cough). Do not administer belinostat in patients with active infections.
Assess for signs and symptoms of tumor lysis syndrome (malaise, tachycardia, hypotension, confusion, delirium, arthralgia, myalgia, muscle spasms or twitches, paresthesia, headache, dizziness, nausea, vomiting, dark urine) in patients with advanced stage disease and/or with high tumor burden. Supportive therapy may be necessary based on severity.
Monitor for nausea, vomiting, and diarrhea. May require antiemetics and antidiarrheals. If Grade 3–4 nausea, vomiting, or diarrhea >7 days despite supportive management occurs, hold belinostat and resume with a ↓ in dose of 25% only when the toxicity is ≤Grade 2.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- Monitor liver function tests before therapy and at start of each cycle.
- Monitor renal function before therapy and at start of each cycle.
- May cause thrombocytopenia, leukopenia, and/or anemia. Monitor CBC at baseline and weekly during therapy. ANC should be ≥1.0 × 10⁹/L and platelet count ≥50 × 10⁹/L prior to each cycle and prior to resuming therapy following toxicity. Discontinue belinostat in patients who have recurrent ANC nadirs <0.5 × 10⁹/L and/or recurrent platelet count nadirs <25 × 10⁹/L after two dose ↓.
- If platelet count ≥25 × 10⁹/L and nadir ANC ≥0.5 × 10⁹/L, continue therapy. If nadir ANC <0.5 × 10⁹/L with any platelet count or platelet count <25 × 10⁹/L with any nadir ANC, ↓ dose by 25% to 750 mg/m².
- Nonhematologic toxicities must be ≤Grade 2 prior to therapy. If any Grade 3 or 4 adverse reaction occurs,↓ dose by 25%; if toxicity is nausea, vomiting, and diarrhea only, ↓ dose if duration is >7 days with supportive care. After two dose reductions for Grade 3 or 4 toxicities, permanently discontinue belinostat.

Implementation ⬆ ⬇

Use double gloves and a protective gown to prepare and administer. If possible, prepare in a biologic safety cabinet or a compounding aseptic containment isolator; eye, face, and respiratory protection may be needed. Prepare and administer in a closed-system drug transfer device. During administration, if there is a potential that the substance could splash or if the patient may resist, use eye and face protection. Discard IV equipment in specially designated containers.

IV Administration:

Intermittent Infusion: Reconstitution: Reconstitute each vial of belinostat by adding 9 mL sterile water for injection into vial. Swirl until no particles are visible. Reconstituted solution may be stored at room temperature for up to 12 hr. Concentration: 50 mg/mL. Diluent: Withdraw volume needed and inject into 250 mL of 0.9% NaCl. Diluted solution may be kept at room temperature for up to 36 hr. Do not use solutions that are cloudy or contain a precipitate. Infuse through a 0.22-micron in-line filter.
Rate: Infuse over 30 min. If infusion site pain or other infusion-related symptoms occur, extend infusion to 45 min.
Y-Site Incompatibility: Do not administer other drugs through same IV line.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of belinostat. Instruct patient to read the Patient Information sheet prior to starting therapy and with each cycle in case of changes.
Advise patient to notify health care professional if signs and symptoms of low platelet counts (unusual bleeding and bruising), low red blood cell count (weakness, tiredness, pale skin, dyspnea), infection (fever, flu-like symptoms, cough, shortness of breath, burning with urination, muscle aches, worsening skin problems), or liver problems (yellowing of skin and whites of eyes, dark urine, itching, pain in upper right stomach area) occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products.
Emphasize the need for periodic lab tests to monitor for side effects.
Rep: Advise women of reproductive potential to use effective contraception during therapy and for 6 mo after last dose and to avoid breastfeeding during therapy and for 2 wk after last dose. Advise men with female partners of reproductive potential to use effective contraception during therapy and for 3 mo after last dose. May impair male fertility.

Evaluation/Desired Outcomes ⬆ ⬇

Decreased spread of relapsed/refractory of peripheral T-cell lymphoma.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

54893- MSN Laboratories Private Limited
- 54893-0074-
  - 54893-0074-4- 20 kg in 1 DRUM (54893-0074-4)

65392- Curia New York, Inc.
- 65392-2509-
  - 65392-2509-0- 20 kg in 1 DRUM (65392-2509-0)

72893- Acrotech Biopharma Inc
- 72893-002- Beleodaq
  - 72893-002-01- 1 VIAL in 1 CARTON (72893-002-01) / 10 mL in 1 VIAL

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇