General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Genetic Implications:

Pronunciation:
be-lin-o-stat

Trade Name(s)

• Beleodaq

Ther. Class.

antineoplastics

Pharm. Class.

histone deacetylase inhibitors

Indications

Relapsed/refractory peripheral T-cell lymphoma.

Action

Acts as a histone deacetylase inhibitor, produces accumulation of acetylated histones and other proteins resulting in cell cycle arrest/apoptosis of cells; may have affinity for tumor cells.

Therapeutic Effect(s):

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

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism and 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)

Contraindication/Precautions

Contraindicated in:

• OB:  Pregnancy;
• Lactation: Lactation.

Use Cautiously in:

• Advanced stage disease/large tumor burden (↑ risk of tumor lysis syndrome);
•   Patients with UGT1A1*28 polymorphism (initial dose ↓ required);
• Moderate or severe renal impairment (CCr <39 mL/min);
• Moderate/severe hepatic impairment;
• Rep:  Women of reproductive potential and men with female partners of reproductive potential;
• Pedi:  Safety and effectiveness not established in children.

Adverse 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 (males), ↑ serum creatinine

Hemat: LEUKOPENIA, ANEMIA, THROMBOCYTOPENIA

Local: infusion site pain

Metabolic: ↓ appetite

Neuro: fatigue, dizziness, headache

Resp: cough

Misc: chills, TUMOR LYSIS SYNDROME, fever, INFECTION

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

Concurrent use of  strong inhibitors of UGT1A1, including  atazanvir  and  gemfibrozil, may ↑ levels and risk of serious toxicity; avoid concurrent use.

Route/Dosage

 IV (Adults): 1000 mg/m² /day on days 1–5 of a 21-day cycle. Cycle may be repeated until disease progression or unacceptable toxicity.  Patients with UGT1A1*28 polymorphism: 750 mg/m²  on days 1–5 of a 21-day cycle. Cycle 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 in patients with advanced stage disease and/or with high tumor burden.
• Monitor for nausea, vomiting, and diarrhea. May require antiemetics and antidiarrheals.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.

• 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 in patients who have recurrent ANC nadirs <0.5 × 10⁹ /L and/or recurrent platelet count nadirs <25 × 10⁹ /L after two dose reductions.
• If platelet count ≥25 x 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 .
• Other toxicities must be NCI-CTCAE Grade 2 or less prior to therapy. Any Grade 3 or 4 adverse reaction, ↓ dose by 25%; if toxicity is nausea, vomiting, and diarrhea only, ↓ dose if duration is >7 days with supportive care.
• May cause hepatotoxicity. Monitor liver function tests before therapy and at start of each cycle. Interrupt or adjust dose until recovery or permanently discontinue if severe.

Implementation

• Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers.

Patient/Family Teaching

• 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.
• Rep:  Advise females of reproductive potential to use effective contraception during and for 6 mo after last dose and to avoid breastfeeding during and for 2 wk after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for 3 mo after last dose. May impair male fertility.
• Emphasize the need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

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