Names and pronunciation
(beh-lih′noh-stat′) Beleodaq
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Drug reference
(beh-lih′noh-stat′) Beleodaq
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Func. class.: Antineoplastic-biologic response modifier
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Chem. class.: Histone deacetylase inhibitor
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Do not confuse: belinostat/beractant
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ACTION: A class I and II inhibitor of the histone deacetylase (HDAC) enzymes. Overexpression of HDACs is present in some cancer cells. HDAC inhibitors have been shown to activate differentiation, inhibit the cell cycle, and induce apoptosis
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USES: For the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL)
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CONTRAINDICATIONS: Hyper- sensitivity, pregnancy Precautions: Hematologic toxicity (throm- bocytopenia, leukopenia, neutropenia, lym- phopenia, anemia), serious infections (pneumonia, sepsis), fatal hepatic toxicity, tumor lysis syndrome (TLS), breastfeeding
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SIDE EFFECTS CNS: Fatigue, headache, dizziness, fever, chills CV: Hypotension, QT prolongation GI: Constipation, anorexia, abdomi- nal pain, nausea, vomiting, diarrhea, hepatotoxicity HEMA: Anemia, thrombocytopenia, neu- tropenia RESP: Dyspnea, cough INTEG: Injection site reactions, rash, phlebitis MISC: Hypokalemia SYST: Multiorgan failure, tumor lysis syn- drome (TLS), serious infections
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INTERACTIONS Increase: belinostat—strong UGT1A1 inhibitors (atazanavir, indinavir); avoid concurrent use if possible Increase: QT prolongation—drugs that prolong QT, assess often Drug/Lab Increase: creatinine, LDH Decrease: platelets, neutrophils, RBC, potassium
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DOSAGE AND ROUTES • Adult: IV 1000 mg/m2 over 30 min on days 1-5 q21days. Reduce the dose to 750 mg/m2 in those who are homozygous for the UGT1A1∗28 allele. Cycles should be repeated until disease progression or unacceptable toxicity
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Available forms: Powder for injection 500 mg (single-use vial)
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Administer: Intermittent IV route • Reconstitution: Add 9 mL of sterile wa- ter for injection/500 mg, swirl until there are no visible particles (50 mg/mL); stable at room temperature for up to 12 hr • Withdraw amount from the reconstituted vial and further dilute in 250 mL 0.9% so- dium chloride for injection, the final solution is stable at room temperature for up to 36 hr, including infusion time; use a 0.22-micron in-line filter; give over 30 min; if pain occurs at infusion site, run over 45 min Dose adjustments due to treatment-related toxicity Hematologic toxicities: • Do not begin the next cycle until the neutrophil count (ANC) is ≥1000/mm3 and platelet count ≥50,000/mm3 • ANC nadir ≥500/mm3 and platelet count nadir ≥25,000/mm3: no dose adjustment • ANC nadir <500/mm3 (any platelet count): begin next cycle of treatment at a reduced dose of 750 mg/m2 • Platelet nadir <25,000/mm3 (any ANC): begin next cycle of treatment at a reduced dose of 750 mg/m2
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Assess: • Hematologic toxicity (thrombocytope- nia, leukopenia, neutropenia, lymphope- nia, anemia): monitor CBC before starting and every week. Dose modifications may be necessary in patients with bone marrow sup- pression and should be determined by the ANC and platelet count nadirs of the previous cycle. Platelet counts should be ≥50,000/mm3 and ANC >1000/mm3 before starting each cycle • Serious infections (pneumonia, sepsis): may be fatal. Do not use in those with an active infection. Use caution in patients with a history of extensive or in- tensive chemotherapy, as they may be at higher risk of life-threatening infections; monitor for dyspnea, cough, characteris- tics of sputum • Fatal hepatic toxicity: monitor LFTs before the start of each cycle. Those with signs of hepatic disease may require dose modification or discontinuation • Tumor lysis syndrome (TLS): those with high tumor burden or advanced- stage disease are at greater risk for de- velopment of TLS; consider tumor lysis prophylaxis with antihyperuricemic agents and hydration beginning 12-24 hr before treatment; for TLS treatment, ad- minister aggressive IV hydration, antihy- peruricemic agents, correct electrolyte abnormalities, and monitor renal function • Renal studies: monitor BUN/creatinine periodically; if renal disease is present, use cautiously • Pregnancy/breastfeeding: consider discontinuing breastfeeding; identify whether the patient is pregnant before using; do not use if pregnant
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Evaluate: • Therapeutic response: prevention of spread of disease
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To avoid use in breastfeeding; not to use in pregnancy; that fertility may be impaired • To report infusion site reactions, rash, severe constipation or diarrhea, abdomi- nal pain, nausea, vomiting • Bleeding: to report increased bruising, bleeding, melanotic or dark tarry stools • Tumor lysis syndrome: to report im- mediately fatigue, dark urine, nausea, weakness, confusion, change in heart rate • Infection: to report sore throat, cough, trouble breathing, flulike symptoms • Hepatic toxicity: to report dark urine, anorexia, yellow skin/eyes, itching, ab- dominal pain • That compliance is needed with prod- uct and lab testing
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PHARMACOKINETICS Half-life of 1.1 hr; 92.9%-95.8% protein bound, 80%-90% metabolized by hepatic UGT1A1; metabolized in the liver, 40% excreted renally, primarily as metabolites; onset, peak, duration unknown
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• Adult: IV 1000 mg/m2 over 30 min on days 1-5 q21days. Reduce the dose to 750 mg/m2 in those who are homozygous for the UGT1A1∗28 allele. Cycles should be repeated until disease progression or unacceptable toxicity
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