(be LIN oh stat)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Beleodaq: 500 mg (1 ea)
Brand Names: U.S.
- Antineoplastic Agent, Histone Deacetylase (HDAC) Inhibitor
Belinostat is a histone deacetylase (HDAC) inhibitor which catalyzes acetyl group removal from protein lysine residues (of histone and some nonhistone proteins). Inhibition of histone deacetylase results in accumulation of acetyl groups, leading to cell cycle arrest and apoptosis. Belinostat has preferential cytotoxicity toward tumor cells versus normal cells.
~114 L/m2 (Steele 2011); mean volume of distribution approaches total body water
Hepatic; predominantly via UGT1A1, also by CYP2A6, CYP2C9, and CYP3A4 to the amide and acid metabolites
Urine (84.8% ± 9.8% over 168 hours, predominantly as metabolites; <2% as unchanged drug); feces (9.7% ± 6.5% over 168 hours)
Time to Peak
At end of infusion (Steele 2011)
~93% to 96%
Special Populations: Hepatic Function Impairment
Belinostat exposure is expected to be increased in hepatic impairment.
Use: Labeled Indications
Peripheral T-cell lymphoma, relapsed or refractory: Treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL).
There are no contraindications listed in the manufacturer's labeling.
Note: ANC should be ≥1,000/mm3 and platelets should be ≥50,000/mm3 prior to each cycle
Peripheral T-cell lymphoma, relapsed or refractory: IV: 1,000 mg/m2 daily on days 1 to 5 every 21 days until disease progression or unacceptable toxicity (O’Connor 2013)
Dosage adjustment for patients with reduced UGT1A1 activity: Reduce initial dose to 750 mg/m2 for patients known to be homozygous for UGT1A1*28 allele.
Refer to adult dosing.
Dosing: Renal Impairment
CrCl >39 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling. However, exposure is not altered; dosage adjustment is not likely necessary.
CrCl ≤39 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (data is insufficient to recommend a dose).
Dosing: Hepatic Impairment
Mild hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling (exposure is expected to be increased in hepatic impairment).
Moderate to severe hepatic impairment (total bilirubin >1.5 times ULN): There are no dosage adjustments provided in the manufacturer's labeling (data is insufficient to recommend a dose).
Dosing: Adjustment for Toxicity
Hematologic toxicity: ANC should be ≥1000/mm3 and platelets should be ≥50,000/mm3 prior to each cycle and prior to resuming treatment following a delay due to toxicity. Resume subsequent treatment according to the following parameters:
Platelets ≥25,000/mm3 and nadir ANC ≥500/mm3: No dosage adjustment necessary (continue treatment without modification).
Nadir ANC <500/mm3 and any platelet count: Reduce dose to 75% of the usual dose (to 750 mg/m2).
Platelets <25,000/mm3 and any nadir ANC: Reduce dose to 75% of the usual dose (to 750 mg/m2).
Recurrent nadir ANC <500/mm3 and/or recurrent nadir platelets <25,000/mm3 following 2 dosage reductions: Discontinue treatment.
Nonhematologic toxicity: Nonhematologic toxicities should be grade 2 or lower prior to retreatment. Resume subsequent treatment according to the following parameters:
Any grade 3 or 4 toxicity (except nausea, vomiting, or diarrhea): Reduce dose to 75% of the usual dose (to 750 mg/m2).
Recurrent grade 3 or 4 toxicity following 2 dosage reductions: Discontinue treatment.
Grade 3 or 4 nausea, vomiting, or diarrhea: Manage with supportive care; reduce the dose only if duration is >7 days with supportive management.
ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient's actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs, 2012).
Reconstitute each 500 mg vial with SWFI 9 mL to a concentration of 50 mg/mL. Swirl vial contents until there are no visible particles in the reconstituted solution. Further dilute the appropriate dose in NS 250 mL; do not use if cloudy or precipitate is present.
IV: Infuse over 30 minutes using a 0.22-micron inline filter; if infusion site pain or other symptoms associated with infusion occur, may increase infusion time to 45 minutes.
Store intact vials at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Retain in original package until use. The reconstituted solution may be stored for 12 hours at 15°C to 25°C (59°F to 77°F). Solutions diluted for infusion in NS may be stored for up to 36 hours (including infusion time) at 15°C to 25°C (59°F to 77°F).
Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination
Atazanavir: May increase the serum concentration of Belinostat. Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Cardiovascular: Peripheral edema (20%), prolonged Q-T interval on ECG (11%; grades 3/4: 4%)
Central nervous system: Fatigue (37%; grades 3/4: 5%), chills (16%; grades 3/4: 1%), headache (15%)
Dermatologic: Skin rash (20%; grades 3/4: 1%), pruritus (16%; grades 3/4: 3%)
Endocrine & metabolic: Increased lactate dehydrogenase (16%; grades 3/4: 2%), hypokalemia (12%; grades 3/4: 4%)
Gastrointestinal: Nausea (42%; grades 3/4: 1%), vomiting (29%; grades 3/4: 1%), constipation (23%; grades 3/4: 1%), diarrhea (23%; grades 3/4: 2%), decreased appetite (15%; grades 3/4: 2%), abdominal pain (11%; grades 3/4: 1%)
Hematologic & oncologic: Anemia (32%; grades 3/4: 11%), thrombocytopenia (16%; grades 3/4: 7%)
Local: Pain at injection site (14%)
Respiratory: Dyspnea (22%; grades 3/4: 6%), cough (19%)
Miscellaneous: Fever (35%; grades 3/4: 2%)
1% to 10%:
Cardiovascular: Hypotension (10%; grades 3/4: 3%), phlebitis (10%; grades 3/4: 1%)
Central nervous system: Dizziness (10%)
Infection: Infection (>2%)
Renal: Increased serum creatinine (>2%)
Respiratory: Pneumonia (>2%)
Miscellaneous: Multi-organ failure (>2%)
<1% (Limited to important or life-threatening): Hepatic failure, leukopenia, sepsis, tumor lysis syndrome, ventricular fibrillation
Concerns related to adverse effects:
• Bone marrow suppression: May cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and/or anemia. Monitor blood counts at baseline and weekly during treatment. May require dosage reduction, treatment delay, or discontinuation.
• Gastrointestinal toxicity: Nausea, vomiting, and diarrhea occur with belinostat; may require management with antiemetic and antidiarrheal medications. In a phase 1 study, nausea/vomiting generally occurred at the end of the infusion each day (rarely persisting beyond day 5 each cycle) and was managed with standard antiemetics (Steele 2011).
• Hepatotoxicity: May cause liver function test abnormalities and fatal hepatotoxicity. Monitor liver function tests at baseline and prior to each cycle. May require dosage reduction, treatment delay, or permanent discontinuation (based on the severity of the hepatotoxicity). Belinostat is metabolized hepatically and increased exposure is expected to occur in patients with hepatic impairment. Patients with moderate to severe hepatic impairment (total bilirubin >1.5 times ULN) were excluded from clinical studies.
• Infection: Serious infections (occasionally fatal), including pneumonia and sepsis, have occurred with treatment. Do not administer in patients with an active infection. Heavily pretreated patients (history of extensive or intensive prior chemotherapy) may be at higher risk for life-threatening infections.
• Tumor lysis syndrome: Tumor lysis syndrome (TLS) has been observed; closely monitor patients with advanced disease and/or high tumor burden. If TLS occurs, initiate appropriate treatment.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Reduced UGT1A1 activity: Belinostat is primarily metabolized by UGT1A1; the initial dose should be reduced in patients known to be homozygous for UGT1A1*28 allele.
Monitor CBC with platelets and differential at baseline and weekly; serum chemistries (including renal and hepatic functions tests) at baseline and before each cycle; monitor for signs/symptoms of gastrointestinal toxicity (eg, nausea, vomiting, diarrhea), tumor lysis syndrome, and infection.
Pregnancy Risk Factor
Animal reproduction studies have not been conducted. Belinostat is a genotoxic drug that targets dividing cells; embryofetal toxicity is expected if exposure occurs during pregnancy. Based on animal data, belinostat may also impair male fertility. Women of reproductive potential should avoid pregnancy during treatment with belinostat.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience constipation, headache, lack of appetite, injection site pain, or abdominal pain. Have patient report immediately to prescriber signs of infection, signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), severe dizziness, passing out, abnormal heartbeat, pale skin, severe nausea, severe vomiting, severe diarrhea, shortness of breath, swelling of arms or legs, severe loss of strength and energy, or signs of tumor lysis syndrome (tachycardia or abnormal heartbeat; any passing out; urinary retention; muscle weakness or cramps; nausea, vomiting, diarrhea or lack of appetite; or feeling sluggish) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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- Drug class: histone deacetylase inhibitors
Other brands: Beleodaq