BELEODAQ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BELEODAQ (BELEODAQ).
Belinostat is a histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDACs, leading to accumulation of acetylated histones and non-histone proteins, resulting in cell cycle arrest and apoptosis in cancer cells.
| Metabolism | Belinostat is metabolized primarily by UGT1A1, with minor contribution from CYP2A6, CYP2C19, and CYP3A4. |
| Excretion | Primarily hepatic metabolism with subsequent biliary excretion; less than 10% of the dose recovered unchanged in urine. |
| Half-life | Terminal elimination half-life approximately 13 hours (range 10-18 hours) based on population pharmacokinetic analysis; supports once-daily dosing. |
| Protein binding | Greater than 90% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution at steady state (Vss) approximately 2000 L (range 1000-4000 L) indicating extensive tissue distribution. |
| Bioavailability | Not applicable (intravenous administration only). |
| Onset of Action | Intravenous administration: clinical response observed after 1-2 cycles (each cycle is 21 days) of treatment. |
| Duration of Action | Duration of response varies; median duration of response in clinical trials was approximately 4-8 months for peripheral T-cell lymphoma. |
1000 mg/m2 intravenously over 30 minutes on days 1-5 of a 21-day cycle.
| Dosage form | POWDER |
| Renal impairment | For GFR 40-59 mL/min: reduce dose to 750 mg/m2. For GFR <40 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 750 mg/m2. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; monitor for toxicity due to potential age-related renal or hepatic impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BELEODAQ (BELEODAQ).
| Breastfeeding | No data available on the presence of belinostat in human milk, its effects on the breastfed infant, or its effects on milk production. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for at least 2 weeks after the last dose. |
| Teratogenic Risk | Based on its mechanism of action (histone deacetylase inhibitor) and animal studies, BELEODAQ is expected to cause fetal harm. There are no adequate and well-controlled studies in pregnant women. Avoid use during pregnancy; advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Severe hepatic impairment (Child-Pugh class C)","Hypersensitivity to belinostat or any component of the formulation"]
| Precautions | ["Hepatotoxicity: Elevated liver enzymes and bilirubin; monitor liver function tests before and during treatment.","Embryofetal toxicity: Can cause fetal harm; advise women of reproductive potential of effective contraception.","Tumor lysis syndrome: Monitor for signs and discontinue treatment if severe.","Gastrointestinal toxicity: Nausea, vomiting, diarrhea; provide antiemetics and supportive care.","Bone marrow suppression: Thrombocytopenia, neutropenia, anemia; monitor blood counts."] |
| Food/Dietary | Grapefruit and grapefruit juice should be avoided due to potential CYP3A4 inhibition, which may increase belinostat concentrations. No other specific food interactions are established. Maintain adequate hydration (2-3 L/day) to reduce risk of tumor lysis syndrome. No restrictions on alcohol but caution due to potential hepatotoxicity. |
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| Fetal Monitoring | If used during pregnancy or if patient becomes pregnant while receiving BELEODAQ, apprise the patient of the potential hazard to the fetus. Monitor pregnancy status in females of reproductive potential. Perform routine blood counts and liver function tests, as belinostat can cause myelosuppression and hepatotoxicity. |
| Fertility Effects | Based on animal studies, BELEODAQ may impair fertility in females and males of reproductive potential. Recommend fertility preservation counseling before treatment. |
| Clinical Pearls | BELEODAQ (belinostat) is a histone deacetylase (HDAC) inhibitor indicated for relapsed or refractory peripheral T-cell lymphoma (PTCL). Administer as a 30-minute IV infusion. Premedicate with antiemetics (e.g., ondansetron) to reduce nausea/vomiting. Monitor liver function tests (LFTs), electrolytes, and blood counts closely; dose reduction or discontinuation may be required for hepatotoxicity or cytopenias. QT prolongation risk: obtain baseline ECG and monitor electrolytes; avoid use in patients with significant QTc >500 ms. Infusion reactions may occur; slow infusion rate if needed. Ensure adequate hydration and consider uricosuric agents for tumor lysis syndrome prophylaxis. BELEODAQ carries a risk of severe and fatal hepatotoxicity; interrupt therapy if AST/ALT >3x ULN or total bilirubin >2x ULN. |
| Patient Advice | Take antiemetics as prescribed before each infusion to prevent nausea and vomiting. · Avoid alcohol and limit intake of raw or undercooked foods to reduce infection risk due to neutropenia. · Report signs of liver problems (jaundice, dark urine, nausea, abdominal pain) immediately. · Use effective contraception during treatment and for at least 4 weeks after the last dose. · Avoid grapefruit and grapefruit juice during treatment as they may interact. · Inform your healthcare provider of all medications, especially blood thinners, antiarrhythmics, and other QT-prolonging drugs. |