ROMIDEPSIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ROMIDEPSIN (ROMIDEPSIN).
Romidepsin is a histone deacetylase (HDAC) inhibitor that inhibits HDAC1 and HDAC2, leading to accumulation of acetylated histones and other proteins, resulting in cell cycle arrest and apoptosis in malignant cells.
| Metabolism | Primarily metabolized by CYP3A4, with minor contributions from CYP3A5, CYP1A1, and CYP2B6. It is also a substrate of P-glycoprotein. |
| Excretion | Primarily hepatic metabolism, with <1% excreted unchanged in urine. Biliary/fecal excretion accounts for ~25% of total clearance. |
| Half-life | Terminal elimination half-life is approximately 3 hours (range 1–5 hours), supporting continuous infusion or repeated dosing schedules. |
| Protein binding | Approximately 92–94% bound to human plasma proteins, primarily albumin and α1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution (Vd) is >1000 L (approximately 1130–1350 L), indicating extensive tissue binding and distribution. |
| Bioavailability | Intravenous: 100% bioavailability; no oral formulation available. |
| Onset of Action | Intravenous: Onset within 1–2 hours, with peak plasma concentrations at end of infusion (4-hour infusion). |
| Duration of Action | Duration of pharmacodynamic effect (e.g., histone acetylation) persists for 24–48 hours despite short half-life, allowing weekly dosing. |
14 mg/m2 intravenously over 4 hours on days 1, 8, and 15 of a 28-day cycle.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for creatinine clearance ≥30 mL/min. Insufficient data for CrCl <30 mL/min or ESRD. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce initial dose to 10 mg/m2. Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no specific dosing guidelines available. |
| Geriatric use | No specific dose adjustment required; monitor for increased toxicity due to age-related organ function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ROMIDEPSIN (ROMIDEPSIN).
| Breastfeeding | No data available on romidepsin excretion in human milk. Due to potential for serious adverse reactions in nursing infants (e.g., myelosuppression, gastrointestinal toxicity), breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose. M/P ratio unknown. |
| Teratogenic Risk | Romidepsin is a histone deacetylase inhibitor classified as Pregnancy Category D. Based on animal studies and its mechanism of action, there is evidence of fetal harm. In the first trimester, there is a high risk of teratogenicity including structural abnormalities and embryolethality. In the second and third trimesters, there is risk of fetal growth restriction, oligohydramnios, and potential adverse effects on fetal hematopoiesis and central nervous system development. Use is contraindicated in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
Romidepsin can cause fatal or life-threatening adverse reactions including cytopenias (thrombocytopenia, neutropenia, anemia) and infections. Monitor blood counts and for signs of infection.
| Serious Effects |
Hypersensitivity to romidepsin or any component of the formulation; concurrent use with strong CYP3A4 inhibitors (e.g., ketoconazole) due to increased risk of QT prolongation and other toxicities.
| Precautions | Bone marrow suppression (thrombocytopenia, neutropenia, lymphopenia, anemia); infections; cardiac toxicities (QT prolongation, arrhythmias); tumor lysis syndrome; hepatotoxicity; nausea, vomiting, and diarrhea; embryo-fetal toxicity; use in pregnancy may cause fetal harm. |
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| Fetal Monitoring | Monitor complete blood counts (CBC) with differential and platelets at baseline and weekly during treatment due to myelosuppression. Assess liver function tests (ALT, AST, bilirubin) and renal function (serum creatinine) periodically. Monitor electrocardiogram (ECG) for QTc prolongation. In pregnant patients, monitor fetal growth and amniotic fluid volume by ultrasound. Assess for signs of infection or bleeding. |
| Fertility Effects | Romidepsin may impair male and female fertility based on animal studies showing testicular degeneration, reduced spermatogenesis, and ovarian atrophy. Human data are limited; advise patients of potential for reduced fertility and consider fertility preservation before treatment. |