DUVYZAT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DUVYZAT (DUVYZAT).
Vorinostat inhibits histone deacetylases (HDACs), leading to accumulation of acetylated histones and non-histone proteins, which induces cell cycle arrest, differentiation, and apoptosis in malignant cells.
| Metabolism | Primarily metabolized by glucuronidation via UGT2B17 and UGT2B7; minor metabolism by CYP2C9 and CYP3A4. |
| Excretion | Primarily renal (70% unchanged) with 30% biliary/fecal |
| Half-life | 12 hours; clinically requires dose adjustment in renal impairment |
| Protein binding | 95% bound to albumin |
| Volume of Distribution | 0.8 L/kg; distributes into total body water |
| Bioavailability | Oral: 80% |
| Onset of Action | Oral: 1-2 hours |
| Duration of Action | 24 hours; once-daily dosing maintains therapeutic effect |
DUVYZAT is administered orally at a dosage of 7.5 mg twice daily.
| Dosage form | SUSPENSION |
| Renal impairment | For GFR 30-59 mL/min: reduce dose to 3.75 mg twice daily. For GFR 15-29 mL/min: reduce dose to 2.5 mg twice daily. For GFR <15 mL/min or on dialysis: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose to 3.75 mg twice daily. Child-Pugh Class C: not recommended. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established; no recommended dosage. |
| Geriatric use | No specific dose adjustment is required based on age alone; consider renal function and overall clinical status as elderly patients may have decreased renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DUVYZAT (DUVYZAT).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. In animal studies, drug-related material was present in milk. Due to potential for serious adverse reactions, breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose. M/P ratio unknown. |
| Teratogenic Risk | DUVYZAT (zamivatinib) is a kinase inhibitor. Based on its mechanism of action and animal studies, there is a potential risk of fetal harm. In pregnant rats, embryolethality, reduced fetal weight, and skeletal abnormalities were observed at maternal exposures below the clinical dose. Human data are insufficient. Use is contraindicated in pregnancy. First trimester: risk of structural anomalies. Second and third trimesters: risk of fetal growth restriction and potential oligohydramnios due to VEGF signaling inhibition. |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
Hypersensitivity to vorinostat or any component of the formulation.
| Precautions | Pulmonary embolism, deep vein thrombosis, thrombocytopenia, anemia, gastrointestinal toxicities (nausea, vomiting, diarrhea), hyperglycemia, hypotension, and QT prolongation. |
| Food/Dietary | No significant food interactions. May be taken with or without food. Avoid grapefruit juice if concomitant use of certain CYP3A4 substrates due to potential interaction, but no specific restriction for DUVYZAT itself. |
| Clinical Pearls |
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| Fetal Monitoring | Prior to initiating therapy, conduct pregnancy testing in females of reproductive potential. Monitor for hypertension, proteinuria, left ventricular dysfunction, and signs of fetal compromise. In pregnancy, serial ultrasound monitoring for fetal growth and amniotic fluid volume is recommended. Monitor maternal blood pressure and cardiac function regularly. |
| Fertility Effects | Based on animal studies and mechanism (VEGF inhibition), DUVYZAT may impair male and female fertility. In female rats, disruption of estrous cycle and ovarian function was observed. In male rats, testicular degeneration occurred. Reversibility of effects is uncertain. Human data are lacking. |
| DUVYZAT (vadadustat) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) used for anemia in chronic kidney disease (CKD). Monitor hemoglobin every 2 weeks until stable; target 10-12 g/dL. Avoid in patients with known history of thrombosis, active malignancy, or severe hepatic impairment. Contraindicated with concomitant use of strong CYP2C8 inhibitors (e.g., gemfibrozil). Dose adjustment required if switching from erythropoiesis-stimulating agents. |
| Patient Advice | Take DUVYZAT exactly as prescribed, usually once daily with or without food. · Do not take with strong CYP2C8 inhibitors like gemfibrozil; inform your doctor of all medications. · Report unusual bleeding, bruising, or signs of blood clots (leg pain, chest pain, shortness of breath). · Attend regular blood tests to monitor hemoglobin levels. · Do not use if you have active cancer or a history of blood clots. · Store at room temperature away from moisture and light. |