ZOLINZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZOLINZA (ZOLINZA).
Histone deacetylase (HDAC) inhibitor; inhibits class I and II HDAC enzymes, leading to accumulation of acetylated histones and non-histone proteins, inducing cell cycle arrest and apoptosis in malignant cells.
| Metabolism | Primarily metabolized via reduction, hydrolysis, and glucuronidation; involved enzymes include CYP450 system (minor), carbonyl reductases, and UDP-glucuronosyltransferases. |
| Excretion | Zolinza (vorinostat) is primarily metabolized via glucuronidation and hydrolysis; renal excretion of unchanged drug is minimal (<1%). Approximately 52% of the dose is recovered in urine as metabolites, and about 43% in feces as metabolites and parent drug. |
| Half-life | The terminal elimination half-life is approximately 2 hours. Due to its short half-life, vorinostat requires twice-daily dosing to maintain therapeutic concentrations. |
| Protein binding | Approximately 71% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | The apparent volume of distribution is approximately 17 L (about 0.24 L/kg for a 70 kg adult), indicating limited extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 70% with moderate interindividual variability; food does not significantly affect absorption. |
| Onset of Action | Oral administration: clinical response (e.g., reduction in cutaneous T-cell lymphoma lesions) is typically observed within 4 to 8 weeks of continuous dosing. |
| Duration of Action | The duration of action is approximately 4 to 6 hours after a single oral dose, based on the half-life and pharmacodynamic effects on histone acetylation. With twice-daily dosing, sustained inhibition of histone deacetylase is achieved. |
400 mg orally once daily with food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): 300 mg once daily. Moderate to severe hepatic impairment (Child-Pugh B or C): not recommended. |
| Pediatric use | Safety and efficacy not established; no recommended dose. |
| Geriatric use | No specific dose adjustment recommended; however, elderly patients may have increased risk of thrombocytopenia and gastrointestinal events; monitor closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZOLINZA (ZOLINZA).
| Breastfeeding | It is unknown whether vorinostat is excreted in human breast milk. However, due to the potential for serious adverse reactions in nursing infants, women should not breastfeed while taking ZOLINZA and for at least 2 weeks after the last dose. The milk-to-plasma ratio (M/P) is not available. |
| Teratogenic Risk | ZOLINZA (vorinostat) is a histone deacetylase inhibitor. Based on animal studies and its mechanism of action, it can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, vorinostat was embryotoxic and caused teratogenic effects including fetal malformations. There are no adequate and well-controlled studies in pregnant women. First trimester exposure carries the highest risk of major congenital malformations. Second and third trimester exposure may increase risk of adverse effects on fetal growth and development. ZOLINZA should be avoided during pregnancy unless the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
No FDA black box warning for this drug.
| Serious Effects |
["Severe hepatic impairment","Pregnancy"]
| Precautions | ["Pulmonary embolism and deep vein thrombosis","Hematologic toxicity (thrombocytopenia, anemia, neutropenia)","Gastrointestinal toxicity (nausea, vomiting, diarrhea)","QT interval prolongation","Hepatic impairment","Fetal harm"] |
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| Fetal Monitoring | If ZOLINZA is used during pregnancy, pregnant women should be monitored for potential fetal harm. Consider ultrasound monitoring for fetal growth and development. Monitor for signs of adverse effects including gastrointestinal toxicity, thrombocytopenia, and anemia. Pregnancy testing should be performed prior to initiation in women of reproductive potential. |
| Fertility Effects | Based on animal studies, vorinostat may impair fertility in males and females. In male rats, decreased testicular weight and impaired spermatogenesis were observed. In female rats, decreased implantation and increased preimplantation loss were noted. The effects on human fertility are unknown. Advise patients of potential risk to reproductive capacity. |