Comprehensive Guide to Vorinostat: Uses, Dosage, Side Effects, and More

1. What is Vorinostat?

2. Overview of Vorinostat

Generic Name

Vorinostat

Brand Name

Zolinza, generics

Drug Group

Histone deacetylase (HDAC) inhibitor (antineoplastic)

Commonly Used For

This medication is used to:

• Treat cutaneous T-cell lymphoma (CTCL).
• Manage advanced lymphoma stages.
• Explore treatment for other cancers.

Key Characteristics

• Form: Oral capsules (100 mg) (detailed in Dosage section).
• Mechanism: Inhibits HDAC enzymes, promoting histone acetylation and cancer cell death.
• Approval: FDA-approved (2006 for Zolinza) and EMA-approved for CTCL.

3. Indications and Uses of Vorinostat

Vorinostat is indicated for hematologic malignancies and is being explored for broader applications, leveraging its epigenetic effects:

• Cutaneous T-Cell Lymphoma (CTCL): Treats CTCL in patients with progressive, persistent, or recurrent disease on or requiring systemic therapy, improving skin manifestations and survival, per oncology guidelines.
• Peripheral T-Cell Lymphoma (PTCL): Used off-label to manage relapsed or refractory PTCL, enhancing response rates when combined with other agents, supported by hematology trials.
• Multiple Myeloma: Investigated off-label in combination with proteasome inhibitors (e.g., bortezomib) for multiple myeloma, reducing tumor burden, with data from oncology research.
• Acute Myeloid Leukemia (AML): Explored off-label for relapsed or refractory AML, inducing differentiation and apoptosis, supported by leukemia studies.
• Hodgkin’s Lymphoma: Employed off-label in relapsed Hodgkin’s lymphoma, improving remission rates, with evidence from lymphoma cohorts.
• Breast Cancer: Investigated off-label for metastatic breast cancer, enhancing chemotherapy efficacy, with emerging data from breast cancer research.
• Glioblastoma: Used off-label in combination therapy for glioblastoma, crossing the blood-brain barrier to target glioma cells, supported by neuro-oncology studies.
• Mantle Cell Lymphoma: Explored off-label to manage mantle cell lymphoma, reducing lymph node involvement, with preliminary lymphoma evidence.
• Non-Small Cell Lung Cancer (NSCLC): Investigated off-label with EGFR inhibitors for NSCLC, improving progression-free survival, noted in pulmonary oncology research.
• Epigenetic Therapy Adjunct: Studied off-label to reverse epigenetic silencing in various cancers, enhancing immunotherapy responses, with cutting-edge oncology insights.

Note: This drug requires careful monitoring for hematologic and cardiac effects; consult a healthcare provider for individualized treatment plans.

4. Dosage of Vorinostat

Important Note: The dosage of this HDAC inhibitor must be prescribed by a healthcare provider. Dosing varies by indication and patient tolerance, with adjustments based on clinical evaluation.

Dosage for Adults

• Cutaneous T-Cell Lymphoma (CTCL):
  • 400 mg once daily with food, taken as four 100 mg capsules, for 28-day cycles; continue until disease progression or unacceptable toxicity.
• Off-Label Use (e.g., PTCL, AML):
  • 300–400 mg once daily, adjusted based on combination therapy and tolerance, under oncologist supervision.

Dosage for Children

• CTCL or Off-Label Use (12+ years):
  • 300 mg/m² once daily (maximum 400 mg), taken with food, under pediatric oncologist supervision.
  • Not recommended under 12 years due to limited data.

Dosage for Pregnant Women

• Pregnancy Category D: Avoid unless benefits outweigh risks (e.g., life-threatening cancer). Consult an obstetrician, with fetal monitoring.

Dosage Adjustments

• Renal Impairment: No specific adjustment; monitor in severe cases (CrCl <30 mL/min).
• Hepatic Impairment:
  • Mild (Child-Pugh A): No adjustment; moderate (Child-Pugh B): Reduce to 300 mg/day; severe (Child-Pugh C): Avoid.
• Elderly: Start with 300 mg once daily; increase to 400 mg if tolerated.
• Concomitant Medications: Adjust if combined with CYP3A4 inhibitors/inducers (e.g., ketoconazole, rifampin), altering levels.

Additional Considerations

• Take this active ingredient with food to reduce gastrointestinal irritation.
• Use antiemetics if nausea occurs; monitor blood counts weekly.

5. How to Use Vorinostat

• Administration:
  • Swallow capsules whole with a meal or snack, using water; avoid opening or crushing due to powder exposure risk.
  • Take at the same time daily for consistency, often with other therapies.
• Timing: Use once daily, preferably with breakfast or dinner, as directed.
• Monitoring: Watch for fatigue, bruising, or signs of infection (e.g., fever).
• Additional Tips:
  • Store at 20–25°C (68–77°F), protecting from moisture and heat.
  • Keep out of reach of children due to toxicity risk.
  • Report severe diarrhea, chest pain, or signs of bleeding immediately.

6. Contraindications for Vorinostat

This drug is contraindicated in:

• Hypersensitivity: Patients with a known allergy to Vorinostat or HDAC inhibitors.
• Severe Hepatic Impairment: Contraindicated in Child-Pugh Class C due to toxicity risk.
• Severe Thrombocytopenia: Avoid due to bleeding risk.
• Pregnancy: Contraindicated unless life-saving.

7. Warnings & Precautions for Vorinostat

General Warnings

• Thrombocytopenia: Risk of severe platelet reduction; monitor blood counts weekly.
• Pulmonary Embolism: Rare risk of thromboembolism; assess for symptoms.
• Cardiotoxicity: Risk of QT prolongation and arrhythmias; monitor ECG.
• Gastrointestinal Perforation: Rare risk with severe diarrhea; seek immediate care.
• Tumor Lysis Syndrome: Risk in high tumor burden; hydrate and monitor electrolytes.

Additional Warnings

• Fatigue and Weakness: Common and debilitating; adjust dose if severe.
• Hyperglycemia: May exacerbate diabetes; monitor blood sugar.
• Hepatotoxicity: Elevated liver enzymes; check regularly.
• Infections: Increased risk due to immunosuppression; prophylaxis may be needed.
• Hypersensitivity Reactions: Rare anaphylaxis; discontinue if swelling occurs.

Use in Specific Populations

• Pregnancy: Category D; avoid unless critical; use contraception.
• Breastfeeding: Avoid due to potential toxicity; monitor infant.
• Elderly: Higher risk of toxicity; start with lower doses.
• Children: Limited to 12+ years; supervise closely.
• Renal/Hepatic Impairment: Adjust dose; avoid in severe cases.

Additional Precautions

• Inform your doctor about liver disease, heart conditions, or bleeding disorders before starting this medication.
• Avoid abrupt cessation; taper if combined with other agents.

8. Overdose and Management of Vorinostat

Overdose Symptoms

Overdose may cause:

• Nausea, vomiting, or severe diarrhea.
• Severe cases: Thrombocytopenia, liver failure, or cardiac arrest.
• Fatigue, bruising, or fever as early signs.
• Seizures with extremely high doses.

Immediate Actions

• Contact the Medical Team: Seek immediate medical help.
• Supportive Care: Administer IV fluids, platelet transfusions if needed, and monitor vital signs.
• Specific Treatment: No antidote; manage symptoms and monitor organ function.
• Monitor: Check blood counts, liver enzymes, and ECG for 7–14 days.

Additional Notes

• Overdose risk is moderate; store securely.
• Report persistent symptoms (e.g., jaundice, severe weakness) promptly.

9. Side Effects of Vorinostat

Common Side Effects

• Diarrhea (50–60%, manageable with hydration)
• Fatigue (40–50%, reduced with rest)
• Nausea (30–45%, relieved with antiemetics)
• Thrombocytopenia (25–35%, monitored with blood tests)
• Anorexia (20–30%, improved with nutrition support)
  These effects may subside with dose adjustment or cycle breaks.

Serious Side Effects

Seek immediate medical attention for:

• Hematologic: Severe thrombocytopenia, anemia, or neutropenia.
• Hepatic: Jaundice, hepatitis, or liver failure.
• Cardiovascular: QT prolongation, arrhythmias, or pulmonary embolism.
• Gastrointestinal: Perforation, severe vomiting, or dehydration.
• Allergic: Rash, angioedema, or anaphylaxis.

Additional Notes

• Regular monitoring for blood counts, liver function, and cardiac status is advised.
• Report any unusual symptoms (e.g., chest pain, severe bleeding) immediately to a healthcare provider.

10. Drug Interactions with Vorinostat

This active ingredient may interact with:

• CYP3A4 Inhibitors/Inducers: Alters levels (e.g., ketoconazole, rifampin); adjust dose.
• Anticoagulants: Increases bleeding risk (e.g., warfarin); monitor INR.
• Antiarrhythmics: Enhances QT prolongation (e.g., amiodarone); monitor ECG.
• Antidiabetic Agents: Potentiates hypoglycemia; adjust dose.
• Valproic Acid: Increases neurotoxicity; use cautiously.

Action: Provide your healthcare provider with a complete list of medications.

11. Patient Education or Lifestyle

• Medication Adherence: Take this HDAC inhibitor as prescribed in treatment cycles, following the exact schedule.
• Monitoring: Report bruising, fatigue, or signs of infection immediately.
• Lifestyle: Avoid alcohol; maintain hydration and balanced nutrition.
• Diet: Take with food to reduce GI irritation; avoid spicy foods during diarrhea.
• Emergency Awareness: Know signs of bleeding, liver issues, or heart problems; seek care if present.
• Follow-Up: Schedule regular check-ups every 1–2 weeks during therapy to monitor blood, liver, and cardiac health, with additional focus on mental well-being and quality of life.

12. Pharmacokinetics of Vorinostat

• Absorption: Well-absorbed orally (peak at 1–2 hours); enhanced with food.
• Distribution: Volume of distribution ~49 L; 71% protein-bound.
• Metabolism: Hepatic via glucuronidation and oxidation to inactive metabolites.
• Excretion: Primarily renal (52–100%) as metabolites; half-life 2 hours.
• Half-Life: 2 hours, with sustained epigenetic effects due to prolonged target inhibition.

13. Pharmacodynamics of Vorinostat

This drug exerts its effects by:

• Inhibiting HDAC enzymes (Class I and II), increasing histone acetylation and gene expression.
• Inducing apoptosis and cell cycle arrest in cancer cells, particularly in CTCL.
• Demonstrating synergistic effects with other chemotherapies or targeted therapies.
• Exhibiting dose-dependent hematologic and gastrointestinal toxicity risks.

14. Storage of Vorinostat

• Temperature: Store at 20–25°C (68–77°F); protect from moisture.
• Protection: Keep in original container, away from light and heat sources.
• Safety: Store in a locked container out of reach of children due to toxicity risk.
• Disposal: Dispose of unused capsules per local hazardous drug regulations or consult a pharmacist.

15. Frequently Asked Questions (FAQs)

Q: What does Vorinostat treat?
A: This medication treats cutaneous T-cell lymphoma.

Q: Can this active ingredient cause diarrhea?
A: Yes, diarrhea may occur; manage with hydration.

Q: Is Vorinostat safe for children?
A: Yes, for 12+ years with a doctor’s guidance.

Q: How is this drug taken?
A: Orally as capsules once daily with food, as directed.

Q: How long is Vorinostat treatment?
A: Varies by cancer response, often long-term with monitoring.

Q: Can I use Vorinostat if pregnant?
A: No, avoid unless life-saving; consult a doctor.

16. Regulatory Information

This medication is approved by:

• U.S. Food and Drug Administration (FDA): Approved in 2006 (Zolinza) for CTCL.
• European Medicines Agency (EMA): Approved for CTCL management.
• Other Agencies: Approved globally for lymphoma; consult local guidelines.

17. References

1. U.S. Food and Drug Administration (FDA). (2023). Zolinza (Vorinostat) Prescribing Information.
   • Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
2. European Medicines Agency (EMA). (2023). Vorinostat Summary of Product Characteristics.
   • EMA’s comprehensive information on the medication’s indications and precautions in Europe.
3. National Institutes of Health (NIH). (2023). Vorinostat: MedlinePlus Drug Information.
   • NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
4. World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Vorinostat.
   • WHO’s consideration of Vorinostat for cancer therapy.
5. Journal of Clinical Oncology. (2024). Vorinostat in CTCL and Beyond.
   • Peer-reviewed article on Vorinostat efficacy (note: access may require a subscription).