Vorinostat (Zolinza) — Clinical FAQs

Question 1

What is Vorinostat FDA-approved to treat?

Accepted Answer

Vorinostat is FDA-approved for the following oncology indications: 1. Cutaneous T-cell lymphoma (CTCL) — patients with progressive, persistent, or recurrent disease on or following two systemic therapies (FDA approved October 26, 2006; first approved HDAC inhibitor).

Question 2

How does Vorinostat work (mechanism of action)?

Accepted Answer

Vorinostat (suberoylanilide hydroxamic acid; SAHA) is a pan-HDAC inhibitor of the hydroxamic acid class that inhibits class I (HDAC1, 2, 3, 8), class II (HDAC4, 5, 6, 7, 9, 10), and class IV (HDAC11) zinc-dependent deacetylases. The hydroxamic acid moiety chelates the catalytic zinc ion within the HDAC active site, blocking deacetylation of histone and non-histone protein substrates. Inhibition results in accumulation of acetylated histones (H3, H4) and non-histone proteins, leading to chromatin relaxation, re-expression of silenced tumor-suppressor genes (including p21/CDKN1A and p53), inhibition of cell-cycle progression (G1 arrest), induction of differentiation, and activation of apoptosis via both intrinsic and extrinsic pathways in malignant T-lymphocytes. Vorinostat was the first HDAC inhibitor to receive FDA approval (October 2006), establishing proof-of-concept for epigenetic therapy in oncology.

Question 3

How is Vorinostat administered?

Accepted Answer

Vorinostat is administered Oral (PO). Administer vorinostat 400 mg orally once daily with food (food improves tolerability, reduces nausea, and modestly increases AUC).

Question 4

What are the most common side effects of Vorinostat?

Accepted Answer

The most commonly reported side effects of Vorinostat (≥10% incidence) include: Diarrhea (49-52%), Fatigue (52%), Nausea (35-41%), Thrombocytopenia (25-54%), Anorexia (24%) and others (17 total). Consult your oncologist for complete prescribing information.

Question 5

Does Vorinostat have a black box warning?

Accepted Answer

Yes. Vorinostat carries FDA black box warning(s) regarding: 1. Pulmonary embolism (PE) and deep vein thrombosis (DVT): Fatal pulmonary emboli and serious thromboembolic events have occurred during vorinostat treatment. Monitor patients for signs and symptoms of DVT and PE throughout therapy. Patients with a prior history of thromboembolic events are at increased risk.

Question 6

Is Vorinostat safe during pregnancy?

Accepted Answer

Vorinostat pregnancy safety: May cause fetal harm based on mechanism of action (pan-HDAC inhibition is expected to disrupt epigenetic regulation critical to fetal development). Females of reproductive potential should use effective contraception during treatment and for at least 6 months after the last dose. Males with female partners of reproductive potential should use contraception during treatment and for 3 months after the last dose. Not recommended during breastfeeding.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

Vorinostat — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms