Vorinostat (1 brand name, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- ZOLINZA
Indications and Usage
ZOLINZA ® is indicated for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies.
Contraindications
None.
Adverse Reactions
The following serious adverse reactions have been associated with ZOLINZA in clinical trials and are discussed in greater detail in other sections of the label: Thromboembolism [see Warnings and Precautions (5.1)] Myelosuppression [see Warnings and Precautions (5.2)] Gastrointestinal Toxicity [see Warnings and Precautions (5.3)] Hyperglycemia [see Warnings and Precautions (5.4)] Clinical Chemistry Abnormalities [see Warnings and Precautions (5.5)] Severe thrombocytopenia when combined with other Histone Deacetylase (HDAC) Inhibitors [see Warnings and Precautions (5.6)]
Mechanism of Action
Vorinostat inhibits the enzymatic activity of histone deacetylases HDAC1, HDAC2 and HDAC3 (Class I) and HDAC6 (Class II) at nanomolar concentrations (IC50<86 nM). These enzymes catalyze the removal of acetyl groups from the lysine residues of proteins, including histones and transcription factors. In some cancer cells, there is an overexpression of HDACs, or an aberrant recruitment of HDACs to oncogenic transcription factors causing hypoacetylation of core nucleosomal histones. Hypoacetylation of histones is associated with a condensed chromatin structure and repression of gene transcription. Inhibition of HDAC activity allows for the accumulation of acetyl groups on the histone lysine residues resulting in an open chromatin structure and transcriptional activation. In vitro, vorinostat causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells. The mechanism of the antineoplastic effect of vorinostat has not been fully characterized.
Overdosage
No specific information is available on the treatment of overdosage of ZOLINZA. In the event of overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required. It is not known if vorinostat is dialyzable.