Instructions for Vorinostat

1. Common name: Vorinostat

Product name:Zolinza

2. Indications:

Vorinostat (Vorinostat) is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients with progressive, persistent, or relapsing disease following two systemic therapies.

3. Usage and dosage:

1. Recommended dose: The recommended dose of vorinostat is 400 mg, once a day, taken with food. Treatment can be continued as long as there is no evidence of disease progression or unacceptable toxicity.

2. Dose adjustment: If the patient is intolerant to the treatment, the dose of vorinostat can be reduced to 300 mg once a day with food. If necessary, the dose can be further reduced to 300 mg once a day with food for 5 consecutive days per week.

For patients with mild to moderate hepatic impairment (bilirubin 1-3 × ULN or AST greater than ULN), reduce the starting dose of vorinostat to 300 mg, once daily, orally with food.

4. Adverse reactions:

The most common drug-related adverse reactions of vorinostat can be divided into 4 comprehensive symptoms: Gastrointestinal symptoms (diarrhea, nausea, anorexia, weight loss, vomiting, constipation), systemic symptoms (fatigue, chills), hematological abnormalities (thrombocytopenia, anemia) and taste disorders (dysgeusia, dry mouth). The most common serious drug-related adverse reactions were pulmonary embolism and anemia. In clinical trials, there were single adverse events such as cholecystitis, death (unexplained), deep vein thrombosis, enterococcal infection, exfoliative dermatitis, gastrointestinal bleeding, infection, lobar pneumonia, myocardial infarction, ischemic stroke, pelvic ureteral obstruction, sepsis, spinal cord injury, streptococcal bacteremia, syncope, T-cell lymphoma, thrombocytopenia, and ureteral obstruction.

5. Storage:

Vorinostat is stored at 20-25°C (68-77°F), with a tolerance of 15-30°C (59-86°F). Vorinostat capsules should not be opened or crushed, and direct contact of the powder with skin or mucous membranes should be avoided. If such contact occurs, wash thoroughly.

6. Mechanism of action:

Vorinostat inhibits the enzymatic activities of histone deacetylase HDAC1, HDAC2 and hda C3 and hda C6 at nanomolar concentrations (IC50<86nM). These enzymes catalyze the removal of acetyl groups fromlysine residues in proteins, including histones and transcription factors. In some cancer cells, hdac is overexpressed, or hdac is abnormally recruited to oncogenic transcription factors, resulting in reduced core nucleosome histone acetylation. Hypoacetylation of histones is associated with condensed chromatin structure and repression of gene transcription. Inhibition of HDAC activity allows the accumulation of acetyl groups on histone lysine residues, leading to open chromatin structure and transcriptional activation. In vitro, vorinostat causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis in some transformed cells. The mechanism of vorinostat's antitumor effects has not been fully determined. xa0

The original drug of vorinostat is not currently on the market in China, and therefore cannot be included in the national medical insurance coverage. Overseas, there is an American version of the original drug, specifications100mg*120 pills per box, which may cost around 100,000 yuan (the price may fluctuate due to exchange rate effects). It is very expensive, and there is currently no generic version of vorinostat produced and launched. For more drug information and specific prices, please consult a medical consultant.