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Common name: panobinostat
Trade name: Farydak
All names: panobinostat, Farydak, panobinostat
Indications:
Combined bortezomib/dexamethasone treatment for multiple myeloma that has been treated with two or more drugs (including bortezomib and immunomodulators).
Usage and dosage:
20mg orally administered on the 1st, 3rd, 5th, 8th, 10th and 12th day of each cycle, 21 days is a cycle, a total of 8 treatment cycles.
If the patient can benefit clinically and has no severe sustained toxic side effects, he may consider continuing the treatment for another 8 cycles at this time.
Adverse reactions:
The most common adverse reactions (≥20%) include diarrhea, fatigue, nausea, peripheral edema, decreased appetite, fever, and vomiting.
The most common non-hematologic laboratory abnormalities (≥40%) include hypophosphatemia, hypokalemia, hyponatremia, and increased creatinine.
The most common hematology laboratory abnormalities (≥60%) include thrombocytopenia, lymphopenia, leukopenia, neutropenia, and anemia.
Contraindications:
Not clear yet.
Precautions:
Diarrhea: Severe diarrhea occurred in 25% of patients receiving Farydak. Diarrhea may occur at any time during treatment. Monitor the patient's hydration status and serum electrolyte levels, including potassium ions and magnesium ions, weekly or as needed for treatment, and adjust the dose of Farydak as needed.
Cardiotoxicity: Severe and fatal cardiac ischemic events, severe arrhythmias, and electrocardiogram abnormalities have occurred in patients treated with Farydak. Treatment with Farydak is contraindicated in patients with a recent history of myocardial infarction or unstable angina.
Bleeding: Serious and fatal bleeding has occurred in patients treated with Farydak.
Myelosuppression: Farydak can cause bone marrow suppression, including severe thrombocytopenia, neutropenia, and anemia. A complete blood count should be performed before treatment with Farydak and every week during treatment (or as needed for treatment). Those over 65 years of age should be monitored more frequently, and dosage adjustments should be made as needed.
Infection: Farydak can cause local or systemic infections, including pneumonia, bacterial infections, invasive fungal infections, and viral infections. Monitor patients for symptoms and signs of infection during treatment. If infection is confirmed, initiate anti-infective treatment and consider whether to suspend or permanently terminate dosing.
Hepatotoxicity: Farydak can cause liver dysfunction, mainly increased levels of transaminases and total bilirubin. Liver function tests need to be performed regularly before and during treatment with Farydak, and dosage adjustments should be made as needed.
Embryo-fetal toxicity: Administration during pregnancy has potential embryo-fetal toxicity. It is recommended that women use effective contraception while taking the medication and for at least one month after completion of treatment. Men are advised to use effective contraception during treatment and for at least 3 months after completion of treatment.
May cause severe and fatal cardiotoxicity and severe diarrhea.
Storage:
Sealed.
Mechanism of action:
Farydak (Panobinostat) is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from lysine residues in histones and some non-histone proteins. Inhibition of HDAC activity leads to increased acetylation of histones, leading to epigenetic changes in chromatin relaxation, resulting in transcriptional activation.
In vitro, Farydak causes the accumulation of acetylated histones and other proteins, inducing cell cycle arrest and/or apoptosis in some transformed cells. Increased levels of acetylated histones were observed in xenografts from mice treated with Farydak. Farydak is more cytotoxic to tumor cells than to normal cells.
By blocking the function of histone deacetylase, it can increase the hyperacetylation of histones and tubulin in a concentration-dependent manner, triggering cell cycle termination and apoptosis without affecting healthy cells.