Vorinostat

What is Vorinostat?

• Vorinostat (Zolinza) is a histone deacetylase (HDAC) inhibitor used to treat cutaneous T-cell lymphoma that recurred (came back) or did not get better during or after treatment with other anticancer drugs.
• It is also being studied in the treatment of other types of cancer.
• It is also called SAHA, suberoylanilide hydroxamic acid.

Vorinostat

Vorinostat2DACS

What are the uses of this medicine?

• Vorinostat (Zolinza) is used for a type of cancer called cutaneous T-cell lymphoma (CTCL), which is a blood cell cancer that affects your skin.
• Zolinza is used when your CTCL gets worse, does not go away, or comes back after you have taken other medicines.

How does this medicine work?

• Vorinostat inhibits the enzymatic activity of histone deacetylases HDAC1, HDAC2 and HDAC3 (Class I) and HDAC6 (Class II).
• 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.
• vorinostat causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

Tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following:

• anticoagulants ('blood thinners') such as warfarin (Coumadin, Jantoven), [[belinostat] (Beleodaq), and valproic acid (Depakene)

Your doctor may want to do blood tests more often if you take:

• valproic acid, a medicine for seizures
• a blood thinner, like Coumadin® (warfarin)

Is this medicine FDA approved?

• Vorinostat was the first histone deacetylase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of CTCL on October 6, 2006.

How should this medicine be used?

Recommended dosage:

• The recommended dose is 400 mg orally once daily with food.
• If patient is intolerant to therapy, reduce the dose to 300 mg orally once daily with food.
• If necessary, reduce the dose further to 300 mg once daily with food for 5 consecutive days each week.
• Reduce dose in patients with mild or moderate hepatic impairment.

Administration:

• Take with food.
• Drink 8 glasses of water every day (at least 8 ounces each).
• This will help to keep you hydrated, especially if you have nausea, vomiting or diarrhea.
• Do not chew or break open the capsule.
• If you break open or crush a capsule, do not touch the capsule or powder.
• If the powder gets on your skin or in your eyes, wash your skin or eyes with lots of water right away.
• Then, call your doctor.
• If you cannot swallow the capsule, tell your doctor.
• You may need a different medicine.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Capsules: 100 mg

This medicine is available in fallowing brand namesː

• Zolinza

What side effects can this medication cause?

The most common side effects of this medicine include:

• Diarrhea
• Constipation
• Nausea
• Vomiting
• Not hungry
• Losing weight
• Dry mouth
• Losing hair
• Change in the way things taste
• Muscle aches
• Itchy skin
• Feeling tired
• Feeling dizzy
• Swelling in the foot, ankle, and leg
• Cold
• Cough
• Chills
• Fever
• Headaches

Zolinza may cause serious side effects which may include:

• Deep Vein Thrombosis
• Pulmonary Embolus
• body- dehydration
• Changes in your blood

What special precautions should I follow?

• Pulmonary embolism occurred in patients receiving Zolinza, and deep vein thrombosis has also been reported. Monitor for signs and symptoms of these events, particularly in patients with a prior history of thromboembolic events.
• Treatment with Zolinza can cause dose-related thrombocytopenia and anemia. Adjust dosage or discontinue treatment with Zolinza as clinically appropriate.
• Gastrointestinal disturbances, including nausea, vomiting and diarrhea, have been reported. Pre-existing nausea, vomiting, and diarrhea should be adequately controlled before beginning therapy with Zolinza.
• Hyperglycemia has been observed in patients receiving Zolinza. Monitor serum glucose every 2 weeks during the first 2 months of therapy and monthly thereafter.
• Obtain chemistry tests, including serum electrolytes, creatinine, magnesium, and calcium, every 2 weeks during the first 2 months of therapy and monthly thereafter. Correct hypokalemia and hypomagnesemia prior to administration of Zolinza. Monitor potassium and magnesium more frequently in symptomatic patients.
• Severe thrombocytopenia leading to gastrointestinal bleeding has been reported with concomitant use of Zolinza and other HDAC inhibitors (e.g., valproic acid). Monitor platelet counts more frequently.
• Based on findings from animal studies and its mechanism of action, Zolinza can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment and for at least 6 months after the last dose. Advise males with female sexual partners of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose.
• Women should not breastfeed while using Zolinza and for up to 1 week after the last dose. Please speak with your doctor.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• No specific information is available on the treatment of overdosage of Zolinza.

Treatment of overdosage:

• 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.

Can this medicine be used in pregnancy?

• Based on its mechanism of action and findings from animal studies, Zolinza can cause fetal harm when administered to a pregnant woman.
• There are insufficient data on Zolinza use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage.

Can this medicine be used in children?

• The safety and effectiveness of Zolinza in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

• The active ingredient is: vorinostat
• The inactive ingredients are: microcrystalline cellulose, sodium croscarmellose, magnesium stearate, titanium dioxide, gelatin, and sodium lauryl sulfate.

Who manufactures and distributes this medicine?

Manuf. for:

• Merck Sharp & Dohme LLC
• Rahway, NJ, USA

Manufactured by:

• Patheon, Inc.
• Mississauga, Ontario, Canada

What should I know about storage and disposal of this medication?

• Store at 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F).
• Procedures for proper handling and disposal of anticancer drugs should be considered.
• Zolinza (vorinostat) capsules should not be opened or crushed.
• Direct contact of the powder in Zolinza capsules with the skin or mucous membranes should be avoided.
• If such contact occurs, wash thoroughly.

• Dailymed label info on Vorinostat
• FDA Vorinostat