Zolinza

Generic name: vorinostat
Drug class: Histone deacetylase inhibitors

What is Zolinza used for?

Zolinza is a prescription medicine that is used to treat a type of lymphoma that affects the skin.

Description

ZOLINZA contains vorinostat, which is described chemically as N-hydroxy-N’-phenyloctanediamide.

The empirical formula is C14H20N2O3. The molecular weight is 264.32 and the structural formula is:

Vorinostat is a white to light orange powder. It is very slightly soluble in water, slightly soluble in ethanol, isopropanol and acetone, freely soluble in dimethyl sulfoxide and insoluble in methylene chloride. It has no chiral centers and is non-hygroscopic. The differential scanning calorimetry ranged from 161.7 (endotherm) to 163.9°C. The pH of saturated water solutions of vorinostat drug substance was 6.6. The pKa of vorinostat was determined to be 9.2.

Each 100 mg ZOLINZA capsule for oral administration contains 100 mg vorinostat and the following inactive ingredients: microcrystalline cellulose, sodium croscarmellose and magnesium stearate. The capsule shell excipients are titanium dioxide, gelatin and sodium lauryl sulfate.

 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.

Before taking Zolinza, tell your doctor:

• If you are allergic to Zolinza; any part of this medicine; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
• If you have any of these health problems: Low potassium or magnesium levels.
• If you are breast-feeding. Do not breast-feed while you take Zolinza and for 1 week after your last dose.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Zolinza with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take Zolinza?

• Tell all of your health care providers that you take Zolinza. This includes your doctors, nurses, pharmacists, and dentists.
• If diarrhea or throwing up happens, talk with the doctor. You will need to make sure to avoid dehydration and electrolyte problems.
• If you have high blood sugar (diabetes), talk with your doctor. This medicine may raise blood sugar.
• Check your blood sugar as you have been told by your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Talk with your doctor about drinking lots of fluids and other ways to prevent fluid loss. If you have a lot of fluid loss, you may have more side effects from Zolinza.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• Blood clots have happened with Zolinza. Tell your doctor if you have ever had a blood clot. Talk with your doctor.
• If you are a man and have sex with a female who could get pregnant, protect her from pregnancy during treatment and for 3 months after your last dose.
• If you are a man and your sex partner gets pregnant while you take Zolinza or within 3 months after your last dose, call your doctor right away.
• This medicine may cause you to not be able to get pregnant. Talk with the doctor.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• If you are able to get pregnant, a pregnancy test will be done within 1 week before you start Zolinza. Talk with your doctor.
• Use birth control that you can trust to prevent pregnancy while taking Zolinza and for 6 months after stopping Zolinza.
• If you get pregnant while taking Zolinza or within 6 months after your last dose, call your doctor right away.

How is Zolinza best taken?

Use Zolinza as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take Zolinza with food.
• Swallow whole. Do not chew, open, or crush.
• Keep taking Zolinza as you have been told by your doctor or other health care provider, even if you feel well.
• If you have trouble swallowing, talk with your doctor.
• If the capsule is opened or broken, do not touch the contents. If the contents are touched or they get in the eyes, wash hands or eyes right away.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.
• If you have upset stomach, throwing up, diarrhea, or are not hungry, talk with your doctor. There may be ways to lower these side effects.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.
• If you are not sure what to do if you miss a dose, call your doctor.

What are the side effects of Zolinza that I need to call my doctor about immediately?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of bleeding like throwing up or coughing up blood; vomit that looks like coffee grounds; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a cause or that get bigger; or bleeding you cannot stop.
• Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Signs of dehydration like dry skin, mouth, or eyes; thirst; fast heartbeat; dizziness; fast breathing; or confusion.
• A fast heartbeat or passing out.
• Swelling in the arms or legs.
• Sweating a lot.
• Anxiety.
• Very upset stomach or throwing up.
• Severe diarrhea.
• Feeling very tired or weak.
• Pale skin.
• Fever.
• Feeling sleepy.
• Call your doctor right away if you have signs of a blood clot like chest pain or pressure; coughing up blood; shortness of breath; swelling, warmth, numbness, change of color, or pain in a leg or arm; or trouble speaking or swallowing.

What are some other side effects of Zolinza?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hair loss.
• Upset stomach or throwing up.
• Diarrhea.
• Constipation.
• Not hungry.
• Weight loss.
• Headache.
• Feeling tired or weak.
• Chills.
• Cough.
• Muscle spasm.
• Change in taste.
• Itching.
• Signs of a common cold.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Zolinza?

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.

Label

PRINCIPAL DISPLAY PANEL – 100 MG CAPSULE BOTTLE LABEL