Istodax

Dosage Forms & Strengths

injectable lyophilized powder

• 10mg/vial plus diluent vial

Cutaneous T-Cell Lymphoma

Indicated for CTCL in patients who have received at least 1 prior systemic therapy

14 mg/m² IV infused over 4 hr on days 1, 8, and 15 of 28-d cycle  

Treatment discontinuation or interruption with or without dose reduction to 10 mg/m² may be required to manage adverse effects

Peripheral T-Cell Lymphoma

Indicated for PTCL in patients who have received at least 1 prior systemic therapy

14 mg/m² IV infused over 4 hr on days 1, 8, and 15 of 28-d cycle  

Treatment discontinuation or interruption with or without dose reduction to 10 mg/sq.meter may be required to manage adverse effects

Dosage Modifications

Nonhematologic toxicities (except alopecia)

• Grade 2 or 3 toxicity: Hold treatment until toxicity declines to Grade 1 or baseline, then restart at 14 mg/m²
• If Grade 3 toxicity recurs, hold treatment until toxicity returns to Grade 1 or baseline and the dose should be permanently reduced to 10 mg/m²
• Grade 4 toxicity: Hold treatment until toxicity declines to Grade 1 or baseline, then the dose should be permanently reduced to 10 mg/m²
• Discontinued if Grade 3 or 4 toxicities recur after dose reduction

Hematologic toxicities

• Grade 3 or 4 neutropenia or thrombocytopenia: Hold treatment until toxicity improves to ANC >1.5×10^9/L and/or platelet count >75×10^9/L or baseline, then restart at 14 mg/m²
• Grade 4 febrile (>38.5 degrees C) neutropenia or thrombocytopenia that requires platelet transfusion: Treatment with romidepsin should be delayed until the specific cytopenia returns to Grade 1 or baseline, and then the dose should be permanently reduced to 10 mg/m²

Renal or hepatic impairment

• Use caution with severe hepatic impairment or end-stage renal disease

Administration

Procedures for safe handling of cytotoxic drugs apply

Safety and efficacy not established

Serious side effects have been reported with Istodax. See the “Istodax Precautions” section.

Common side effects of Istodax include:

• nausea, vomiting, diarrhea
• loss of appetite
• tiredness

Tell your doctor if you have any side effect that bothers you or does not go away.

These are not all the possible side effects of Istodax. For more information, ask your doctor or pharmacist.

Ask your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Since this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.
 

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Cutaneous T-cell Lymphoma

Treatment of cutaneous T-cell lymphoma (CTCL; e.g., mycosis fungoides, Sézary syndrome) in adult patients who have received at least 1 prior systemic therapy.1 3 4 15

Designated an orphan drug by the FDA for use in this condition.2

Absorption

Exhibits linear pharmacokinetics across dosages ranging from 1–24.9 mg/m2 when given as an IV infusion over 4 hours in patients with advanced cancers.1 22 No accumulation of plasma romidepsin concentrations observed after repeated dosing.1

Distribution

Extent

Not known whether distributed into human milk.1

Plasma Protein Binding

92–94% (mainly to α1-acid glycoprotein).1

Elimination

Metabolism

Extensively metabolized, principally by CYP3A4 and, to a lesser extent, by CYP3A5, CYP1A1, CYP2B6, and CYP2C19.1 15 22

Half-life

Terminal half-life is approximately 3 hours.1 22

Special Populations

In a population pharmacokinetic analysis, pharmacokinetics of romidepsin not substantially affected by mild hepatic impairment.1

In a population pharmacokinetic analysis, pharmacokinetics not substantially affected by mild (Clcr of 50–80 mL/minute), moderate (Clcr of 30–50 mL/minute), or severe (Clcr <30 mL/minute) renal impairment.1 Effect of end-stage renal disease on romidepsin pharmacokinetics not studied.1

Age, gender, or race did not appear to affect the pharmacokinetics of romidepsin in a population pharmacokinetic analysis.1 In a limited number of pediatric patients (aged from 2–21 years), pharmacokinetics of romidepsin were similar to those reported in adults in a phase I trial.14

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and to check for unwanted effects. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Romidepsin can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

You may get infections more easily while using this medicine. These can occur during treatment and within 30 days after the last dose. Tell your doctor right away if you have a fever, cough, shortness of breath, burning on urination, flu-like symptoms, muscle aches, or worsening skin problems.

This medicine may cause heart rhythm changes, such as a condition called QT prolongation. It may change the way your heart beats and cause fainting or serious side effects. Contact your doctor right away if you have fast, pounding, or uneven heartbeats, chest pain, or shortness of breath.

This medicine may cause a serious type of reaction called tumor lysis syndrome. Your doctor may give you a medicine to help prevent this. Call your doctor right away if you have a decrease or change in urine amount, joint pain, stiffness, or swelling, lower back, side, or stomach pain, rapid weight gain, swelling of the feet or lower legs, or unusual tiredness or weakness.

Cancer medicines can cause nausea and/or vomiting even after receiving medicines to prevent it. Ask your doctor or nurse about other ways to control these side effects.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

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 or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
• Signs of electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up.
• Swelling in the arms or legs.
• Shortness of breath.
• Chest pain or pressure or a fast heartbeat.
• A heartbeat that does not feel normal.
• Dizziness or passing out.
• Feeling very tired or weak.
• Not able to pass urine or change in how much urine is passed.
• Patients with cancer who take Istodax may be at a greater risk of getting a bad health problem called tumor lysis syndrome (TLS). Sometimes, this has been deadly. Call your doctor right away if you have a fast heartbeat or a heartbeat that does not feel normal; any passing out; trouble passing urine; muscle weakness or cramps; upset stomach, throwing up, loose stools, or not able to eat; or feel sluggish.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Istodax, please talk with your doctor, nurse, pharmacist, or other health care provider.
• 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.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Istodax (romidepsin). It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Istodax.

Review Date: October 4, 2017

Istodax is injected into a vein through an IV. A healthcare provider will give you this injection. The medicine must be given slowly through an IV infusion, and can take up to 4 hours to complete.

You may be given other medication to prevent nausea or vomiting while you are receiving Istodax.

Istodax is usually given every 7 days for 3 weeks. This treatment cycle may be repeated 28 days after your first dose. Your doctor will determine how long to treat you with Istodax.

Istodax can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

Your heart function may also need to be checked using an electrocardiograph or ECG (sometimes called an EKG).

If you have ever had hepatitis B, Istodax can cause this condition to come back or get worse. You will need frequent blood tests to check your liver function during treatment and for several months after you stop using this medicine.

Call your doctor for instructions if you miss an appointment for your Istodax injection.