Ixazomib

What is ixazomib used for?

Ixazomib is a prescription medicine that is used to treat multiple myeloma. This medicine is taken with other drugs. Be sure you know about the warnings, benefits, and risks of these other drugs. Talk with the doctor if you have questions or concerns about any of the drugs.

Description

NINLARO (ixazomib) is an antineoplastic agent. Ixazomib citrate, a prodrug, rapidly hydrolyzes under physiological conditions to its biologically active form, ixazomib. The chemical name of ixazomib citrate is 1,3,2-dioxaborolane-4,4-diacetic acid, 2-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-5-oxo- and the structural formula is:

The molecular formula for ixazomib citrate is C20H23BCl2N2O9 and its molecular weight is 517.12. Ixazomib citrate has one chiral center and is the R-stereoisomer. The solubility of ixazomib citrate in 0.1N HCl (pH 1.2) at 37°C is 0.61 mg/mL (reported as ixazomib). The solubility increases as the pH increases.

NINLARO (ixazomib) capsules for oral use contain 4, 3 or 2.3 mg of ixazomib equivalent to 5.7, 4.3 or 3.3 mg of ixazomib citrate, respectively. Inactive ingredients include microcrystalline cellulose, magnesium stearate, and talc. Capsule shells contain gelatin and titanium dioxide. The 4 mg capsule shell contains red and yellow iron oxide, the 3 mg capsule shell contains black iron oxide and the 2.3 mg capsule shell contains red iron oxide. The printing ink contains shellac, propylene glycol, potassium hydroxide, and black iron oxide.

 Mechanism of Action

Ixazomib is a reversible proteasome inhibitor. Ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome.

Ixazomib induced apoptosis of multiple myeloma cell lines in vitro. Ixazomib demonstrated in vitro cytotoxicity against myeloma cells from patients who had relapsed after multiple prior therapies, including bortezomib, lenalidomide, and dexamethasone. The combination of ixazomib and lenalidomide demonstrated synergistic cytotoxic effects in multiple myeloma cell lines. In vivo, ixazomib demonstrated antitumor activity in a mouse multiple myeloma tumor xenograft model.

Before taking ixazomib, tell your doctor:

• If you are allergic to ixazomib; 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 are taking any of these drugs: Carbamazepine, phenytoin, rifampin, or St. John’s wort.
• If you are breast-feeding. Do not breast-feed while you take ixazomib.

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

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 ixazomib 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 ixazomib?

• Tell all of your health care providers that you take ixazomib. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• Low white blood cell counts have rarely happened with ixazomib. This may lead to a higher chance of getting an infection. Tell your doctor if you have ever had a low white blood cell count. Call your doctor right away if you have signs of infection like fever, chills, or sore throat.
• If you touch a broken capsule, or the drug inside the capsule, wash the area with soap and water.
• If a broken capsule or the drug inside the capsule touches your eyes, rinse your eyes right away with water.
• You may need to take another drug to prevent herpes zoster (shingles). Talk with your doctor.
• Patients with cancer who take ixazomib may be at a greater risk of getting a severe health problem called tumor lysis syndrome (TLS).This may lead to death. Call your doctor right away if you have a fast or abnormal heartbeat; any passing out; trouble passing urine; muscle weakness or cramps; upset stomach, throwing up, diarrhea, or not able to eat; or feel sluggish.
• Very bad and sometimes deadly blood problems like thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) have happened with ixazomib in some people. Call your doctor right away if you feel very tired or weak or have any bruising or bleeding; dark urine or yellow skin or eyes; pale skin; change in the amount of urine passed; change in eyesight; change in strength on 1 side is greater than the other, trouble speaking or thinking, or change in balance; or fever.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• Women must use birth control while taking ixazomib and for some time after the last dose. Ask your doctor how long to use birth control. If you get pregnant, call your doctor right away.
• This medicine is taken with dexamethasone. Dexamethasone may cause birth control pills and other hormone-based birth control to not work as well to prevent pregnancy. If you are using a hormone-based birth control, you need to also use a barrier form of birth control like a condom if you are taking dexamethasone.
• Men with a partner who may get pregnant must use birth control while taking ixazomib and for some time after the last dose. Ask your doctor how long to use birth control. If your partner gets pregnant, call the doctor right away.

How is ixazomib best taken?

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

• You will need to take special care when handling ixazomib. Check with the doctor or pharmacist to see how to handle ixazomib.
• This medicine is not taken every day. Be sure you know how to take it. Talk with your doctor if you have questions.
• Take ixazomib at the same time of day.
• Take on an empty stomach at least 1 hour before or 2 hours after meals unless your doctor has told you otherwise.
• Swallow whole with a drink of water.
• Do not open the capsules.
• Do not chew or crush.
• If you throw up after taking a dose, do not repeat the dose. Take your next dose at your normal time.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is less than 3 days (72 hours) until your next dose, skip the missed dose. Take your next dose on your normal day.
• Do not take 2 doses at the same time or extra doses.

What are the side effects of ixazomib 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 liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• A burning, numbness, or tingling feeling that is not normal.
• Weakness.
• Swelling in the arms or legs.
• Weight gain.
• Change in eyesight, eye pain, or very bad eye irritation.
• Shingles.
• Purple spots or redness of the skin.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
• A very bad and sometimes deadly brain problem called posterior reversible encephalopathy syndrome (PRES) has happened with ixazomib. Call your doctor right away if you have signs like feeling confused, lowered alertness, change in eyesight, loss of eyesight, seizures, or very bad headache.

What are some other side effects of ixazomib?

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:

• Back pain.
• Constipation, diarrhea, throwing up, and upset stomach are common with ixazomib. If these happen, talk with your doctor about ways to lower these side effects. Call your doctor right away if any of these effects bother you, do not go away, or get very bad.

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 ixazomib?

• Store in the original container at room temperature.
• Protect from heat.
• Do not freeze.
• 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.