Ixazomib

Unless your doctor tells you otherwise, continue your normal diet.

Take the missed dose as soon as you remember it. However, if it is within 72 hours (3 days) of your next scheduled dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to ixazomib.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Dosage Forms & Strengths

capsule

• 2.3mg
• 3mg
• 4mg

Multiple Myeloma

Indicated in combination with lenalidomide and dexamethasone for patients with multiple myeloma who have received at least 1 prior therapy

Treatment should be continued until disease progression or unacceptable toxicity

Starting doses

• Ixazomib: 4 mg PO on days 1, 8, and 15 of a 28-day cycle; take 1 hr ac or 2 hr pc
• Lenalidomide: 25 mg PO on days 1-21 of a 28-day cycle; take with or without food
• Dexamethasone: 40 mg PO in morning on days 1, 8, 15, and 22 of a 28-day cycle

Dosage Modifications

Also refer to lenalidomide monograph

Hepatic impairment

• Mild: No dosage adjustment required
• Moderate (TB >1.5-3 x ULN) or severe (TB >3 ULN): Decrease starting dose to 3 mg

Renal impairment

• Mild-to-moderate: No dosage adjustment required
• Severe (CrCl <30 mL/min) or ESRD requiring dialysis: Decrease starting dose to 3 mg; ixazomib is not dialyzable and therefore can be administered without regard to the timing of dialysis

Dose reductions

• If starting dose is 4 mg
  • First reduction to: 3 mg
  • Second reduction to: 2.3 mg

Thrombocytopenia

• Platelet count <30,000/mm³
  • Withhold ixazomib and lenalidomide until platelet count is at least 30,000/mm³
  • Following recovery, resume lenalidomide at the next lower dose according to its prescribing information and resume ixazomib at its most recent dose
  • If platelet count falls to <30,000/mm³ again, withhold ixazomib and lenalidomide until platelet count is at least 30,000/mm³
  • Following recovery, resume ixazomib at the next lower dose and resume lenalidomide at its most recent dose*
  • *For additional occurrences, alternate dose modification of lenalidomide and ixazomib

Neutropenia

• ANC count <500/mm³
  • Withhold ixazomib and lenalidomide until ANC is at least 500/mm³
  • Consider adding G-CSF as per clinical guidelines
  • Following recovery, resume lenalidomide at the next lower dose according to its prescribing information and resume ixazomib at its most recent dose
  • If ANC falls to <500/mm³ again, withhold ixazomib and lenalidomide until ANC is at least 500/mm³
  • Following recovery, resume ixazomib at the next lower dose and resume lenalidomide at its most recent dose*
  • *For additional occurrences, alternate dose modification of lenalidomide and ixazomib

Rash

• Grade 2 or 3
  • Withhold lenalidomide until rash recovers to ≤grade 1
  • Following recovery, resume lenalidomide at the next lower dose according to its prescribing information
  • If grade 2 or 3 rash occurs again, withhold ixazomib and lenalidomide until rash recovers to ≤grade 1
  • Following recovery, resume ixazomib at the next lower dose and resume lenalidomide at its most recent dose*
  • *For additional occurrences, alternate dose modification of lenalidomide and ixazomib
• Grade 4
  • Discontinue treatment regimen

Peripheral neuropathy

• Grade 1 with pain or grade 2
  • Withhold ixazomib until peripheral neuropathy recovers to ≤grade 1 without pain or patient's baseline
  • Following recovery, resume ixazomib at its most recent dose
• Grade 2 with pain or grade 3
  • Withhold ixazomib
  • Toxicities should, at the physician’s discretion, generally recover to patient’s baseline condition or ≤grade 1 prior to resuming ixazomib
  • Following recovery, resume ixazomib at the next lower dose
• Grade 4
  • Discontinue treatment regimen

Other nonhematologic toxicities

• Withhold ixazomib
• Toxicities should, at the physician’s discretion, generally recover to patient’s baseline condition or ≤grade 1 prior to resuming ixazomib
• If attributable to ixazomib, resume at the next lower dose following recovery

Dosing Considerations

Consider antiviral prophylaxis to decrease the risk of herpes zoster reactivation

Monitor before each new cycle of therapy

• ANC should be at least 1,000/mm³
• Platelet count should be at least 75,000/mm³
• Nonhematologic toxicities should, at the physician’s discretion, generally be recovered to patient’s baseline condition or ≤grade 1

Safety and efficacy not established

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.

Do not use ixazomib with lenalidomide if you are pregnant, or if you are a man and your sexual partner is pregnant. Lenalidomide is known to cause severe, life-threatening birth defects or death of a baby if the mother or the father is taking this medicine at the time of conception or during pregnancy.

Usual Adult Dose for Multiple Myeloma:

4 mg orally once a week on Days 1, 8, and 15 of a 28-day cycle

Comments:
-This drug should be taken once a week on the same day and at approximately the same time for the first 3 weeks of a 4-week cycle.
-This drug should be taken at least 1 hour before or 2 hours after food.
-The whole capsule should be swallowed with water (not crushed, chewed, or opened).
-If a dose is delayed or missed, the dose should be taken only if the next scheduled dose is 72 or more hours away. A missed dose should not be taken within 72 hours of the next scheduled dose. A double dose should not be taken to make up for the missed dose.
-If vomiting occurs after taking a dose, the patient should not repeat the dose. The patient should resume dosing at the time of the next scheduled dose.
-Antiviral prophylaxis should be considered to decrease the risk of herpes zoster reactivation.
-Treatment should be continued until disease progression or unacceptable toxicity.
-Prior to initiating a new cycle of therapy:
1) Absolute neutrophil count should be at least 1000/mm3
2) Platelet count should be at least 75,000/mm3
3) Nonhematologic toxicities should, at physician discretion, generally be recovered to patient baseline condition or Grade 1 or lower
-This drug is only given in combination with lenalidomide and dexamethasone; the manufacturer recommended dose of lenalidomide is 25 mg orally on Days 1 through 21 of a 28-day treatment cycle and dexamethasone is 40 mg orally on Days 1, 8, 15, and 22 of a 28-day treatment cycle. For additional information regarding lenalidomide and dexamethasone, refer to their prescribing information.

Use: Treatment of multiple myeloma (in combination with lenalidomide and dexamethasone) in patients who have received at least one prior therapy

In the U.S.

• Ninlaro

Available Dosage Forms:

• Capsule

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Proteasome Inhibitor

Ixazomib is used in combination with lenalidomide and dexamethasone to treat multiple myeloma (a type of bone marrow cancer) in patients who have received at least one prior treatment. It interferes with the growth of cancer cells, which are eventually destroyed by the body. Ixazomib is an antineoplastic agent (cancer medicine).

ixazomib is available only with your doctor's prescription.

It is very important that your doctor check you at regular visits while you are using ixazomib to make sure that the medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using ixazomib while you are pregnant can harm your unborn baby. Use an effective form of birth control while you are using ixazomib and for 90 days after your final dose to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

This can lower the number of your platelets, which are necessary for proper blood clotting. Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, or pinpoint red spots on your skin while receiving ixazomib.

Cancer medicines can cause diarrhea, constipation, nausea, or vomiting in most people, sometimes even after receiving medicines to prevent it. Ask your doctor or nurse about other ways to control these side effects.

Check with your doctor right away if you are having burning, numbness, tingling, or painful sensations in the arms, hands, legs, or feet. These could be symptoms of a condition called peripheral neuropathy.

ixazomib may cause fluid retention (edema) in some patients. Tell your doctor right away if you have bloating or swelling of face, arms, hands, lower legs, or feet, tingling of hands or feet, or unusual weight gain or loss.

If you develop a skin rash or redness or discoloration of the skin, check with your doctor as soon as possible.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

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 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 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.
• 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.
• 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 this medicine. 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.

Pharmacokinetics of ixazomib (at a dose of 3 mg) were evaluated in patients with normal renal function (CrCl ≥90 mL/minute), severe impairment (CrCl <30 mL/minute) or ESRD requiring dialysis. The mean AUC was 39% higher in patients with severe renal impairment and in ESRD requiring dialysis (as compared with patients with normal renal function).

Multiple myeloma: Treatment of multiple myeloma (in combination with lenalidomide and dexamethasone) in patients who have received at least one prior therapy

There are no contraindications listed in the manufacturer's labeling.

-Severe renal impairment (CrCl less than 30 mL/min) or end-stage renal disease (ESRD) requiring dialysis: Reduce the starting dose of this drug to 3 mg
-Refer to the lenalidomide prescribing information for dosing recommendations in patients with renal impairment.