Ninlaro

What is Ninlaro?

Ninlaro is a prescription medicine used to treat multiple myeloma in combination with the medicines Revlimid (lenalidomide) and dexamethasone, in people who have received at least one prior treatment for their multiple myeloma.

It is not known if Ninlaro is safe and effective in children.

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.

What should I tell my healthcare provider before taking Ninlaro?

Before taking Ninlaro, tell your healthcare provider about all of your medical conditions, including if you:

• have liver problems
• have kidney problems or are on dialysis
• are pregnant or plan to become pregnant. Ninlaro can harm your unborn baby.
  • Avoid becoming pregnant during treatment with Ninlaro.
  • Females who are able to become pregnant must use effective birth control during treatment and for 90 days after your final dose of Ninlaro.
  • Males with a female partner who is able to become pregnant must use effective birth control during treatment and for 90 days after your final dose of Ninlaro.
  • Talk to your healthcare provider about birth control methods that may be right for you.
  • Tell your healthcare provider right away if you or your partner become pregnant while you are receiving Ninlaro.
• are breastfeeding or plan to breastfeed. It is not known if Ninlaro passes into breast milk. Do not breastfeed during treatment with Ninlaro.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Talk to your healthcare provider before starting any new medicines during treatment with Ninlaro.

How should I take Ninlaro?

• Take Ninlaro exactly as your healthcare provider tells you to take it. Do not change your dose or stop taking Ninlaro without talking to your healthcare provider first.
• Ninlaro is taken in “cycles.” Each cycle lasts 4 weeks (28 days).
  • The usual dose of Ninlaro is 1 capsule taken 1 time each week, on the same day of the week for the first 3 weeks of each cycle.
  • Take each dose of Ninlaro at about the same time of day.
  • Take Revlimid (lenalidomide) and dexamethasone exactly as your healthcare provider tells you to.
  • Your healthcare provider will do blood tests during treatment with Ninlaro to check for side effects.
  • Your healthcare provider may change your dose or stop Ninlaro, Revlimid (lenalidomide), or dexamethasone if you have side effects.
• Take Ninlaro at least 1 hour before or at least 2 hours after food.
• On the days that you take both Ninlaro and dexamethasone, do not take Ninlaro and dexamethasone at the same time. Take dexamethasone with food.
• Swallow Ninlaro capsules whole with water. Do not crush, chew or open the capsule.
• Avoid direct contact with the capsule contents. If you accidentally get powder from the Ninlaro capsule on your skin, wash the area well with soap and water. If you accidentally get powder from the Ninlaro capsule in your eyes, flush your eyes well with water.
• If you miss a dose of Ninlaro, or if you are late taking a dose, take the dose as long as the next scheduled dose is more than 3 days (72 hours) away. Do not take a missed dose of Ninlaro if it is within 3 days (72 hours) of your next scheduled dose.
• If you vomit after taking a dose of Ninlaro, do not repeat the dose. Take your next dose of Ninlaro on the next scheduled day and time.
• Your doctor may prescribe a medicine to take with NINLARO to decrease the risk of the chicken pox virus (herpes zoster) coming back (reactivation).
• If you take more Ninlaro than your healthcare provider tells you to take, call your healthcare provider right away or go to the nearest hospital emergency room.

What are the possible side effects of Ninlaro?

Ninlaro may cause serious side effects, including:

• Low platelet counts (thrombocytopenia). Low platelet counts are common with Ninlaro, and can sometimes be serious. You may need platelet transfusions if your counts are too low. Tell your healthcare provider if you have any signs of low platelet counts, including bleeding and easy bruising.
• Stomach and intestinal (gastrointestinal) problems. Diarrhea, constipation, nausea, and vomiting are common with Ninlaro, and can sometimes be severe. Call your healthcare provider if you get any of these symptoms and they do not go away during treatment with Ninlaro. Your healthcare provider may prescribe medicine to help treat your symptoms.
• Nerve problems. Nerve problems are common with Ninlaro and may also be severe. Tell your healthcare provider if you get any new or worsening symptoms, including:
  • tingling
  • numbness
  • pain
  • a burning feeling in your feet or hands
  • weakness in your arms or legs
• Swelling. Swelling is common with Ninlaro and can sometimes be severe. Tell your healthcare provider if you develop swelling in your arms, hands, legs, ankles, or feet, or if you gain weight from swelling.
• Skin reactions. Tell your healthcare provider if you get a new or worsening rash.
• Thrombotic microangiopathy (TMA). This is a condition involving blood clots and injury to small blood vessels that may cause harm to your kidneys, brain, and other organs, and may lead to death. Get medical help right away if you get any of the following signs or symptoms during treatment with Ninlaro:
  • fever
  • nausea
  • bruising
  • nose bleeds
  • tiredness
  • decreased urination
• Liver problems. Tell your healthcare provider if you get these signs of a liver problem:
  • yellowing of your skin or the whites of your eyes
  • pain in your right upper stomach-area

Other common side effects have occurred. Tell your healthcare provider if you get new or worsening signs or symptoms of the following:

• back pain
• skin rash and pain (shingles) as a result of reactivation of the chicken pox virus (herpes zoster)
• lowered white blood cells called neutrophils (neutropenia) that may increase the risk of infection
• vision conditions including blurred vision, dry eye and pink eye (conjunctivitis)

These are not all the possible side effects of Ninlaro. Call your doctor for medical advice

These are not all the possible side effects of Ninlaro. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Ninlaro

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Ninlaro for a condition for which it was not prescribed. Do not give Ninlaro to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Ninlaro that is written for healthcare professionals.

How should I store Ninlaro?

• Store Ninlaro at room temperature. Do not store above 86°F (30°C).
• Do not freeze Ninlaro.
• Store Ninlaro capsules in the original packaging until just before each use.
• Ask your pharmacist or healthcare provider about how to dispose of (throw away) unused Ninlaro.

Keep Ninlaro and all medicines out of the reach of children.

What are the ingredients in Ninlaro?

Active ingredient: ixazomib

Inactive ingredients: microcrystalline cellulose, magnesium stearate, and talc

Capsule shells: gelatin and titanium dioxide. The 4 mg capsule shell contains red and yellow iron oxide. The 3 mg capsule shell contains black iron oxide. The 2.3 mg capsule shell contains red iron oxide. The printing ink contains shellac, propylene glycol, potassium hydroxide, and black iron oxide.

Label

PRINCIPAL DISPLAY PANEL – 4 MG CAPSULE BLISTER PACK

• RX only
• PRESS
  &
  HOLD
  HERE
• Contains 1 Capsule
  Please read Package Insert before use.
• NDC 63020-080-01
• NINLARO®
  (ixazomib) capsules
• 4 mg
• Takeda

PULL OUT HERE

PRINCIPAL DISPLAY PANEL – 3 MG CAPSULE BLISTER PACK

• RX only
• PRESS
  &
  HOLD
  HERE
• Contains 1 Capsule
  Please read Package Insert before use.
• NDC 63020-079-01
• NINLARO®
  (ixazomib) capsules
• 3 mg
• Takeda
• PULL OUT HERE

PRINCIPAL DISPLAY PANEL – 2.3 MG CAPSULE DOSE BLISTER

• RX only
• PRESS
  &
  HOLD
  HERE
• Contains 1 Capsule
  Please read Package Insert before use.
• NDC 63020-078-01
• NINLARO®
  (ixazomib) capsules
• 2.3 mg
• Takeda

PULL OUT HERE

SRC: NLM .