NINLARO (Ixazomib)
Proteasome inhibitor for the treatment of multiple myeloma
NINLARO (ixazomib) is the first oral proteasome inhibitor approved for the treatment of multiple myeloma. It is used in combination with lenalidomide and dexamethasone in adult patients who have received at least one prior therapy. By blocking proteasome function, ixazomib causes the accumulation of toxic proteins inside myeloma cells, leading to their death. This guide covers uses, dosage, side effects, drug interactions, and important safety information based on EMA and FDA-approved prescribing data.
Quick Facts
Key Takeaways
- NINLARO is the first oral proteasome inhibitor, taken once weekly as a capsule for multiple myeloma treatment.
- It is always used in combination with lenalidomide and dexamethasone in 28-day treatment cycles.
- The capsule must be taken on an empty stomach (at least 1 hour before or 2 hours after food) and swallowed whole.
- Common side effects include low platelet counts, nausea, diarrhea, peripheral neuropathy, and skin rash.
- Effective contraception is required during treatment and for 90 days after the last dose for both men and women.
What Is NINLARO and What Is It Used For?
NINLARO contains the active substance ixazomib, which belongs to a class of cancer medicines known as proteasome inhibitors. Proteasomes are structures inside every cell that break down proteins the cell no longer needs. This protein recycling process is essential for normal cell function and survival. Myeloma cells, however, produce abnormally large quantities of protein and are therefore highly dependent on proteasome activity to avoid toxic protein accumulation.
By blocking proteasome function, ixazomib disrupts the ability of myeloma cells to recycle their excess proteins. This leads to a buildup of defective and unwanted proteins within the cell, which triggers a cascade of events that ultimately causes the myeloma cell to self-destruct through a process called apoptosis. Normal cells also rely on proteasomes, but myeloma cells are disproportionately affected because of their exceptionally high rate of protein production.
NINLARO is specifically indicated for the treatment of adults with multiple myeloma who have already received at least one prior therapy. It is not used as a standalone treatment. Instead, it is given as part of a three-drug regimen alongside lenalidomide (an immunomodulatory agent) and dexamethasone (a corticosteroid). This combination has been shown in large clinical trials, including the landmark TOURMALINE-MM1 study, to significantly improve progression-free survival compared to lenalidomide and dexamethasone alone.
What Is Multiple Myeloma?
Multiple myeloma is a cancer of the bone marrow that affects plasma cells, a type of white blood cell responsible for producing antibodies to fight infections. In multiple myeloma, abnormal plasma cells (called myeloma cells) multiply uncontrollably and accumulate in the bone marrow. These cancerous cells crowd out healthy blood cells and produce large amounts of abnormal proteins that can damage bones, kidneys, and the immune system.
Symptoms of multiple myeloma often include bone pain (particularly in the spine and ribs), frequent infections, fatigue, kidney problems, and anemia. The disease is typically incurable but highly treatable, and most patients undergo multiple lines of therapy over the course of their illness. Proteasome inhibitors like NINLARO are a cornerstone of modern myeloma treatment, and the availability of an oral formulation offers significant convenience compared to injectable alternatives such as bortezomib.
The goal of treatment with NINLARO, lenalidomide, and dexamethasone is to reduce the number of myeloma cells, control disease progression, relieve symptoms, and improve quality of life. Treatment is continued for as long as the patient derives clinical benefit or until unacceptable side effects occur.
What Should You Know Before Taking NINLARO?
Contraindications
NINLARO must not be used by patients who have a known hypersensitivity (allergy) to ixazomib or to any of the excipients in the formulation. Allergic reactions can include symptoms such as swelling of the face, lips, tongue, or throat, difficulty breathing or swallowing, wheezing, chest tightness, dizziness, itching, and hives (angioedema or anaphylactic reaction). If you experience any signs of a severe allergic reaction, seek immediate medical attention.
Because NINLARO is always used in combination with lenalidomide and dexamethasone, you must also meet the eligibility criteria for those medicines. Lenalidomide has its own set of strict contraindications, particularly regarding pregnancy, and patients must comply with the lenalidomide pregnancy prevention program. Refer to the prescribing information for lenalidomide and dexamethasone for their full list of contraindications.
Warnings and Precautions
Before starting NINLARO and throughout treatment, discuss the following conditions with your healthcare team to determine whether dose adjustments or additional monitoring are required:
- Thrombocytopenia: NINLARO can cause significant drops in platelet counts. Your doctor will monitor blood counts regularly, particularly in the first several cycles. If you notice unusual bruising, bleeding gums, or nosebleeds, contact your doctor promptly.
- Gastrointestinal toxicity: Persistent nausea, vomiting, or diarrhea may occur and may require supportive care, dose modification, or antiemetic medication.
- Peripheral neuropathy: NINLARO can cause or worsen nerve damage in the hands and feet, manifesting as tingling, numbness, or burning sensations. Report any new or worsening symptoms to your doctor.
- Peripheral edema: Swelling in the legs, ankles, or feet has been reported. Your doctor should evaluate the cause and may adjust your treatment.
- Severe skin reactions: Rare but serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported. Stop taking NINLARO immediately and seek medical attention if you develop a severe rash with blistering, peeling skin, or mouth sores.
- Thrombotic microangiopathy: This rare but serious condition involves damage to small blood vessels and can cause fatigue, fever, bruising, bleeding, decreased urination, swelling, confusion, vision loss, and seizures. Report these symptoms immediately.
- Hepatic impairment: If you have liver problems, your doctor may prescribe a reduced dose of NINLARO (3 mg instead of 4 mg).
- Renal impairment: If you have severe kidney problems or require dialysis, a reduced dose of 3 mg may be prescribed.
Your doctor will perform regular blood tests before each treatment cycle and periodically during treatment to monitor platelet counts, liver function, and other blood parameters. NINLARO is not recommended for use in children and adolescents under 18 years of age, as safety and efficacy have not been established in this population.
Pregnancy and Breastfeeding
NINLARO is not recommended during pregnancy as it may cause harm to the unborn child. Breastfeeding should be discontinued during treatment with NINLARO. Both women and men of childbearing potential must use effective contraception during treatment and for 90 days after the last dose.
If you are pregnant, think you may be pregnant, or are planning to have a baby, consult your doctor before taking NINLARO. Women who use hormonal contraceptives should also use a barrier method of contraception. If you or your partner becomes pregnant during treatment, inform your doctor immediately.
Because NINLARO is given in combination with lenalidomide, which is a known teratogen (causes birth defects), strict adherence to the lenalidomide pregnancy prevention program is essential. Refer to the lenalidomide prescribing information for detailed requirements regarding pregnancy testing, contraception, and distribution restrictions.
Driving and Operating Machinery
NINLARO may cause fatigue and dizziness. If you experience these side effects, do not drive or operate machinery until you know how the medication affects you. This effect should be considered when evaluating your ability to perform tasks that require alertness.
How Does NINLARO Interact with Other Drugs?
Ixazomib is metabolized by multiple CYP enzymes and non-CYP proteins. Drug interactions can occur when other medicines affect these metabolic pathways, either by increasing the breakdown of ixazomib (reducing its efficacy) or by inhibiting its metabolism (potentially increasing toxicity). It is essential to inform your doctor, pharmacist, or nurse about all medications you are taking, including prescription drugs, over-the-counter medicines, vitamins, and herbal supplements.
Major Interactions to Avoid
| Drug | Type | Effect | Recommendation |
|---|---|---|---|
| Carbamazepine | Strong CYP3A Inducer | Significantly reduces ixazomib blood levels | Avoid combination |
| Phenytoin | Strong CYP3A Inducer | Significantly reduces ixazomib blood levels | Avoid combination |
| Rifampicin | Strong CYP3A Inducer | Reduces ixazomib AUC by approximately 74% | Avoid combination |
| St. John's Wort (Hypericum perforatum) | Strong CYP3A Inducer | May significantly reduce ixazomib exposure | Avoid combination |
Other Considerations
Clinical pharmacokinetic studies have shown that co-administration of ixazomib with strong CYP3A inhibitors (such as clarithromycin) does not significantly affect ixazomib exposure, so no dose adjustment is necessary with CYP3A inhibitors. However, because ixazomib is used in combination with lenalidomide and dexamethasone, potential interactions with these companion medications should also be considered.
Dexamethasone is a moderate CYP3A inducer, but the effect of dexamethasone at the doses used in the NINLARO regimen has been accounted for in clinical trials, and no additional dose adjustments are required. Always provide your treatment team with a complete and updated list of all substances you are taking, as unexpected interactions may occur with newly started medications.
What Is the Correct Dosage of NINLARO?
NINLARO must be prescribed by a physician experienced in the treatment of multiple myeloma. The treatment follows a strict 28-day cycle schedule, and adherence to the correct timing is essential for optimal outcomes. NINLARO is always taken in combination with two other medications, and each has its own dosing schedule within the cycle.
Standard 28-Day Cycle
| Medication | Dose | Schedule | Route |
|---|---|---|---|
| NINLARO (ixazomib) | 4 mg | Days 1, 8, 15 (once weekly for 3 weeks, then 1 week off) | Oral capsule |
| Lenalidomide | 25 mg | Days 1-21 (daily for 3 weeks, then 1 week off) | Oral capsule |
| Dexamethasone | 40 mg | Days 1, 8, 15, 22 (once weekly for all 4 weeks) | Oral |
Dose Adjustments
Your doctor may reduce the NINLARO dose from 4 mg to 3 mg, or from 3 mg to 2.3 mg, based on your individual tolerance and the occurrence of side effects. Common reasons for dose reduction include significant thrombocytopenia (low platelets), severe gastrointestinal symptoms, peripheral neuropathy, or skin reactions. Dose modifications for lenalidomide and dexamethasone may also be necessary and are determined independently.
Hepatic or Renal Impairment
Patients with moderate or severe hepatic impairment, or severe renal impairment (creatinine clearance < 30 mL/min) or those on dialysis, should receive a reduced starting dose of 3 mg. NINLARO is not removed by dialysis, so it may be administered without regard to the timing of dialysis sessions.
How to Take NINLARO
- Timing: Take NINLARO at least one hour before or at least two hours after a meal. Food can affect absorption.
- Swallow whole: The capsule must be swallowed whole with water. Do not crush, chew, or open the capsule.
- Avoid skin contact: Do not allow the capsule contents to come into contact with your skin. If accidental contact occurs, wash thoroughly with soap and water.
- Same day each week: Take NINLARO on the same day of the week at approximately the same time for consistency.
- Broken capsule: If a capsule breaks, avoid contact with the powder and clean up carefully to prevent dust inhalation.
Missed Dose
If you miss a dose or your dose is delayed, take it only if there are more than 72 hours (3 days) until the next scheduled dose. Do not take a missed dose if fewer than 72 hours remain before the next dose. Do not take a double dose to make up for a missed one. If you vomit after taking a dose, do not take an additional dose; take the next dose on schedule.
Overdose
Accidental overdose can cause serious side effects. If you take more NINLARO than prescribed, contact your doctor immediately or go to your nearest emergency department. Bring the medication packaging with you. Overdose symptoms may include an exaggeration of the known side effects, particularly severe thrombocytopenia and gastrointestinal toxicity.
Duration of Treatment
Treatment with NINLARO should continue for as long as your doctor determines that you are benefiting from the therapy. There is no fixed number of cycles. Treatment is typically continued until disease progression occurs or until the side effects become intolerable. Do not stop taking NINLARO without consulting your doctor, even if you feel well, as this could lead to disease progression.
What Are the Side Effects of NINLARO?
Like all medicines, NINLARO can cause side effects, although not everyone will experience them. Some side effects are common and manageable with supportive care, while others are rare but serious and require immediate medical attention. Your treatment team will monitor you closely throughout therapy and adjust your dose if necessary.
Reddish, non-raised, target-like or circular patches on the trunk, often with central blistering, skin peeling, ulcers of the mouth, throat, nose, genitals, or eyes. These serious skin rashes may be preceded by fever and flu-like symptoms (signs of Stevens-Johnson syndrome or toxic epidermal necrolysis).
Very Common
- Thrombocytopenia (low platelets) — increased risk of bruising and nosebleeds
- Nausea, vomiting, and diarrhea
- Constipation
- Peripheral neuropathy (numbness, tingling, or burning in hands/feet)
- Peripheral edema (swelling in legs or feet)
- Skin rash (may be itchy, localized or widespread)
- Back pain
- Upper respiratory tract infection (cold symptoms)
- Fatigue or weakness
- Fever (pyrexia)
- Joint pain (arthralgia)
- Neutropenia (low white blood cells, increased infection risk)
- Decreased appetite
- Cardiac arrhythmia (irregular heartbeat)
- Vision problems, including blurred vision, dry eyes, and conjunctivitis
- Bronchitis (cough, chest discomfort, or nasal congestion)
Common
- Herpes zoster reactivation (shingles) — skin rash and pain
- Hypotension (low blood pressure)
- Heart failure (shortness of breath, persistent cough, or wheezing)
- Jaundice (yellowing of eyes and skin, a sign of liver dysfunction)
- Hypokalemia (low potassium levels in the blood)
Rare
- Stevens-Johnson syndrome / toxic epidermal necrolysis — severe blistering skin reactions
- Sweet's syndrome — red or purple nodular skin lesions
- Transverse myelitis — muscle weakness, numbness in toes/feet, difficulty walking
- Posterior reversible encephalopathy syndrome (PRES) — vision changes, altered consciousness, seizures
- Tumor lysis syndrome — dizziness, decreased urination, confusion, vomiting, nausea, swelling, shortness of breath, or heart rhythm disturbances
- Thrombotic microangiopathy / thrombotic thrombocytopenic purpura — fatigue, fever, bruising, bleeding, decreased urination, swelling, confusion, vision loss, seizures
- Angioedema / anaphylaxis — swelling of face, lips, tongue, or throat; difficulty breathing or swallowing
Managing Side Effects
Many of the common side effects of NINLARO can be managed with supportive care. Anti-nausea medications (antiemetics) may be prescribed to manage gastrointestinal symptoms. Platelet counts typically follow a cyclical pattern, dropping around days 14-21 and recovering by the start of the next cycle. Your doctor will monitor this closely and may delay treatment or reduce doses if counts fall too low.
Herpes zoster (shingles) prophylaxis with an antiviral medication such as acyclovir or valacyclovir is recommended during NINLARO treatment to prevent viral reactivation. Discuss with your doctor whether prophylactic antiviral therapy is appropriate for you.
If you experience any side effects, even those not listed here, report them to your healthcare provider. Prompt reporting helps your treatment team make timely adjustments and ensures the best possible outcome from your therapy.
How Should You Store NINLARO?
- Temperature: Store at or below 30°C (86°F). Do not freeze.
- Packaging: Keep in the original blister packaging (sealed in a wallet pack inside the carton) to protect from moisture.
- Handling: Do not remove capsules from the blister pack until you are ready to take your dose.
- Inspection: Do not use if the packaging appears damaged or tampered with.
- Expiry: Do not use after the expiry date printed on the blister pack, wallet, and carton (EXP). The expiry date refers to the last day of that month.
- Children: Keep out of the sight and reach of children.
- Disposal: Do not dispose of medicines via wastewater or household waste. Return unused medicines to your pharmacy for proper disposal to help protect the environment.
What Does NINLARO Contain?
| Strength | Ixazomib Citrate | Capsule Color | Capsule Size | Markings |
|---|---|---|---|---|
| 2.3 mg | 3.3 mg | Light pink | Size 4 | "Takeda" / "2.3 mg" in black ink |
| 3 mg | 4.3 mg | Light gray | Size 4 | "Takeda" / "3 mg" in black ink |
| 4 mg | 5.7 mg | Light orange | Size 3 | "Takeda" / "4 mg" in black ink |
Inactive Ingredients
All three capsule strengths share the same inactive ingredients:
- Capsule contents: Microcrystalline cellulose, magnesium stearate, and talc.
- Capsule shell: Gelatin, titanium dioxide (E171), and iron oxide colorants (E172) — red iron oxide for 2.3 mg, black iron oxide for 3 mg, and yellow plus red iron oxide for 4 mg capsules.
- Printing ink: Shellac, propylene glycol, potassium hydroxide, and black iron oxide (E172).
Packaging
Each package contains 3 hard capsules in a blister strip, sealed in a wallet pack, which is then placed inside an outer carton. The wallet packaging provides additional moisture protection, which is important for maintaining the stability of the ixazomib citrate formulation.
Frequently Asked Questions About NINLARO
NINLARO (ixazomib) is used to treat adult patients with multiple myeloma who have received at least one prior therapy. It is always given in combination with lenalidomide and dexamethasone as part of a 28-day treatment cycle. NINLARO works by inhibiting proteasomes, causing cancer cells to accumulate toxic proteins and ultimately die.
NINLARO is taken once weekly on days 1, 8, and 15 of each 28-day cycle. The recommended starting dose is 4 mg. Take it on an empty stomach, at least one hour before or two hours after a meal. Swallow the capsule whole with water. Do not crush, chew, or open the capsule. Take it on the same day each week.
The most common side effects include low platelet counts (thrombocytopenia), nausea, vomiting, diarrhea, constipation, peripheral neuropathy (tingling or numbness in hands/feet), swelling in the legs or feet, skin rash, back pain, upper respiratory infections, fatigue, fever, and decreased appetite. Most of these can be managed with supportive care and dose adjustments.
No. NINLARO should be taken on an empty stomach. Take it at least one hour before a meal or at least two hours after a meal. Food, particularly high-fat meals, can alter the absorption of ixazomib and potentially affect its efficacy. Always swallow the capsule whole with water.
If you miss a dose, take it only if there are more than 72 hours (3 days) until the next scheduled dose. If fewer than 72 hours remain, skip the missed dose and take the next one as scheduled. Never take a double dose. If you vomit after taking a dose, do not take an extra dose.
Treatment continues for as long as your doctor determines it is beneficial. There is no fixed duration. Each cycle is 28 days, and patients typically undergo many cycles. Treatment is generally continued until the disease progresses or side effects become intolerable. Do not stop treatment without consulting your doctor.
References
- European Medicines Agency (EMA). NINLARO (ixazomib) — Summary of Product Characteristics. Last updated 2024. Available at: ema.europa.eu/en/medicines/human/EPAR/ninlaro
- Moreau P, Masszi T, Grzasko N, et al. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016;374(17):1621-1634. doi:10.1056/NEJMoa1516282
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 2.2025.
- Dimopoulos MA, Gay F, Schjesvold F, et al. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2019;393(10168):253-264. doi:10.1016/S0140-6736(18)33003-4
- U.S. Food and Drug Administration (FDA). NINLARO Prescribing Information. Revised 2024. Available at: FDA NINLARO Label
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd List, 2023.
- Rajkumar SV. Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol. 2024;99(1):94-114. doi:10.1002/ajh.27122
- European Society for Medical Oncology (ESMO). Multiple Myeloma: ESMO Clinical Practice Guidelines. Ann Oncol. 2021;32(3):309-322.
About the Medical Editorial Team
This article has been written and reviewed by our team of medical specialists in oncology, hematology, and clinical pharmacology. All information is based on the latest EMA and FDA-approved prescribing data, peer-reviewed clinical trials, and international treatment guidelines from NCCN, ESMO, and WHO. Our editorial process follows the GRADE evidence framework to ensure the highest standards of medical accuracy.
- Initial draft by medical writer with oncology expertise
- Peer review by board-certified hematologist/oncologist
- Pharmacological review by clinical pharmacologist
- Final review by iMedic Medical Review Board
- Evidence Level 1A (systematic reviews, RCTs)
- GRADE evidence framework compliance
- No commercial funding or conflicts of interest
- Regular updates based on new evidence