Ninlaro Side Effects Center

What Is Ninlaro?

Ninlaro (ixazomib) is a proteasome inhibitor indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.

What Are Side Effects of Ninlaro?

Common side effects of Ninlaro include:

diarrhea,
constipation,
low levels of platelets in the blood (thrombocytopenia),
low levels of white blood cells (neutropenia),
weakness/numbness/pain in the hands and feet,
nausea,
swelling in the hands and feet,
vomiting,
back pain,
rash, and
eye disorders including dry eye, blurred vision, and conjunctivitis.

Dosage for Ninlaro

The recommended starting dose of Ninlaro is 4 mg taken orally on Days 1, 8, and 15 of a 28-day cycle.

What Drugs, Substances, or Supplements Interact with Ninlaro?

Ninlaro may interact with strong CYP3A inducers (such as rifampin, phenytoin, carbamazepine, and St. John's Wort). Tell your doctor all medications and supplements you use.

Ninlaro During Pregnancy and Breastfeeding

Ninlaro is not recommended for use during pregnancy; it may harm a fetus. Women should avoid becoming pregnant while being treated with Ninlaro. Male and female patients of childbearing potential must use contraceptives during and for 90 days following treatment. Breastfeeding is not recommended while taking Ninlaro.

Additional Information

Our Ninlaro (ixazomib) capsules Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Ninlaro Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Ixazomib can cause life-threatening blood clots in the small blood vessels inside your organs, such as your brain or kidneys. Seek medical help right away if you have symptoms of this condition, such as a fever, tiredness, decreased urination, bruising, or nosebleeds.

Call your doctor at once if you have:

severe ongoing nausea, vomiting, diarrhea, or constipation;
a new or worsening skin rash;
blurred vision, dry or red eyes;
back pain;
fluid retention--swelling in your hands or feet, rapid weight gain;
liver problems--upper stomach pain, jaundice (yellowing of the skin or eyes);
low levels of platelets in your blood--easy bruising, unusual bleeding, purple or red spots under your skin;
low white blood cell counts--fever, cold or flu symptoms, cough, sore throat, swollen gums, mouth sores, skin sores;
nerve problems--numbness, tingling, pain, burning feeling in your hands or feet, weakness in your arms or legs; or
signs of shingles--flu-like symptoms, tingly or painful blistering rash on one side of your body.

Common side effects may include:

nerve problems or swelling in your hands or feet;
low blood platelets;
diarrhea, constipation;
nausea, vomiting; or
back pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Ninlaro Professional Information

SIDE EFFECTS

The following adverse reactions are described in detail in other sections of the prescribing information:

Thrombocytopenia [see WARNINGS AND PRECAUTIONS]
Gastrointestinal Toxicities [see WARNINGS AND PRECAUTIONS]
Peripheral Neuropathy [see WARNINGS AND PRECAUTIONS]
Peripheral Edema [see WARNINGS AND PRECAUTIONS]
Cutaneous Reactions [see WARNINGS AND PRECAUTIONS]
Thrombotic Microangiopathy [see WARNINGS AND PRECAUTIONS]
Hepatotoxicity [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety population from the randomized, double-blind, placebo-controlled clinical study included 720 patients with relapsed and/or refractory multiple myeloma, who received NINLARO in combination with lenalidomide and dexamethasone (NINLARO regimen; N=360) or placebo in combination with lenalidomide and dexamethasone (placebo regimen; N=360).

The most frequently reported adverse reactions (≥ 20%) in the NINLARO regimen and greater than the placebo regimen were diarrhea, constipation, thrombocytopenia, peripheral neuropathy, nausea, peripheral edema, vomiting, and back pain. Serious adverse reactions reported in ≥ 2% of patients included thrombocytopenia (2%) and diarrhea (2%). For each adverse reaction, one or more of the three drugs was discontinued in ≤ 1% of patients in the NINLARO regimen.

Table 4 summarizes the adverse reactions occurring in at least 5% of patients with at least a 5% difference between the NINLARO regimen and the placebo regimen.

Table 4: Non-Hematologic Adverse Reactions Occurring in ≥ 5% of Patients with a ≥ 5% Difference Between the NINLARO Regimen and the Placebo Regimen (All Grades, Grade 3 and Grade 4)

System Organ Class / Preferred Term	NINLARO + Lenalidomide and Dexamethasone N=360			Placebo + Lenalidomide and Dexamethasone N=360
	N (%)			N (%)
	All	Grade 3	Grade 4	All	Grade 3	Grade 4
Infections and infestations
Upper respiratory tract infection	69 (19)	1 (< 1)	0	52 (14)	2 (< 1)	0
Nervous system disorders
Peripheral neuropathies*	100 (28)	7 (2)	0	77 (21)	7 (2)	0
Gastrointestinal disorders
Diarrhea	151 (42)	22 (6)	0	130 (36)	8 (2)	0
Constipation	122 (34)	1 (< 1)	0	90 (25)	1 (< 1)	0
Nausea	92 (26)	6 (2)	0	74 (21)	0	0
Vomiting	79 (22)	4 (1)	0	38 (11)	2 (< 1)	0
Skin and subcutaneous tissue disorders
Rash*	68 (19)	9 (3)	0	38 (11)	5 (1)	0
usculoskeletal and connective tissue disorders
Back pain	74 (21)	2 (< 1)	0	57 (16)	9 (3)	0
General disorders and administration site conditions
Edema peripheral	91 (25)	8 (2)	0	66 (18)	4 (1)	0
Note: Adverse reactions included as preferred terms are based on MedDRA version 16.0. *Represents a pooling of preferred terms

Table 5 represents pooled information from adverse event and laboratory data.

Table 5: Thrombocytopenia and Neutropenia

	NINLARO + Lenalidomide and Dexamethasone N=360		Placebo + Lenalidomide and Dexamethasone N=360
	N (%)		N (%)
	Any Grade	Grade 3-4	Any Grade	Grade 3-4
Thrombocytopenia	281 (78)	93 (26)	196 (54)	39 (11)
Neutropenia	240 (67)	93 (26)	239 (66)	107 (30)

Herpes Zoster

Herpes zoster was reported in 4% of patients in the NINLARO regimen and 2% of patients in the placebo regimen. Antiviral prophylaxis was allowed at the healthcare provider’s discretion. Patients treated in the NINLARO regimen who received antiviral prophylaxis had a lower incidence (< 1%) of herpes zoster infection compared to patients who did not receive prophylaxis (6%).

Eye Disorders

Eye disorders were reported with many different preferred terms but in aggregate, the frequency was 26% in patients in the NINLARO regimen and 16% of patients in the placebo regimen. The most common adverse reactions were blurred vision (6% in the NINLARO regimen and 3% in the placebo regimen), dry eye (5% in the NINLARO regimen and 1% in the placebo regimen), and conjunctivitis (6% in the NINLARO regimen and 1% in the placebo regimen). Grade 3 adverse reactions were reported in 2% of patients in the NINLARO regimen and 1% in the placebo regimen.

Adverse Reactions Reported Outside Of The Randomized Controlled Trial

The following serious adverse reactions have each been reported at a frequency of < 1%: acute febrile neutrophilic dermatosis (Sweet’s syndrome), Stevens-Johnson syndrome, transverse myelitis, posterior reversible encephalopathy syndrome, tumor lysis syndrome, and thrombotic thrombocytopenic purpura.

DRUG INTERACTIONS

Strong CYP3A Inducers

Avoid concomitant administration of NINLARO with strong CYP3A inducers (such as rifampin, phenytoin, carbamazepine, and St. John’s Wort) [see CLINICAL PHARMACOLOGY].

Read the entire FDA prescribing information for Ninlaro (Ixazomib Capsules)