Ixazomib
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Handling and access
NIOSH hazardous drug
Table 1NIOSH lists ixazomib as a hazardous drug. AHFS class: 10:00 antineoplastic agents.
- The package insert includes manufacturer's special handling information (MSHI). Follow it when preparing, administering, and disposing of this drug.
Handle with the precautions your facility uses for hazardous drugs (USP <800>). NIOSH's Managing Hazardous Drug Exposures lists controls by drug form and activity.
Dosing in kidney impairment
Dosage in Patients with Renal Impairment Reduce the starting dose of NINLARO to 3 mg in patients with severe renal impairment (creatinine clearance less than 30 mL/min) or end-stage renal disease (ESRD) requiring dialysis. NINLARO is not dialyzable and therefore can be administered without regard to the timing of dialysis [see Use in Specific Populations and Clinical Pharmacology ] .
Refer to the lenalidomide prescribing information for dosing recommendations in patients with renal impairment.
| Recommended starting doseRecommended starting dose of 3 mg in patients with moderate or severe hepatic impairment, severe renal impairment or end-stage renal disease requiring dialysis [see Dosage and Administration (2.3, 2.4)]. | First reduction to | Second reduction to | Discontinue |
| 4 mg | 3 mg | 2.3 mg |
Dosing in liver impairment
Dosage in Patients with Hepatic Impairment Reduce the starting dose of NINLARO to 3 mg in patients with moderate (total bilirubin greater than 1.5-3 × ULN) or severe (total bilirubin greater than 3 × ULN) hepatic impairment [see Use in Specific Populations and Clinical Pharmacology ] .
| Recommended starting doseRecommended starting dose of 3 mg in patients with moderate or severe hepatic impairment, severe renal impairment or end-stage renal disease requiring dialysis [see Dosage and Administration (2.3, 2.4)]. | First reduction to | Second reduction to | Discontinue |
| 4 mg | 3 mg | 2.3 mg |
Preparation and administration
Dosing and Administration Guidelines NINLARO in combination with lenalidomide and dexamethasone The recommended starting dose of NINLARO is 4 mg administered orally once a week on Days 1, 8, and 15 of a 28-day treatment cycle. The recommended starting dose of lenalidomide is 25 mg administered daily on Days 1 through 21 of a 28-day treatment cycle.
The recommended starting dose of dexamethasone is 40 mg administered on Days 1, 8, 15, and 22 of a 28-day treatment cycle. [See table below.] Day Cycle (a 4-week cycle) - Week 1 Week 2 Week 3 Week 4 - Day 1 Days 2-7 Day 8 Days 9-14 Day 15 Days 16-21 Day 22 Days 23-28 NINLARO ✔ - ✔ - ✔ - - - Lenalidomide ✔ ✔ Daily ✔ ✔ Daily ✔ ✔ Daily - - Dexamethasone ✔ - ✔ - ✔ - ✔ - For additional information regarding lenalidomide and dexamethasone, refer to their prescribing information.
NINLARO should be taken once a week on the same day and at approximately the same time for the first three weeks of a four week cycle. The importance of carefully following all dosage instructions should be discussed with patients starting treatment. Instruct patients to take the recommended dosage as directed, because overdosage has led to deaths [see Overdosage ] .
NINLARO should be taken at least one hour before or at least two hours after food [see Clinical Pharmacology ] . The whole capsule should be swallowed with water. The capsule should not be crushed, chewed or opened [see How Supplied/Storage and Handling ] . If a NINLARO dose is delayed or missed, the dose should be taken only if the next scheduled dose is ≥72 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. Prior to initiating a new cycle of therapy: Absolute neutrophil count should be at least 1,000/mm 3 Platelet count should be at least 75,000/mm 3 Non-hematologic toxicities should, at the healthcare provider's discretion, generally be recovered to patient's baseline condition or Grade 1 or lower Treatment should be continued until disease progression or unacceptable toxicity.
Concomitant Medications Consider antiviral prophylaxis in patients being treated with NINLARO to decrease the risk of herpes zoster reactivation [see Adverse Reactions ] .
Drug interactions
Check ixazomib against a medication listLabel text (2 paragraphs)
Strong CYP3A inducers : Avoid concomitant use with NINLARO. ( 7.1 , 12.3 )
7.1 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 (12.3) ] .
Contraindications
None. None. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
E*Likelihood score E*: Unproven but suspected cause of clinically apparent liver injury.
Ixazomib is a small molecule proteasome inhibitor that is used in combination with other antineoplastic agents to treat refractory multiple myeloma. Ixazomib is associated with a low rate of serum enzyme elevations during treatment and to rare instances of clinically apparent, acute liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on its mechanism of action [see Clinical Pharmacology (12.1) ] and data from animal reproduction studies, NINLARO can cause fetal harm when administered to a pregnant woman. There are no available data on NINLARO use in pregnant women to evaluate drug-associated risk. Ixazomib caused embryo-fetal toxicity in pregnant rats and rabbits at doses resulting in exposures that were slightly higher than those observed in patients receiving the recommended dose (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In an embryo-fetal development study in pregnant rabbits there were increases in fetal skeletal variations/abnormalities (fused caudal vertebrae, number of lumbar vertebrae, and full supernumerary ribs) at doses that were also maternally toxic (≥0.3 mg/kg). Exposures in the rabbit at 0.3 mg/kg were 1.9 times the clinical time averaged exposures at the recommended dose of 4 mg.
In a rat dose range-finding embryo-fetal development study, at doses that were maternally toxic, there were decreases in fetal weights, a trend towards decreased fetal viability, and increased post-implantation losses at 0.6 mg/kg. Exposures in rats at the dose of 0.6 mg/kg was 2.5 times the clinical time averaged exposures at the recommended dose of 4 mg.
Breastfeeding (LactMed)
No information is available on the clinical use of ixazomib during breastfeeding. Because its half-life is about 9.5 days, it is likely to accumulate in the infant. It is also given in combination with leflunomide and dexamethasone, which may increase the risk to the infant. The manufacturer recommends that breastfeeding be discontinued during ixazomib therapy and for 90 days after the last dose.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.