Ninlaro

Multiple myeloma — in combination with lenalidomide and dexamethasone, for patients who have received at least one prior therapy

4 mg orally on Days 1, 8, and 15 of a 28-day cycle in combination with lenalidomide 25 mg Days 1-21 and dexamethasone 40 mg Days 1, 8, 15, 22
Take on empty stomach at least 1 hour before or 2 hours after food
Dose reductions: 3 mg, then 2.3 mg
Moderate hepatic impairment/severe renal impairment: Reduce starting dose to 3 mg

Capsules: 2.3 mg, 3 mg, 4 mg

None listed.

• Thrombocytopenia: 78% (Grade 3: 14%, Grade 4: 6%). Monitor platelet counts at least monthly. Nadir between Days 14-21.
• GI Toxicities: Diarrhea (42%), constipation (34%), nausea (26%), vomiting (22%). Antiemetics and antidiarrheal agents may be needed.
• Peripheral Neuropathy: 28% (Grade 3: 2%). Monitor and dose-modify.
• Peripheral Edema: 25% (Grade 3: 2%).
• Cutaneous Reactions: Rash (19%). Stevens-Johnson syndrome reported rarely.
• Thrombotic Microangiopathy: Including TTP and HUS.
• Hepatotoxicity: Monitor LFTs regularly. Drug-induced liver injury, hepatic failure, and death reported.
• Embryo-Fetal Toxicity

Diarrhea (42%), constipation (34%), thrombocytopenia (78%), nausea (26%), peripheral neuropathy (28%), peripheral edema (25%), vomiting (22%), back pain (21%), rash (19%), upper respiratory tract infection (19%), decreased appetite (11%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Ixazomib is an oral proteasome inhibitor that reversibly binds the beta 5 subunit of the 20S proteasome with high selectivity. It inhibits the chymotrypsin-like activity of the proteasome, leading to accumulation of polyubiquitinated proteins, activation of the unfolded protein response, cell cycle arrest, and apoptosis. As an oral agent, it offers a convenient alternative to IV proteasome inhibitors like carfilzomib and bortezomib.

Tmax: 1 hour. Absolute bioavailability: 58%. Half-life: 9.5 days. Protein binding: 99%. Metabolized by multiple CYP enzymes and non-CYP proteins. Urinary excretion (62%), fecal excretion (22%).

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• TOURMALINE-MM1 — Ixazomib + lenalidomide/dex vs. placebo + lenalidomide/dex in relapsed MM. Phase III, n=722.
  🔬 NCT01564537 ↗ 📄 Primary Publication ↗

Ninlaro has FDA-approved indications across the following cancer types covered on PipelineEvidence: