ixazomib (Rx)

Brand and Other Names:Ninlaro
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 2.3mg
  • 3mg
  • 4mg

Multiple Myeloma

Indicated in patients who have received at least 1 prior therapy

Use in combination with lenalidomide and dexamethasone

Continue treatment until disease progression or unacceptable toxicity

Starting doses

  • Ixazomib: 4 mg PO on days 1, 8, and 15 of a 28-day cycle; take 1 hr ac or 2 hr pc
  • Lenalidomide: 25 mg PO on days 1-21 of a 28-day cycle; take with or without food
  • Dexamethasone: 40 mg PO in morning on days 1, 8, 15, and 22 of a 28-day cycle

Dosage Modifications

Also refer to lenalidomide monograph

Dose reductions

  • For starting dose of 4 mg
    • First reduction: 3 mg
    • Second reduction: 2.3 mg
    • Unable to tolerate 2.3-mg dose: Discontinue therapy

Thrombocytopenia

  • Platelet count <30,000/m3
    • Withhold ixazomib and lenalidomide until platelet count ≥30,000/mm3
    • Following recovery, resume lenalidomide at next lower dose according to prescribing information and resume ixazomib at most recent dose
    • If recurs, withhold ixazomib and lenalidomide until platelet count ≥30,000/mm3, then resume ixazomib at next lower dose and resume lenalidomide at most recent dose*
    • *For additional occurrences, alternate dose modification of lenalidomide and ixazomib

Neutropenia

  • ANC count <500/mm3
    • Withhold ixazomib and lenalidomide until ANC ≥500/mm3; consider adding G-CSF as per clinical guidelines
    • Once resolved, resume lenalidomide at next lower dose according to prescribing information and resume ixazomib at most recent dose
    • If recurs, withhold ixazomib and lenalidomide until ANC ≥500/mm3 and resume ixazomib at next lower dose and resume lenalidomide at most recent dose*
    • *For additional occurrences, alternate dose modification of lenalidomide and ixazomib

Rash

  • Grade 2 or 3
    • Withhold lenalidomide until rash recovers to Grade ≤1 and then resume lenalidomide at next lower dose according to its prescribing information
    • If recurs, withhold ixazomib and lenalidomide until rash recovers to Grade ≤1
    • Following recovery, resume ixazomib at next lower dose and resume lenalidomide at most recent dose*
    • *For additional occurrences, alternate dose modification of lenalidomide and ixazomib
  • Grade 4
    • Discontinue treatment regimen

Peripheral neuropathy

  • Grade 1 with pain or Grade 2
    • Withhold ixazomib until peripheral neuropathy recovers to Grade ≤1 without pain or baseline
    • Following recovery, resume ixazomib at most recent dose
  • Grade 2 with pain or Grade 3
    • Withhold ixazomib
    • Toxicities should, at the physician’s discretion, generally recover to baseline condition or Grade ≤1 before resuming ixazomib
    • Following recovery, resume ixazomib at the next lower dose
  • Grade 4
    • Discontinue treatment regimen

Other nonhematological toxicities

  • Grade 3 or 4: Withhold ixazomib; toxicities should generally recover to patient’s baseline condition or Grade ≤1 before resuming ; resume at next lower dose following recover

Hepatic impairment

  • Mild (TB ≤1.5x ULN and any AST): No dosage adjustment required
  • Moderate or severe (TB >1.5x ULN and any AST): Decrease starting dose to 3 mg

Renal impairment

  • Mild-to-moderate (CrCl ≥30 mL/min): No dosage adjustment required
  • Severe (CrCl <30 mL/min) or end-stage renal disease requiring dialysis: Reduce starting dose to 3 mg; ixazomib is not dialyzable and therefore can be administered without regard to timing of dialysis

Dosing Considerations

Consider antiviral prophylaxis to decrease the risk of herpes zoster reactivation

Monitor before each new cycle of therapy

  • ANC should be at least 1,000/mm³
  • Platelet count should be at least 75,000/mm³
  • Nonhematologic toxicities should, at the physician’s discretion, generally be recovered to patient’s baseline condition or ≤grade 1

Limitations of use

  • Not recommended for maintenance setting or in newly diagnosed multiple myeloma in combination with lenalidomide and dexamethasone outside of controlled clinical trials

Safety and efficacy not established

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Interactions

Interaction Checker

and ixazomib

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            Contraindicated (0)

              Serious - Use Alternative (28)

              • abametapir

                abametapir will increase the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

              • apalutamide

                apalutamide will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

              • bosentan

                bosentan will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • carbamazepine

                carbamazepine will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • dabrafenib

                dabrafenib will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • dexamethasone

                dexamethasone will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • efavirenz

                efavirenz will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • enzalutamide

                enzalutamide will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • eslicarbazepine acetate

                eslicarbazepine acetate will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • etravirine

                etravirine will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • fosphenytoin

                fosphenytoin will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • ivosidenib

                ivosidenib will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

              • lumacaftor/ivacaftor

                lumacaftor/ivacaftor will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • mitotane

                mitotane will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • nafcillin

                nafcillin will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • nevirapine

                nevirapine will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • oxcarbazepine

                oxcarbazepine will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • palifermin

                palifermin increases toxicity of ixazomib by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.

              • pentobarbital

                pentobarbital will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • phenobarbital

                phenobarbital will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • phenytoin

                phenytoin will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • primidone

                primidone will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • rifabutin

                rifabutin will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • rifampin

                rifampin will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • rifapentine

                rifapentine will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • St John's Wort

                St John's Wort will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

              • tucatinib

                tucatinib will increase the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

              • voxelotor

                voxelotor will increase the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

              Monitor Closely (11)

              • belzutifan

                belzutifan will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

              • cenobamate

                cenobamate will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

              • elagolix

                elagolix decreases levels of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

              • encorafenib

                encorafenib, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

              • fedratinib

                fedratinib will increase the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              • lorlatinib

                lorlatinib will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • rucaparib

                rucaparib will increase the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

              • siponimod

                siponimod and ixazomib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

              • stiripentol

                stiripentol, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              • tazemetostat

                tazemetostat will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • tecovirimat

                tecovirimat will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

              Minor (22)

              • atazanavir

                atazanavir, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • clarithromycin

                clarithromycin, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • cobicistat

                cobicistat, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • conivaptan

                conivaptan, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • darunavir

                darunavir, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • elvitegravir/cobicistat/emtricitabine/tenofovir DF

                elvitegravir/cobicistat/emtricitabine/tenofovir DF, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • fosamprenavir

                fosamprenavir, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • grapefruit

                grapefruit, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • idelalisib

                idelalisib, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • imatinib

                imatinib, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • indinavir

                indinavir, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • isoniazid

                isoniazid, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • lopinavir

                lopinavir, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • nefazodone

                nefazodone, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • nelfinavir

                nelfinavir, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • nicardipine

                nicardipine, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • posaconazole

                posaconazole, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • ribociclib

                ribociclib will increase the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • ritonavir

                ritonavir, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • saquinavir

                saquinavir, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • tipranavir

                tipranavir, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

              • voriconazole

                voriconazole, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

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              Adverse Effects

              Percentages listed are for any grade toxicity unless otherwise stated

              >10%

              Thrombocytopenia (78%)

              Neutropenia (67%)

              Diarrhea (42%)

              Constipation (34%)

              Peripheral neuropathies (28%)

              Nausea (26%)

              Thrombocytopenia, grade 3-4 (26%)

              Neutropenia, grade 3-4 (26%)

              Peripheral edema (25%)

              Vomiting (22%)

              Back pain (21%)

              Upper respiratory tract infection (19%)

              Rash (19%)

              1-10%

              Diarrhea, grade 3 (6%)

              Blurred vision (6%)

              Conjunctivitis (6%)

              Dry eye (5%)

              Herpes zoster, without antiviral prophylaxis (4%)

              Rash, grade 3 (3%)

              Peripheral edema (2%)

              Peripheral neuropathies, grade 3 (2%)

              Nausea, grade 3 (2%)

              Vomiting, grade 3 (1%)

              <1%

              Herpes zoster, with antiviral prophylaxis

              Drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic, and hepatotoxicity

              Upper respiratory tract infection, grade 3

              Constipation, grade 3

              Back pain, grade 3

              Acute febrile neutrophilic dermatosis (Sweet syndrome)

              Stevens-Johnson syndrome

              Transverse myelitis

              Posterior reversible encephalopathy syndrome

              Tumor lysis syndrome

              Thrombotic thrombocytopenic purpura

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              Warnings

              Contraindications

              None

              Cautions

              Cases, sometimes fatal, of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), reported; monitor for signs and symptoms of TTP/HUS; if TTP/HUS is suspected, stop therapy, and evaluate; if TTP/HUS is excluded, consider restarting therapy; safety of reinitiating therapy in patients previously experiencing TTP/HUS not known

              Thrombocytopenia reported with platelet nadirs typically occurring between days 14 and 21 of each 28-day cycle and recovery to baseline by the start of the next cycle; monitor platelet counts at least monthly during treatment; consider more frequent monitoring during the first 3 cycles

              Diarrhea, constipation, nausea, and vomiting reported, occasionally requiring use of antidiarrheals, antiemetics, and supportive care

              Peripheral neuropathy reported; monitor for symptoms; new or worsening peripheral neuropathy may require dose modification

              Peripheral edema reported; evaluate for underlying causes and provide supportive care, as necessary; adjust dosing of dexamethasone per its prescribing information or ixazomib for Grade 3 or 4 symptoms

              Cutaneous reactions reported, including maculopapular and macular rash; manage with supportive care or with dose modification if Grade ≥2; Stevens-Johnson syndrome, including a fatal case, reported; discontinue therapy if Stevens-Johnson syndrome occurs and manage as clinically indicated

              Rare occurrence of drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic, and hepatotoxicity reported; monitor hepatic enzymes regularly and adjust dosing for Grade 3 or 4 symptoms

              Herpes zoster infection reported; consider antiviral prophylaxis during therapy to decrease risk of herpes zoster reactivation

              Can cause fetal harm when administered to a pregnant woman based on the mechanism of action and findings in animals

              Maintenance treatment for multiple myeloma in clinical trial resulted in increased deaths; therefore, not recommended for maintenance treatment outside of controlled trials

              Drug interaction overview

              • Substrate of CYP3A4
              • Strong CYP3A4 inducers
                • Avoid coadministration
                • Rifampin (a strong CYP3A4 inducer) decreased ixazomib Cmax by 54% and AUC by 74%
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              Pregnancy & Lactation

              Pregnancy

              Can cause fetal harm when administered to a pregnant woman

              There are no human data available regarding the potential effect of ixazomib on pregnancy or development of the embryo or fetus

              Animal studies

              • Ixazomib caused embryofetal toxicity in pregnant rats and rabbits at doses resulting in exposures that were slightly higher than those observed in patients receiving the recommended dose
              • Increases in fetal skeletal variations/abnormalities (fused caudal vertebrae, number of lumbar vertebrae, and full supernumerary ribs) in rabbit studies
              • Decrease fetal weights, a trend towards decreased fetal viability, and increased postimplantation losses were observed in rat studies

              Contraception

              • Advise women of the potential risk to a fetus and to avoid becoming pregnant while being treated
              • Male and female patients of childbearing potential must use effective contraceptive measures during and for 90 days following the final dose
              • Dexamethasone is known to be a weak to moderate inducer of CYP3A4 as well as other enzymes and transporters; because drug is administered with dexamethasone, consider risk for reduced efficacy of contraceptives; advise women using hormonal contraceptives to also use a barrier method of contraception

              Lactation

              No data are available in human milk; effects of drug on breastfed infant, or effects of drug on milk production; because potential for serious adverse reactions from drug in breastfed infants is unknown, advise nursing women not to breastfeed during treatment and for 90 days after last dose

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Reversible proteasome inhibitor; preferentially binds and inhibits the chymotrypsinlike activity of the beta 5 subunit of the 20S proteasome

              Absorption

              Absolute bioavailability: 58%

              Peak plasma time: 1 hr

              A food effect study conducted in patients with a single 4-mg dose showed that a high-fat meal decreased AUC by 28% and Cmax by 69% (see Administration)

              Distribution

              Protein bound: 99% bound to plasma proteins and distributes into RBCs with a blood-to-plasma ratio of 10

              Vd: 543 L

              Metabolism

              Metabolism by multiple CYP enzymes and non-CYP proteins is expected to be the major clearance mechanism

              Elimination

              Half-life: 9.5 days

              Systemic clearance: 1.9 L/hr

              Excretion: 62% urine (<3.5% unchanged); 22% feces

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              Administration

              Oral Administration

              Take once a week on the same day and at approximately the same time for the first 3 weeks of a 4-week cycle

              Taken at least 1 hr before or 2 hr after food

              Swallow capsule whole with water; do not crush, chew, or open

              Consult patients on the following

              • Discuss the importance of carefully following all dosage instructions starting treatment
              • Advise to take recommended dosage as directed; overdosage has led to death

              Missed or vomited dose

              • Delayed or missed dose: Take dose only if next scheduled dose is ≥72 hr away; do not double dose to make up for missed dose
              • Vomited dose: Do not repeat dose; resume dosing at the time of the next scheduled dose

              Storage

              Store at room temperature; not to exceed 30°C (86°F)

              Do not freeze

              Store capsules in original packaging until immediately prior to use

              Chemotherapy handling and disposal

              • Cytotoxic drug
              • Avoid direct contact with the capsule contents
              • In case of capsule breakage, avoid direct contact of capsule contents with the skin or eyes
              • In case of capsule breakage, avoid direct contact of capsule contents with the skin or eyes
              • If contact occurs with the skin, wash thoroughly with soap and water
              • If contact occurs with the eyes, flush thoroughly with water
              • Any unused medicinal product or waste material should be disposed in accordance with local requirements
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              Images

              BRAND FORM. UNIT PRICE PILL IMAGE
              Ninlaro oral
              -
              3 mg capsule
              Ninlaro oral
              -
              4 mg capsule
              Ninlaro oral
              -
              2.3 mg capsule

              Copyright © 2010 First DataBank, Inc.

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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

              To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

              Adding plans allows you to:

              • View the formulary and any restrictions for each plan.
              • Manage and view all your plans together – even plans in different states.
              • Compare formulary status to other drugs in the same class.
              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
              Additional Offers
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.