Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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 (12)
- 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.
- lenacapavir
lenacapavir will increase the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- 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 (26)
- acetazolamide
acetazolamide will increase the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- 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.
- cyclophosphamide
cyclophosphamide will increase the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- 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.
- larotrectinib
larotrectinib will increase the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- 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.
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
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%
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.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
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
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Ninlaro oral - | 3 mg capsule |  | |
| Ninlaro oral - | 2.3 mg capsule |  | |
| Ninlaro oral - | 4 mg capsule |  |
Copyright © 2010 First DataBank, Inc.
Formulary
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