ixazomib

Absorption: 58% absorbed following oral administration; bioavailability ↓ by high-fat foods.

Distribution: Extensively distributed to tissues.

Protein Binding: 99%.

Metabolism/Excretion: Metabolized by multiple CYP450 enzymes (including CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). 62% excreted in urine (<3.5% as unchanged drug), 22% excreted in feces.

Half-Life: 9.5 days.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Maintenance setting (may ↑ risk of mortality);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Moderate or severe hepatic impairment (↓ dose);
Severe renal impairment or end stage renal disease (↓ dose);
Rep: Women and men of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema

Derm: rash, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

EENT: blurred vision, conjunctivitis, dry eye

GI: constipation, diarrhea, nausea, vomiting, HEPATOTOXICITY

Hemat: HEMOLYTIC UREMIC SYNDROME, NEUTROPENIA, THROMBOCYTOPENIA, THROMBOTIC MICROANGIOPATHY, THROMBOTIC THROMBOCYTOPENIC PURPURA

MS: back pain

Neuro: peripheral neuropathy

Misc: herpes zoster infection

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inducers, including carbamazepine, phenytoin, and rifampin, may ↓ levels and effectiveness; avoid concurrent use.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults ): 4 mg on Days 1, 8, and 15 of a 28-day treatment cycle.

Hepatic Impairment

(Adults ): Moderate or severe hepatic impairment (total bilirubin >1.5× upper limit of normal): 3 mg on Days 1, 8, and 15 of a 28-day treatment cycle.

Renal Impairment

(Adults ): CCr <30 mL/min or requiring dialysis: 3 mg on Days 1, 8, and 15 of a 28-day treatment cycle.

Availability ⬆ ⬇

Capsules: 2.3 mg; 3 mg; 4 mg

Assessment ⬆ ⬇

Assess for rash (usually maculopapular or macular) periodically during therapy. If Grade 2 or 3 rash occurs, withhold lenalidomide until rash recovers to ≤Grade 1; then resume lenalidomide at next lower dose. If Grade 2 or 3 rash occurs again, withhold ixazomib and lenalidomide until rash ≤Grade 1; then resume ixazomib at next lower dose and resume lenalidomide at most recent dose. If Grade 4 rash occurs, permanently discontinue ixazomib.
Assess for signs and symptoms of peripheral neuropathy periodically during therapy. If Grade 1 peripheral neuropathy with pain or Grade 2 peripheral neuropathy occurs, withhold ixazomib until peripheral neuropathy recovers to ≤Grade 1 without pain or patient's baseline; then resume ixazomib at most recent dose. If Grade 2 peripheral neuropathy with pain or Grade 3 peripheral neuropathy occurs, withhold ixazomib until return to patient’s baseline condition or ≤Grade 1 peripheral neuropathy; then resume ixazomib at next lower dose. If Grade 4 peripheral neuropathy occurs, discontinue ixazomib.
Monitor for signs and symptoms of thrombotic microangiopathy (fever, easy bleeding or bruising, tiredness, decreased urination) during therapy. If symptoms occur, hold ixazomib and evaluate. If diagnosis is excluded, may consider restarting therapy.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
Prior to each 28-day cycle, ANC should be ≥1,000/mm³, platelet count should be ≥75,000/mm³, and nonhematologic toxicities should be recovered to patient’s baseline condition or ≤Grade 1.
For patients taking ixazomib, lenalidomide, and dexamethasone, if ANC <500/mm³, withhold ixazomib and lenalidomide until ANC ≥500/mm³; then resume lenalidomide at next lower dose and resume ixazomib at most recent dose. Consider adding granulocyte stimulating factor (G-CSF) as per clinical guidelines. If ANC <500/mm³ again, withhold ixazomib and lenalidomide until ANC ≥500/mm³; then resume ixazomib at next lower dose and resume lenalidomide at most recent dose.
- Monitor platelet counts at least monthly during therapy and more frequently during 1st three cycles. Nadir of thrombocytopenia usually occurs Days 14–21 of each 28-day cycle and recovery to baseline by start of next cycle. If platelet count ≤30,000/mm³, withhold ixazomib and lenalidomide until platelet count is ≥30,000/mm³; then resume lenalidomide at next lower dose and resume ixazomib at most recent dose. If platelet count <30,000/mm³ again, withhold ixazomib and lenalidomide until platelet count is ≥30,000/mm³; then resume ixazomib at next lower dose and resume lenalidomide at most recent dose.
- Monitor hepatic enzymes periodically during therapy and adjust dosing for Grade 3 or 4 symptoms.

Implementation ⬆ ⬇

Consider starting antiviral prophylaxis prior therapy to decrease risk of herpes zoster infection.
PO: Administer once weekly on same day and at same time for first 3 wk of 4-wk cycle. Take capsules at least 1 hr before or at least 2 hr after food. DNC: Swallow capsule whole with water; do not open, crush, or chew.
- Avoid direct contact with capsule contents. If powder from the capsule comes in contact with skin, wash area well with soap and water. If powder from capsule gets in the eyes, flush eyes well with water.
- Dexamethasone should be taken with food and not with ixazomib.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take ixazomib as directed and to avoid contact with capsule contents. Take delayed or missed doses only if next scheduled dose is ≥72 hr away. Do not take within 72 hr of next scheduled dose, and do not double doses. If vomiting occurs after taking dose, omit dose and resume dosing at time of next scheduled dose. Advise patient to read Patient Information sheet prior to starting therapy and with each Rx refill in case of changes.
Caution patient to avoid direct contact with capsule contents. If powder accidentally gets on skin, wash area well with soap and water. If in eyes, flush eyes well with water.
Advise patient to notify health care professional if signs and symptoms of thrombocytopenia (bleeding, easy bruising); thrombotic microangiopathy; GI problems (diarrhea, constipation, nausea, vomiting); peripheral neuropathy (tingling, numbness, pain, burning in feet or hands, weakness in arms or legs); liver problems (yellowing of skin or whites of eyes, pain in right upper abdomen); swelling in arms, hands, legs, ankles, or feet; weight gain from swelling; new or worsening rash; or back pain occurs.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
Rep: May cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential to use effective nonhormonal contraception during and for 90 days after last dose and to avoid breastfeeding during and for 90 days after last dose. Advise patient to notify health care professional immediately if pregnancy is suspected.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇