imlunestrant

Absorption: 32% absorbed following oral administration. Absorption ↑ with low-fat meals.

Distribution: Extensively distributed to tissues.

Protein Binding: >99%.

Metabolism/Excretion: Primarily metabolized by the liver via sulfation, CYP3A4, and glucuronidation (by UGT1A1, UGT1A3, UGT1A8, UGT1A9, and UGT1A10). Primarily excreted in the feces (97%; 62% as unchanged drug), with 0.3% excreted in the urine.

Half-Life: 30 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	4 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Moderate or severe hepatic impairment (↓ dose);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: flushing, pruritus

F and E: hypocalcemia

GI: ↑liver enzymes, abdominal pain, constipation, diarrhea, nausea, ↓appetite, dyspepsia, stomatitis, vomiting

GU: ↓fertility

Hemat: anemia, neutropenia, thrombocytopenia

Metab: hypercholesterolemia, hypertriglyceridemia

MS: pain

Neuro: fatigue, headache

Resp: cough

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A inhibitors, including itraconazole, may ↑ levels and risk of toxicity; avoid concurrent use. If concurrent use necessary, ↓ imlunestrant dose.
Strong CYP3A inducers, including carbamazepine, may ↓ levels and effectiveness; avoid concurrent use. If concurrent use necessary, ↑ imlunestrant dose.
May ↑ levels and risk of toxicity of P-glycoprotein substrates, including digoxin; avoid concurrent use.
May ↑ levels and risk of toxicity of breast cancer resistance protein substrates, including rosuvastatin; avoid concurrent use.

Drug-Natural Products:

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

Drug-Food:

Grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent use.

Route/Dosage ⬆ ⬇

Pre/perimenopausal women and men should receive a gonadotropin-releasing hormone agonist according to current clinical practice standards.
PO (Adults ): 400 mg once daily. Continue until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A inhibitor: 200 mg once daily. Continue until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A inducer: 600 mg once daily. Continue until disease progression or unacceptable toxicity.

Hepatic Impairment

PO (Adults ): Moderate or severe hepatic impairment: 200 mg once daily. Continue until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Film-coated tablets: 200 mg

Assessment ⬆ ⬇

Monitor for signs/symptoms of hepatotoxicity (fatigue, nausea, upper abdominal pain, jaundice, scleral icterus, dark urine, clay-colored stools).

Lab Test Considerations:

Verify pregnancy status before initiating treatment.
Select patients for treatment of ER-positive, HER2-negative advanced or metastatic breast cancer based on the presence of ESR1 mutation(s) in a plasma specimen using an FDA-approved test.
Monitor ALT and AST during therapy as clinically indicated. May ↑ liver enzymes. If persistent or recurrent AST/ALT >3–5 times upper limit of normal (ULN) occurs: Hold therapy until enzymes return to baseline or to >ULN–3 times ULN; then restart at same dose. If AST/ALT within normal range at baseline and ↑ to > 5–20 times ULN: Hold therapy until enzymes return to baseline or to >ULN–3 times ULN; then ↓ to 200 mg once daily; permanently discontinue if unable to tolerate 200 mg once daily. If AST/ALT >ULN at baseline, and ↑ to AST/ALT >3 times baseline (if AST/ALT >1.5 times ULN at baseline) or AST/ALT >8 times ULN (whichever is the lower threshold): Hold therapy until enzymes return to baseline or to > ULN–3 times ULN; then ↓ to 200 mg once daily; permanently discontinue if unable to tolerate 200 mg once daily. If ALT or AST <1.5 times ULN at baseline and ↑ to ≥3 times ULN concurrent with total bilirubin ≥2 times ULN with no cholestasis): Permanently discontinue imlunestrant. If ALT or AST ≥1.5 times ULN at baseline and ↑ to ≥2 times baseline concurrent with total bilirubin ≥2 times ULN with no cholestasis: Permanently discontinue imlunestrant. If AST/ALT >20 times ULN: Permanently discontinue imlunestrant.
Perform lipid panel prior to initiation and then periodically. May cause hypertriglyceridemia.

Implementation ⬆ ⬇

PO: Administer on an empty stomach 2 hr before food or 1 hr after food at approximately the same time each day. DNC: Swallow tablets whole. Do not split, crush, or chew.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of imlunestrant. Advise patient to take as directed at same time each day on an empty stomach (2 hr before food or 1 hr after food). Instruct patient if dose is missed by ≥6 hr or vomiting occurs, skip the dose and take next regularly scheduled dose. Advise patient to read Patient Information before starting therapy or each Rx refill in case of changes.
Explain need for continued medical follow-up to assess effectiveness and possible side effects of medication. Periodic lab tests will be needed.
Counsel patient to avoid grapefruit juice and grapefruit products.
Advise patient to immediately report signs/symptoms of hepatotoxicity.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Advise use of effective contraception in women of reproductive potential and in men with female partners of reproductive potential during therapy and for 1 wk after last dose. Advise women to not breastfeed during treatment and for 1 wk after the last dose.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇