selinexor

Therapeutic Classification: antineoplastics

Pharmacologic Classification: nuclear export inhibitors

REMS

Relapsed or refractory multiple myeloma in patients who have received at ≥4 previous therapies and whose disease is refractory to at ≥2 proteasome inhibitors, ≥2 immunomodulatory agents, and an anti-CD38 monoclonal antibody (in combination with dexamethasone).

Inhibits exportin 1 which inhibits nuclear export of tumor suppression proteins, growth regulators, and mRNAs of oncogenic proteins. This action leads to accumulation of tumor suppression proteins in the nucleus of the tumor cell, reduction in oncogenic proteins and tumor cell apoptosis.

Therapeutic effects:

Decreased progression of multiple myeloma.

Absorption: Unknown.

Distribution: Extensively distributed to tissues.

Protein Binding: 95%.

Metabolism/Excretion: Metabolized by the CYP3A4 isoenzyme, UDP-glucuronosyltransferases (UGTs), and glutathione S-transferases. Excretion pathway unknown.

Half-Life: 6–8 hr.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	4 hr	unknown

Contraindicated in:

OB: Pregnancy (may cause fetal harm);
Lactation: Lactation.

Use Cautiously in:

Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established;
Geri: risk of adverse reactions.

Drug-drug:

None reported.

PO (Adults ): 80 mg on Days 1 and 3 of each week; continue until disease progression or unacceptable toxicity.

Monitor for signs and symptoms of bleeding. Interrupt and/or reduce dose, or permanently discontinue based on severity of adverse reaction. Use platelet transfusion and/or other treatments as clinically indicated.
Assess for fatigue periodically during therapy. If Grade 2 lasting > 7 days OR Grade 3, hold dose. Monitor until fatigue resolves to Grade 1 or baseline. Restart selinexor at 1 dose level lower.
Monitor for nausea, vomiting, and diarrhea during therapy. If Grade 1 or 2 nausea (oral intake decreased without significant weight loss, dehydration or malnutrition) OR Grade 1 or 2 vomiting (5 or fewer episodes per day) occurs, maintain therapy and initiate additional anti-nausea medications. If Grade 3 nausea (inadequate oral caloric or fluid intake) OR Grade 3 or higher vomiting (6 or more episodes per day) occurs, hold selinexor. Monitor until nausea or vomiting has resolved to ≤Grade 2 or baseline. Start additional anti-nausea medications. Restart therapy at 1 dose level lower. If Grade 2 diarrhea (increase of 4 to 6 stools per day over baseline) occurs, first occurrence, continue therapy and institute supportive care. 2nd and subsequent occurrence, Reduce dose by 1 dose level. Institute supportive care. If ≥Grade 3 (increase of 7 stools or more per day over baseline; hospitalization indicated) occurs, hold selinexor and institute supportive care. Monitor until diarrhea resolves to ≤ Grade 2. Restart therapy at 1 dose level lower.
May cause anorexia and weight loss. If weight loss of 10% to < 20% OR anorexia associated with significant weight loss or malnutrition occurs, hold selinexor and institute supportive care. Monitor until weight returns to > 90% of baseline weight. Restart therapy at 1 dose level lower.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.Monitor CBC, platelet counts standard blood chemistry, and body weight at baseline and during treatment as clinically indicated. Monitor more frequently during the first 2 mo of therapy. Thrombocytopenia:If platelet count 25,000 to < 75,000/mcL, reduce dose by 1 level. If platelet count 25,000 to < 75,000/mcL with concurrent bleeding, hold dose. Restart at 1 dose level lower after bleeding has resolved. If platelet count < 25,000/mcL, hold dose. Monitor until platelet count returns to at least 50,000/mcL. Restart at 1 dose level lower. Neutropenia:If absolute neutrophil count (ANC) of 0.5 – 1.0 x 10⁹ /L without fever, reduce by 1 dose level. If ANC <0.5 x 10⁹ /L OR febrile neutropenia, hold dose. Monitor until ANC returns to 1.0 x 109 /L or higher. • Restart at 1 dose level lower. Anemia:If hemoglobin < 8.0 g/dL, reduce dose by 1 dose level. Administer blood transfusions and/or other treatments per clinical guidelines. If life-threatening consequences occur, hold dose. Monitor hemoglobin until levels return to ≥8 g/dL. Restart therapy at 1 dose level lower. Administer blood transfusions and/or other treatments per clinical guidelines. Hyponatremia:If sodium level ≤130 mmol/L, hold dose and provide supportive care. Monitor until sodium levels return to ≥130 mmol/L. Restart therapy at 1 dose level lower.

Maintain hydration status. Consider IV hydration for patients at risk of dehydration.
Provide prophylactic concomitant therapy with a 5-HT3 antagonist and/or other anti-nausea agents before and during therapy.
Dose reduction recommendations:1st reduction, 100 mg once weekly; 2nd reduction, 80 mg once weekly; 3rd reduction, 60 mg weekly. If patient cannot tolerate 60 mg weekly dose, discontinue therapy.
PO: Administer tablets with dexamethasone 20 mg at the same time each day on Days 1 and 3 of each week. DNC: Swallow tablets whole; do not crush, break, or chew.

Instruct patient to take selinexor as directed. If a dose is missed or patient vomits, omit dose and take dose at next regularly scheduled time.
Advise patients to maintain adequate fluid and caloric intake during therapy.
May cause confusion and dizziness. Advise patient to avoid driving or other activities requiring alertness until response to the medication is known.
Instruct patient to notify health care professional if signs of bleeding, fatigue, shortness of breath, nausea, vomiting, diarrhea, decreased appetite, weight loss, or infection (chills, fever) occurs.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken, to avoid alcohol, and to consult health care professional before taking any new medications.
Rep: May cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during and for 1 wk after last dose of therapy. Advise females to avoid breastfeeding and for 1 wk after last dose of therapy. May impair male and female fertility.

Decreased progression of multiple myeloma.

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Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

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US Brand Names ⬆