Selinexor

Indications

Selinexor is used for: Multiple Myeloma

Adult Dose

Multiple Myeloma Indicated in combination with dexamethasone for adults with relapsed or refractory multiple myeloma (RRMM) who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody 80 mg PO plus dexamethasone 20 mg PO on Days 1 and 3 of each week Continue until disease progression or unacceptable toxicity Concomitant treatment Maintain adequate fluid and caloric intake throughout treatment Consider IV hydration for patients at risk of dehydration Provide prophylactic concomitant treatment with a 5–HT3 antagonist and/or other antinausea agents before and during treatment Hepatic impairment Mild: No significant differences in pharmacokinetics observed Moderate-to-severe: Effect on pharmacokinetics unknown

Child Dose

Renal Dose

Renal impairment Mild-to-severe (CrCl 15-89 mL/min): No significant differences in pharmacokinetics observed ESRD (CrCl <15 mL/min) or hemodialysis: Effect on pharmacokinetics unknown

Administration

May take with or without food

Contra Indications

Precautions

High incidence of thrombocytopenia reported; median time to onset of first event was 22 days; some patients experienced bleeding; rare reports of death resulting from fatal hemorrhage Neutropenia commonly reported, potentially increasing infection risk Nausea and/or vomiting commonly occurs; follow recommendations for adequate hydration and prophylactic antiemetics Diarrhea commonly reported; monitor for dehydration and provide supportive care as required Anorexia and weight loss reported Hyponatremia may rapidly occur (median onset 8 days) and may be severe Infections reported; most infections were not associated with neutropenia and were caused by nonopportunistic organisms Neurological toxicity may occur, including dizziness, syncope, depressed level of consciousness, and mental status changes (including delirium and confused state) Embryofetal toxicity can occur

Pregnancy-Lactation

Pregnancy Based on animal studies and its mechanism of action, selinexor can cause fetal harm if administered to pregnant women Verify pregnancy status of females of reproductive potential before initiating selinexor Animal studies Administration to pregnant rats during organogenesis resulted in structural abnormalities and alterations to growth at exposures below those clinically recommended for humans Contraception Females of reproductive potential: Use effective contraception during treatment and for 1 week after the last dose Males with female partner of reproductive potential: Use effective contraception during treatment and for 1 week after the last dose Infertility Based on animal studies, selinexor may impair fertility in females and males Lactation No data are available regarding the presence of selinexor or its metabolites in human milk, or their effects on the breastfed child or milk production Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 1 week after the last dose

Interactions

Side Effects

Side effects of Selinexor : >10% (All Grades) Thrombocytopenia (74%) Fatigue (73%) Nausea (72%) Anemia (59%) Decreased appetite (53%) Weight decreased (47%) Diarrhea (44%) Vomiting (41%) Hyponatremia (39%) Neutropenia (34%) Leukopenia (28%) Constipation (25%) Dyspnea (24%) Upper respiratory tract infection (21%) Cough (16%) Mental status changes (16%) Pyrexia (16%) Hyperglycemia (15%) Dizziness (15%) Insomnia (15%) Lymphopenia (15%) Dehydration (14%) Hypercreatinemia (14%) Pneumonia (13%) Epistaxis (12%) Hypokalemia (12%) Dysgeusia (11%) >10% (Grades ≥3) Thrombocytopenia (61%) Anemia (40%) Fatigue (22%) Hyponatremia (22%) Neutropenia (21%) Leukopenia (11%) 1-10% (All Grades) Blurred vision (10%) Headache (10%)

Mode of Action

Selective inhibitor of nuclear export (SINE) of tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1) XPO1 inhibition leads to accumulation of TSPs in the nucleus, reductions in several oncoproteins (eg, c–myc, cyclin D1), cell cycle arrest, and apoptosis of cancer cells Selinexor demonstrated proapoptotic activity in vitro in multiple myeloma cell lines, patient tumor samples, and murine xenograft model