XPOVIO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XPOVIO (XPOVIO).
Selective inhibitor of nuclear export (SINE) that binds to and inhibits exportin 1 (XPO1), blocking the nuclear export of tumor suppressor proteins (e.g., p53, IκB) and growth regulators, leading to their nuclear accumulation and reactivation, thereby inducing apoptosis in cancer cells.
| Metabolism | Primarily metabolized by CYP3A4 and to a minor extent by CYP2C19, UGTs, and other CYP enzymes. |
| Excretion | Primarily metabolized by CYP3A4 and other pathways; <1% excreted unchanged in urine; fecal excretion accounts for ~80% of total clearance, with renal elimination minimal (<2% of dose). |
| Half-life | Terminal half-life ranges from 6 to 10 hours (mean ~7.5 h) in patients with relapsed/refractory multiple myeloma; supports twice-weekly dosing with food. |
| Protein binding | ~95% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Mean Vd/F approximately 100 L (1.4 L/kg for a 70 kg patient), indicating extensive tissue distribution. |
| Bioavailability | Absolute oral bioavailability is approximately 70–80% when administered with a low-fat meal; higher fat meals increase exposure. |
| Onset of Action | Clinical effect (reduction in tumor burden) observed within 1–2 weeks of initiating therapy at approved dosing regimen (80 mg twice weekly). |
| Duration of Action | Duration of response varies; median progression-free survival approximately 8.6 months in the STORM study; continuous dosing until progression or unacceptable toxicity. |
XPOVIO (selinexor) is administered orally at a dose of 80 mg (four 20 mg tablets) on days 1 and 3 of each week for multiple myeloma. For diffuse large B-cell lymphoma, the recommended dose is 60 mg (three 20 mg tablets) on days 1 and 3 of each week.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-89 mL/min: no adjustment needed. For GFR 15-29 mL/min: reduce dose by 25%. For GFR <15 mL/min or on dialysis: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 25%. Child-Pugh Class C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment based on age alone. Elderly patients may have increased risk of adverse effects (e.g., hyponatremia, neutropenia); monitor closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XPOVIO (XPOVIO).
| Breastfeeding | No data on the presence of selinexor in human milk, effects on the breastfed infant, or milk production. Due to the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for 1 week after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | XPOVIO (selinexor) is contraindicated in pregnancy. Based on its mechanism of action (XPO1 inhibitor) and animal studies, it can cause fetal harm when administered to a pregnant woman. No adequate human data exist. First trimester: high risk of embryotoxicity and teratogenicity; second and third trimesters: risk of fetal toxicity and impaired growth. Effective contraception is required for females of reproductive potential during treatment and for 1 week after the last dose. |
■ FDA Black Box Warning
XPOVIO can cause serious and fatal infections. Interrupt treatment for suspected infection. Monitor for signs and symptoms of infection and treat promptly.
| Serious Effects |
Concomitant use with strong CYP3A4 inhibitors or inducers
| Precautions | ["Serious infections (fatal and non-fatal)","Myelosuppression (thrombocytopenia, neutropenia, anemia)","Fetal harm (based on animal studies)","Gastrointestinal toxicity (nausea, vomiting, diarrhea)","Hyponatremia","Neurologic toxicity (confusion, dizziness, ataxia)","Cataracts"] |
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| Fetal Monitoring | Monitor complete blood counts (CBC) with differential, platelet count, and electrolytes (sodium, potassium, phosphate, calcium) at baseline and periodically during therapy. Assess for signs of infection, bleeding, and hepatic or renal dysfunction. Perform pregnancy testing in females of reproductive potential prior to initiation of therapy and periodically as clinically indicated. |
| Fertility Effects | Based on animal studies, selinexor may impair fertility in both males and females. In males, effects on spermatogenesis have been observed. The reversibility of these effects is unknown. |