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. |
| Molecular Weight | 535 |
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 | Avoid use during first trimester; based on mechanism of action and animal studies, XPOVIO (selinexor) is expected to cause fetal harm. Advise effective contraception. |
| 2nd trimester | Avoid use during second trimester; there are no adequate human data, but animal studies show embryofetal toxicity. |
| 3rd trimester | Avoid use during third trimester; potential risk to fetus outweighs benefits. Consider alternative therapies. |
Clinical note
Comprehensive clinical and safety monograph for XPOVIO (XPOVIO).
| Placental transfer | Selinexor is expected to cross the placenta based on its molecular weight (535.0 Da) and lipophilic properties, though specific human data are lacking. Animal studies show embryofetal transfer. |
| Breastfeeding | It is unknown whether selinexor is excreted in human milk. Due to potential serious adverse reactions in nursing infants, women should not breastfeed 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 |
Concurrent use with strong CYP3A4 inducersConcurrent use with strong CYP3A4 inhibitorsPatients with known hypersensitivity to selinexor or any excipients
| 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 |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they increase selinexor exposure via CYP3A4 inhibition. Avoid St. John's wort and other strong CYP3A4 inducers like rifampin. High-fat meals decrease absorption; take on an empty stomach (at least 1 hour before or 2 hours after food). Maintain adequate oral hydration to prevent hyponatremia and dehydration. |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| 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. |
| 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. |
| Clinical Pearls | XPOVIO (selinexor) is a selective inhibitor of nuclear export (SINE) compound that blocks XPO1. It is used in combination with dexamethasone for relapsed/refractory multiple myeloma (RRMM) and with rituximab, gemcitabine, and oxaliplatin for relapsed/refractory DLBCL. Monitor for thrombocytopenia, neutropenia, hyponatremia, and nausea/vomiting. Administer antiemetics prophylactically. Dose adjustments are required for hepatic impairment (Child-Pugh B or C) and severe renal impairment (CrCl <30 mL/min). Avoid concurrent strong CYP3A4 inducers or inhibitors unless dose adjustments are made. Electrolyte disturbances (especially hyponatremia) are common; correct before initiation. |
| Patient Advice | Take exactly as prescribed. Do not change dose or stop without consulting your doctor. · XPOVIO can cause low blood cell counts; report any signs of infection, unusual bruising, or bleeding. · Nausea and vomiting are common; take anti-nausea medications as directed and maintain hydration. · Monitor for electrolyte imbalances; report confusion, weakness, or muscle cramps. · Avoid grapefruit and grapefruit juice during treatment. · Women of childbearing age must use effective contraception during and for at least 1 week after last dose. · Do not breastfeed while taking XPOVIO and for at least 1 week after last dose. · Take tablets whole with water; do not crush, chew, or split. · If you miss a dose, skip it and resume regular schedule; do not double dose. · Report any new or worsening symptoms such as fatigue, shortness of breath, or vision changes. |