Xpovio
Xpovio Uses, Dosage, Side Effects, Food Interaction and all others data.
Xpovio is a first-in-class selective inhibitor of nuclear transport (SINE) compound. It is currently approved for the treatment of multiple myeloma, a cancer which forms from antibody-producing plasma cells. This condition is typically treated with high dose bortezomib and dexamethasone chemotherapy followed by autologous stem-cell transplant. Other chemotherapies for multiple myeloma include lenalidomide and dexamethasone, thalidomide, and may include melphalan if the patient is not eligible for transplant. Xpovio was approved by the FDA in June 2019. It was granted fast track and orphan designation as well as accelerated approval based on single arm, open label trial data. The Bortezomib, Xpovio, and Dexamethasone in Patients With Multiple Myeloma (BOSTON) trial is planned to finish in 2020.
Xpovio causes cell cycle arrest and apoptosis in cancer cells.
| Trade Name | Xpovio |
| Availability | Prescription only |
| Generic | Selinexor |
| Selinexor Other Names | Selinexor |
| Related Drugs | prednisone, rituximab, Rituxan, doxorubicin, cyclophosphamide, Revlimid, vincristine, Velcade, Darzalex, Pomalyst |
| Weight | 20mg, |
| Type | Oral tablet |
| Formula | C17H11F6N7O |
| Weight | Average: 443.313 Monoisotopic: 443.09292698 |
| Protein binding | Selinexor is 95% bound to plasma proteins. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Xpovio is indicated for the treatment of relapsed or refractory multiple myeloma in combination with dexamethasone. Patients must have received at least 4 prior therapies and have disease which is refractory to least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody.
Xpovio is also used to associated treatment for these conditions: Refractory Multiple Myeloma
How Xpovio works
Xpovio binds to and inhibits exportin-1 (XPO1). XPO1 is a nuclear exporter protein which contains a pocket to which nuclear proteins can bind. When complexed with these proteins and Ran, activated through guanosine triphosphate (GTP) binding, the XPO1-protein-Ran-GTP complex is able to exit the nucleus through a nuclear pore. Once outside, GTP is hydrolyzed and the complex dissociates. The inhibition of this process in cancer cells allows the targets of XPO1, many of which are tumor suppressors, to collect in the nucleus and result in increased transcription of tumor suppressor genes. Tumor suppressor proteins known to be affected by XPO1 inhibition include p53, p73, adenomatous polyposis coli, retinoblastoma, forkhead box protein O, breast cancer 1, nucleophosmin, and merlin. Regulators of cell cycle progression are also affected, namely p21, p27, galectin-3, and Tob. Inhibitor of NFκB also collects in the nucleus as a result leading to reduced activity of NFκB, a known contributor to cancer. XPO1 participates in the formation of a complex with eukaryotic initiation factor 4E and contributes to the transport of messenger RNA for several oncegenes including cell cycle promotors, cyclin D1, cyclin E, and CDK2/4/6, as well as antiapoptotic proteins, Mcl-1 and Bcl-xL. These wide ranging changes in protein expression and gene transcription culminate in cell cycle arrest and the promotion of apoptosis in cancer cells.
Food Interaction
- Take with or without food. Co-administration with food does not affect pharmacokinetics.
Xpovio Disease Interaction
Moderate: GI toxicities, hepatic dysfunction, hyponatremia, neurological toxicities, neutropenia, renal dysfunction, thrombocytopenia, weight loss
Volume of Distribution
The mean apparent volume of distribution is 125 L. A phase 1 study reported mean apparent volumes of distribution ranging from 1.9-2.9 L/kg in their investigation of food and formulation effects.
Elimination Route
A single 80 mg dose of selinexor produces a mean Cmax of 680 ng/mL and a mean AUC of 5386 ng*h/mL. This relationship is dose proportion over the range of 3-85 mg/m2 which encompasses the range of 0.06-1.8 times the approved dosage. The official FDA labeling reports the Tmax as 4 hours but phase 1 studies have found a range of 2-4 hours. Administering selinexor with food, either a high or low fat meal, results in an increase in the AUC of approximately 15-20% but this is not expected to be clinically significant.
Half Life
Xpovio has a mean half-life of elimination of 6-8 hours.
Clearance
Xpovio has a mean apparent clearance of 17.9 L/h.
Innovators Monograph
You find simplified version here Xpovio
