Selinex 20mg (Selinexor)

COMPOSITION :
Selinex tablet: Each film coated tablet contains Selinexor
INN 20 mg.
PHARMACOLOGY :
Mechanism of Action
In nonclinical studies, Selinexor reversibly inhibits nuclear
export of tumor suppressor proteins (TSPs), growth
regulators, and mRNAs of oncogenic proteins by blocking
exportin 1 (XPO1). XPO1 inhibition by Selinexor leads to
accumulation of TSPs in the nucleus, reductions in several
oncoproteins, such as c‐myc and cyclin D1, cell cycle
arrest, and apoptosis of cancer cells. Selinexor demonstrat-
ed pro‐apoptotic activity in vitro in multiple myeloma cell
lines and patient tumor samples, and in murine xenograft
models.
Pharmacokinetic properties :
Following a single‐dose administration of Selinexor 80 mg,
the mean (standard deviation) peak plasma concentration
(Cmax) was 680 (124) ng/mL and the mean AUC was 5386
(1116) ng h/mL. Selinexor Cmax and AUC increased
proportionally over doses from 3 mg/m2 to 85 mg/m2 (0.06
to 1.8 times the approved recommended dose based on
1.7 m2 body surface area). No clinically relevant
accumulation at steady state was observed.
Absorption :
The Cmax is reached within 4 hours following oral
administration of Selinexor.
Effect of food :
Concomitant administration of a high‐fat meal (800 to 1,000
calories with approximately 50% of total caloric content of
the meal from fat) did not affect the pharmacokinetics of
Selinexor to a clinically significant extent.
Distribution
The apparent volume of distribution of Selinexor is 125 L in
patients with cancer. The protein binding of Selinexor is
95%.
Elimination
following a single dose of SELINEXOR, the mean half‐life is
6 to 8 hours. The apparent total clearance of Selinexor is
17.9 L/h in patients with cancer.
Metabolism
Selinexor is metabolized by CYP3A4, multiple
UDP‐ glucuronosyltransferases (UGTs) and glutathione
S‐ transferases (GSTs).
Specific Populations :
No clinically significant differences in the pharmacokinetics
of Selinexor were observed based on age (18 to 94 years
old), sex, ethnicity, mild to severe renal impairment (CLCR:
15 to 89 mL/min, estimated by the Cockcroft‐ Gault
equation). The effect of end‐stage renal disease (CLCR <15
mL/min) or hemodialysis on Selinexor pharmacokinetics is
unknown. Mild hepatic impairment had no clinically
significant effect on the pharmacokinetics of Selinexor. The
effect of moderate and severe hepatic impairment on
Selinexor pharmacokinetics is unknown.
Drug Interaction Studies :
Clinical Studies
No dedicated drug interaction studies have been
performed with Selinexor.
In vitro Studies
CYP Enzymes: Selinexor does not inhi