Plerixafor

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Warning

H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]

P264, P264+P265, P280, P302+P352, P305+P351+P338, P321, P332+P317, P337+P317, and P362+P364 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Plerixafor has not been linked to instances of significant serum enzyme elevations during therapy nor to cases of clinically apparent liver injury. In multiple large prelicensure as well as postmarketing controlled trials, neither ALT elevations or acute liver injury were mentioned as adverse events or reasons for drop out, early discontinuation of therapy or dose modification. There have been no published reports of liver injury attributed to plerixafor, and it has been used as a possible means of treatment in animal models of acute liver failure. Thus, clinically apparent liver injury due to plerixafor must be rare, if it exists at all.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Plerixafor

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

L03AX16

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Plerixafor is a bicyclam derivative that antagonizes C-X-C chemokine receptor type 4 (CXCR4) by binding to three acidic residues in the ligand-binding pocket: Asp171, Asp262, and Glu288. Blood levels of CD34+ cells peaked between 6 and 9 hours after the administration of 0.24 mg/kg plerixafor in healthy subjects. In combination with a granulocyte-colony stimulating factor (G-CSF), circulating CD34+ cells in the peripheral blood peaked between 10 and 14 hours. The use of plerixafor is not associated with QT/QTc prolongation at single doses up to 0.40 mg/kg. Serious hypersensitivity reactions, such as anaphylactic-type reactions, have occurred in patients receiving plerixafor. The use of plerixafor may also cause tumor cell mobilization in leukemia patients, splenic enlargement and rupture, embryo-fetal toxicity, and hematologic effects, such as leukocytosis and thrombocytopenia. When used in combination with G-CSF for hematopoietic stem cell mobilization‚ plerixafor may lead to the release of tumor cells from the marrow and their subsequent collection in the leukapheresis product.

Plerixafor inhibits the C-X-C chemokine receptor type 4 (CXCR4) on CD34+ cells and reversibly blocks the binding of its ligand, stromal cell-derived factor-1-alpha (SDF-1α). SDF-1α and CXCR4 play a role in the trafficking and homing of human hematopoietic stem cells (HSCs) to the marrow compartment. In the marrow, stem cell CXCR4 can help anchor HSCs to the marrow matrix, either directly via SDF-1α or through the induction of other adhesion molecules. By blocking the interaction between SDF-1α and CXCR4 with plerixafor, the mobilization of progenitor cells is triggered. Adding granulocyte-colony stimulating factor (G-CSF) to enhance CD34+ cell mobilization increases the yield of stem cells, an important determinant of graft adequacy.

Plerixafor has a distribution half-life of 0.3 hours and a terminal population half-life of 5.3 hours in patients with normal renal function. In studies with healthy subjects and patients, the terminal half-life in plasma ranges between 3 and 5 hours. In patients with non-Hodgkin lymphoma, the terminal half-life of plerixafor is 4.4 hours, and in patients with multiple myeloma, the terminal half-life is 5.6 hours.