XAFTRID

Indications

• Mobilization of haematopoietic stem cells for autologous transplantation

Mechanism of action

Plerixafor inhibits the C-X-C chemokine receptor type 4 (CXCR4) on CD34+ cells, blocking the binding of its ligand, stromal cell-derived factor-1-alpha (SDF-1α). This inhibition disrupts the trafficking and homing of hematopoietic stem cells to the bone marrow, thus promoting their mobilization into the peripheral blood. The efficacy of plerixafor is enhanced when used in conjunction with granulocyte-colony stimulating factor (G-CSF), which increases the yield of stem cells necessary for transplantation.

Pharmacodynamics

Plerixafor is a bicyclam derivative that antagonizes CXCR4 by binding to specific acidic residues in the receptor's ligand-binding pocket. Following administration, peak levels of CD34+ cells are observed in the peripheral blood approximately 6 to 9 hours after a dose of 0.24 mg/kg. When combined with G-CSF, this peak occurs between 10 and 14 hours. The drug has not been associated with QT/QTc prolongation at doses up to 0.40 mg/kg. However, it may cause serious side effects including hypersensitivity reactions, tumor cell mobilization in leukemia patients, and various hematologic effects such as leukocytosis.

Pharmacokinetics

Plerixafor is administered via subcutaneous injection. Its pharmacokinetics can be influenced by renal function, as creatinine clearance may necessitate dose adjustment. The distribution and elimination half-life, along with the metabolism pathways, are not extensively detailed in the provided sources. Routine monitoring of hematologic parameters is recommended to assess the effects and potential adverse reactions following administration.

Adverse effects

• Chest pain
• Hypokalaemia
• Skin eruption
• Myalgia
• Nausea
• Flatulence
• Gastrointestinal discomfort
• Headache
• Malaise
• Musculoskeletal pain
• Vomiting
• Postural hypotension
• Syncope
• Splenomegaly
• Tumor cell mobilization
• Leukocytosis
• Thrombocytopenia

Precautions

• Myelosuppressive chemotherapy
• Acute leukaemia
• Monitor platelets and white blood cell count
• Caution in patients with renal impairment; dose adjustments may be necessary

Pregnancy

Teratogenic in animal studies, effective contraception should be used during treatment.

Breast-feeding

Manufacturer advises to avoid; no information available.

Storage

Store in a refrigerator (2 to 8 degrees Celsius). Protect from light.

Formulations

• Solution for injection: 6 mg/0.6 ml pre-filled syringes

Mechanism of action

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.

Pharmacodynamics

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.