motixafortide (Aphexda)

Indications

• for use in combination with filgrastim to mobilize hematopoietic stem cells to the peripheral blood for collection & subsequent autologous hematopoietic stem cell transplantation in patients with multiple myeloma

Contraindications

• pregnancy (potential risk to fetus)

Dosage

• filgrastim 10 ug/kg SC QD for 4 days prior to 1st dose of motixafortide & on each day prior to apheresis
• premedicate with diphenhydramine, famotidine, montelukat & acetaminophen
• motixafortide 1.25 mg/kg SC over 2 minutes 10-14 hours prior to the 1st apheresis
  • a 2nd dose 10-14 hours prior to the 3rd apheresis

Pharmacokinetics

• peak plasma time: 0.25-1.17 hr
• >99% protein bound
• volume of distribution: 27 liter
• metabolized into small peptides & individual amino acids
• catabolism may occur in both blood & hepatic microsomes
• no ative metabolites
• elimination 1/2 life: ~2 hr

Adverse effects

• injection-site pain (53%), erythema (27%), pruritus (24%)
• pruritus (38%)
• flushing (33%)
• back pain (21%)
• paresthesia (19%)
• rash (16%)
• hypokalemia (15%)
• nausea (14%)
• urticaria (14%)
• erythema (12%)
• exfoliative generalized dermatitis (<10%)
• ear swelling (<10%)
• pyrexia (<10%), chills (<10%)
• dizziness (<10%)
• tremor (<10%)
• hypertension (<10%)

Mechanism of action

• inhibits C-X-C motif chemokine receptor 4 (CXCR4) blocks binding of its cognate ligand, stromal-derived factor 1-alpha/ C-X-C motif chemokine ligand 12 (SDF-1alpha/CXCL12)
  • SDF-1alpha& CXCL12 play a role in trafficking & homing of hematopoietic stem cells to the marrow compartment

More general terms

• hematologic agent

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=91865076