motixafortide (Rx)

>10%

All grades

• Injection-site pain (53%)
• Pruritus (38%)
• Flushing (33%)
• Injection-site erythema (27%)
• Injection-site pruritus (24%)
• Back pain (21%)
• Paresthesia (19%)
• Rash (16%)
• Hypokalemia (15%)
• Nausea (14%)
• Urticaria (14%)
• Erythema (12%)

Grade ≥3

• Pruritus (11%)

1-10%

Dermatitis, exfoliative generalized (<10%)

Ear swelling (<10%)

Pyrexia (<10%)

Chills (<10%)

Dizziness (<10%)

Tremor (<10%)

Hypertension (<10%)

Grade ≥3

• Injection-site pain (7%)
• Flushing (7%)
• Hypokalemia (4.3%)
• Urticaria (1.1%)

Contraindications

History of serious hypersensitivity to motixafortide

Cautions

Anaphylactic shock and hypersensitivity reactions

• Anaphylactic shock reported
• Time to anaphylactic shock was between 5 and 30 minutes after drug administration
• Pruritus, flushing, urticaria, rash, erythema, vomiting, nausea, and chills were also reported
• Premedicate all patients before each dose with a triple-drug premedication regimen that includes an H1- antihistamine, an H2 blocker, and a leukotriene inhibitor
• Patients receiving concomitant negative chronotropic drugs (eg, beta-blockers) may be at greater risk for hypotension in case of hypersensitivity reaction
• When appropriate, replace beta-blockers with nonchronotropic drugs
• Administer only in a setting where personnel and therapies are immediately available for the treatment of anaphylaxis and other systemic reactions
• Monitor for signs or symptoms of hypersensitivity reactions for 1 hr following administration

Injection-site reactions

• Injection-site reactions reported
• Symptoms included pain, erythema, pruritus, bruising, discomfort, induration, mass, nodule, rash, swelling, and urticaria
• Premedicate with an analgesic medication (eg, acetaminophen) before each dose
• Use analgesic medication and local treatments postdose, as needed

Tumor cell mobilization in patients with leukemia

• When used for hematopoietic stem cell (HSC) mobilization, motixafortide may cause mobilization of leukemic cells and subsequent contamination of the apheresis product
• Therefore, it is not intended for HSC mobilization and harvest in patients with leukemia

Leukocytosis

• Administration in conjunction with filgrastim increases circulating leukocytes as well as HSC populations
• Monitor white blood cell counts during use

Potential for tumor cell mobilization

• When used in combination with filgrastim for HSC mobilization, tumor cells may be released from the marrow and subsequently collected in leukapheresis product
• Effect of potential reinfusion of tumor cells has not been well-studied

Embryo fetal toxicity

• On the basis of its mechanism of action, can cause fetal harm when administered to pregnant females

Pregnancy

On the basis of its mechanism of action, can cause fetal harm when administered to pregnant females

Advise pregnant females of potential risk to fetus

Verify pregnancy status in females of reproductive potential before initiating

Animal studies

• Animal models link dysfunction in CXCR4/SDF-1 signaling to adverse outcomes in mammalian embryo-fetal development and suggest risks to normal placental development
• No animal studies have been conducted to evaluate the effect of motixafortide on reproduction and fetal development

Contraception

• Advise females of reproductive potential to use effective contraception during treatment and for 8 days after final dose

Lactation

Data are not available on presence of motixafortide in human milk, effects on breastfed children, or effects on milk production

Advise females not to breastfeed during treatment and for 8 days after final dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Inhibitor of C-X-C motif chemokine receptor 4 (CXCR4) and blocks binding of its cognate ligand, stromal-derived factor-1α (SDF-1α)/C-X-C motif chemokine ligand 12 (CXCL12)

SDF-1α and CXCR4 play a role in trafficking and homing of human HSCs to the marrow compartment

Once in the marrow, stem cell CXCR4 can help anchor these cells to the marrow matrix, either directly via SDF-1α or through the induction of other adhesion molecules

Motixafortide treatment resulted in leukocytosis, and elevations in circulating hematopoietic stem and progenitor cells into peripheral circulation in mice, rats, dogs, and humans

Absorption

Peak plasma time: 0.25-1.17 hr

Distribution

Protein bound: >99%

Vd: 27 L

Metabolism

Undergoes nonspecific degradation into small peptides and individual amino acids and their derivatives by catabolic pathways

Catabolism can occur in both blood and liver microsomes

No prominent unique human metabolites identified

Elimination

Half-life: ~2 hr

Total clearance: 46.5 L/hr

SC Preparation

More than 1 vial may be needed for a full dose

Calculate dose, total volume of reconstituted solution required, and number of vials required on the basis of patient’s actual body weight

Remove vial(s) from refrigerator and let sit at least 30 minutes to reach room temperature (20-25ºC [68-77ºF])

Reconstitution

• Reconstitute each vial with 2 mL of 0.45% NaCl resulting in concentration of 36.5 mg/mL and permitting withdrawal of up to 1.7 mL (62 mg)
• Alternatively, reconstitute each vial with 1 mL of sterile water for injection and 1 mL of 0.9% NaCl
• Gently swirl and invert for up to 3 minutes slowly until powder is completely dissolved
• Inspect reconstituted solution for discoloration and particulate matter; should appear clear and colorless
• Discard if reconstituted solution is discolored or cloudy or contains visible particulates
• Withdraw required dosage volume from vial(s) into an appropriately sized syringe
• Each injection volume should not exceed 2 mL
• Divide doses requiring >2 mL into multiple syringes to allow different injection sites

SC Administration

Administer by slow SC injection (~2 minutes)

Administer injection into abdomen, back or side of upper arms, or thighs

Rotate injection sites

Do not inject into scar tissue or areas that are reddened, inflamed, or swollen

If injecting into abdomen, avoid 5-cm diameter circle around the navel

If >1 injection needed for a single dose, injection sites should be at least 2 cm away from previous injection locations

Discard unused portion of the drug

Monitor patients for 1 hour after administration

Storage

Unopened vials

• Store at 2-8ºC (36-46ºF) in original carton to protect from light

Reconstituted solution

• If needed, may refrigerate at 2-8ºC (36-46ºF) or store at room temperature at 20-25ºC (68-77ºF) for up to 24 hr protected from light