Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 62mg/single-dose vial
Multiple Myeloma
Indicated in combination with filgrastim to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma
Filgrastim dosing
- Administer filgrastim 10 mcg/kg SC qDay x4 days before first dose of motixafortide and on each day before each apheresis
Premedication
- Premedicate before each dose of motixafortide to reduce risk of hypersensitivity and injection-site reactions
-
Regimen includes
- Administer the following ~30-60 minutes before motixafortide injection
- Diphenhydramine (12.5 mg IV or 25-50 mg PO, or another H1-antihistamine), AND
- H2 blocker (eg, famotidine), AND
- Leukotriene inhibitor (eg, montelukast)
- An analgesic medication (eg, acetaminophen) is also recommended
Motixafortide dosing
- Dosing is on actual body weight
- 1.25 mg/kg SC (over ~2 minutes) 10-14 hr before initiating first apheresis
- A second dose can be administered 10-14 hr before third apheresis, if necessary
Dosage Modifications
Renal impairment
- Mild-to-moderate: Pharmacokinetic profile not significantly affected
- Severe: Pharmacokinetic profile not studied
Hepatic impairment
- Mild: Pharmacokinetic profile not affected
- Moderate-to-severe: Pharmacokinetic profile not studied
Dosing Considerations
Verify pregnancy status in females of reproductive potential before initiating
Safety and efficacy not established
Adverse Effects
>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%)
Warnings
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 & Lactation
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.Pharmacology
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
Administration
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
Images
Formulary
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