Motixafortide (Monograph)

Drug class: Hematopoietic Agents

Medically reviewed by Drugs.com on Jul 10, 2024. Written by ASHP.

Introduction

Hematopoietic stem cell mobilizer; C-X-C motif chemokine receptor 4 (CXCR4) inhibitor.

Uses for Motixafortide

Mobilization of Hematopoietic Stem Cells

Used in combination with filgrastim to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma. Designated an orphan drug by FDA for this use.

American Society of Clinical Oncology (ASCO) and Cancer Care Ontario has published evidence-based recommendations for patients with multiple myeloma undergoing autologous transplantation; however, specific place in therapy of motixafortide for mobilization of hematopoietic stem cells has not yet been established.

Motixafortide Dosage and Administration

General

Pretreatment Screening

Verify pregnancy status in females of reproductive potential prior to initiating motixafortide.

Patient Monitoring

Monitor patients for signs and symptoms of anaphylactic shock and hypersensitivity reactions for 1 hour following administration of motixafortide.
Monitor WBC counts during motixafortide therapy.

Premedication and Prophylaxis

To reduce the risk of hypersensitivity and injection site reactions, administer the following premedications 30–60 minutes prior to each motixafortide injection: an H1-antihistamine (e.g., diphenhydramine 12.5 mg IV or 25–50 mg orally), an H2-blocker (e.g., famotidine), and a leukotriene inhibitor (e.g., montelukast); addition of an analgesic (e.g., acetaminophen) is also recommended.

Dispensing and Administration Precautions

Administer motixafortide only in a setting where personnel and therapies are immediately available for treatment of anaphylaxis and other systemic reactions.

Administration

Sub-Q Administration

Administer by sub-Q injection.

Available as lyophilized powder in single-dose vial for reconstitution prior to sub-Q injection.

Administer filgrastim 10 mcg/kg sub-Q once daily for 4 days prior to the first dose of motixafortide and on each day prior to each apheresis.

Reconstitute lyophilized powder before use. (See Reconstitution under Dosage and Administration.)

Prior to administration, withdraw required volume from motixafortide vial(s) into an appropriately sized syringe.

Administer injection in abdomen, back or side of the upper arms, or thighs. Rotate injection sites. Do not inject into scar tissue or areas that are reddened, inflamed, or swollen. If injecting into the abdomen, avoid a 5 cm diameter circle around the navel. If >1 injection needed for a single dose, ensure injection sites are ≥2 cm apart from previous injection locations.

Each injection volume should not exceed 2 mL. Divide doses requiring >2 mL into multiple syringes to allow different injection sites.

Discard unused drug portions. Monitor patients for 1 hour after administration.

Reconstitution

Remove vials from refrigerator and allow to reach room temperature at 20–25°C for ≥30 minutes prior to reconstitution. Use aseptic technique for preparation and administration. Calculate dosage, total volume of reconstituted motixafortide solution required, and number of vials required based on the patient's actual body weight; >1 vial may be needed for a full dose.

Reconstitute each vial with 2 mL of 0.45% sodium chloride injection at room temperature (20–25°C), resulting in a concentration of 36.5 mg/mL and allowing withdrawal of up to 1.7 mL (62 mg). Alternatively, can reconstitute each vial with 1 mL of sterile water for injection plus 1 mL of 0.9% sodium chloride.

Gently swirl and invert vial for up to 3 minutes slowly until powder is fully dissolved.

Inspect reconstituted solution for discoloration and particulate matter; do not use if solution discolored, cloudy, or contains visible particulates.

Dosage

Dosage of motixafortide acetate expressed in terms of motixafortide.

Adults

Mobilization of Hematopoietic Stem Cells

Sub-Q

Recommended dose is 1.25 mg/kg (based on actual body weight) by slow (approximately 2 minutes) sub-Q injection 10–14 hours prior to initiation of the first apheresis.

Initiate motixafortide after filgrastim has been administered daily for 4 days.

If needed, administer a second dose of motixafortide 10–14 hours before a third apheresis.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time.

Cautions for Motixafortide

Contraindications

History of serious hypersensitivity reactions to motixafortide.

Warnings/Precautions

Anaphylactic Shock and Hypersensitivity Reactions

Anaphylactic shock and hypersensitivity reactions reported. Symptoms of hypersensitivity reactions included pruritus, flushing, urticaria, rash, erythema, vomiting, nausea, and chills.

Premedicate all patients 30–60 minutes prior to each dose of motixafortide with an H1-antihistamine, an H2 blocker, and a leukotriene inhibitor.

Patients receiving concomitant negative chronotropic drugs (e.g., beta blockers) may be at higher risk for hypotension with hypersensitivity reactions; when appropriate, replace beta blockers with non-chronotropic drugs.

Administer only in a setting where adequate personnel/treatments immediately available to manage anaphylaxis and other systemic reactions.

Monitor for signs or symptoms of hypersensitivity reactions for 1 hour following administration. Manage reactions promptly.

Injection Site Reactions

Injection site reactions (e.g., pain, erythema, pruritus, bruising, discomfort, induration, mass, nodule, rash, swelling, urticaria), including severe cases, reported.

Premedicate patients with an analgesic (e.g., acetaminophen) prior to each dose. Administer analgesic medication and local treatments following the dose, as needed.

Tumor Cell Mobilization in Patients with Leukemia

May cause mobilization of leukemic cells and subsequent contamination of the apheresis product.

Not intended for HSC mobilization and harvest in patients with leukemia.

Leukocytosis

Use in conjunction with filgrastim increases leukocytes and HSC populations in peripheral circulation.

Monitor WBC counts during use.

Potential for Tumor Cell Mobilization

When used in combination with filgrastim for HSC mobilization, tumor cells released from marrow could be collected in leukapheresis product.

Potential effect of tumor cell reinfusion unknown.

Fetal/Neonatal Morbidity and Mortality

Can cause fetal harm based on mechanism of action. Animal models link dysfunction in CXCR4/SDF-1 signaling to adverse outcomes in mammalian embryo-fetal development and suggest risks to normal placental development.

Apprise patients of potential fetal hazard if used during pregnancy. Advise females of reproductive potential to use effective contraception during treatment and for 8 days after the last dose.

Immunogenicity

No pre-existing or treatment-emergent (≤8 weeks post-administration) anti-drug antibodies detected in patients with multiple myeloma who received 1 or 2 doses of motixafortide in combination with filgrastim for HSC mobilization.

Specific Populations

Pregnancy

Can cause fetal harm based on mechanism of action. No available data on use in pregnant women to inform risk of embryo-fetal toxicity; however, animal models link dysfunction in CXCR4/SDF-1 signaling to adverse outcomes in mammalian embryo-fetal development and suggest risks to placental development.

Verify pregnancy status in females of reproductive potential prior to initiation. Apprise patients of potential hazard to fetus if motixafortide used during pregnancy.

Lactation

Unknown whether distributes into human milk, or affects milk production or breast-fed child.

Because of potential serious adverse reactions in the breast-fed child, advise females that breast-feeding is not recommended during treatment and for 8 days after the last dose.

Females and Males of Reproductive Potential

Verify pregnancy status in females of reproductive potential prior to initiation.

Advise females of reproductive potential to use effective contraception during treatment and for 8 days after the last dose.

Pediatric Use

Safety and effectiveness not established.

Geriatric Use

No overall differences in safety or effectiveness observed between geriatric patients (≥65 years of age) and younger adults.

Hepatic Impairment

No impact of mild hepatic impairment on motixafortide pharmacokinetics. Effects of moderate to severe hepatic impairment not studied to date; however, risk for adverse reactions due to increased exposure is low since motixafortide administered as a single dose.

Renal Impairment

No significant impact of mild to moderate renal impairment on motixafortide pharmacokinetics. Effects of severe renal impairment on motixafortide clearance not studied to date; however, significant effect not anticipated.

Common Adverse Effects

Most common adverse effects (>20%): injection site reactions, injection site pain, injection site erythema, injection site pruritus, pruritus, flushing, back pain.

Drug Interactions

In vitro studies showed lack of significant CYP inhibition in human hepatocytes, lack of CYP induction potential in human hepatocytes, and low potential for transporter-mediated interactions.

Low potential for both metabolism- and transporter-mediated drug interactions; no such reactions anticipated.

Motixafortide Pharmacokinetics

Absorption

Bioavailability

Pharmacokinetics following sub-Q administration adequately described by a 3-compartment model with first-order absorption, dose-dependent relative bioavailability, and linear elimination kinetics.

Minimal to no drug accumulation observed following once-daily dose administration; single-dose pharmacokinetic profile considered representative of a steady state profile.

Following sub-Q injection (as either a single or repeated dose of 0.24–2 mg/kg), time to peak plasma concentration approximately 0.25–1.17 hours.

Following administration (as monotherapy) in healthy volunteers, CD34+ cell counts increased with time, reaching maximal levels at 16 hours postdose; counts declined slightly thereafter but remained elevated well above baseline at last observation (24 hours postdose).

Special Populations

Higher relative bioavailability and 10% higher exposure observed in female patients compared with males for a weight-based dose of motixafortide; not considered clinically important.

Distribution

Extent

Unknown whether distributes into human milk.

Plasma Protein Binding

>99%.

Elimination

Metabolism

Undergoes non-specific degradation via catabolic pathways in both blood and liver microsomes into small peptides and individual amino acids and their derivatives.

Elimination Route

Animal data suggest that motixafortide metabolites mainly excreted via kidneys; biliary excretion minimal.

In animal studies, the total amount of radiolabeled motixafortide excreted in urine was approximately 80% of the dose administered; no parent drug detected in urine and nometabolite exceeded 30% of total clearance.

Half-life

Approximately 2 hours.

Special Populations

Age and race/ethnicity not expected to affect motixafortide pharmacokinetics.

Stability

Storage

Parenteral

Injection for Sub-Q Use

Unopened vials: 2–8°C; store in original carton to protect from light.

Reconstituted solution: if needed, store refrigerated at 2–8°C or at room temperature at 20–25°C for ≤24 hours protected from light; discard after 24 hours storage under refrigeration or at room temperature.

Actions

Inhibitor of C-X-C Motif Chemokine Receptor 4 (CXCR4) that blocks the binding of its cognate ligand, stromal-derived factor-1α (SDF-1α)/C-X-C Motif Chemokine Ligand 12 (CXCL12).
Both SDF-1α and CXCR4 play a role in trafficking of hematopoietic stem cells to the bone marrow; CXCR4 helps anchor stem cells to marrow matrix (either directly via SDF-1α or through induction of other adhesion molecules).
Motixafortide treatment results in leukocytosis and elevations in circulating hematopoietic stem and progenitor cells into peripheral circulation.
Stem cells mobilized by motixafortide capable of engraftment with long-term repopulating capacity in a rodent transplantation model.

Advice to Patients

Advise patients of the risk of anaphylactic and hypersensitivity reactions (e.g., pruritus, flushing, urticaria, rash, vomiting, nausea, chills) during and after motixafortide injection, and to immediately report such signs and symptoms to clinicians.
Advise patients that motixafortide may cause injection site reactions (e.g., pain, redness, swelling).
Advise females of reproductive potential to use effective contraceptive methods during treatment and for 8 days after the last dose of motixafortide.
Advise females of reproductive potential of the potential risk to a fetus. Advise females to contact their clinician if they become pregnant or if they suspect pregnancy during treatment.
Advise women that breast-feeding is not recommended during treatment and for 8 days after the last dose of motixafortide.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.