Motixafortide (Monograph)

Brand name: Aphexda
Drug class: Hematopoietic Agents

Introduction

Motixafortide acetate, a C-X-C motif chemokine receptor 4 (CXCR4) inhibitor, is a hematopoietic stem cell mobilizer.

Uses for Motixafortide

Motixafortide acetate has the following uses:

Motixafortide is indicated in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.

Motixafortide Dosage and Administration

General

Motixafortide acetate is available in the following dosage form(s) and strength(s):

For injection: 62 mg (of motixafortide) as a lyophilized powder in a single-dose vial for reconstitution.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

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

• Premedicate all patients before each dose of motixafortide to reduce the risk of hypersensitivity and injection site reactions.

• Reconstitute motixafortide lyophilized powder prior to subcutaneous administration.

• Recommended dosage of motixafortide is 1.25 mg/kg based on actual body weight administered by slow (approximately 2 minutes) subcutaneous injection 10 to 14 hours prior to initiation of apheresis.

• A second dose of motixafortide can be administered 10 to 14 hours prior to a third apheresis, if necessary.

• Monitor patients for 1 hour after administration.

• See Full Prescribing Information for additional instructions on preparation and administration of the drug.

Related/similar drugs

Carvykti, Abecma, Velcade, Tecvayli, Revlimid, Darzalex, Pomalyst

Cautions for Motixafortide

Contraindications

History of serious hypersensitivity to motixafortide acetate.

Warnings/Precautions

Anaphylactic Shock and Hypersensitivity Reactions

Anaphylactic shock occurred in 0.7% of motixafortide-treated patients in clinical studies (n=407). The time to anaphylactic shock was between 5 minutes and 30 minutes after drug administration. Hypersensitivity reactions occurred in 7.6% of motixafortide-treated patients in the GENESIS study. In addition, pruritus, flushing, urticaria, rash, erythema, vomiting, nausea and chills have been reported.

Premedicate all patients prior to each dose of motixafortide 30-60 minutes prior to administration with a triple-drug premedication regimen that includes an H1-antihistamine, an H2 blocker, and a leukotriene inhibitor. Patients receiving concomitant negative chronotropic drugs (e.g., beta blockers) may be more at risk for hypotension in case of hypersensitivity reaction. When appropriate, beta blockers should be replaced with non-chronotropic drugs.

Administer motixafortide only in a setting where personnel and therapies are immediately available for the treatment of anaphylaxis and other systemic reactions. Monitor patients for signs or symptoms of hypersensitivity reactions for 1 hour following administration of motixafortide and manage reactions promptly.

Injection Site Reactions

Injection site reactions were reported in 73% of patients receiving motixafortide in the GENESIS trial. Symptoms of injection site reactions included pain, erythema, pruritus, bruising, discomfort, induration, mass, nodule, rash, swelling, and urticaria. Among 92 patients treated with motixafortide, the highest severity of the reactions was severe in 9%.

Premedicate with an analgesic medication (e.g., acetaminophen) prior to each motixafortide dose. Use analgesic medication and local treatments postdose, as needed.

Tumor Cell Mobilization in Patients with Leukemia

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

Leukocytosis

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

Potential for Tumor Cell Mobilization

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

Embryo-fetal Toxicity

Based on its mechanism of action, motixafortide can cause fetal harm when administered to a pregnant woman. Animal models link dysfunction in CXCR4/SDF-1 signaling to adverse outcomes in mammalian embryo-fetal development and suggest risks to normal placental development.

Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with motixafortide and for 8 days after the final dose.

Specific Populations

Pregnancy

Based on its mechanism of action, motixafortide can cause fetal harm when administered to a pregnant woman. There are no available data with motixafortide use in pregnant women informing the risk of embryo-fetal toxicity. Animal models link dysfunction in CXCR4/SDF-1 signaling to adverse outcomes in mammalian embryo-fetal development and suggest risk to normal placental development. No animal studies have been conducted to evaluate the effect of motixafortide on reproduction and fetal development. Advise pregnant women of the potential risk to a fetus.

The background risk of major birth defects and miscarriages for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation

There are no data on the presence of motixafortide in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential serious adverse reactions in the breastfed child, advise females that breastfeeding is not recommended during motixafortide treatment and for 8 days after the final dose.

Females and Males of Reproductive Potential

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

Motixafortide can cause fetal harm when administered to pregnant women. Advise females of reproductive potential to use effective contraception during treatment with motixafortide and for 8 days after the final dose.

Pediatric Use

The safety and effectiveness of motixafortide have not been established in pediatric patients.

Geriatric Use

Of the total number of patients in the GENESIS study, 33.8% were ≥65 years of age, while 1.25% were ≥75 years of age in the motixafortide arm. No overall differences in safety or effectiveness were observed between these patients and younger patients.

Common Adverse Effects

Most common adverse reactions (incidence >20%) are injection site reactions, injection site pain, injection site erythema, injection site pruritus, pruritus, flushing, and back pain.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Motixafortide is an inhibitor of the C-X-C Motif Chemokine Receptor 4 (CXCR4) and blocks the 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 the trafficking and homing on human hematopoietic stem cells 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.

Treatment with motixafortide resulted in leukocytosis, and elevations in circulating hematopoietic stem and progenitor cells into the peripheral circulation in mice, rats, dogs, and humans.

Stem cells mobilized by motixafortide were 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 healthcare professionals.

• Advise patients that motixafortide may cause injection site reactions, such as pain, redness, and swelling.

• Advise females of reproductive potential to use effective contraceptive methods during motixafortide treatment and for 8 days after the administration of the drug.

• Advise females of reproductive potential of the potential risk to a fetus. Advise females to contact their healthcare provider if they become pregnant or if pregnancy is suspected during treatment with motixafortide.

• Advise women that breastfeeding is not recommended during treatment with motixafortide and for 8 days following the last dose.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

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.

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