Axatilimab-csfr (Monograph)

Brand name: Niktimvo
Drug class: Other Miscellaneous Therapeutic Agents

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

Introduction

Axatilimab-csfr is a colony stimulating factor-1 receptor (CSF-1R)-blocking antibody.

Uses for Axatilimab-csfr

Axatilimab has the following uses:

Axatilimab is indicated for the treatment of chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg.

Axatilimab-csfr Dosage and Administration

General

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

Injection: 50 mg/mL solution in a single-dose vial.

Dosage

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

Dosage and Administration in Adults and Pediatric Patients Weighing ≥40 kg

Administer only as an IV infusion over 30 minutes through a dedicated infusion line that includes a sterile, low-protein binding 0.2- micron in-line or add-on polyethersulfone (PES) filter.
Dilute commercially available injection solution prior to administration.
The recommended dosage of axatilimab is 0.3 mg/kg (maximum 35 mg) every 2 weeks in adult and pediatric patients weighing 40 kg and above until disease progression or unacceptable toxicity.
See Full Prescribing Information for dosage modifications for adverse reactions and preparation and administration instructions.

Cautions for Axatilimab-csfr

Contraindications

None.

Warnings/Precautions

Infusion-related Reactions

Axatilimab can cause infusion-related reactions. Infusion-related reactions, including hypersensitivity reactions, occurred in 18% of patients who received axatilimab-csfr in the clinical trial (AGAVE-201), with Grade 3 or 4 reactions in 1.3%.

Premedicate with an antihistamine and an antipyretic for patients who have previously experienced an infusion-related reaction to axatilimab. Monitor patients for signs and symptoms of infusion-related reactions, including fever, chills, rash, flushing, dyspnea, and hypertension. Interrupt or slow the rate of infusion or permanently discontinue axatilimab based on severity of the reaction.

Embryo-fetal Toxicity

Based on its mechanism of action, axatilimab may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with axatilimab and for 30 days after the last dose.

Specific Populations

Pregnancy

Based on its mechanism of action, axatilimab may cause fetal harm when administered to pregnant women. There are no available data on the use of axatilimab-csfr in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with the drug.

Targeted mutation of colony stimulating factor-1 receptor (CSF-1R) or CSF-1 in rodent models results in prenatal and perinatal death, deficits in growth, and pleiotropic impact on multiple organ systems, including skeletal and reproductive. Regulation by CSF-1R on non-mononuclear phagocytic cells and macrophages plays a role in the innate immune protection of the fetus and in pregnancy maintenance and embryo-fetal development. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, axatilimab has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus.

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 axatilimab-csfr in human milk or the effects on the breastfed child or milk production. Maternal IgG is known to be present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 30 days after the last dose of axatilimab.

Females and Males of Reproductive Potential

Axatilimab may cause fetal harm when administered to a pregnant woman.

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

Advise females of reproductive potential to use effective contraception during treatment with axatilimab and for 30 days after the last dose.

Pediatric Use

The safety and effectiveness of axatilimab-csfr for the treatment of chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy have been established in pediatric patients weighing at least 40 kg. Use of axatilimab in pediatric patients weighing at least 40 kg is supported by evidence from clinical trials that included 3 children (ages 6 to less than 12 years old) and 5 adolescents (ages 12 to less than 17 years old). The safety and effectiveness of axatilimab have not been established in pediatric patients weighing less than 40 kg.

Compared to adult and pediatric patients weighing 40 kg and above, patients weighing less than 40 kg had lower maximum concentration, trough concentration, and average concentration at the same weight-based dosage.

Based on findings of thickening of the growth plate and metaphysis and/or degeneration of the growth plate in the femur in animals, monitor bone growth and development in pediatric patients.

Geriatric Use

Of the 79 patients with cGVHD treated with axatilimab-csfr, 21 (26.6%) were 65 years of age and older, and 2 (2.5%) were 75 years of age and older. No overall differences in the safety or effectiveness of axatilimab have been observed between patients 65 years of age and older and younger patients.

Common Adverse Effects

The most common (≥ 15%) adverse reactions, including laboratory abnormalities, are increased AST, infection (pathogen unspecified), increased ALT, decreased phosphate, decreased hemoglobin, viral infection, increased GGT, musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased CPK, increased ALP, nausea, headache, diarrhea, cough, bacterial infection, pyrexia, and dyspnea.

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

Axatilimab is a monoclonal antibody that binds to colony stimulating factor-1 receptors (CSF-1R) expressed on monocytes and macrophages. Blocking CSF-1R with axatilimab reduces the levels of these circulating proinflammatory and profibrotic monocytes and monocyte-derived macrophages, as demonstrated by a reduction of nonclassical monocyte counts in nonclinical studies with axatilimab, and inhibits the activity of pathogenic macrophages in tissues.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information).
Advise patients and caregivers that reactions related to the infusion may occur during axatilimab treatment. Inform patients and caregivers of the signs and symptoms of infusion-related reactions and to seek medical care should signs and symptoms occur.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy. Advise females of reproductive potential to use effective contraception during treatment with axatilimab and for 30 days after the last dose.
Advise women not to breastfeed during treatment and for 30 days after the last dose of axatilimab.

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.