Axatilimab-csfr
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parth Vikram Singh, MBBS[2]
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Overview
Axatilimab-csfr is a colony stimulating factor-1 receptor (CSF-1R)-blocking antibody that is FDA approved 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.. Common adverse reactions include *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..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
- Administer only as an intravenous infusion over 30 minutes.
- The recommended dosage of NIKTIMVO is 0.3 mg/kg (maximum 35 mg) every 2 weeks in adult and pediatric patients weighing 40 kg and above.
DOSAGE FORMS AND STRENGTHS
Injection: 9 mg/0.18 mL solution in a single-dose vial.
Injection: 22 mg/0.44 mL solution in a single-dose vial.
Injection: 50 mg/mL solution in a single-dose vial.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Axatilimab-csfr in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Axatilimab-csfr in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
- Treatment of chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy in pediatric patients weighing at least 40 kg.
The recommended dosage of NIKTIMVO is 0.3 mg/kg (maximum 35 mg) every 2 weeks in pediatric patients weighing 40 kg and above
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Axatilimab-csfr in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Axatilimab-csfr in pediatric patients.
Contraindications
None.
Warnings
Infusion-Related Reactions
- NIKTIMVO can cause infusion-related reactions. Infusion-related reactions, including hypersensitivity reactions, occurred in 18% of patients who received NIKTIMVO 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 NIKTIMVO.
- 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 NIKTIMVO based on severity of the reaction.
Embryo-Fetal Toxicity
- Based on its mechanism of action, NIKTIMVO 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 NIKTIMVO and for 30 days after the last dose.
Adverse Reactions
Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Chronic Graft-Versus-Host Disease
- The safety of NIKTIMVO was evaluated in 79 adult and pediatric patients with cGVHD treated with NIKTIMVO 0.3 mg/kg intravenously every 2 weeks in the AGAVE 201 trial.
- The median duration of treatment was 10.3 months (range: 0.5 to 28.6 months), and 73.4% were treated for more than 6 months.
- Serious adverse reactions occurred in 44% of patients who received NIKTIMVO. Serious adverse reactions in more than 2 patients included infection (pathogen unspecified), viral infection, and respiratory failure.
- Permanent discontinuation of NIKTIMVO due to an adverse reaction occurred in 10% of patients and dose reduction due to adverse reaction occurred in 8% of patients.
- Dose interruptions due to an adverse reaction occurred in 44% of patients. The adverse reactions leading to dose interruption in more than 2 patients were viral infection, infection (pathogen unspecified), bacterial infection, musculoskeletal pain, and pyrexia.
- The most common (≥ 15%) adverse reactions, including laboratory abnormalities, were increased AST, infection (pathogen unspecified), increased ALT, decreased phosphate, decreased hemoglobin, viral infection, increased gamma glutamyl transferase (GGT), musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased CPK, increased ALP, nausea, headache, diarrhea, cough, bacterial infection, pyrexia, and dyspnea.
Table 2 summarizes the nonlaboratory adverse reactions in AGAVE-201.
Clinically relevant adverse reactions in < 10% of patients who received NIKTIMVO included: • Eye disorders: periorbital edema • Skin and subcutaneous skin disorders: pruritus • Vascular disorders: hypertension Table 3 summarizes the laboratory abnormalities in AGAVE-201.
Antibody–Associated Adverse Reactions
In 276 patients with cGVHD who received NIKTIMVO in clinical trials, among the patients who developed anti-drug antibodies (ADAs), hypersensitivity reactions occurred in 26% (13/50) of patients with neutralizing antibodies (NAb) and in 4% (2/45) of those without NAb.
Postmarketing Experience
There is limited information regarding Axatilimab-csfr Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Axatilimab-csfr Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Risk Summary
- Based on its mechanism of action, NIKTIMVO may cause fetal harm when administered to pregnant women.There are no available data on the use of NIKTIMVO in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with axatilimab-csfr.
- Targeted mutation of 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, NIKTIMVO 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.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Axatilimab-csfr in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Axatilimab-csfr during labor and delivery.
Nursing Mothers
Risk Summary
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 NIKTIMVO.
Pediatric Use
- The safety and effectiveness of NIKTIMVO for the treatment of 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 NIKTIMVO 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 NIKTIMVO 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.
Geriatic Use
- Of the 79 patients with cGVHD treated with NIKTIMVO, 21 (26.6%) were 65 years and older, and 2 (2.5%) were 75 years and older.
- No overall differences in the safety or effectiveness of NIKTIMVO have been observed between patients 65 years of age and older and younger patients.
Gender
There is no FDA guidance on the use of Axatilimab-csfr with respect to specific gender populations.
Race
There is no FDA guidance on the use of Axatilimab-csfr with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Axatilimab-csfr in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Axatilimab-csfr in patients with hepatic impairment.
Females of Reproductive Potential and Males
NIKTIMVO may cause fetal harm when administered to a pregnant woman.
Pregnancy Testing
Verify pregnancy status in females of reproductive potential prior to initiating NIKTIMVO.
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with NIKTIMVO and for 30 days after the last dose of NIKTIMVO.
Immunocompromised Patients
There is no FDA guidance one the use of Axatilimab-csfr in patients who are immunocompromised.
Administration and Monitoring
Administration
Recommended Dosage
For patients weighing at least 40 kg, administer NIKTIMVO 0.3 mg/kg, up to a maximum dose of 35 mg, as an intravenous infusion over 30 minutes every 2 weeks until progression or unacceptable toxicity.
Dosage Modifications for Adverse Reactions
Monitor aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine phosphokinase (CPK), amylase, and lipase prior to the start of NIKTIMVO therapy, every 2 weeks for the first month, and every 1 to 2 months thereafter until abnormalities are resolved.
For recommended NIKTIMVO dosage modifications due to adverse reactions, see Table 1.
Preparation and Administration
Preparation • Use aseptic technique to prepare NIKTIMVO. • Visually inspect the vial for particulate matter and discoloration prior to dilution. NIKTIMVO is a slightly opalescent, pale brownish yellow solution. Discard the vial if the solution is cloudy, discolored, or contains visible particles. • Do not shake the vial. • Determine the dose and total volume of NIKTIMVO solution needed. Each mL of NIKTIMVO contains 50 mg of axatilimab-csfr. Dilution • Withdraw the calculated volume of NIKTIMVO solution from the vial and add it into an intravenous infusion bag made of polyvinyl chloride (PVC), polyolefin, polyolefin with polyamide, or ethylene vinyl acetate (EVA) containing 0.9% Sodium Chloride Injection to achieve a final concentration between the range of 0.24 mg/mL and 0.75 mg/mL. • Discard vial with any unused portion. • Mix diluted solution by gentle inversion. Do not shake. • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The diluted solution is a clear to slightly opalescent, colorless solution that may contain trace amounts of translucent to white particles. Discard if the solution is cloudy, discolored, or contains extraneous particulate matter other than trace amounts of translucent to white particles. Storage of diluted NIKTIMVO solution • Immediately use diluted NIKTIMVO solution. If not used immediately, the diluted solution can be stored:
- At room temperature [up to 25°C (77°F)] for no more than 4 hours from the time of preparation to the end of the infusion.
OR
- Refrigerated at 2°C to 8°C (36°F to 46°F) for no more than 24 hours. If refrigerated, allow the diluted solution to come to room temperature prior to administration. The diluted solution must be administered within 4 hours (including infusion time) once it is removed from the refrigerator. • Do not freeze or shake the diluted solution. Administration • Administer diluted NIKTIMVO solution by intravenous 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. • Do not co administer other drugs through the same infusion line. • After administration, flush the infusion line with 0.9% Sodium Chloride Injection.
Monitoring
There is limited information regarding Axatilimab-csfr Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Axatilimab-csfr and IV administrations.
Overdosage
There is limited information regarding Axatilimab-csfr overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Axatilimab-csfr Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Axatilimab-csfr Mechanism of Action in the drug label.
Structure
Axatilimab-csfr is a CSF-1R–blocking antibody. Axatilimab-csfr is a humanized IgG4 ( kappa light chain ) monoclonal antibody produced in Chinese hamster ovary cells. Axatilimab-csfr has an approximate molecular weight of 150 kDa.
NIKTIMVO ( axatilimab-csfr ) injection is a sterile, preservative-free, slightly opalescent, pale brownish yellow solution for intravenous use. The solution is free from visible particles.
Each single-dose vial contains 9 mg, 22 mg, or 50 mg of axatilimab-csfr at a concentration of 50 mg/mL. Each mL of solution contains citric acid monohydrate ( 3.6 mg ) , glycine ( 9.38 mg ) , polysorbate 80 ( 0.5 mg ) , sodium citrate ( 8.49 mg ) , sucrose ( 42.79 mg ) and Water for Injection, USP. The pH is 5.0.
Pharmacodynamics
There is limited information regarding Axatilimab-csfr Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Axatilimab-csfr Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Axatilimab-csfr Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Axatilimab-csfr Clinical Studies in the drug label.
How Supplied
There is limited information regarding Axatilimab-csfr How Supplied in the drug label.
Storage
There is limited information regarding Axatilimab-csfr Storage in the drug label.
Images
Drug Images
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Patient Counseling Information
There is limited information regarding Axatilimab-csfr Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Axatilimab-csfr interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Axatilimab-csfr Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Axatilimab-csfr Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.