Exdensur

Drug overview for EXDENSUR (depemokimab-ulaa):

Generic name: DEPEMOKIMAB-ULAA (DEP-e-MOK-i-mab)
Drug class: Monoclonal Antibody, Human Interleukin 5 Antagonist
Therapeutic class: Respiratory Therapy Agents

Depemokimab-ulaa, a humanized immunoglobulin G (IgG)1 kappa monoclonal antibody, is an interleukin-5 (IL-5) antagonist.

No enhanced Uses information available for this drug.

DRUG IMAGES

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The following indications for EXDENSUR (depemokimab-ulaa) have been approved by the FDA:

Indications:
Eosinophilic asthma

Professional Synonyms:
Asthma with eosinophilic phenotype
Asthmatic pulmonary eosinophilia

Dosing information for EXDENSUR
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
EXDENSUR 100 MG/ML SYRINGE	Maintenance	Adults inject 100 mg by subcutaneous route every 6 months

The following drug interaction information is available for EXDENSUR (depemokimab-ulaa):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 2 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
IgG Antibodies and Derivatives/Efgartigimod-alfa SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3) DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3)	VYVGART, VYVGART HYTRULO
IgG Antibodies and Derivatives/Nipocalimab-aahu SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3) DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3)	IMAAVY

Drug Interaction

Drug Names

IgG Antibodies and Derivatives/Efgartigimod-alfa

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3)

VYVGART, VYVGART HYTRULO

IgG Antibodies and Derivatives/Nipocalimab-aahu

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3)

IMAAVY

There are 1 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
IgG Antibodies and Derivatives/Rozanolixizumab-noli SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3) DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)	RYSTIGGO

Drug Interaction

Drug Names

IgG Antibodies and Derivatives/Rozanolixizumab-noli

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3)

DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)

RYSTIGGO

Severe List
Parasitic infection

More Frequent	Less Frequent
Allergic rhinitis Arthralgia Influenza Injection site sequelae Pharyngitis Upper respiratory infection	None.

Rare/Very Rare
None.

The following precautions are available for EXDENSUR (depemokimab-ulaa):

Pediatric
Pregnant
Lactation
Geriatric

The safety and effectiveness of depemokimab-ulaa for add-on maintenance treatment of severe asthma characterized by an eosinophilic phenotype have been established in pediatric patients 12 years of age and older. Use of depemokimab-ulaa for this indication is supported by evidence from adequate and well-controlled trials (SWIFT-1 and SWIFT-2) in adults and pediatric patients 12 years of age and older, and pharmacokinetic data in pediatric patients 12 years of age and older. A total of 30 pediatric patients 12 to 17 years of age with asthma were enrolled in the SWIFT-1 and SWIFT-2 trials, of whom 15 received depemokimab-ulaa 100 mg.

Pharmacokinetic and pharmacodynamic data have demonstrated no clinically significant differences in systemic exposure of depemokimab-ulaa and reduction in blood eosinophil counts in pediatric patients 12 years of age and older compared to that observed in adults following administration of the recommended dosage of depemokimab-ulaa. The safety of depemokimab-ulaa in pediatric patients 12 years of age and older was generally similar to that of the adult population in SWIFT-1 and SWIFT-2. The safety and effectiveness of depemokimab-ulaa have not been established in pediatric patients younger than 12 years of age.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Available data from clinical trials with depemokimab-ulaa use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with asthma in pregnancy. Transport of endogenous IgG antibodies and monoclonal antibodies, such as depemokimab-ulaa, across the placenta increases as pregnancy progresses and peaks during the third trimester.

The impact of the drug's triple amino acid substitution (YTE) modification on placental transfer is uncertain; however, the presence of the YTE modification may lead to prolonged and increased exposure of the infant exposed in utero, and the potential of clinical impact is unknown and should be considered. No treatment-related effects on embryofetal or postnatal development have been shown in animal studies targeting IL-5 signaling pathways. The background risk of major birth defects and miscarriage for the indicated population(s) is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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. Pregnant women exposed to depemokimab-ulaa, or their healthcare providers, should report depemokimab-ulaa exposure by calling 1-888-825-5249. In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother, and prematurity, low birth weight, and small for gestational age in the neonate. The level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control.

There are no data on the presence of depemokimab-ulaa in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. However, depemokimab-ulaa is a humanized monoclonal antibody (immunoglobulin G1 (IgG1) kappa), and maternal IgG is present in human milk in small amounts. The effects of local GI exposure and the extent of systemic exposure in the breastfed infant to depemokimab-ulaa are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for depemokimab-ulaa, and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.

Of the 501 patients with asthma treated with depemokimab-ulaa, 133 (27%) were 65 years of age and older and 22 (4%) were 75 years of age and older. No overall differences in safety or effectiveness were observed between these patients and younger patients.