Hemlibra

Drug overview for HEMLIBRA (emicizumab-kxwh):

Generic name: EMICIZUMAB-KXWH (EM-i-SIZ-ue-mab)
Drug class: Antihemophilic Products
Therapeutic class: Hematological Agents

Emicizumab is a humanized bispecific monoclonal antibody that binds to human factor IX/IXa and factor X/Xa.

No enhanced Uses information available for this drug.

DRUG IMAGES

HEMLIBRA 12 MG/0.4 ML VIAL

The following indications for HEMLIBRA (emicizumab-kxwh) have been approved by the FDA:

Indications:
Bleeding prevention in hereditary factor VIII deficiency

Professional Synonyms:
Bleeding prevention in classic hemophilia
Bleeding prevention in congenital factor VIII deficiency
Bleeding prevention in hemophilia A
Bleeding prophylaxis in hemophilia A
Hemorrhage prophylaxis in hemophilia A
Prevention of bleeding episode in hemophilia A

The following drug interaction information is available for HEMLIBRA (emicizumab-kxwh):

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

Moderate List
No disease contraindications

The following adverse reaction information is available for HEMLIBRA (emicizumab-kxwh):

Overview
Severe
Less Severe

Adverse reaction overview.

Most common adverse reactions (incidence >=10%) are injection site reactions, headache, and arthralgia.

There are 6 severe adverse reactions.

More Frequent	Less Frequent
None.	Thromboembolic disorder

Rare/Very Rare
Angioedema Dermal necrosis Rhabdomyolysis Thrombophlebitis Thrombotic thrombocytopenic purpura

There are 10 less severe adverse reactions.

More Frequent	Less Frequent
Arthralgia Headache disorder Injection site sequelae	Diarrhea Fever Injection site erythema Injection site pain

Rare/Very Rare
Myalgia Skin rash Urticaria

The following precautions are available for HEMLIBRA (emicizumab-kxwh):

Pediatric
Pregnant
Lactation
Geriatric

The clinical efficacy and safety of emicizumab-kxwh have been established in pediatric patients in the HAVEN 1, 2, 3, and 4 trials. Together, these trials included 47 patients 12 years to <18 years of age, 55 patients 2 years to <12 years of age, and 5 patients 1 month to <2 years of age. No differences in efficacy were observed between these age groups.

There are currently limited clinical trial data on the use of emicizumab in infants <6 months of age; however, clinical experience supports the prophylactic efficacy of the drug in infants. The pharmacokinetic exposure in these patients is likely to be less than in older children. Trough plasma concentrations of emicizumab at steady state are comparable between adults and pediatric patients >6 months of age at equivalent weight-based doses.

Concentrations of emicizumab in patients <6 months of age are expected to be lower than in older patients. Adverse effects in emicizumab-treated pediatric patients were generally similar to those observed in adult patients with hemophilia A receiving the drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

There are no clinical data on use of emicizumab-kxwh in pregnant women. Animal reproductive studies have not been conducted with the drug. Because it is not known whether emicizumab can cause fetal harm or can affect reproduction capacity, use emicizumab during pregnancy only if the potential benefit for the mother outweighs the potential risk to the fetus.

It is not known whether emicizumab is distributed into human milk or if the drug has any effect on milk production or the nursing infant. Since human immune globulin (IgG) is present in human milk, distribution of emicizumab into milk is possible. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for emicizumab and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.

Clinical trials experience in patients >=65 years of age is insufficient to determine whether these patients respond differently to emicizumab than younger patients. Other reported clinical experience has not identified a difference in response between geriatric patients and younger patients.

Bleeding prevention in hereditary factor VIII deficiency
D66	Hereditary factor VIII deficiency