Garadacimab-gxii (Monograph)

Brand name: Andembry
Drug class: Factor XIIa Inhibitors

Introduction

Garadacimab-gxii, a recombinant fully human monoclonal antibody, is an activated Factor XII (FXIIa) inhibitor.¹

Uses for Garadacimab-gxii

Garadacimab-gxii has the following uses:

Garadacimab-gxii is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older.¹

Garadacimab-gxii Dosage and Administration

General

Garadacimab-gxii is available in the following dosage form(s) and strength(s):

Injection:¹

• 200 mg/1.2 mL solution in single-dose prefilled autoinjector¹

• 200 mg/1.2 mL (167 mg/mL) solution in single-dose prefilled syringe with needle safety device¹

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 and Pediatric Patients ≥12 Years of Age

Dosage and Administration

• For subcutaneous use only.¹

• Recommended dosage: Initial loading dose of 400 mg (two 200-mg injections) administered subcutaneously followed by maintenance dosage of 200 mg once monthly.¹

• Intended for self-administration or administration by a caregiver.¹ See full prescribing information for preparation and administration instructions.¹

Cautions for Garadacimab-gxii

Contraindications

None.¹

Warnings/Precautions

Warnings and Precautions

None.¹

Specific Populations

Pregnancy

There are no available data on garadacimab-gxii use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.¹ Monoclonal antibodies such as garadacimab-gxii are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy.¹ In an embryo-fetal development study in pregnant rabbits, garadacimab-gxii produced no evidence of fetal harm at doses up to approximately 100 times the exposure achieved at the maximum recommended human dose (MRHD) of 200 mg once monthly.¹ In a pre- and post-natal development study in rabbits, garadacimab-gxii had no effects on survival, growth, or development of F₁offspring at doses resulting in approximately 76 times the exposure achieved at the MRHD.¹

The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown.¹ All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.¹ 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. ¹

Lactation

There are no data on the presence of garadacimab-gxii or its metabolite in either human or animal milk, the effects on the breastfed infant, or the effects on milk production.¹ Maternal IgG is known to be present in human milk.¹ The effects of local GI exposure and limited systemic exposure in the breastfed infant to garadacimab-gxii are unknown.¹

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for garadacimab-gxii and any potential adverse effects on the breastfed infant from garadacimab-gxii or the underlying maternal condition.¹

Pediatric Use

The safety and effectiveness of garadacimab-gxii for prophylaxis to prevent attacks of HAE have been established in pediatric patients 12 years of age and older.¹ Use of garadacimab-gxii for this indication is supported by evidence from a total of 6 pediatric patients 12 years of age and older enrolled in the VANGUARD study who received treatment with garadacimab-gxii 400 mg loading dose administered subcutaneously followed by a maintenance dosage of 200 mg subcutaneously every month (n=4) or placebo (n=2).¹ Results of the subgroup analysis for pediatric patients 12 years of age and older were consistent with study results for adult patients. ¹

The safety and effectiveness of garadacimab-gxii have not been established in pediatric patients younger than 12 years of age.¹

Geriatric Use

Of the total number of garadacimab-gxii-treated patients in the clinical study for prophylaxis to prevent attacks of HAE, 6 (9%) were 65 years of age and older.¹ No overall differences in safety or effectiveness of garadacimab-gxii have been observed between patients 65 years of age and older and younger adult patients.¹

Common Adverse Effects

Most common adverse reactions (incidence ≥ 7%) are nasopharyngitis and abdominal pain.¹

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:

• Drug Interference with Laboratory Test: Garadacimab-gxii can prolong activated partial thromboplastin time (aPTT) due to an interaction of garadacimab-gxii with the aPTT assay.¹

Actions

Mechanism of Action

Garadacimab-gxii is an inhibitor of activated FXII that binds to the catalytic domain of activated Factor XII (FXIIa and βFXIIa) and inhibits its catalytic activity.¹ FXII is the first factor activated in the contact activation pathway and initiates the inflammatory bradykinin-producing kallikrein-kinin system.¹ The inhibition of FXIIa decreases the activation of prekallikrein to kallikrein and the generation of bradykinin, which is associated with inflammation and swelling in HAE attacks, thus reducing the cascade of events leading to an HAE attack.¹

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).¹

• Instruct patients that garadacimab-gxii is for subcutaneous use and intended for self-administration or administration by caregiver.¹

• Instruct patients and/or caregivers on the proper preparation and subcutaneous administration techniques of garadacimab-gxii.¹

• Instruct patients and/or caregivers to administer garadacimab-gxii subcutaneously into the upper arm, thigh or abdomen ensuring to stay 1 inch (2 cm) away from the navel.¹

• Instruct patients or caregivers in proper disposal technique for prefilled autoinjector or prefilled syringe with needle safety device and advise them not to reuse these items.¹

• Instruct patients to dispose of the prefilled autoinjector or prefilled syringe with needle safety device in a sharps disposal container (closed puncture-resistant container).¹

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.

Related/similar drugs

Biological Products Related to garadacimab

Find detailed information on biosimilars for this medication.

Medical Disclaimer