Overview
11 DESCRIPTION Garadacimab-gxii, an activated Factor XII (FXIIa) inhibitor, is a recombinant, fully human, monoclonal antibody (IgG4/ λ -light chain) produced in Chinese Hamster Ovary (CHO) cells. Based on the amino acid sequence, the molecular weight of garadacimab-gxii is approximately 148 kDa.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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. FXII is the first factor activated in the contact activation pathway and initiates the inflammatory bradykinin-producing kallikrein-kinin system. 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. 12.2 Pharmacodynamics Garadacimab-gxii concentration-dependent inhibition of FXIIa-mediated kallikrein activity was observed in patients with HAE.
Indications
- 1 INDICATIONS AND USAGE ANDEMBRY is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. ANDEMBRY is an activated Factor XII (FXIIa) inhibitor (monoclonal antibody) indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. ( 1 )
Common Doses
- 400 mg
- 200 mg
Dosage
2 DOSAGE AND ADMINISTRATION Recommended Dosage : Initial loading dose of 400 mg (two 200 mg injections) administered subcutaneously followed by maintenance dosage of 200 mg once monthly. ( 2.1 ) Subcutaneous use only. ( 2.2 ) Patients may self-administer. See full prescribing information for preparation and administration instructions. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage of ANDEMBRY is an initial loading dose of 400 mg (two injections of 200 mg) administered subcutaneously on the first day of treatment followed by a maintenance dosage of 200 mg administered subcutaneously...
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS Most common adverse reactions (incidence ≥ 7%) are nasopharyngitis and abdominal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact CSL Behring at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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.
Interactions
- 7 DRUG INTERACTIONS Drug Interference with Laboratory Test: ANDEMBRY can prolong activated partial thromboplastin time (aPTT) due to an interaction of garadacimab-gxii with the aPTT assay. ( 7.1 ) 7.1 Drug Interference with Laboratory Test Coagulation Tests ANDEMBRY can prolong activated partial thromboplastin time (aPTT) due to an interaction of garadacimab-gxii with the aPTT assay. The reagents used in the aPTT laboratory test initiate intrinsic coagulation through the activation of FXII in the contact system, therefore inhibition of plasma FXIIa by ANDEMBRY can prolong aPTT in this assay...