Overview
11 DESCRIPTION Lanadelumab-flyo, a plasma kallikrein inhibitor, is a non-plasma derived, recombinant, fully human, monoclonal antibody (IgG1/κ-light chain) produced in Chinese Hamster Ovary (CHO) cells. Based on the amino acid sequence, the molecular weight of the non-glycosylated lanadelumab-flyo is 146 kDa. The calculated molecular mass of the fully reduced light chain is 23 kDa.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Lanadelumab-flyo is a fully human monoclonal antibody (IgG1/κ-light chain) that binds plasma kallikrein and inhibits its proteolytic activity. Plasma kallikrein is a protease that cleaves high-molecular-weight-kininogen (HMWK) to generate cleaved HMWK (cHMWK) and bradykinin, a potent vasodilator that increases vascular permeability resulting in swelling and pain associated with HAE. In patients with HAE due to C1-inhibitor (C1-INH) deficiency or dysfunction, normal regulation of plasma kallikrein activity is not present, which leads to uncontrolled increases in plasma kallikrein activity and results in angioedema attacks. Lanadelumab-flyo decreases plasma kallikrein activity to control excess bradykinin generation in patients with HAE. 12.
Indications
- 1 INDICATIONS AND USAGE TAKHZYRO ® is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 2 years and older. TAKHZYRO is a plasma kallikrein inhibitor (monoclonal antibody) indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 2 years and older. ( 1 )
Common Doses
- 300 mg
- 150 mg
- 1 mL
- 2 mL
Dosage
2 DOSAGE AND ADMINISTRATION For subcutaneous use only. Recommended Dosage: Adult and pediatric patients 12 years of age and older: administer 300 mg every 2 weeks by the patient or caregiver. Dosing interval every 4 weeks may be considered in some patients. ( 2.1 ) Pediatric patients 6 to less than 12 years of age: administer 150 mg every 2 weeks by a healthcare provider or caregiver. Dosing interval every 4 weeks may be considered in some patients. ( 2.2 ) Pediatric patients 2 to less than 6 years of age: administer 150 mg every 4 weeks by a healthcare provider or caregiver. ( 2.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The most common adverse reactions (≥10%) are injection site reactions, upper respiratory infections, headache, rash, dizziness, diarrhea, and myalgia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-877-TAKEDA-7 (1-877-825-3327) 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...
Interactions
- 7 DRUG INTERACTIONS No dedicated drug interaction studies have been conducted [see Clinical Pharmacology (12.3) ]. No dedicated drug interaction studies have been conducted. ( 7 ) 7.1 Drug-Laboratory Test Interactions Coagulation tests TAKHZYRO can increase activated partial thromboplastin time (aPTT) due to an interaction of TAKHZYRO with the aPTT assay. The reagents used in the aPTT laboratory test initiate intrinsic coagulation through the activation of plasma kallikrein in the contact system. Inhibition of plasma kallikrein by TAKHZYRO can increase aPTT in this assay.