Lanadelumab
Indications
Lanadelumab is used for:
Hereditary Angioedema
Adult Dose
Hereditary Angioedema
Indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE)
300 mg SC q2Weeks
Dosing interval of 300 mg SC q4Weeks is also effective and may be considered if patient is well controlled (attack free) for >6 months
Child Dose
Hereditary Angioedema
Indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and adolescents aged ?12 years
<12 years: Safety and efficacy not established
>12 years:300 mg SC q2Weeks
Dosing interval of 300 mg SC q4Weeks is also effective and may be considered if patient is well controlled (attack free) for >6 months
Renal Dose
Administration
SC Preparation
Remove vial or prepared syringe from refrigerator 15 minutes before injecting to allow it to equilibrate to room temperature; avoid vigorous agitation of the vial
Using aseptic technique, withdraw dose from vial using an 18-gauge needle; change needle on syringe to a 27-gauge, 0.5-inch needle or other needle suitable for SC injection
Administer within 2 hr of preparing the dosing syringe if left at room temperature
Discard any unused portions of drug remaining in the vial and syringe
SC Administration
For SC administration only
Intended for self-administration or administration by a caregiver following training by a healthcare professional
Clean injection site with alcohol wipe and allow to dry completely
Inject complete dose SC into the abdomen, thigh, or upper arm (caregiver only)
Inject in area at least 2 inches (5 cm) away from the navel or any scars; do not inject in area that is bruised, swollen, or painful
Rotate injection sites
Contra Indications
Hypersensitivity
Precautions
Hypersensitivity reactions reported; if severe hypersensitivity reaction occurs, discontinue lanadelumab and institute appropriate treatment
Pregnancy-Lactation
Pregnancy
There are no available data regarding use in pregnant women
Animal studies
Monoclonal antibodies 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
An enhanced prenatal and postnatal development study conducted in pregnant monkeys at doses resulting in exposures of up to 33 times the exposure achieved (on an AUC basis) at the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus
Lactation
There are no data on the presence of lanadelumab in human milk, its effects on the breastfed infant, or its effects on milk production
Detected in the milk of lactating cynomolgus monkeys at ~0.2% of the maternal plasma concentration
Consider the development and health benefits of breastfeeding along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition
Interactions
Side Effects
Side effects of Lanadelumab :
>10%
300 mg q2Week dosing
Injection site reaction (56%)
Upper respiratory tract infection (44%)
Headache (33%)
Myalgia (11%)
300 mg q4Week dosing
Injection site reaction (45%)
Upper respiratory tract infection (31%)
Headache (21%)
1-10%
Increased AST or ALT (2%)
Hypersensitivity (1%)
300 mg q2Week dosing
Rash (4%)
Dizziness (4%)
Diarrhea (4%)
300 mg q4Week dosing
Rash (10%)
Dizziness (10%)
Mode of Action
Human monoclonal antibody (IgG1 kappa-light chain) that targets plasma kallikrein and inhibits proteolytic activity to control excess bradykinin generated with HAE
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 caused by 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