lanadelumab (Rx)

>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%)

Contraindications

None

Cautions

Hypersensitivity reactions reported; if severe hypersensitivity reaction occurs, discontinue lanadelumab and institute appropriate treatment

Interaction with aPPT assay

• Can increase activated partial thromboplastin time (aPTT) owing to an interaction with the aPTT assay
• 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 lanadelumab can increase aPTT in this assay

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

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism 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

Absorption

Every 2 week dosing

• Peak plasma time: 4.11 days
• Peak plasma concentration, steady-state: 34.4 mcg/mL
• Minimum concentration, steady-state: 25.4 mcg/mL
• AUC, steady-state: 408 mcg·day/mL

Every 4 week dosing

• Peak plasma time: 5.17 days
• Peak plasma concentration, steady-state: 23.3 mcg/mL
• Minimum concentration, steady-state: 8.77 mcg/mL
• AUC, steady-state: 441 mcg·day/mL

Distribution

Vd: 16.6 L (q2wk dosing); 14.9 L (q4wk dosing)

Elimination

Every 2 week dosing

• Half-life: 15 days
• Clearance: 0.809 L/day

Every 4 week dosing

• Half-life: 14.2 days
• Clearance: 0.742 L/day

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

2 to <12 years: May be administered by a healthcare provider or caregiver

≥12 years: May be administered by patient or caregive

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

Storage

Unopened vials or syringe

• Refrigerate at 2-8°C (36-46°F)
• Do not freeze
• Do not shake
• Store in original carton to protect from light

Prepared syringe

• Refrigerate at 2-8°C (36-46°F)
• Must be used within 8 hr of preparation