Introduction
Lanadelumab (brand name Takhzyro®) is a fully human monoclonal antibody (IgG1κ) specifically designed for the prevention of hereditary angioedema (HAE) attacks. Approved by the FDA in 2018 and by the EMA in 2019, it represents a significant advancement in prophylactic HAE treatment by targeting plasma kallikrein, a key mediator in the pathophysiology of HAE attacks.
Mechanism of Action
Lanadelumab binds specifically to plasma kallikrein with high affinity, inhibiting its proteolytic activity. This prevents the cleavage of high-molecular-weight kininogen (HMWK), thereby reducing the generation of bradykinin—the primary mediator responsible for increased vascular permeability and angioedema attacks in HAE patients. By targeting this specific pathway, lanadelumab provides targeted prophylaxis against HAE attacks.
Indications
Lanadelumab is indicated for:
- Routine prevention of angioedema attacks in patients aged 12 years and older with hereditary angioedema (types I and II)
- Not indicated for treatment of acute HAE attacks
Dosage and Administration
Standard dosing: 300 mg administered subcutaneously every 2 weeks Alternative dosing: 300 mg every 4 weeks may be considered for patients who are well-controlled (attack-free) for more than 6 months Administration:- For subcutaneous injection only
- Prefilled syringe (300 mg/2 mL)
- Rotate injection sites (thigh, abdomen, or upper arm)
- Allow refrigerated medication to reach room temperature (30 minutes) before injection
- Do not shake the product
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Pediatric: Safety and efficacy established in patients ≥12 years
- Geriatric: No specific recommendations; use clinical judgment
Pharmacokinetics
Absorption: Bioavailability approximately 73% following subcutaneous administration Distribution: Volume of distribution ~6.3 L; minimal extravascular distribution Metabolism: Expected to be metabolized via proteolytic enzymes into small peptides and amino acids Elimination: Half-life ~14.3 days; clearance ~0.008 L/hour Time to peak concentration: ~4 days post-dose Steady-state: Achieved after approximately 70 days of repeated dosingContraindications
- History of hypersensitivity to lanadelumab or any component of the formulation
- Active infection requiring systemic antibiotic therapy (relative contraindication)
Warnings and Precautions
Hypersensitivity reactions: Although rare, monitor patients for signs of hypersensitivity Infections: Theoretical risk of increased susceptibility to certain infections; monitor for signs of infection Immunogenicity: Potential for anti-lanadelumab antibody development (low incidence in clinical trials) Pregnancy: No human data; use only if potential benefit justifies potential risk Lactation: Unknown if excreted in human milk; consider developmental and health benefits of breastfeeding Vaccinations: Live vaccines should be administered at least 4 weeks before starting lanadelumabDrug Interactions
No formal drug interaction studies conducted. Theoretical considerations:
- Potential interaction with other kallikrein inhibitors (avoid concomitant use)
- No expected interactions with cytochrome P450 substrates
- Use caution with other immunomodulatory agents
Adverse Effects
Most common (≥10%):- Injection site reactions (45%): pain, erythema, bruising
- Upper respiratory tract infections (19%)
- Headache (15%)
- Rash (12%)
- Myalgia (11%)
- Hypersensitivity reactions (<1%)
- Development of anti-lanadelumab antibodies (2.6% in clinical trials)
Monitoring Parameters
Baseline:- HAE attack frequency and severity
- Comprehensive medical history
- Allergy assessment
- HAE attack frequency and characteristics
- Injection site reactions
- Signs of hypersensitivity
- Infection monitoring
- Patient adherence and technique assessment
- Quality of life measures
- Antibody development (if clinically indicated)
- Continued efficacy assessment
Patient Education
Key points to discuss:- Lanadelumab is for prevention, not acute treatment of attacks
- Proper injection technique and rotation of sites
- Recognition and management of injection site reactions
- Importance of adherence to dosing schedule
- Carry emergency treatment for breakthrough attacks
- Report signs of hypersensitivity or infection promptly
- Storage requirements: refrigerate at 2-8°C; do not freeze
- Travel considerations for medication storage and administration
- Continue to avoid known HAE triggers
- Inform all healthcare providers about lanadelumab use
References
1. Banerji A, Riedl MA, Bernstein JA, et al. Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks: A Randomized Clinical Trial. JAMA. 2018;320(20):2108-2121. 2. Takhzyro® (lanadelumab) [prescribing information]. Lexington, MA: Dyax Corp; 2021. 3. Longhurst H, Cicardi M, Craig T, et al. Prevention of hereditary angioedema attacks with a subcutaneous C1 inhibitor. N Engl J Med. 2017;376(12):1131-1140. 4. EMA Assessment Report: Takhzyro. European Medicines Agency; 2019. 5. Busse PJ, Christiansen SC. Hereditary Angioedema. N Engl J Med. 2020;382(12):1136-1148. 6. Riedl MA, Bernstein JA, Li H, et al. Recombinant human C1-inhibitor for the treatment of acute angioedema attacks in patients with hereditary angioedema. J Allergy Clin Immunol. 2010;126(4):821-827. 7. Zuraw BL, Bernstein JA, Lang DM, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol. 2013;131(6):1491-1493.