Introduction
Takhzyro (lanadelumab-flyo) is a first-in-class monoclonal antibody specifically developed for the prevention of hereditary angioedema (HAE) attacks. Approved by the FDA in 2018, 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
Takhzyro works by selectively binding to and inhibiting plasma kallikrein, a serine protease that plays a central role in the pathogenesis of HAE attacks. By inhibiting plasma kallikrein, Takhzyro prevents the excessive generation of bradykinin—the primary mediator responsible for increased vascular permeability and edema formation in HAE. This targeted mechanism differs from earlier treatments that addressed symptoms rather than the underlying biochemical pathway.
Indications
Takhzyro is indicated for:
- Prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients 12 years of age and older
- Both type I and type II HAE (C1 esterase inhibitor deficiency)
Dosage and Administration
Standard dosing: 300 mg administered subcutaneously every 2 weeks Alternative dosing: For patients well-controlled on 300 mg every 2 weeks, may consider 300 mg every 4 weeks Administration:- For subcutaneous injection only
- Administer in the abdomen, thigh, or upper arm
- Rotate injection sites
- Allow refrigerated medication to reach room temperature (30 minutes) before administration
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No dosage adjustment necessary
- Pediatric: Safety and efficacy established for patients ≥12 years
- Geriatric: No specific recommendations
Pharmacokinetics
Absorption: Bioavailability approximately 73% following subcutaneous administration Distribution: Steady-state volume of distribution approximately 11.8 L Metabolism: Expected to be metabolized via proteolytic pathways into small peptides and amino acids Elimination: Half-life approximately 14 days Time to steady-state: Approximately 70 daysContraindications
- Known hypersensitivity to lanadelumab or any component of the formulation
- History of anaphylaxis to lanadelumab
Warnings and Precautions
Hypersensitivity reactions: Monitor patients for signs of hypersensitivity, including anaphylaxis Injection site reactions: May occur; rotate injection sites and monitor for local reactions Immunogenicity: As with all therapeutic proteins, there is potential for immunogenicity Pregnancy: No adequate human data; use only if potential benefit justifies potential risk Lactation: Unknown if excreted in human milk; consider developmental and health benefitsDrug Interactions
No formal drug interaction studies have been conducted. However:
- Theoretical potential for interactions with other medications that affect the kallikrein-kinin system
- No expected interactions with cytochrome P450 substrates
Adverse Effects
Most common adverse reactions (≥10%):- Injection site reactions (45%)
- Upper respiratory tract infection (20%)
- Headache (15%)
- Rash (12%)
- Myalgia (11%)
- Dizziness (10%)
- Hypersensitivity reactions (including anaphylaxis) <1%
Monitoring Parameters
- Frequency and severity of HAE attacks
- Injection site reactions
- Signs of hypersensitivity reactions
- Liver function tests (baseline and as clinically indicated)
- Patient quality of life and treatment satisfaction
Patient Education
Key points for patients:- Takhzyro is used to prevent HAE attacks, not to treat acute attacks
- Learn proper injection technique from healthcare provider
- Rotate injection sites to minimize reactions
- Recognize signs of hypersensitivity (rash, itching, swelling, dizziness)
- Keep a record of attack frequency and severity
- Store medication refrigerated (2°C to 8°C); do not freeze
- Dispose of used needles and syringes in approved sharps container
- Continue to carry acute treatment for breakthrough attacks
References
1. US Food and Drug Administration. Takhzyro prescribing information. 2018. 2. Banerji A, et al. Effect of lanadelumab compared with placebo on prevention of hereditary angioedema attacks: A randomized clinical trial. JAMA. 2018;320(20):2108-2121. 3. Riedl MA, et al. Sustained efficacy and safety of lanadelumab for prevention of hereditary angioedema attacks: Final results of the HELP Study extension. J Allergy Clin Immunol. 2020;145(Suppl 2):AB231. 4. Longhurst HJ, et al. Lanadelumab for prophylactic treatment of hereditary angioedema: A review of clinical efficacy and safety. Ther Adv Rare Dis. 2021;2:1-12. 5. Zuraw BL, et al. Hereditary angioedema with normal C1 inhibitor: Update on evaluation and treatment. J Allergy Clin Immunol Pract. 2021;9(1):132-140.
This monograph is for educational purposes only and should not replace professional medical advice. Always consult with a healthcare provider for specific medical recommendations.