Lanadelumab-flyo (Monograph)

Brand name: Takhzyro
Drug class: Kallikrein Inhibitors

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Recombinant fully human immunoglobulin G₁ (IgG₁) kappa light chain monoclonal antibody; plasma kallikrein inhibitor.

Uses for Lanadelumab-flyo

Hereditary Angioedema

Used for prophylaxis of hereditary angioedema (HAE) attacks in adults and pediatric patients ≥2 years of age. Designated an orphan drug by FDA for this use.

Considered a first-line option in patients requiring prophylactic therapy for HAE.

The need for long-term prophylaxis in patients with HAE should be individualized based on factors such as severity of disease, frequency of attacks, patient's quality of life, availability of resources, and patient response to on-demand therapy.

All patients receiving long-term prophylaxis should also have an on-demand treatment (e.g., C1-esterase inhibitor concentrate, ecallantide, icatibant) available at all times.

Lanadelumab-flyo Dosage and Administration

Administration

Sub-Q Administration

Administer by sub-Q injection only.

Intended for self-administration or administration by a healthcare provider or caregiver after appropriate training.

Adult and pediatric patients ≥12 years of age may self-administer lanadelumab-flyo. A healthcare provider or caregiver should administer lanadelumab-flyo to pediatric patients 2 to <12 years of age.

Remove vial or prefilled syringe from refrigeration 15 minutes before administration to allow solution to equilibrate to room temperature.

Inspect the drug prior to use; do not use if the solution appears discolored or contains visible particles.

Avoid vigorous agitation of the vial or prefilled syringe.

Prefilled Syringes

Using aseptic technique, administer sub-Q injection into the abdomen, thigh, or upper arm.

Contains no preservatives; discard any unused portion of drug remaining in the prefilled syringe.

Single-dose Vials

Use aseptic technique to withdraw prescribed dose from vial using a syringe and 18-gauge needle. Prior to sub-Q injection, change needle to a 27-gauge, one-half inch needle or other needle suitable for sub-Q injection.

Administer sub-Q injection into the abdomen, thigh, or upper arm. In clinical studies, most patients self-administered the drug over 10–60 seconds.

If refrigerated, remove syringe from refrigerator 15 minutes before use to allow drug to reach room temperature prior to injection.

Contains no preservatives; discard any unused portion remaining in vial.

Dosage

Pediatric Patients

Hereditary Angioedema

Prophylaxis of Angioedema Attacks

Sub-Q

Adolescents ≥12 years of age: 300 mg every 2 weeks. May consider extending dosing interval to every 4 weeks in patients whose disease is well-controlled (i.e., attack free) for >6 months.

6 to <12 years of age: 150 mg every 2 weeks. May consider extending dosing interval to every 4 weeks in patients whose disease is well-controlled (i.e., attack free) for >6 months.

2 to <6 years of age: 150 mg every 4 weeks.

Adults

Hereditary Angioedema

Prophylaxis of Angioedema Attacks

Sub-Q

300 mg every 2 weeks. May consider extending dosing interval to every 4 weeks in patients whose disease is well-controlled (i.e., attack free) for >6 months.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Lanadelumab-flyo

Contraindications

None.

Warnings/Precautions

Hypersensitivity Reactions

Hypersensitivity reactions reported.

If a severe hypersensitivity reaction occurs, discontinue drug and initiate appropriate treatment.

Immunogenicity

Potential for immunogenicity with all therapeutic proteins, including lanadelumab. Anti-drug antibodies, including neutralizing antibodies, reported; however, adverse effects on pharmacokinetics, pharmacodynamics, safety, or efficacy not observed.

Specific Populations

Pregnancy

Not studied in pregnant women; adverse embryofetal effects not observed in animal studies. Crosses the placenta in monkeys.

Potential for effects on fetus expected to be greater during the third trimester.

Lactation

Not known whether lanadelumab-flyo is distributed into human milk, affects milk production, or affects breast-fed infants. Detected in milk in monkeys.

Consider developmental and health benefits of breast-feeding along with mother's clinical need for lanadelumab-flyo and any potential adverse effects on breast-fed infant from drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established in pediatric patients <2 years of age.

Safety and efficacy in patients 12 to <18 years of age consistent with overall study results in pivotal efficacy study. Use in patients 2 to <12 years of age supported by extrapolation of efficacy data from initial pivotal clinical trial, with additional pharmacokinetic analyses showing similar drug exposures between adults (>18 years of age) and pediatric patients (2 to <12 years of age), and safety and pharmacodynamic data from an open-label, multicenter study in pediatric patients with HAE aged 2 to <12 years.

Drug not expected to impact growth.

Geriatric Use

In pivotal efficacy study, 4% of patients were ≥65 years of age. No overall differences in safety or efficacy observed between these patients and younger adults; however, possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.

Hepatic Impairment

Not studied in individuals with hepatic impairment; pharmacokinetics not expected to be affected by hepatic function.

Renal Impairment

Not studied in individuals with renal impairment; pharmacokinetics not expected to be affected by renal function.

Common Adverse Effects

Common adverse effects (≥10%): Injection site reactions (e.g., pain, erythema, bruising), upper respiratory tract infection, headache, rash, myalgia, dizziness, diarrhea.

Drug Interactions

No formal drug interaction studies performed to date.

Use of rescue medications, such as plasma-derived and recombinant complement 1 (C1)-esterase inhibitor (human), icatibant, or ecallantide, had no effect on clearance and volume of distribution of lanadelumab.

Concomitant use of analgesic, antibacterial, antihistamine, anti-inflammatory, or antirheumatic drugs had no effect on clearance and volume of distribution of lanadelumab.

Lanadelumab-flyo Pharmacokinetics

Absorption

Bioavailability

Exhibits approximately linear pharmacokinetics following sub-Q administration of therapeutic doses in patients with HAE.

Peak plasma concentrations achieved in about 4–5 days; steady state reached in approximately 70 days.

Mean accumulation ratio at steady state of 1.44, 1.42, or 2.43, observed in patients receiving sub-Q dosage of 150 mg every 4 weeks, 300 mg every 4 weeks, or 300 mg every 2 weeks, respectively.

Special Populations

Pharmacokinetics do not appear to be altered in patients with mild (eGFR 60–89 mL/minute per 1.73 m²) or moderate (eGFR 30–59 mL/minute per 1.73 m²) renal impairment.

AUC increased about 37% in pediatric patients 12 to <18 years of age compared with adults; not considered clinically important.

Exposure decreases with increasing body weight; however, not considered clinically important.

Age, sex, and race do not appear to affect pharmacokinetics of the drug after correcting for body weight.

Distribution

Extent

Not known whether drug is distributed into human milk.

Elimination

Metabolism

Metabolism not studied to date; expected to be consistent with other endogenous antibodies, involving proteolysis in the liver and phagocytic cells of the immune system into small peptides and amino acids.

Half-life

14–15 days.

Stability

Storage

Parenteral

Injection for Sub-Q Use

2–8°C in original container to protect from light; do not freeze and do not shake.

Single-dose vials: Administer within 2 hours of preparing dosing syringe. Alternatively, may store syringe at 2–8°C for up to 8 hours following preparation.

Actions

Recombinant fully human IgG₁ kappa light chain monoclonal antibody that inhibits plasma kallikrein.
Binds to plasma kallikrein and inhibits its proteolytic activity.
In patients with HAE, low plasma concentrations of functionally active C1-esterase inhibitor result in unrestrained activity of plasma kallikrein and excess bradykinin levels, leading to increased vascular permeability and angioedema; by decreasing plasma kallikrein activity, lanadelumab controls excess bradykinin generation.

Advice to Patients

Advise patients to read manufacturer's patient information and instructions for use.
Provide instructions and training to patients and/or caregivers on proper sub-Q administration. Advise patients and/or caregivers on proper syringe and needle disposal and importance of not reusing these items.
Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Lanadelumab-flyo
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for subcutaneous use	150 mg/mL	Takhzyro (available as single-dose prefilled syringes)
		300 mg/2 mL	Takhzyro (available as single-dose vials and prefilled syringes)	Takeda