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Lanadelumab-flyo

Class: Complement Inhibitors
Chemical Name: Immunoglobulin G1, anti-(human plasma kallikrein) (human monoclonal DX-2930 heavy chain), disulfide with human monoclonal DX-2930 light chain, dimer
Molecular Formula: C6468H10016N1728O2012S48
CAS Number: 1426055-14-2
Brands: Takhzyro

Medically reviewed by Drugs.com on Sep 7, 2021. Written by ASHP.

Introduction

Lanadelumab-flyo, a plasma kallikrein inhibitor (monoclonal antibody), is a complement inhibitor.

Uses for Lanadelumab-flyo

Lanadelumab-flyo has the following uses:

Lanadelumab-flyo is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients 12 years and older.

Lanadelumab-flyo Dosage and Administration

General

Lanadelumab-flyo is available in the following dosage form(s) and strength(s):

Injection: 300 mg/2 mL (150 mg/mL) solution in a single-dose vial.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Pediatric Patients

Dosage and Administration in Adolescents ≥12 Years of Age
  • The recommended starting dose is 300 mg every 2 weeks. A dosing interval of 300 mg every 4 weeks is also effective and may be considered if the patient is well-controlled (e.g., attack free) for more than 6 months.

  • Lanadelumab-flyo is administered subcutaneously only.

  • Lanadelumab-flyo is provided as a ready-to-use solution in a single-dose vial that does not require additional reconstitution or dilution for administration. Lanadelumab-flyo is supplied as a clear to slightly opalescent, colorless to slightly yellow solution. Do not use the vial if it appears discolored or contains visible particles. Avoid vigorous agitation of the vial.

  • Lanadelumab-flyo is intended for self-administration or administration by a caregiver. The patient or caregiver should be trained by a healthcare professional.

  • Take the lanadelumab-flyo vial out of the refrigerator 15 minutes before injecting to allow it to equilibrate to room temperature.

  • Using aseptic technique, withdraw the prescribed dose of lanadelumab-flyo from the vial using an 18-gauge needle. Change the needle on the syringe to a 27-gauge, ½-inch needle or other needle suitable for subcutaneous injection. Inject lanadelumab-flyo subcutaneously into the abdomen, thigh, or upper arm. Patients should inject the complete dose as prescribed by their physician. In clinical studies, the majority of patients self-administered lanadelumab-flyo over 10 to 60 seconds.

  • Lanadelumab-flyo should be administered within 2 hours of preparing the dosing syringe. After the dosing syringe is prepared, it can be refrigerated at 36ºF to 46ºF (2°C to 8°C) and must be used within 8 hours.

  • Discard any unused portions of drug remaining in the vial and syringe.

Adults

Dosage and Administration in Adults ≥18 Years of Age
  • The recommended starting dose is 300 mg every 2 weeks. A dosing interval of 300 mg every 4 weeks is also effective and may be considered if the patient is well-controlled (e.g., attack free) for more than 6 months.

  • Lanadelumab-flyo is administered subcutaneously only.

  • Lanadelumab-flyo is provided as a ready-to-use solution in a single-dose vial that does not require additional reconstitution or dilution for administration. Lanadelumab-flyo is supplied as a clear to slightly opalescent, colorless to slightly yellow solution. Do not use the vial if it appears discolored or contains visible particles. Avoid vigorous agitation of the vial.

  • Lanadelumab-flyo is intended for self-administration or administration by a caregiver. The patient or caregiver should be trained by a healthcare professional.

  • Take the lanadelumab-flyo vial out of the refrigerator 15 minutes before injecting to allow it to equilibrate to room temperature.

  • Using aseptic technique, withdraw the prescribed dose of lanadelumab-flyo from the vial using an 18-gauge needle. Change the needle on the syringe to a 27-gauge, ½-inch needle or other needle suitable for subcutaneous injection. Inject lanadelumab-flyo subcutaneously into the abdomen, thigh, or upper arm. Patients should inject the complete dose as prescribed by their physician. In clinical studies, the majority of patients self-administered lanadelumab-flyo over 10 to 60 seconds.

  • Lanadelumab-flyo should be administered within 2 hours of preparing the dosing syringe. After the dosing syringe is prepared, it can be refrigerated at 36ºF to 46ºF (2°C to 8°C) and must be used within 8 hours.

  • Discard any unused portions of drug remaining in the vial and syringe.

Cautions for Lanadelumab-flyo

Contraindications

None.

Warnings/Precautions

Hypersensitivity Reactions

Hypersensitivity reactions have been observed. In case of a severe hypersensitivity reaction, discontinue lanadelumab-flyo administration and institute appropriate treatment.

Specific Populations

Pregnancy

Risk Summary: There are no available data on lanadelumab-flyo use in pregnant women to inform any drug associated risks. Monoclonal antibodies such as lanadelumab-flyo 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 pre-and postnatal development (ePPND) 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.

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Animal Data: In the ePPND study, pregnant cynomolgus monkeys were administered lanadelumab-flyo once weekly at subcutaneous doses resulting in up to 33 times the exposure at the MRHD (on an AUC basis with maternal subcutaneous doses up to 50 mg/kg/week) from gestation day 20, at the beginning of organogenesis, through to parturition. There were no lanadelumab-flyo-related effects on maintenance of pregnancy or parturition. Maternal lanadelumab-flyo treatment had no effects on embryo-fetal development, survival, growth, or postnatal development of offspring through 3 months of age. Lanadelumab-flyo crossed the placenta in monkeys. Offspring were exposed to lanadelumab-flyo at approximately 50% of the maternal plasma concentration out to postnatal day 21 (PND 21). Lanadelumab-flyo concentrations were approximately equivalent in maternal and offspring plasma at PND 90.

Lactation

Risk Summary: There are no data on the presence of lanadelumab-flyo in human milk, its effects on the breastfed infant, or its effects on milk production. Lanadelumab-flyo was detected in the milk of lactating cynomolgus monkeys at approximately 0.2% of the maternal plasma concentration. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for lanadelumab-flyo and any potential adverse effects on the breastfed infant from lanadelumab-flyo or from the underlying maternal condition.

Animal Data: Available pharmacokinetic data in cynomolgus monkeys have shown excretion of lanadelumab-flyo in milk at approximately 0.2% of the maternal plasma level.

Pediatric Use

The safety and efficacy of lanadelumab-flyo were evaluated in a subgroup of patients (N=10) aged 12 to <18 years in Trial 1. Results of the subgroup analysis by age were consistent with overall study results. An additional 13 adolescent patients aged 12 to <18 years were enrolled in the open-label extension study.

The safety and efficacy of lanadelumab-flyo in pediatric patients <12 years of age have not been established.

Geriatric Use

The safety and efficacy of lanadelumab-flyo were evaluated in a subgroup of patients (N=5) aged ≥65 years in Trial 1. Results of the subgroup analysis by age were consistent with overall study results.

Common Adverse Effects

The most common adverse reactions are injection site reactions, upper respiratory infections, headache, rash, myalgia, dizziness, and diarrhea.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

No dedicated drug interaction studies have been conducted.

Actions

Mechanism Of Action

Lanadelumab-flyo is a fully human monoclonal antibody (IgG1/κ-light chain) that binds plasma kallikrein and inhibits its proteolytic activity. 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 due to 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. Lanadelumab-flyo decreases plasma kallikrein activity to control excess bradykinin generation in patients with HAE.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Inform patients of the risks and benefits of lanadelumab-flyo before prescribing or administering to the patient.

Hypersensitivity

Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions.

Self-administration:

Ensure that the patient/caregiver receives clear instructions and training on subcutaneous administration and has demonstrated the ability to perform a subcutaneous injection.

Instruct patients or caregivers in the technique of proper syringe and needle disposal, and advise them not to reuse these items. Instruct patients to dispose needles and syringes in a puncture-resistant container.

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

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, Solution

300 mg/2 mL

Takhzyro

Dyax Corp.

AHFS Drug Information. © Copyright 2021, Selected Revisions September 17, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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