These Highlights Do Not Include All The Information Needed To Use Takhzyro®

Pediatric Patients 6 to Less Than 12 Years of Age

The recommended starting dosage in pediatric patients 6 to less than 12 years of age is 150 mg administered subcutaneously q2wks. A dosing interval of 150 mg q4wks may be considered if the patient is well-controlled (e.g., attack free) for more than 6 months.

Storage and Handling

• Store the prefilled syringes and vials refrigerated at 36°F to 46°F (2°C to 8°C).
• Do not freeze. Do not shake.
• Keep the prefilled syringe and vial in the original carton to protect from light.

There is no clinical experience with overdosage of TAKHZYRO.

Lanadelumab-flyo, a plasma kallikrein inhibitor, is a non-plasma derived, recombinant, fully human, monoclonal antibody (IgG1/κ-light chain) produced in Chinese Hamster Ovary (CHO) cells. Based on the amino acid sequence, the molecular weight of the non-glycosylated lanadelumab-flyo is 146 kDa. The calculated molecular mass of the fully reduced light chain is 23 kDa. The calculated molecular mass of the fully reduced and non-glycosylated heavy chain is 49 kDa.

TAKHZYRO (lanadelumab-flyo) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution for subcutaneous use.

Each mL of ready-to-use TAKHZYRO solution contains 150 mg of lanadelumab-flyo, citric acid monohydrate (4.1 mg), L-histidine (7.8 mg), polysorbate 80 (0.1 mg), sodium chloride (5.3 mg), sodium phosphate dibasic dihydrate (5.3 mg), and Water for Injection, USP. The solution has a pH of approximately 6.0.

The safety and effectiveness of TAKHZYRO for prophylaxis to prevent attacks of hereditary angioedema (HAE) have been established in pediatric patients 2 years of age and older.

Use of TAKHZYRO for this indication in patients 12 years of age and older was supported by a subgroup analysis by age of 10 patients aged 12 to <18 years in Trial 1 (a randomized, double-blind, placebo-controlled parallel-group study in adult and pediatric patients 12 years of age and older with HAE). Results of the subgroup analysis by age were consistent with overall study results. An additional 13 pediatric patients aged 12 to <18 years were enrolled in the open-label extension study [see Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14)].

Use of TAKHZYRO for this indication in patients 2 to less than 12 years of age was supported by extrapolation of efficacy data from Trial 1, an adequate and well controlled study in adult and pediatric (12 to less than 18 years of age) patients, with additional pharmacokinetic analyses showing similar drug exposures between adults (>18 years of age) and pediatric patients (2 to less than 12 years of age), and safety and pharmacodynamic data from an open-label, multicenter study in pediatric patients with HAE aged 2 to less than 12 years that enrolled 21 patients (4 patients were aged 2 to less than 6 years and 17 patients were 6 to less than 12 years of age) [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3)]. The pharmacodynamic response observed in this trial for pediatric patients 2 to less than 12 years of age was similar to that seen in adult and pediatric patients 12 years of age and older [see Clinical Pharmacology (12.2)].

The safety and effectiveness of TAKHZYRO in pediatric patients less than 2 years of age have not been established.

The safety and effectiveness of TAKHZYRO 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 [see Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14)].

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of lanadelumab-flyo or of other lanadelumab products.

In Trial 1 with adult and pediatric patients 12 years of age and older, 10 (12%) lanadelumab-flyo-treated and 2 (5%) placebo-treated patients had at least 1 anti-drug antibody (ADA)-positive sample during the 26-week treatment period; antibody titers were low (range: 20 to 1280). The ADA response observed was transient in 2/10 lanadelumab-flyo and 1/2 placebo-treated patients. Pre-existing low titer antibodies were observed in 3 lanadelumab-flyo-treated patients and 1 placebo-treated patient with ADAs. Two patients receiving 150 mg q4wks had low titer antibodies classified as neutralizing.

In an open-label, multicenter study in pediatric patients 2 to less than 12 years of age, 3/20 (15%) lanadelumab-treated patients who completed the study developed ADAs during the 52-week treatment period; all of whom were in the 6 to less than 12 years age group. The ADA response observed was transient in all 3 patients. None of these patients had pre-existing antibodies. One patient had neutralizing antibodies.

The development of ADA including neutralizing antibodies against lanadelumab-flyo did not appear to adversely affect pharmacokinetics (PK), pharmacodynamics (PD), safety or clinical response.

None.

The most common adverse reactions (≥10%) are injection site reactions, upper respiratory infections, headache, rash, dizziness, diarrhea, and myalgia. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

No dedicated drug interaction studies have been conducted [see Clinical Pharmacology (12.3)].

TAKHZYRO^® (tak-ZYE-roe)

(lanadelumab-flyo)

injection, for subcutaneous use

single-dose 1 mL prefilled syringe

This Instructions for Use contains information on how to inject TAKHZYRO. Please make sure to read, understand, and follow the Instructions for Use before injecting TAKHZYRO.

A healthcare provider should show you how to prepare and inject TAKHZYRO properly before you use it for the first time. Contact your healthcare provider if you have any questions.

Questions?

For product or service-related questions, call 1-877-TAKEDA-7 (1-877-825-3327) or go to www.TAKHZYRO.com.

Manufactured by:

Takeda Pharmaceuticals U.S.A., Inc.

Cambridge, MA 02142

U.S. License No. 1898

TAKHZYRO is a registered trademark of Dyax Corp. Takeda and

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Approved: 1/2025

In adult and pediatric (12 to less than 18 years) patients, concentration-dependent inhibition of plasma kallikrein, measured as reduction of cHMWK levels, was demonstrated after subcutaneous administration of TAKHZYRO 150 mg q4wks, 300 mg q4wks or 300 mg q2wks in patients with HAE.

For pediatric patients 2 to less than 6 years (150 mg q4wks) and 6 to less than 12 years (150 mg q2wks), the observed mean percent change from baseline cHMWK levels was similar to that observed in adult and pediatric (12 to less than 18 years) patients (300 mg q2wks or 300 mg q4wks).

Following subcutaneous administration, the pharmacokinetics of lanadelumab-flyo was approximately dose-proportional in the therapeutic dose range in patients with HAE (Table 2). The pharmacokinetic properties and exposure (steady state) of lanadelumab-flyo in HAE patients, following subcutaneous administration of 150 mg q4wks, 300 mg q4wks and 300 mg q2wks, are provided in Table 2. Following subcutaneous administration of TAKHZYRO, peak plasma concentrations are reached within 5 days, and terminal elimination half-life is ~2 weeks. The anticipated time to reach steady state concentration was approximately 70 days. At steady-state, the mean accumulation ratio is approximately 1.44, 1.42, and 2.43 for dosing regimen of 150 mg q4wks, 300 mg q4wks and 300 mg q2wks, respectively.

TAKHZYRO^® is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 2 years and older.

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.

Hypersensitivity reactions have been observed. In case of a severe hypersensitivity reaction, discontinue TAKHZYRO administration and institute appropriate treatment. (5.1)

For subcutaneous use only.

Recommended Dosage:

• Adult and pediatric patients 12 years of age and older: administer 300 mg every 2 weeks by the patient or caregiver. Dosing interval every 4 weeks may be considered in some patients. (2.1)
• Pediatric patients 6 to less than 12 years of age: administer 150 mg every 2 weeks by a healthcare provider or caregiver. Dosing interval every 4 weeks may be considered in some patients. (2.2)
• Pediatric patients 2 to less than 6 years of age: administer 150 mg every 4 weeks by a healthcare provider or caregiver. (2.2)
• See Full Prescribing Information for Administration Instructions. (2.3)

TAKHZYRO is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution available in the following presentations.

• Injection: 150 mg/1 mL (150 mg/mL) solution in a single-dose prefilled syringe
• Injection: 300 mg/2 mL (150 mg/mL) solution in a single-dose prefilled syringe
• Injection: 300 mg/2 mL (150 mg/mL) solution in a single-dose vial

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

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Rx Only

NDC 47783-644-01

TAKHZYRO^®

(lanadelumab-flyo)

injection

300 mg/2 mL (150 mg/mL)

Single-dose Vial, for Subcutaneous use only.

2 mL

1 single-dose vial.

Takeda

NDC 47783-646-01

PREFILLED

SYRINGE

TAKHZYRO ^®

(lanadelumab-flyo)

injection

300 mg/2 mL (150 mg/mL)

1 single-dose prefilled syringe.

For Subcutaneous use only.

Must be refrigerated, store at 36°F to 46°F (2°C to 8°C)

in the original carton to protect from light. Do not freeze.

Do not shake. Keep out of reach of children.

2 mL

Single-dose syringe

Rx Only

TAKHZYRO is administered subcutaneously only.

TAKHZYRO is intended for administration by a healthcare provider, patient or caregiver.

The patient or caregiver should be trained in subcutaneous injection technique by a healthcare professional.

• Adult and pediatric patients 12 years of age and older: TAKHZYRO may be administered by the patient or caregiver.
• Pediatric patients 2 to less than 12 years of age: TAKHZYRO should be administered by a healthcare provider or caregiver.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use TAKHZYRO if the solution appears discolored or contains visible particles. TAKHZYRO is a clear to slightly opalescent, colorless to slightly yellow solution.

NDC 47783-645-01

TAKHZYRO^®

(lanadelumab-flyo)

injection

150 mg/mL

For Subcutaneous use only.

Single-dose prefilled syringe

Store refrigerated at 36°F to 46°F (2°C to 8°C).

Takeda Pharmaceuticals U.S.A., Inc. | U.S. License No. 1898

LOT

EXP

Rx Only

0757712

NDC 47783-645-01

PREFILLED

SYRINGE

TAKHZYRO ^®

(lanadelumab-flyo)

injection

150 mg/mL

Attention: For pediatric use (2 to less than 12 years)

For Subcutaneous use only.

1 single-dose prefilled syringe.

Must be refrigerated, store at 36°F to 46°F (2°C to 8°C)

in the original carton to protect from light. Do not freeze.

Do not shake. Keep out of reach of children.

1 mL

Single-dose syringe

Rx Only

Animal studies have not been conducted to evaluate the carcinogenic potential of lanadelumab-flyo. Published literature supports bradykinin, which is elevated in HAE, as a pro-tumorigenic molecule. However, the malignancy risk in humans from an antibody that inhibits plasma kallikrein activity, such as lanadelumab-flyo, which lowers bradykinin levels, is currently unknown.

Male and female fertility were unaffected based upon no observed adverse histopathological findings in the reproductive organs from sexually mature cynomolgus monkeys that received lanadelumab-flyo for 13 weeks at subcutaneous doses up to 50 mg/kg/week (resulting in approximately 22 times the exposure at the MRHD on an AUC basis).

The recommended starting dosage in adult and pediatric patients 12 years of age and older is 300 mg administered subcutaneously every 2 weeks (q2wks). A dosing interval of 300 mg every 4 weeks (q4wks) is also effective and may be considered if the patient is well-controlled (e.g., attack free) for more than 6 months.

Pediatric Patients 6 to Less Than 12 Years of Age

The recommended starting dosage in pediatric patients 6 to less than 12 years of age is 150 mg administered subcutaneously q2wks. A dosing interval of 150 mg q4wks may be considered if the patient is well-controlled (e.g., attack free) for more than 6 months.

Storage and Handling

• Store the prefilled syringes and vials refrigerated at 36°F to 46°F (2°C to 8°C).
• Do not freeze. Do not shake.
• Keep the prefilled syringe and vial in the original carton to protect from light.

There is no clinical experience with overdosage of TAKHZYRO.

Lanadelumab-flyo, a plasma kallikrein inhibitor, is a non-plasma derived, recombinant, fully human, monoclonal antibody (IgG1/κ-light chain) produced in Chinese Hamster Ovary (CHO) cells. Based on the amino acid sequence, the molecular weight of the non-glycosylated lanadelumab-flyo is 146 kDa. The calculated molecular mass of the fully reduced light chain is 23 kDa. The calculated molecular mass of the fully reduced and non-glycosylated heavy chain is 49 kDa.

TAKHZYRO (lanadelumab-flyo) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution for subcutaneous use.

Each mL of ready-to-use TAKHZYRO solution contains 150 mg of lanadelumab-flyo, citric acid monohydrate (4.1 mg), L-histidine (7.8 mg), polysorbate 80 (0.1 mg), sodium chloride (5.3 mg), sodium phosphate dibasic dihydrate (5.3 mg), and Water for Injection, USP. The solution has a pH of approximately 6.0.

The safety and effectiveness of TAKHZYRO for prophylaxis to prevent attacks of hereditary angioedema (HAE) have been established in pediatric patients 2 years of age and older.

Use of TAKHZYRO for this indication in patients 12 years of age and older was supported by a subgroup analysis by age of 10 patients aged 12 to <18 years in Trial 1 (a randomized, double-blind, placebo-controlled parallel-group study in adult and pediatric patients 12 years of age and older with HAE). Results of the subgroup analysis by age were consistent with overall study results. An additional 13 pediatric patients aged 12 to <18 years were enrolled in the open-label extension study [see Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14)].

Use of TAKHZYRO for this indication in patients 2 to less than 12 years of age was supported by extrapolation of efficacy data from Trial 1, an adequate and well controlled study in adult and pediatric (12 to less than 18 years of age) patients, with additional pharmacokinetic analyses showing similar drug exposures between adults (>18 years of age) and pediatric patients (2 to less than 12 years of age), and safety and pharmacodynamic data from an open-label, multicenter study in pediatric patients with HAE aged 2 to less than 12 years that enrolled 21 patients (4 patients were aged 2 to less than 6 years and 17 patients were 6 to less than 12 years of age) [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3)]. The pharmacodynamic response observed in this trial for pediatric patients 2 to less than 12 years of age was similar to that seen in adult and pediatric patients 12 years of age and older [see Clinical Pharmacology (12.2)].

The safety and effectiveness of TAKHZYRO in pediatric patients less than 2 years of age have not been established.

The safety and effectiveness of TAKHZYRO 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 [see Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14)].

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of lanadelumab-flyo or of other lanadelumab products.

In Trial 1 with adult and pediatric patients 12 years of age and older, 10 (12%) lanadelumab-flyo-treated and 2 (5%) placebo-treated patients had at least 1 anti-drug antibody (ADA)-positive sample during the 26-week treatment period; antibody titers were low (range: 20 to 1280). The ADA response observed was transient in 2/10 lanadelumab-flyo and 1/2 placebo-treated patients. Pre-existing low titer antibodies were observed in 3 lanadelumab-flyo-treated patients and 1 placebo-treated patient with ADAs. Two patients receiving 150 mg q4wks had low titer antibodies classified as neutralizing.

In an open-label, multicenter study in pediatric patients 2 to less than 12 years of age, 3/20 (15%) lanadelumab-treated patients who completed the study developed ADAs during the 52-week treatment period; all of whom were in the 6 to less than 12 years age group. The ADA response observed was transient in all 3 patients. None of these patients had pre-existing antibodies. One patient had neutralizing antibodies.

The development of ADA including neutralizing antibodies against lanadelumab-flyo did not appear to adversely affect pharmacokinetics (PK), pharmacodynamics (PD), safety or clinical response.

None.

The most common adverse reactions (≥10%) are injection site reactions, upper respiratory infections, headache, rash, dizziness, diarrhea, and myalgia. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

No dedicated drug interaction studies have been conducted [see Clinical Pharmacology (12.3)].

TAKHZYRO^® (tak-ZYE-roe)

(lanadelumab-flyo)

injection, for subcutaneous use

single-dose 1 mL prefilled syringe

This Instructions for Use contains information on how to inject TAKHZYRO. Please make sure to read, understand, and follow the Instructions for Use before injecting TAKHZYRO.

A healthcare provider should show you how to prepare and inject TAKHZYRO properly before you use it for the first time. Contact your healthcare provider if you have any questions.

Questions?

For product or service-related questions, call 1-877-TAKEDA-7 (1-877-825-3327) or go to www.TAKHZYRO.com.

Manufactured by:

Takeda Pharmaceuticals U.S.A., Inc.

Cambridge, MA 02142

U.S. License No. 1898

TAKHZYRO is a registered trademark of Dyax Corp. Takeda and

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Approved: 1/2025

In adult and pediatric (12 to less than 18 years) patients, concentration-dependent inhibition of plasma kallikrein, measured as reduction of cHMWK levels, was demonstrated after subcutaneous administration of TAKHZYRO 150 mg q4wks, 300 mg q4wks or 300 mg q2wks in patients with HAE.

For pediatric patients 2 to less than 6 years (150 mg q4wks) and 6 to less than 12 years (150 mg q2wks), the observed mean percent change from baseline cHMWK levels was similar to that observed in adult and pediatric (12 to less than 18 years) patients (300 mg q2wks or 300 mg q4wks).

Following subcutaneous administration, the pharmacokinetics of lanadelumab-flyo was approximately dose-proportional in the therapeutic dose range in patients with HAE (Table 2). The pharmacokinetic properties and exposure (steady state) of lanadelumab-flyo in HAE patients, following subcutaneous administration of 150 mg q4wks, 300 mg q4wks and 300 mg q2wks, are provided in Table 2. Following subcutaneous administration of TAKHZYRO, peak plasma concentrations are reached within 5 days, and terminal elimination half-life is ~2 weeks. The anticipated time to reach steady state concentration was approximately 70 days. At steady-state, the mean accumulation ratio is approximately 1.44, 1.42, and 2.43 for dosing regimen of 150 mg q4wks, 300 mg q4wks and 300 mg q2wks, respectively.

TAKHZYRO^® is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 2 years and older.

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.

Hypersensitivity reactions have been observed. In case of a severe hypersensitivity reaction, discontinue TAKHZYRO administration and institute appropriate treatment. (5.1)

For subcutaneous use only.

Recommended Dosage:

• Adult and pediatric patients 12 years of age and older: administer 300 mg every 2 weeks by the patient or caregiver. Dosing interval every 4 weeks may be considered in some patients. (2.1)
• Pediatric patients 6 to less than 12 years of age: administer 150 mg every 2 weeks by a healthcare provider or caregiver. Dosing interval every 4 weeks may be considered in some patients. (2.2)
• Pediatric patients 2 to less than 6 years of age: administer 150 mg every 4 weeks by a healthcare provider or caregiver. (2.2)
• See Full Prescribing Information for Administration Instructions. (2.3)

TAKHZYRO is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution available in the following presentations.

• Injection: 150 mg/1 mL (150 mg/mL) solution in a single-dose prefilled syringe
• Injection: 300 mg/2 mL (150 mg/mL) solution in a single-dose prefilled syringe
• Injection: 300 mg/2 mL (150 mg/mL) solution in a single-dose vial

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

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Rx Only

NDC 47783-644-01

TAKHZYRO^®

(lanadelumab-flyo)

injection

300 mg/2 mL (150 mg/mL)

Single-dose Vial, for Subcutaneous use only.

2 mL

1 single-dose vial.

Takeda

NDC 47783-646-01

PREFILLED

SYRINGE

TAKHZYRO ^®

(lanadelumab-flyo)

injection

300 mg/2 mL (150 mg/mL)

1 single-dose prefilled syringe.

For Subcutaneous use only.

Must be refrigerated, store at 36°F to 46°F (2°C to 8°C)

in the original carton to protect from light. Do not freeze.

Do not shake. Keep out of reach of children.

2 mL

Single-dose syringe

Rx Only

TAKHZYRO is administered subcutaneously only.

TAKHZYRO is intended for administration by a healthcare provider, patient or caregiver.

The patient or caregiver should be trained in subcutaneous injection technique by a healthcare professional.

• Adult and pediatric patients 12 years of age and older: TAKHZYRO may be administered by the patient or caregiver.
• Pediatric patients 2 to less than 12 years of age: TAKHZYRO should be administered by a healthcare provider or caregiver.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use TAKHZYRO if the solution appears discolored or contains visible particles. TAKHZYRO is a clear to slightly opalescent, colorless to slightly yellow solution.

NDC 47783-645-01

TAKHZYRO^®

(lanadelumab-flyo)

injection

150 mg/mL

For Subcutaneous use only.

Single-dose prefilled syringe

Store refrigerated at 36°F to 46°F (2°C to 8°C).

Takeda Pharmaceuticals U.S.A., Inc. | U.S. License No. 1898

LOT

EXP

Rx Only

0757712

NDC 47783-645-01

PREFILLED

SYRINGE

TAKHZYRO ^®

(lanadelumab-flyo)

injection

150 mg/mL

Attention: For pediatric use (2 to less than 12 years)

For Subcutaneous use only.

1 single-dose prefilled syringe.

Must be refrigerated, store at 36°F to 46°F (2°C to 8°C)

in the original carton to protect from light. Do not freeze.

Do not shake. Keep out of reach of children.

1 mL

Single-dose syringe

Rx Only

Animal studies have not been conducted to evaluate the carcinogenic potential of lanadelumab-flyo. Published literature supports bradykinin, which is elevated in HAE, as a pro-tumorigenic molecule. However, the malignancy risk in humans from an antibody that inhibits plasma kallikrein activity, such as lanadelumab-flyo, which lowers bradykinin levels, is currently unknown.

Male and female fertility were unaffected based upon no observed adverse histopathological findings in the reproductive organs from sexually mature cynomolgus monkeys that received lanadelumab-flyo for 13 weeks at subcutaneous doses up to 50 mg/kg/week (resulting in approximately 22 times the exposure at the MRHD on an AUC basis).

The recommended starting dosage in adult and pediatric patients 12 years of age and older is 300 mg administered subcutaneously every 2 weeks (q2wks). A dosing interval of 300 mg every 4 weeks (q4wks) is also effective and may be considered if the patient is well-controlled (e.g., attack free) for more than 6 months.