DRUG INTERACTIONS -

­ No dedicated drug interaction studies have been conducted

1 Drug-Laboratory Test Interactions Coagulation tests TAKHZYRO can increase activated partial thromboplastin time (aPTT) due to an interaction of TAKHZYRO with the aPTT assay.

BRIEF SUMMARY

TANADELUMAB- (Aug 2018)

Indn-       To treat  typrs I and II  heriditary angioedema

Comp-    Injection: 300 mg/2 mL (150 mg/mL) solution in a single-dose vial. • Administer 300 mg every 2 weeks. Dosing every 4 weeks may be considered in some patients

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

CI-  ­ None.

WARNINGS-

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

Pat Inform

 Inform patients of the risks and benefits of TAKHZYRO before prescribing or administering to the patient.

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

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U.S. FDA APPROVED  DRUGS DURING 2018

Sr.No-  33

ADVERSE REACTIONS-

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

CONTRAINDICATIONS-

­ None.

WARNINGS AND PRECAUTIONS -

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

 PATIENT COUNSELING INFORMATION-

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

Inform patients of the risks and benefits of TAKHZYRO 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.

Manufactured by: Dyax Corp. 300 Shire Way Lexington, MA 02421 U.S. License No. 1789 TAKHZYROTM is a trademark or registered trademark of Dyax Corp., a wholly-owned, indirect subsidiary of Shire plc. SHIRE and the Shire Logo are trademarks or registered trademarks of Shire Pharmaceutical Holdings Ireland Limited or its affiliates. ©2018 Shire. All rights reserve

 CLINICAL PHARMACOLOGY

1 Mechanism of Action--

 Lanadelumab-flyo is a fully human monoclonal antibody (IgG1/?-light chain) that binds plasma kallikrein and inhibits its proteolytic activity.

2 Pharmacodynamics-                                                                                           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. TAKHZYRO did not prolong the QT/QTc interval.

3 Pharmacokinetics- Following subcutaneous administration, the pharmacokinetics of lanadelumab-flyo was approximately dose-proportional in the therapeutic dose range in patients with HAE (Table 2).

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-

There are no available data on TAKHZYRO use in pregnant women to inform any drug associated risks.

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.

2. 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.

3.Pediatric use-

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

4.Geriatric Use The safety and efficacy of TAKHZYRO were evaluated in a subgroup of patients (N=5) aged =65 years in Trial 1.

OVERDOSAGE -

There is no clinical experience with overdosage of TAKHZYRO.