BRIEF SUMMARY

FREMANEZUMAB-(Sep -2018)

Indn-        For the preventive treatment of migraine in adults

Comp-        Injection: 225 mg/1.5 mL solution in a single-dose prefilled syringe.                • Two subcutaneous dosing options of AJOVY are available to administer the recommended dosage: o 225 mg monthly, or o 675 mg every 3 months (quarterly)         

 • The 675 mg quarterly dosage is administered as three consecutive injections of 225 mg each.

ADR-      The most common adverse reactions (=5% and greater than placebo) were injection site reactions

CI-   AJOVY is contraindicated in patients with serious hypersensitivity to fremanezumab-vfrm or to any of the excipients.

WARNINGS -

 Hypersensitivity Reactions: If hypersensitivity occurs, consider discontinuing AJOVY and institute appropriate therapy.

Pat Inform-

Information on Preparation and Administration-                                                    Provide guidance to patients and caregivers on proper subcutaneous administration technique, including aseptic technique, and how to use the single-dose prefilled syringe

Instruct patients and/or caregivers to read and follow the Instructions for Use each time they use AJOVY.

Instruct patients prescribed the regimen of 675 mg every 3 months to administer the dosage as three consecutive subcutaneous injections of 225 mg each

==============================================================

U.S. FDA APPROVED  DRUGS DURING 2018

Sr.No-  37

ADVERSE REACTIONS-

The most common adverse reactions (=5% and greater than placebo) were injection site reactions

 CONTRAINDICATIONS-

 AJOVY is contraindicated in patients with serious hypersensitivity to fremanezumab-vfrm or to any of the excipients.

WARNINGS AND PRECAUTIONS-

 Hypersensitivity Reactions: If hypersensitivity occurs, consider discontinuing AJOVY and institute appropriate therapy.

ADVERSE REACTIONS-

The most common adverse reactions (=5% and greater than placebo) were injection site reactions. 

PATIENT COUNSELING INFORMATION-

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

Information on Preparation and Administration-                                                    Provide guidance to patients and caregivers on proper subcutaneous administration technique, including aseptic technique, and how to use the single-dose prefilled syringe

Instruct patients and/or caregivers to read and follow the Instructions for Use each time they use AJOVY.

Instruct patients prescribed the regimen of 675 mg every 3 months to administer the dosage as three consecutive subcutaneous injections of 225 mg each

 Hypersensitivity Reactions-                                                                                          Inform patients about the signs and symptoms of hypersensitivity reactions and that these reactions can occur up to 1 month after administration.

Advise patients to contact their healthcare provider immediately if signs or symptoms of hypersensitivity reactions occur 

Manufactured by: Teva Pharmaceuticals USA, Inc. North Wales, PA 19454 US License No. xxxx AJOVY™ (fremanezumab-vfrm), its use, or its process of manufacture, may be protected by one or more United States patents, including US 8,007,794, US 8,586,045 and US 9,896,502. ©2018 Teva Pharmaceuticals USA, Inc. AJO-001

CLINICAL PHARMACOLOGY

1. Mechanism of Action-

Fremanezumab-vfrm is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor.

2. Pharmacodynamics-

The relationship between the pharmacodynamic activity and the mechanism(s) by which fremanezumab-vfrm exerts its clinical effects is unknown.

3. Pharmacokinetics-                                                                                               

Absorption -After single subcutaneous (SC) administrations of 225 mg, 675 mg, and 900 mg fremanezumabvfrm, median time to maximum concentrations (tmax) was 5 to 7 days.

Dose-proportionality, based on population PK, was observed between 225 mg to 900 mg.

Steady state was achieved by approximately 168 days (about 6 months) following 225 mg SC monthly and 675 mg SC quarterly dosing regimens.

Median accumulation ratio, based on once-monthly and oncequarterly dosing regimens, is approximately 2.3 and 1.2, respectively.

Distribution-                                                                                                       Fremanezumab-vfrm has an apparent volume of distribution of approximately 6 liters, suggesting minimal distribution to the extravascular tissues.

Metabolism-                                                                                                                  Similar to other monoclonal antibodies, fremanezumab-vfrm is degraded by enzymatic proteolysis into small peptides and amino acids.

Elimination-                                                                                                           Fremanezumab-vfrm apparent clearance was approximately 0.141 L/day. Fremanezumab-vfrm was estimated to have a half-life of approximately 31 days.

Specific Populations-                                                                                                        A population PK analysis assessing effects of age, race, sex, and weight was conducted on data from 2287 subjects. No dose adjustments are recommended for AJOVY.

Patients with Hepatic or Renal Impairment -                                                       Hepatic/renal impairment is not expected to affect the pharmacokinetics of fremanezumab.

A population PK analysis of integrated data from the AJOVY clinical studies did not reveal a difference in the pharmacokinetics of fremanezumab in patients with mild hepatic impairment, relative to those with normal hepatic function.

Drug Interactions-                                                                                                Fremanezumab is not metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

Additionally, the effects of medications for the acute treatment (specifically analgesics, ergots, and triptans) and preventive treatment of migraine were evaluated in a population PK model, and found not to influence fremanezumab exposure.

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-

 There are no adequate data on the developmental risk associated with the use of AJOVY in pregnant women. AJOVY has a long half-life'.

This should be taken into consideration for women who are pregnant or plan to become pregnant while using AJOVY

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

2. Lactation Risk Summary-                                                                                      There are no data on the presence of fremanezumab-vfrm in human milk, the effects on the breastfed infant, or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for AJOVY and any potential adverse effects on the breastfed infant from AJOVY or from the underlying maternal condition.

3. Pediatric Use-                                                                                                         Safety and effectiveness in pediatric patients have not been established.

4. Geriatric Use-                                                                                                            Clinical studies of AJOVY did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.