Drug Interaction Studies-                                                                                           P450 Enzymes Erenumab-aooe is not metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

Oral Contraceptives-                                                                                                        In an open-label drug interaction study in healthy female volunteers, erenumab-aooe (140 mg subcutaneous, single-dose) did not affect the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and norgestimate.

Sumatriptan In a study in healthy volunteers, concomitant administration of erenumab-aooe with sumatriptan had no effect on the pharmacokinetics of sumatriptan 

U.S. FDA APPROVED  DRUGS DURING 2018

Sr.No-  11

ADVERSE REACTIONS

 -The most common adverse reactions in AIMOVIG clinical studies (occurring in at least 3% of treated patients and more often than placebo) are injection site reactions and constipation

 CONTRAINDICATIONS

­ None 

ADVERSE REACTIONS

­ The most common adverse reactions in AIMOVIG clinical studies                                 (occurring in at least 3% of treated patients and more often than placebo)                         are injection site reactions and constipation

PATIENT COUNSELING INFORMATION

Advise the patient 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 autoinjector or single-dose prefilled syringe. 

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

Instruct patients prescribed 140 mg to administer the once monthly dosage as two separate subcutaneous injections of 70 mg each.

Advise latex-sensitive patients that the needle shield within the white cap of the AIMOVIG prefilled autoinjector and gray needle cap of the AIMOVIG prefilled syringe contain dry natural rubber (a derivative of latex) that may cause allergic reactions in individuals sensitive to latex. 

Manufactured by:                                                                                                         Amgen Inc. One Amgen Center Drive Thousand Oaks, CA 91320-1799 USA U.S. License No. 1080

Marketed by:                                                                                                             Amgen Inc. (Thousand Oaks, CA 91320), and Novartis Pharmaceuticals Corporation (East Hanover, NJ 07936) Patent: http://pat.amgen.com/aimovig/ © 2018 Amgen Inc.

 CLINICAL PHARMACOLOGY

1.Mechanism of Action

Erenumab-aooe is a human monoclonal antibody that binds to the calcitonin gene-related peptide (CGRP) receptor and antagonizes CGRP receptor function.

2. Pharmacodynamics                                                                                                      In a randomized, double-blind, placebo-controlled study in healthy volunteers, concomitant administration of erenumab-aooe (140 mg intravenous, single-dose) with sumatriptan (12 mg subcutaneous, given as two 6 mg doses separated by one hour) had no effect on resting blood pressure compared with sumatriptan alone. AIMOVIG is for subcutaneous use only.

3.Pharmacokinetics-                                                                                           Erenumab-aooe exhibits non-linear kinetics as a result of binding to the CGRP receptor.

The Cmax mean and AUClast mean following subcutaneous administration of a 70 mg once monthly and a 140 mg once monthly dose in healthy volunteers or migraine patients,showed Less than 2-fold accumulation was observed in trough serum concentrations (Cmin) for episodic and chronic migraine patients following subcutaneous administration of 70 mg once monthly and 140 mg once monthly doses. 

 Serum trough concentrations approached steady state by 3 months of dosing. The effective half-life of erenumab-aooe is 28 days. 

Absorption-                                                                                                             Following a single subcutaneous dose of 70 mg or 140 mg erenumab-aooe administered to healthy adults, median peak serum concentrations were attained in approximately 6 days, and estimated absolute bioavailability was 82%.

Distribution-                                                                                                          Following a single 140 mg intravenous dose, the mean (SD) volume of distribution during the terminal phase (Vz) was estimated to be 3.86 (0.77) L.

Metabolism and Excretion-                                                                                          Two elimination phases were observed for erenumab-aooe.                                              At low concentrations, the elimination is predominantly through saturable binding to target (CGRP receptor), while at higher concentrations the elimination of erenumab-aooe is largely through a non-specific, non-saturable proteolytic pathway.

Specific Populations-                                                                                                    The pharmacokinetics of erenumab-aooe were not affected by age, gender, race, or subtypes of migraine spectrum (episodic or chronic migraine) based on population pharmacokinetics analysis.

Patients with Renal or Hepatic Impairment-                                                     Population pharmacokinetic analysis of integrated data from the AIMOVIG clinical studies did not reveal a difference in the pharmacokinetics of erenumab-aooe in patients with mild or moderate renal impairment relative to those with normal renal function.

Patients with severe renal impairment                                                                    (eGFR < 30 mL/min/1.73 m 2 ) have not been studied. No dedicated clinical studies were conducted to evaluate the effect of hepatic impairment or renal impairment on the pharmacokinetics of erenumab-aooe.                                                                          Renal or hepatic impairment is not expected to affect pharmacokinetics of erenumab-aooe.

Drug Interaction Studies-                                                                                           P450 Enzymes Erenumab-aooe is not metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

Oral Contraceptives-                                                                                                        In an open-label drug interaction study in healthy female volunteers, erenumab-aooe (140 mg subcutaneous, single-dose) did not affect the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and norgestimate.

Sumatriptan In a study in healthy volunteers, concomitant administration of erenumab-aooe with sumatriptan had no effect on the pharmacokinetics of sumatriptan 

USE IN SPECIFIC POPULATIONS

1.Pregnancy Risk Summary-                                                                                       There are no adequate data on the developmental risk associated with the use of AIMOVIG in pregnant women.

No adverse effects on offspring were observed when pregnant monkeys were administered erenumab-aooe throughout gestation..Serum erenumab-aooe exposures in pregnant monkeys were greater than those in humans at clinical doses.

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.

The estimated rate of major birth defects (2.2%-2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine.

2.Lactation Risk Summary

There are no data on the presence of erenumab-aooe 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 AIMOVIG and any potential adverse effects on the breastfed infant from AIMOVIG 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 AIMOVIG did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.