BRIEF SUMMARY

GALCANEZUMAB- (Sep 2018)

Indn-          For preventive treatment of migraine in adults       

Comp -         •Injection: 120 mg/mL solution in a single-dose prefilled pen                    •For subcutaneous use only.                                                                                               •Recommended dosage: 240 mg loading dose (administered as two consecutive injections of 120 mg each), followed by monthly doses of 120 mg.                                    •Administer in the abdomen, thigh, back of the upper arm, or buttocks subcutaneously.

ADR-    The most common adverse reactions (incidence =2% and at least 2% greater than placebo) in  clinical studies were injection site reactions.

 WARNINGS AND PRECAUTIONS-

Hypersensitivity Reactions:                                                                                             If a serious hypersensitivity reaction occurs, discontinue administration of EMGALITY and initiate appropriate therapy. Hypersensitivity reactions could occur days after administration, and may be prolonged.

Pat Inform 

Instructions on Self-Administration:                                                                                 Provide guidance to patients and/or caregivers on proper subcutaneous injection technique, including aseptic technique, and how to use the prefilled pen or prefilled syringe correctly [see Instructions for Use]. Instruct patients and/or caregivers to read and follow the Instructions for Use each time they use 

Hypersensitivity Reactions:                                                                                               Advise patients to seek immediate medical attention if they experience any symptoms of serious or severe hypersensitivity reactions.

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U.S. FDA APPROVED  DRUGS DURING 2018

Sr.No-  39

ADVERSE REACTIONS-

The most common adverse reactions (incidence =2% and at least 2% greater than placebo) in EMGALITY clinical studies were injection site reactions.

CONTRAINDICATIONS-

EMGALITY is contraindicated in patients with serious hypersensitivity to galcanezumab-gnlm or to any of the excipients.

 WARNINGS AND PRECAUTIONS-

Hypersensitivity Reactions:                                                                                             If a serious hypersensitivity reaction occurs, discontinue administration of EMGALITY and initiate appropriate therapy. Hypersensitivity reactions could occur days after administration, and may be prolonged.

 PATIENT COUNSELING INFORMATION-

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

Instructions on Self-Administration:                                                                                 Provide guidance to patients and/or caregivers on proper subcutaneous injection technique, including aseptic technique, and how to use the prefilled pen or prefilled syringe correctly [see Instructions for Use]. Instruct patients and/or caregivers to read and follow the Instructions for Use each time they use EMGALITY.

Hypersensitivity Reactions:                                                                                               Advise patients to seek immediate medical attention if they experience any symptoms of serious or severe hypersensitivity reactions.

For more information go to www.emgality.com or call 1-833-EMGALITY (1-833-364-2548).

Literature issued: 9/2018

Eli Lilly and Company, Indianapolis, IN 46285, USA US License Number 1891

CLINICAL PHARMACOLOGY-

1. Mechanism of Action-                                                                                                     Galcanezumab-gnlm is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor.

2. Pharmacodynamics-                                                                                                       There are no relevant data on the pharmacodynamic effects of galcanezumab-gnlm.

3. Pharmacokinetics-                                                                                                         Galcanezumab-gnlm exhibits linear pharmacokinetics and exposure increases proportionally with doses between 1 and 600 mg.

A loading dose of 240 mg achieved the serum galcanezumab-gnlm steady-state concentration after the first dose. The time to maximum concentration is 5 days, and the elimination half-life is 27 days.     

 There was no difference in pharmacokinetic parameters between healthy volunteers and patients with episodic or chronic migraine

Absorption-                                                                                                                     Following a subcutaneous dose of galcanezumab-gnlm, the time to maximum concentration was about 5 days. Injection site location did not significantly influence the absorption of galcanezumab-gnlm.

Distribution-                                                                                                                       The apparent volume of distribution (V/F) of galcanezumab-gnlm was 7.3 L (34% Inter Individual Variability [IIV]).

Metabolism and Elimination-                                                                                             Galcanezumab-gnlm is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

The apparent clearance (CL/F) of galcanezumab-gnlm was 0.008 L/h and the elimination half-life of galcanezumab was approximately 27 days.

Specific Populations Age, Sex, Weight, Race, Ethnicity-                                               The pharmacokinetics of galcanezumab-gnlm were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetics analysis. Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab-gnlm.

Patients with Renal or Hepatic Impairment-                                                                    Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab-gnlm.

 Population pharmacokinetic analysis of integrated data from the galcanezumab-gnlm clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab-gnlm in patients with mild or moderate renal impairment.

Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied. Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab-gnlm.

No dedicated clinical studies were conducted to evaluate the effect of hepatic impairment or renal impairment on the pharmacokinetics of galcanezumab-gnlm.                                                                                                      

Drug Interaction Studies P450 Enzymes-                          

Galcanezumab-gnlm is not metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely

USE IN SPECIFIC POPULATIONS-

1. Pregnancy

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

 Administration of galcanezumab-gnlm to rats and rabbits during the period of organogenesis or to rats throughout pregnancy and lactation at plasma exposures greater than that expected clinically did not result in adverse effects on development.

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.

Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Published data have suggested that women with migraine may be at increased risk of preeclampsia during pregnancy .

2. Lactation Risk Summary -                                                                                             There are no data on the presence of galcanezumab-gnlm 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 EMGALITY and any potential adverse effects on the breastfed infant from EMGALITY 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 EMGALITY did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.