Eszopiclone

WARNING: COMPLEX SLEEP BEHAVIORS

BOXED WARNING SECTION

WARNING: COMPLEX SLEEP BEHAVIORS Complex sleep behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur following use of eszopiclone tablets. Some of these events may result in serious injuries, including death. Discontinue eszopiclone tablets immediately if a patient experiences a complex sleep behavior [ see Contraindications ( 4 ) and Warnings and Precautions (5.1) ].

1 INDICATIONS & USAGE

INDICATIONS & USAGE SECTION

Eszopiclone tablets are indicated for the treatment of insomnia. In controlled outpatient and sleep laboratory studies, eszopiclone tablets administered at bedtime decreased sleep latency and improved sleep maintenance. The clinical trials performed in support of efficacy were up to 6 months in duration. The final formal assessments of sleep latency and maintenance were performed at 4 weeks in the 6-week study (adults only), at the end of both 2-week studies (elderly only) and at the end of the 6-month study (adults only).

2 DOSAGE & ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

Use the lowest effective dose for the patient.

3 DOSAGE FORMS & STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

Eszopiclone tablets, USP are available in 1 mg, 2 mg and 3 mg strengths for oral administration. Eszopiclone tablets, USP 3 mg are dark blue, round, biconvex, film coated tablet, debossed with "L 36" on one side and plain on other side. Eszopiclone tablets, USP 2 mg are are white, round, biconvex, film coated tablet, debossed with "L 35" on one side and plain on other side. Eszopiclone tablets, USP 1 mg are light blue, round, biconvex, film coated tablet, debossed with "L 34" on one side and plain on other side.

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

• Eszopiclone tablets are contraindicated in patients who have experienced complex sleep behaviors after taking eszopiclone tablets [ see Warnings and Precautions (5.1) ]. • Eszopiclone tablets are contraindicated in patients with known hypersensitivity to eszopiclone. Hypersensitivity reactions include anaphylaxis and angioedema [ see Warnings and Precautions ( 5.3 ) ].

5 WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

The following are described in more detail in the Warnings and Precautions section of the label: • Complex Sleep Behaviors [ see Boxed Warning and Warnings and Precautions ( 5.1 ) ] • CNS Depressant Effects and Next-Day Impairment [ see Warnings and Precautions ( 5.2 ) ] • Need to Evaluate for Comorbid Diagnoses [ see Warnings and Precautions ( 5.3 ) ] • Severe Anaphylactic and Anaphylactoid Reactions [ see Warnings and Precautions ( 5.4 ) ] • Abnormal Thinking and Behavioral Changes [ see Warnings and Precautions ( 5.5 ) ] • Withdrawal Effects [see Warnings and Precautions ( 5.6 ) ] • Timing of Drug Administration [see Warnings and Precautions ( 5.7 ) ] • Special Populations [ see Warnings and Precautions ( 5.8 ) ] 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 clinical practice. The premarketing development program for eszopiclone tablets included eszopiclone exposures in patients and/or normal subjects from two different groups of studies: approximately 400 normal subjects in clinical pharmacology/pharmacokinetic studies, and approximately 1550 patients in placebo-controlled clinical effectiveness studies, corresponding to approximately 263 patient-exposure years. The conditions and duration of treatment with eszopiclone varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, and short-term and longer-term exposure. Adverse reactions were assessed by collecting adverse events, results of physical examinations, vital signs, weights, laboratory analyses, and ECGs. The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, adverse reaction of the type listed. A reaction was considered treatment-emergent if it occurred for the first time or worsened while the patient was receiving therapy following baseline evaluation.

7 DRUG INTERACTIONS

DRUG INTERACTIONS SECTION

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

9 DRUG ABUSE AND DEPENDENCE

DRUG ABUSE AND DEPENDENCE SECTION

10 OVERDOSAGE

OVERDOSAGE SECTION

In clinical trials with eszopiclone, one case of overdose with up to 36 mg of eszopiclone was reported in which the subject fully recovered. Since commercial marketing began, spontaneous cases of eszopiclone overdoses up to 270 mg (90 times the maximum recommended dose of eszopiclone) have been reported, in which patients have recovered. Fatalities related to eszopiclone overdoses were reported only in combination with other CNS drugs or alcohol.

11 DESCRIPTION

DESCRIPTION SECTION

Eszopiclone, USP is a nonbenzodiazepine hypnotic agent that is a pyrrolopyrazine derivative of the cyclopyrrolone class. The chemical name of eszopiclone is (+)-(5S)-6-(5chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b] pyrazin-5-yl 4-methylpiperazine-1carboxylate. Its molecular weight is 388.81, and its empirical formula is C17H17ClN6O3. Eszopiclone, USP has a single chiral center with an (S)-configuration. It has the following chemical structure: Eszopiclone, USP is a white to light-yellow crystalline solid. Eszopiclone is very slightly soluble in water, slightly soluble in ethanol, and soluble in phosphate buffer (pH 3.2). Eszopiclone, USP is formulated as film-coated tablets for oral administration. Eszopiclone tablets, USP contain 1 mg, 2 mg, or 3 mg eszopiclone, USP and the following inactive ingredients: dibasic calcium phosphate dihydrate, colloidal silicon dioxide, croscarmellose sodium, hypromellose, lactose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, titanium dioxide, and triacetin. In addition, both the 1 mg and 3 mg tablets contain FD&C Blue #2.

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

The effect of eszopiclone on reducing sleep latency and improving sleep maintenance was established in studies with 2100 subjects (ages 18 to 86) with chronic and transient insomnia in six placebo-controlled trials of up to 6 months’ duration. Two of these trials were in elderly patients (n=523). Overall, at the recommended adult dose (2 to 3 mg) and elderly dose (1 to 2 mg), eszopiclone significantly decreased sleep latency and improved measures of sleep maintenance (objectively measured as WASO and subjectively measured as total sleep time).

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

Eszopiclone tablets, USP 1 mg are light blue, round, biconvex, film-coated tablet, debossed with "L 34" on one side and plain on other side. Product: 71335-0598 NDC: 71335-0598-1 30 TABLET, FILM COATED in a BOTTLE NDC: 71335-0598-2 60 TABLET, FILM COATED in a BOTTLE NDC: 71335-0598-3 90 TABLET, FILM COATED in a BOTTLE NDC: 71335-0598-4 10 TABLET, FILM COATED in a BOTTLE NDC: 71335-0598-5 120 TABLET, FILM COATED in a BOTTLE NDC: 71335-0598-6 100 TABLET, FILM COATED in a BOTTLE Eszopiclone tablets, USP 2 mg are white, round, biconvex, film-coated tablet, debossed with "L 35" on one side and plain on other side. Product: 71335-0089 NDC: 71335-0089-1 30 TABLET, FILM COATED in a BOTTLE NDC: 71335-0089-2 60 TABLET, FILM COATED in a BOTTLE NDC: 71335-0089-3 90 TABLET, FILM COATED in a BOTTLE NDC: 71335-0089-4 120 TABLET, FILM COATED in a BOTTLE NDC: 71335-0089-5 20 TABLET, FILM COATED in a BOTTLE NDC: 71335-0089-6 100 TABLET, FILM COATED in a BOTTLE NDC: 71335-0089-7 28 TABLET, FILM COATED in a BOTTLE NDC: 71335-0089-8 10 TABLET, FILM COATED in a BOTTLE Eszopiclone tablets, USP 3 mg are dark blue, round, biconvex, film-coated tablet, debossed with "L 36" on one side and plain on other side. Product: 71335-0116 NDC: 71335-0116-1 30 TABLET, FILM COATED in a BOTTLE NDC: 71335-0116-2 60 TABLET, FILM COATED in a BOTTLE NDC: 71335-0116-3 90 TABLET, FILM COATED in a BOTTLE NDC: 71335-0116-4 120 TABLET, FILM COATED in a BOTTLE NDC: 71335-0116-5 20 TABLET, FILM COATED in a BOTTLE NDC: 71335-0116-6 28 TABLET, FILM COATED in a BOTTLE NDC: 71335-0116-7 15 TABLET, FILM COATED in a BOTTLE NDC: 71335-0116-8 100 TABLET, FILM COATED in a BOTTLE Store at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Preserve in tight containers. Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

See FDA-approved patient labeling (Medication Guide). Inform patients and their families about the benefits and risks of treatment with eszopiclone. Inform patients of the availability of a Medication Guide and instruct them to read the Medication Guide prior to initiating treatment with eszopiclone and with each prescription refill. Review the eszopiclone Medication Guide with every patient prior to initiation of treatment. Instruct patients or caregivers that eszopiclone should be taken only as prescribed. Complex Sleep Behaviors Instruct patients and their families that eszopiclone tablets may cause complex sleep behaviors, including sleep-walking, sleep-driving, preparing and eating food, making phone calls, or having sex while not being fully awake. Serious injuries and death have occurred during complex sleep behavior episodes. Tell patients to discontinue eszopiclone tablets and notify their healthcare provider immediately if they develop any of these symptoms [ see Boxed Warning, Warnings and Precautions ( 5.1 ) ]. CNS Depressant Effects and Next-Day Impairment Tell patients that eszopiclone can cause next-day impairment even when used as prescribed, and that this risk is increased if dosing instructions are not carefully followed. Caution patients taking the 3 mg dose against driving and other activities requiring complete mental alertness the day after use. Inform patients that impairment can be present despite feeling fully awake. Advise patients that increased drowsiness and decreased consciousness may increase the risk of falls in some patients [see Warnings and Precautions ( 5.2) ] . Severe Anaphylactic and Anaphylactoid Reactions Inform patients that severe anaphylactic and anaphylactoid reactions have occurred with eszopiclone. Describe the signs/symptoms of these reactions and advise patients to seek medical attention immediately if any of them occur [ see Warnings and Precautions ( 5.4 ) ]. Sleep-driving and Other Complex Behaviors Instruct patients and their families that sedative hypnotics can cause abnormal thinking and behavior change, including "sleep driving" and other complex behaviors while not being fully awake (preparing and eating food, making phone calls, or having sex). Tell patients to call you immediately if they develop any of these symptoms. Suicide Tell patients to immediately report any suicidal thoughts. Alcohol and Other Drugs Ask patients about alcohol consumption, medicines they are taking, and drugs they may be taking without a prescription. Advise patients not to use eszopiclone if they drank alcohol that evening or before bed. Tolerance, Abuse, and Dependence Tell patients not to increase the dose of eszopiclone on their own, and to inform you if they believe the drug "does not work". Administration Instructions Patients should be counseled to take eszopiclone right before they get into bed and only when they are able to stay in bed a full night (7–8 hours) before being active again. Eszopiclone tablets should not be taken with or immediately after a meal. Advise patients NOT to take eszopiclone if they drank alcohol that evening. Manufactured for: Macleods Pharma USA, INC, Plainsboro, NJ 08536. Manufactured by: Macleods Pharmaceuticals Ltd. Baddi, Himachal Pradesh, India. Revised: September 2019

SPL MEDGUIDE SECTION

SPL MEDGUIDE SECTION

MEDICATION GUIDE Eszopiclone Tablets, Coated C-IV (ES-zoe-PIK-lone) Read the Medication Guide that comes with eszopiclone tablets before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about your medical condition or treatment. What is the most important information I should know about eszopiclone tablets? • Do not take more eszopiclone tablets than prescribed. • Do not take eszopiclone tablets unless you are able to stay in bed a full night (7 to 8 hours) before you must be active again. • Take eszopiclone tablets right before you get in bed, not sooner. Eszopiclone tablets may cause serious side effects, including: Complex sleep behaviors that have caused serious injury and death. After taking eszopiclone tablets, you may get up out of bed while not being fully awake and do an activity that you do not know you are doing (complex sleep behaviors). The next morning, you may not remember that you did anything during the night. These activities may occur with eszopiclone tablets whether or not you drink alcohol or take other medicines that make you sleepy. Reported activities and behaviors include : • doing activities when you are asleep like: o making and eating food o talking on the phone o having sex o driving a car (“sleep-driving”) o sleep walking Stop taking eszopiclone tablets and call your healthcare provider right away if you find out that you have done any of the above activities after taking eszopiclone tablets. The morning after you take eszopiclone tablets your ability to drive safely and think clearly may be decreased. You also may experience sleepiness during the day. Do not take eszopiclone tablets if you : • have ever experienced a complex sleep behavior (such as driving a car, making and eating food, talking on the phone or having sex while not fully awake) after taking eszopiclone tablets. • drank alcohol that evening or before bed • take other medicines that can make you sleepy. Talk to your doctor about all of your medicines. Your doctor will tell you if you can take eszopiclone tablets with your other medicines. • cannot get a full night’s sleep What are eszopiclone tablets? Eszopiclone tablets are a sedative-hypnotic (sleep) medicine. Eszopiclone tablets are used in adults for the treatment of a sleep problem called insomnia. Symptoms of insomnia include: · trouble falling asleep · waking up often during the night Eszopiclone is not for children. Eszopiclone is a federally controlled substance (C-IV) because it can be abused or lead to dependence. Keep eszopiclone tablets in a safe place to prevent misuse and abuse. Selling or giving away eszopiclone may harm others, and is against the law. Tell your doctor if you have ever abused or been dependent on alcohol, prescription medicines or street drugs. Who should not take eszopiclone tablets? • Do not take eszopiclone tablets if you have ever had a complex sleep behavior happen after taking eszopiclone tablets. • Do not take eszopiclone tablets if you are allergic to anything in it. See the end of this Medication Guide for a complete list of ingredients in eszopiclone tablets. Eszopiclone tablets may not be right for you. Before starting eszopiclone tablets, tell your doctor about all of your health conditions, including if you: · have a history of depression, mental illness, or suicidal thoughts · have a history of drug or alcohol abuse or addiction · have liver disease · are pregnant, planning to become pregnant, or breastfeeding Tell your doctor about all of the medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements. Medicines can interact with each other, sometimes causing serious side effects. Do not take eszopiclone tablets with other medicines that can make you sleepy. Know the medicines you take. Keep a list of your medicines with you to show your doctor and pharmacist each time you get a new medicine. How should I take eszopiclone tablets? · Take eszopiclone tablets exactly as prescribed. Do not take more eszopiclone tablets than prescribed for you. · Take eszopiclone tablets right before you get into bed. · Do not take eszopiclone tablets with or right after a meal. · Do not take eszopiclone tablets unless you are able to get a full night’s sleep before you must be active again. · Call your doctor if your insomnia worsens or is not better within 7 to 10 days. This may mean that there is another condition causing your sleep problems. · If you take too much eszopiclone tablets or overdose, call your doctor or poison control center right away, or get emergency treatment. What are the possible side effects of eszopiclone tablets? Possible serious side effects of eszopiclone tablets include: · getting out of bed while not being fully awake and doing an activity that you do not know you are doing. (See “What is the most important information I should know about eszopiclone tablets?) · abnormal thoughts and behavior . Symptoms include more outgoing or aggressive behavior than normal, confusion, agitation, acting strangely, hallucinations, worsening of depression, and suicidal thoughts or actions. · memory loss · anxiety · severe allergic reactions . Symptoms include swelling of the tongue or throat, trouble breathing, and nausea and vomiting. Get emergency medical help if you get these symptoms after taking eszopiclone tablets. Call your doctor right away if you have any of the above side effects or any other side effects that worry you while using eszopiclone tablets. The most common side effects of eszopiclone tablets are: · unpleasant taste in mouth, dry mouth · drowsiness · dizziness · headache · symptoms of the common cold You may still feel drowsy the next day after taking eszopiclone tablets. Do not drive or do other dangerous activities after taking eszopiclone tablets until you feel fully awake. These are not all the side effects of eszopiclone tablets. Ask your doctor or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store eszopiclone tablets ? · Store eszopiclone tablets at room temperature, between 59°F to 86°F (15°C to 30°C). · Do not use eszopiclone tablets after the expiration date. · Keep eszopiclone tablets and all medicines out of reach of children. General Information about eszopiclone tablets. · Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. · Do not use eszopiclone tablets for a condition for which it was not prescribed. · Do not share eszopiclone tablets with other people, even if you think they have the same symptoms that you have. It may harm them and is against the law. This Medication Guide summarizes the most important information about eszopiclone tablets. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about eszopiclone tablets that is written for healthcare professionals. · For customer service, call 1-888-943-3210. · To report side effects, call 1-888-943-3210. What are the ingredients in eszopiclone tablets ? Active Ingredient: eszopiclone Inactive Ingredients: dibasiccalcium phosphate dihydrate, colloidal silicon dioxide, croscarmellose sodium, hypromellose, lactose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, titanium dioxide, and triacetin. In addition, both the 1 mg and 3 mg tablets contain FD&C Blue #2 This Medication Guide has been approved by the U.S. Food and Drug Administration. Manufacture for: Macleods Pharma USA, INC,. Plainsboro, NJ 08536 Manufactured by: Macleods Pharmaceuticals Ltd. Baddi, Himachal Pradesh, India. Revised: 09/2019

Eszopiclone 2mg (CIV) Tablet

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Eszopiclone 3mg (CIV) Tablet

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Eszopiclone 1mg (CIV) Tablet

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL