FDA Label for Eszopiclone
View Indications, Usage & Precautions
Eszopiclone Product Label
The following document was submitted to the FDA by the labeler of this product Advanced Rx Pharmacy Of Tennessee, Llc. The document includes published materials associated whith this product with the essential scientific information about this product as well as other prescribing information. Product labels may durg indications and usage, generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, warnings, inactive ingredients, etc.
Medication Guide 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
Overdosage Section
OVERDOSAGE
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.
10.1 Signs and Symptoms
Signs and symptoms of overdose effects of CNS depressants can be expected to present as exaggerations of the pharmacological effects noted in preclinical testing. Impairment of consciousness ranging from somnolence to coma has been described. Rare individual instances of fatal outcomes following overdose with racemic zopiclone have been reported in European postmarketing reports, most often associated with overdose with other CNS-depressant agents.
10.2 Recommended Treatment
General symptomatic and supportive measures should be used along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. Flumazenil may be useful. As in all cases of drug overdose, respiration, pulse, blood pressure, and other appropriate signs should be monitored and general supportive measures employed. Hypotension and CNS depression should be monitored and treated by appropriate medical intervention. Consider monitoring methemoglobin in the setting of high-dose overdosage. The value of dialysis in the treatment of overdosage has not been determined.
As with the management of all overdosage, the possibility of multiple drug ingestion should be considered. The physician may wish to consider contacting a poison control center for up-todate information on the management of hypnotic drug product overdosage.
Adverse Reactions Section
ADVERSE REACTIONS
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.
6.1 Clinical Trials Experience
Adverse Reactions Resulting in Discontinuation of Treatment
In placebo-controlled, parallel-group clinical trials in the elderly, 3.8% of 208 patients who received placebo, 2.3% of 215 patients who received 2 mg eszopiclone, and 1.4% of 72 patients who received 1 mg eszopiclone discontinued treatment due to an adverse reaction. In the 6-week parallel-group study in adults, no patients in the 3 mg arm discontinued because of an adverse reaction.
In the long-term 6-month study in adult insomnia patients, 7.2% of 195 patients who received placebo and 12.8% of 593 patients who received 3 mg eszopiclone discontinued due to an adverse reaction. No reaction that resulted in discontinuation occurred at a rate of greater than 2%.
Adverse Reactions Observed at an Incidence of ≥2% in Controlled Trials
Table 1 shows the incidence of adverse reactions from a Phase 3 placebo-controlled study of eszopiclone at doses of 2 or 3 mg in nonelderly adults. Treatment duration in this trial was 44 days. The table includes only reactions that occurred in 2% or more of patients treated with eszopiclone 2 mg or 3 mg in which the incidence in patients treated with eszopiclone was greater than the incidence in placebo-treated patients.
Table 1: Incidence (%) of Adverse Reactions in a 6-Week Placebo-Controlled Study in Nonelderly Adults with eszopiclone 1
Adverse Reaction
Placebo
(n=99)
Eszopiclone 2 mg
(n=104)
Eszopiclone 3 mg
(n=105)
Body as a Whole
Headache
13
21
17
Viral Infection
1
3
3
Digestive System
Dry Mouth
3
5
7
Dyspepsia
4
4
5
Nausea 4
5
4
Vomiting 1
3
0
Nervous System
Anxiety 0
3
1
Confusion
0
0
3
Depression
0
4
1
Dizziness
4
5
7
Hallucinations
0
1
3
Libido Decreased
0
0
3
Nervousness
3
5
0
Somnolence
3
10
8
Respiratory System
Infection
3
5
10
Skin and Appendages
Rash 1
3
4
Special Senses
Unpleasant Taste
3
17
34
Urogenital System
Dysmenorrhea *
0
3
0
Gynecomastia **
0
3
0
1 Reactions for which the eszopiclone incidence was equal to or less than placebo are not listed on the table, but included the following: abnormal dreams, accidental injury, back pain, diarrhea, flu syndrome, myalgia, pain, pharyngitis, and rhinitis.
* Gender-specific adverse reaction in females
** Gender-specific adverse reaction in males
Adverse reactions from Table 1 that suggest a dose-response relationship in adults include viral infection, dry mouth, dizziness, hallucinations, infection, rash, and unpleasant taste, with this relationship clearest for unpleasant taste.
Table 2 shows the incidence of adverse reactions from combined Phase 3 placebo-controlled studies of eszopiclone at doses of 1 or 2 mg in elderly adults (ages 65 to 86). Treatment duration in these trials was 14 days. The table includes only reactions that occurred in 2% or more of patients treated with eszopiclone 1 mg or 2 mg in which the incidence in patients treated with eszopiclone was greater than the incidence in placebo-treated patients.
Table 2: Incidence (%) of Adverse Reactions in Elderly Adults (Ages 65 to 86 Years) in 2-Week Placebo-Controlled Trials with Eszopiclone 1
Adverse Reactions
Placebo (n=208)
Eszopiclone
1 mg (n=72)
Eszopiclone
2 mg (n=215)
Body as a Whole
Accidental Injury
1
0
3
Headache
14
15
13
Pain
2
4
5
Digestive System
Diarrhea
2
4
2
Dry Mouth
2
3
7
Dyspepsia
2
6
2
Nervous System
Abnormal Dreams
0
3
1
Dizziness
2
1
6
Nervousness
1
0
2
Neuralgia
0
3
0
Skin and Appendages
Pruritus
1
4
1
Special Senses
Unpleasant Taste
0
8
12
Urogenital System
Urinary Tract Infection
0
3
0
1 Reactions for which the eszopiclone incidence was equal to or less than placebo are not listed on the table, but included the following: abdominal pain, asthenia, nausea, rash, and somnolence.
Adverse reactions from Table 2 that suggest a dose-response relationship in elderly adults include pain, dry mouth, and unpleasant taste, with this relationship again clearest for unpleasant taste.
These figures cannot be used to predict the incidence of adverse reactions in the course of usual medical practice because patient characteristics and other factors may differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contributions of drug and nondrug factors to the adverse reaction incidence rate in the population studied.
Other Reactions Observed During the Premarketing Evaluation of Eszopiclone.
Following is a list of modified COSTART terms that reflect adverse reactions as defined in the introduction to the Adverse Reactions section and reported by approximately 1550 subjects treated with eszopiclone at doses in the range of 1 to 3.5 mg/day during Phase 2 and 3 clinical trials throughout the United States and Canada. All reported reactions are included except those already listed in Tables 1 and 2 or elsewhere in labeling, minor reactions common in the general population, and reactions unlikely to be drug related. Although the reactions reported occurred during treatment with eszopiclone, they were not necessarily caused by it.
Reactions are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse reactions are those that occurred on one or more occasions in at least 1/100 patients; infrequent adverse reactions are those that occurred in fewer than 1/100 patients but in at least 1/1,000 patients; rare adverse reactions are those that occurred in fewer than 1/1,000 patients. Gender-specific reactions are categorized based on their incidence for the appropriate gender.
Body as a Whole: Frequent: chest pain; Infrequent: allergic reaction, cellulitis, face edema, fever, halitosis, heat stroke, hernia, malaise, neck rigidity, photosensitivity.
Cardiovascular System: Frequent: migraine; Infrequent: hypertension; Rare: thrombophlebitis.
Digestive System: Infrequent: anorexia, cholelithiasis, increased appetite, melena, mouth ulceration, thirst, ulcerative stomatitis; Rare: colitis, dysphagia, gastritis, hepatitis, hepatomegaly, liver damage, stomach ulcer, stomatitis, tongue edema, rectal hemorrhage.
Hemic and Lymphatic System: Infrequent: anemia, lymphadenopathy.
Metabolic and Nutritional: Frequent: peripheral edema; Infrequent: hypercholesteremia, weight gain, weight loss; Rare: dehydration, gout, hyperlipemia, hypokalemia.
Musculoskeletal System: Infrequent: arthritis, bursitis, joint disorder (mainly swelling, stiffness, and pain), leg cramps, myasthenia, twitching; Rare: arthrosis, myopathy, ptosis.
Nervous System: Infrequent: agitation, apathy, ataxia, emotional lability, hostility, hypertonia, hypesthesia, incoordination, insomnia, memory impairment, neurosis, nystagmus, paresthesia, reflexes decreased, thinking abnormal (mainly difficulty concentrating), vertigo; Rare: abnormal gait, euphoria, hyperesthesia, hypokinesia, neuritis, neuropathy, stupor, tremor.
Respiratory System: Infrequent: asthma, bronchitis, dyspnea, epistaxis, hiccup, laryngitis.
Skin and Appendages: Infrequent: acne, alopecia, contact dermatitis, dry skin, eczema, skin discoloration, sweating, urticaria; Rare: erythema multiforme, furunculosis, herpes zoster, hirsutism, maculopapular rash, vesiculobullous rash.
Special Senses: Infrequent: conjunctivitis, dry eyes, ear pain, otitis externa, otitis media, tinnitus, vestibular disorder; Rare: hyperacusis, iritis, mydriasis, photophobia.
Urogenital System: Infrequent: amenorrhea, breast engorgement, breast enlargement, breast neoplasm, breast pain, cystitis, dysuria, female lactation, hematuria, kidney calculus, kidney pain, mastitis, menorrhagia, metrorrhagia, urinary frequency, urinary incontinence, uterine hemorrhage, vaginal hemorrhage, vaginitis; Rare: oliguria, pyelonephritis, urethritis.
6.2 Postmarketing Experience
In addition to the adverse reactions observed during clinical trials, dysosmia, an olfactory dysfunction that is characterized by distortion of the sense of smell, has been reported during postmarketing surveillance with eszopiclone. Because this event is reported spontaneously from a population of unknown size, it is not possible to estimate the frequency of this event.
Dosage And Administration Section
DOSAGE & ADMINISTRATION
Use the lowest effective dose for the patient.
2.1 Dosage in Adults
The recommended starting dose is 1 mg. Dosing can be raised to 2 mg or 3 mg if clinically indicated. In some patients, the higher morning blood levels of eszopiclone tablets following use of the 2 mg or 3 mg dose increase the risk of next day impairment of driving and other activities that require full alertness [see Warnings and Precautions (5.1)]. The total dose of eszopiclone tablets should not exceed 3 mg, once daily immediately before bedtime [see Warnings and Precautions (5.6)].
2.2 Geriatric or Debilitated Patients
The total dose of eszopiclone tablets should not exceed 2 mg in elderly or debilitated patients.
2.3 Patients with Severe Hepatic Impairment, or Taking Potent CYP3A4 Inhibitors
In patients with severe hepatic impairment, or in patients coadministered eszopiclone with potent CYP3A4 inhibitors, the total dose of eszopiclone tablets should not exceed 2 mg [see Warnings and Precautions (5.7)].
2.4 Use with CNS Depressants
Dosage adjustments may be necessary when eszopiclone tablets are combined with other central nervous system (CNS) depressant drugs because of the potentially additive effects [see Warnings and Precautions (5.1)].
2.5 Administration with Food
Taking eszopiclone tablets with or immediately after a heavy, high-fat meal results in slower absorption and would be expected to reduce the effect of eszopiclone tablets on sleep latency [see Clinical Pharmacology (12.3)].
Indications And Usage Section
INDICATIONS & USAGE
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).
* Please review the disclaimer below.