Zolpidem Tartrate

Dosage Forms And Strengths

AMBIEN CR is available as extended-release tablets containing 6.25 mg or 12.5 mg of zolpidem tartrate for oral administration. Tablets are not scored.

AMBIEN CR 6.25 mg tablets are pink, round, bi-convex, and debossed with A~ on one side.

AMBIEN CR 12.5 mg tablets are blue, round, bi-convex, and debossed with A~ on one side.

Storage And Handling

AMBIEN CR 6.25 mg tablets are composed of two layers* and are coated, pink, round, biconvex, debossed with A~ on one side and supplied as:

AMBIEN CR 12.5 mg tablets are composed of two layers* and are coated, blue, round, biconvex, debossed with A~ on one side and supplied as:

*Layers are covered by the coating and are indistinguishable.

Store between 15°-25° C (59°-77°F). Limited excursions permissible up to 30° C (86°F)

sanofi-aventis U.S. LLC Bridgewater, NJ 08807 A SANOFI COMPANY. Revised: Dec 2016

Included as part of the PRECAUTIONS section.

Zolpidem is a sedative, also called a hypnotic. It affects chemicals in your brain that may become unbalanced and cause sleep problems (insomnia).

Zolpidem is used to treat insomnia. The immediate-release forms of zolpidem are Ambien, Intermezzo,Edluar, and Zolpimist, which are used to help you fall asleep. The extended-release form of zolpidem is Ambien CR, which has a first layer that dissolves quickly to help you fall asleep, and a second layer that dissolves slowly to help you stay asleep.

Ambien, Edluar, and Zolpimist are used to help you fall asleep when you first go to bed. Intermezzo, is used to help you fall back to sleep if you wake up in the middle of the night and then have trouble sleeping.

Your doctor will determine which form of zolpidem is best for you.

Zolpidem may also be used for purposes not listed in this medication guide.

Some people using this medicine have engaged in activity such as driving, eating, or making phone calls and later having no memory of the activity. If this happens to you, stop taking zolpidem and talk with your doctor about another treatment for your sleep disorder.

You should not use this medication if you are allergic to zolpidem. Zolpidem tablets may contain lactose. Use caution if you are sensitive to lactose.

To make sure zolpidem is safe for you, tell your doctor if you have:

• kidney disease;
• liver disease;
• lung disease such as asthma, bronchitis, emphysema, or chronic obstructive pulmonary disease (COPD);
• sleep apnea (breathing stops during sleep);
• myasthenia gravis;
• a history of depression, mental illness, or suicidal thoughts; or
• a history of drug or alcohol addiction.

Zolpidem may be habit forming and should be used only by the person it was prescribed for. Never share zolpidem with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

FDA pregnancy category C. It is not known whether zolpidem will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Zolpidem can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

The sedative effects of zolpidem may be stronger in older adults.

Do not give this medicine to anyone younger than 18 years of age.

It is dangerous to try and purchase zolpidem on the Internet or from vendors outside of the United States. Medications distributed from Internet sales may contain dangerous ingredients, or may not be distributed by a licensed pharmacy. Samples of zolpidem purchased on the Internet have been found to contain haloperidol (Haldol), a potent antipsychotic drug with dangerous side effects. For more information, contact the U.S. Food and Drug Administration (FDA) or visit www.fda.gov/buyonlineguide.

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

• CNS-depressant effects and next-day impairment [see WARNINGS AND PRECAUTIONS]
• Serious anaphylactic and anaphylactoid reactions [see WARNINGS AND PRECAUTIONS]
• Abnormal thinking and behavior changes, and complex behaviors [see WARNINGS AND PRECAUTIONS]
• Withdrawal effects [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Approximately 4% of 1,701 patients who received zolpidem at all doses (1.25 to 90 mg) in U.S. premarketing clinical trials discontinued treatment because of an adverse reaction. Reactions most commonly associated with discontinuation from U.S. trials were daytime drowsiness (0.5%), dizziness (0.4%), headache (0.5%), nausea (0.6%), and vomiting (0.5%). Approximately 4% of 1,959 patients who received zolpidem at all doses (1 to 50 mg) in similar foreign trials discontinued treatment because of an adverse reaction. Reactions most commonly associated with discontinuation from these trials were daytime drowsiness (1.1%), dizziness/vertigo (0.8%), amnesia (0.5%), nausea (0.5%), headache (0.4%), and falls (0.4%).

Data from a clinical study in which selective serotonin reuptake inhibitor (SSRI)-treated patients were given zolpidem revealed that four of the seven discontinuations during double-blind treatment with zolpidem (n=95) were associated with impaired concentration, continuing or aggravated depression, and manic reaction; one patient treated with placebo (n =97) was discontinued after an attempted suicide.

During short-term treatment (up to 10 nights) with AMBIEN at doses up to 10 mg, the most commonly observed adverse reactions associated with the use of zolpidem and seen at statistically significant differences from placebo-treated patients were drowsiness (reported by 2% of zolpidem patients), dizziness (1%), and diarrhea (1%). During longer-term treatment (28 to 35 nights) with zolpidem at doses up to 10 mg, the most commonly observed adverse reactions associated with the use of zolpidem and seen at statistically significant differences from placebo-treated patients were dizziness (5%) and drugged feelings (3%).

The following tables enumerate treatment-emergent adverse reactions frequencies that were observed at an incidence equal to 1% or greater among patients with insomnia who received zolpidem tartrate and at a greater incidence than placebo in U.S. placebo-controlled trials. Events reported by investigators were classified utilizing a modified World Health Organization (WHO) dictionary of preferred terms for the purpose of establishing event frequencies. The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice, in which patient characteristics and other factors differ from those that prevailed in these clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigators involving related drug products and uses, since each group of drug trials is conducted under a different set of conditions. However, the cited figures provide the physician with a basis for estimating the relative contribution of drug and nondrug factors to the incidence of side effects in the population studied.

The following table was derived from results of 11 placebo-controlled short-term U.S. efficacy trials involving zolpidem in doses ranging from 1.25 to 20 mg. The table is limited to data from doses up to and including 10 mg, the highest dose recommended for use.

Incidence of Treatment-Emergent Adverse Experiences in Placebo-Controlled Clinical Trials Lasting up to 10 Nights (Percentage of patients reporting)

The following table was derived from results of three placebo-controlled long-term efficacy trials involving AMBIEN (zolpidem tartrate). These trials involved patients with chronic insomnia who were treated for 28 to 35 nights with zolpidem at doses of 5, 10, or 15 mg. The table is limited to data from doses up to and including 10 mg, the highest dose recommended for use. The table includes only adverse events occurring at an incidence of at least 1% for zolpidem patients.

Incidence of Treatment-Emergent Adverse Experiences in Placebo-Controlled Clinical Trials Lasting up to 35 Nights (Percentage of patients reporting)

There is evidence from dose comparison trials suggesting a dose relationship for many of the adverse reactions associated with zolpidem use, particularly for certain CNS and gastrointestinal adverse events.

AMBIEN was administered to,660 subjects in clinical trials throughout the U.S., Canada, and Europe. Treatment-emergent adverse events associated with clinical trial participation were recorded by clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals experiencing treatment-emergent adverse events, similar types of untoward events were grouped into a smaller number of standardized event categories and classified utilizing a modified World Health Organization (WHO) dictionary of preferred terms.

The frequencies presented, therefore, represent the proportions of the 3,660 individuals exposed to zolpidem, at all doses, who experienced an event of the type cited on at least one occasion while receiving zolpidem. All reported treatment-emergent adverse events are included, except those already listed in the table above of adverse events in placebo-controlled studies, those coding terms that are so general as to be uninformative, and those events where a drug cause was remote. It is important to emphasize that, although the events reported did occur during treatment with AMBIEN, they were not necessarily caused by it.

Adverse events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in greater than 1/100 subjects; infrequent adverse events are those occurring in 1/100 to 1/1,000 patients; rare events are those occurring in less than 1/1,000 patients.

Autonomic nervous system:

Infrequent: increased sweating, pallor, postural hypotenson, syncope. Rare: abnormal accommodation, altered saliva, flushing, glaucoma, hypotension, impotence, increased saliva, tenesmus.

Body as a whole:

Frequent: asthenia. Infrequent: edema, falling, fatigue, fever, malaise, trauma. Rare: allergic reaction, allergy aggravated, anaphylactic shock, face edema, hot flashes, increased ESR, pain, restless legs, rigors, tolerance increased, weight decrease.

Cardiovascular system:

Infrequent: cerebrovascular disorder, hypertension, tachycardia. Rare: angina pectoris, arrhythmia, arteritis, circulatory failure, extrasystoles, hypertension aggravated, myocardial infarction, phlebitis, pulmonary embolism, pulmonary edema, varicose veins, ventricular tachycardia.

Central and peripheral nervous system:

Frequent: ataxia, confusion, euphoria, headache, insomnia, vertigo Infrequent: agitation, anxiety, decreased cognition, detached, difficulty concentrating, dysarthria, emotional lability, hallucination, hypoesthesia, illusion, leg cramps, migraine, nervousness, paresthesia, sleeping (after daytime dosing), speech disorder, stupor, tremor. Rare: abnormal gait, abnormal thinking, aggressive reaction, apathy, appetite increased, decreased libido, delusion, dementia, depersonalization, dysphasia, feeling strange, hypokinesia, hypotonia, hysteria, intoxicated feeling, manic reaction, neuralgia, neuritis, neuropathy, neurosis, panic attacks, paresis, personality disorder, somnambulism, suicide attempts, tetany, yawning.

Gastrointestinal system:

Frequent: dyspepsia, hiccup, nausea. Infrequent: anorexia, constipation, dysphagia, flatulence, gastroenteritis, vomiting. Rare: enteritis, eructation, esophagospasm, gastritis, hemorrhoids, intestinal obstruction, rectal hemorrhage, tooth caries.

Hematologic and lymphatic system:

Rare: anemia, hyperhemoglobinemia, leukopenia, lymphadenopathy, macrocytic anemia, purpura, thrombosis.

Immunologic system:

Infrequent: infection. Rare: abscess herpes simplex herpes zoster, otitis externa, otitis media.

Liver and biliary system:

Infrequent: abnormal hepatic function, increased SGPT. Rare: bilirubinemia, increased SGOT.

Metabolic and nutritional:

Infrequent: hyperglycemia, thirst. Rare: gout, hypercholesteremia, hyperlipidemia, increased alkaline phosphatase, increased BUN, periorbital edema.

Musculoskeletal system:

Frequent: arthralgia, myalgia. Infrequent: arthritis. Rare: arthrosis, muscle weakness, sciatica, tendinitis.

Reproductive system:

Infrequent: menstrual disorder, vaginitis. Rare: breast fibroadenosis, breast neoplasm, breast pain.

Respiratory system:

Frequent: upper respiratory infection, lower respiratory infection. Infrequent: bronchitis, coughing, dyspnea, rhinitis. Rare: bronchospasm, respiratory depression, epistaxis, hypoxia, laryngitis, pneumonia.

Skin and appendages:

Infrequent: pruritus. Rare: acne, bullous eruption, dermatitis, furunculosis, injection-site inflammation, photosensitivity reaction, urticaria.

Special senses:

Frequent: diplopia, vision abnormal. Infrequent: eye irritation, eye pain, scleritis, taste perversion, tinnitus. Rare: conjunctivitis, corneal ulceration, lacrimation abnormal, parosmia, photopsia.

Urogenital system:

Frequent: urinary tract infection. Infrequent: cystitis, urinary incontinence. Rare: acute renal failure, dysuria, micturition frequency, nocturia, polyuria, pyelonephritis, renal pain, urinary retention.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of AMBIEN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Liver and biliary system: acute hepatocellular, cholestatic or mixed liver injury with or without jaundice (i.e., bilirubin >2×ULN, alkaline phosphatase ≥2×ULN, transaminase ≥5×ULN).

Read the entire FDA prescribing information for Ambien (Zolpidem Tartrate)

Imidazopyridine-derivative sedative and hypnotic;1 2 3 4 89 type A GABA (GABAA)-receptor agonist;1 89 structurally unrelated to benzodiazepines and other sedatives and hypnotics.1 2 3 89

Insomnia

Conventional tablets, oral spray, or sublingual tablets (Edluar) used for short-term management of insomnia characterized by difficulties with sleep initiation.1 92 93 Decreases sleep latency in patients with chronic or transient insomnia;1 2 3 22 no substantial evidence of diminished effectiveness during the end of each night’s use (early morning insomnia) despite short half-life.1 14 19 20

Extended-release tablets used for management of insomnia characterized by difficulty with sleep onset or sleep maintenance.89 97 May not be an appropriate treatment choice for patients (men or women) who need to drive or perform activities that require full alertness the next morning (see CNS Depression and Next-day Impairment under Cautions).95

Sublingual tablets (Intermezzo) used as needed for management of insomnia when middle-of-the-night awakening is followed by difficulty returning to sleep; for use only when ≥4 hours remain before planned time of awakening.94 98 99

General

• Reevaluate patient if zolpidem is to be used for more than 2–3 weeks.23 79 (See Adequate Patient Evaluation under Cautions.)

• Consider gradual dosage reduction (e.g., over several nights) when discontinuing therapy.1 77 78 (See Withdrawal Effects under Cautions.)

Administration

Administer orally (as conventional tablets, extended-release tablets, or an oral solution using a metered-dose spray pump) or sublingually (as sublingual tablets).1 89 92 93 94

Oral Administration

Do not administer with or immediately after a meal in order to facilitate onset of sleep.1 89 92 (See Food under Pharmacokinetics.)

Administer only once per night immediately before bedtime, at least 7–8 hours before planned time of awakening.1

Administer only once per night immediately before bedtime, at least 7–8 hours before planned time of awakening.89

Swallow extended-release tablets whole; do not divide, crush, or chew.89

Administer only once per night immediately before bedtime, at least 7–8 hours before planned time of awakening.92

Consult the manufacturer’s patient instructions for detailed information on use of the spray pump.92

Prior to initial use, prime spray pump by actuating 5 sprays.92 If not used for ≥14 days, prime spray pump again by actuating 1 spray.92

To administer, hold container upright with spray opening pointed directly into the mouth and fully press down on pump to ensure that a full dose is sprayed directly into the mouth over the tongue.92 Administer 1 or 2 sprays (5 mg per spray) based on indicated dose.92

Each 8.2-g container delivers about 60 metered sprays after initial priming.92 Number of available doses depends on number of sprays per dose and frequency of priming.92 Discard oral spray when labeled number of actuations (60 sprays) used.92

No special requirements for cleaning and maintaining the spray pump.92

Sublingual Administration

Do not administer with or immediately after a meal in order to facilitate onset of sleep.93 94 (See Food under Pharmacokinetics.)

Administer only once per night immediately before bedtime, at least 7–8 hours before planned time of awakening.93

Place tablet under tongue, where it will disintegrate.93 Do not swallow or administer tablet with water.93

Administer in bed, only once per night as needed if middle-of-the-night awakening is followed by difficulty returning to sleep, and only if ≥4 hours remain before planned time of awakening.94

Place tablet under tongue and allow to disintegrate completely before swallowing.94 Do not swallow tablet whole.94

Remove tablet from pouch just prior to administration.94

Dosage

Available as zolpidem tartrate; dosage expressed in terms of the salt.1 89 92 93 94

Use smallest effective dose.1 89 92 93 95

Adults

Women: Initially, 5 mg.1 92 93 95

Men: Initially, 5 or 10 mg.1 92 93 95

Dose of 5 mg should be effective in most women and many men.95 If 5 mg is not effective in men or women, may increase dose to 10 mg.1 92 93 95

In some patients, higher morning blood concentrations following a 10-mg dose increase risk of next-day impairment of driving and other activities requiring full alertness.1 92 93 95 (See CNS Depression and Next-day Impairment under Cautions.)

Initial doses for women and men differ because clearance is slower in women.1 92 93 95 (See Elimination: Special Populations, under Pharmacokinetics.)

Women: Initially, 6.25 mg.89 95

Men: Initially, 6.25 or 12.5 mg.89 95

Dose of 6.25 mg should be effective in most women and many men.95 If 6.25 mg is not effective in men or women, may increase dose to 12.5 mg.89 95

In some patients, higher morning blood concentrations following a 12.5-mg dose increase risk of next-day impairment of driving and other activities requiring full alertness.89 95 (See CNS Depression and Next-day Impairment under Cautions.)

Initial doses for women and men differ because clearance is slower in women.89 95 (See Elimination: Special Populations, under Pharmacokinetics.)

Women: 1.75 mg.94

Men: 3.5 mg.94

Doses for women and men differ because clearance is slower in women.94 (See Elimination: Special Populations, under Pharmacokineticsand also see CNS Depression and Next-day Impairment under Cautions.)

Men or women receiving concomitant CNS depressant: 1.75 mg.94 (See CNS Depression and Next-day Impairment under Cautions and also see Specific Drugs under Interactions.)

Prescribing Limits

Adults

Maximum 10 mg once daily immediately before bedtime.1 92 93

Maximum 12.5 mg once daily immediately before bedtime.89

Women: Maximum 1.75 mg once per night.94

Men: Maximum 3.5 mg once per night.94

Special Populations

Hepatic Impairment

Prolonged elimination.81 89 (See Absorption: Special Populations and also Elimination: Special Populations, under Pharmacokinetics.)

Conventional tablets, oral spray, or sublingual tablets (Edluar): 5 mg once daily immediately before bedtime.1 92 93

Extended-release tablets: 6.25 mg once daily immediately before bedtime.89

Sublingual tablets (Intermezzo): 1.75 mg only once per night if needed.94

Renal Impairment

Possible pharmacokinetic alterations.2 3 81 (See Elimination: Special Populations, under Pharmacokinetics.) Manufacturers state that dosage adjustment is not necessary;1 89 92 93 94 some clinicians recommend that dosage reduction be considered.2 3 81

Geriatric Patients

Possible increased sensitivity to sedatives and hypnotics.1 89 92 93 94 (See Geriatric Use under Cautions.)

Conventional tablets, oral spray, or sublingual tablets (Edluar): 5 mg once daily immediately before bedtime.1 92 93

Extended-release tablets: 6.25 mg once daily immediately before bedtime.89

Sublingual tablets (Intermezzo): In men and women >65 years of age, 1.75 mg only once per night if needed.94

Debilitated Patients

Possible increased sensitivity to sedatives and hypnotics.1 89 92 93

Conventional tablets, oral spray, or sublingual tablets (Edluar): 5 mg once daily immediately before bedtime.1 92 93

Extended-release tablets: 6.25 mg once daily immediately before bedtime.89

Absorption

Bioavailability

Conventional tablets: Rapidly absorbed from GI tract following oral administration, with peak plasma concentrations attained in about 1.6 hours.1 Absolute bioavailability is about 70%.87

Extended-release tablets: Exhibit biphasic absorption characteristics; rapid initial absorption following oral administration (similar to conventional tablets), but with extended plasma concentrations beyond 3 hours after administration.89 Peak plasma concentrations are attained in about 1.5 hours.89

Oral spray: Bioequivalent to conventional tablets.92 Rapidly absorbed from oral mucosa and GI tract, with peak plasma concentrations attained in about 0.9 hours.92

Sublingual tablets (Edluar): Bioequivalent to conventional tablets with respect to peak concentration and AUC.93 Rapidly absorbed, with peak plasma concentrations attained in about 82 minutes.93

Sublingual tablets (Intermezzo): Rapidly absorbed, with peak plasma concentrations attained in about 35–75 minutes.94

Food

Conventional tablets: Food decreases AUC by 15%, decreases peak plasma concentration by 25%, and prolongs time to peak plasma concentration by 60%.1

Extended-release tablets: Food decreases AUC by 23%, decreases peak plasma concentration by 30%, and prolongs time to peak plasma concentration by about 2 hours (from 2 hours to 4 hours).89

Oral spray: Food decreases AUC by 27%, decreases peak plasma concentration by 58%, and prolongs time to peak plasma concentration by 225% (from 0.8 hours to 2.6 hours).92

Sublingual tablets (Edluar): Food decreases AUC by 20%, decreases peak plasma concentration by 31%, and prolongs time to peak plasma concentration by 28% (from 82 minutes to 105 minutes).93

Sublingual tablets (Intermezzo): Food decreases AUC by 19%, decreases peak plasma concentration by 42%, and prolongs time to peak plasma concentration to nearly 3 hours.94

Plasma Concentrations

Blood concentrations >50 ng/mL may impair driving to a degree that increases risk of a motor vehicle accident.95 (See CNS Depression and Next-day Impairment under Cautions.)

Special Populations

Zolpidem exposure is greater in women than in men receiving the same dose.1 89 92 93 94 Peak concentration and AUC are increased by 45% (for immediate-release formulation) or by 50 and 75%, respectively (for extended-release tablets), in women compared with men;1 92 93 94 concentrations 6–12 hours after a dose of extended-release zolpidem are 2–3 times higher in women than in men.89

Zolpidem exposure is greater in geriatric patients than in younger adults receiving the same dose.1 94 Peak concentration and AUC are increased by 50 and 64%, respectively (for conventional tablets), and by 34 and 30%, respectively (for 3.5-mg sublingual tablets), in geriatric individuals compared with younger adults.1 94 Peak concentrations and AUC are lower in geriatric individuals receiving 1.75-mg dose than in younger adults receiving 3.5-mg dose.94

In patients with chronic hepatic impairment, peak plasma concentration and AUC (for conventional tablets) are 2 and 5 times higher, respectively, than in healthy individuals.1 89 Extended-release tablets not studied to date in patients with hepatic impairment.89

Distribution

Extent

Distributed into milk in small amounts.1 89 92 93 94 100

Plasma Protein Binding

Approximately 92–93%.1 87 89 92 93 94

Elimination

Metabolism

Metabolized in the liver via oxidation and hydroxylation, principally by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6.1 88 No active metabolites.1 87 89 92 93 94

Elimination Route

Excreted principally in urine as inactive metabolites.1 89 92 93 94

Half-life

Approximately 2.5–3 hours.1 87 89 92 93 94

Special Populations

Eliminated more slowly in women than in men; lower doses recommended for women since use of same dose in women and men would result in greater drug exposure and increased susceptibility to next-day impairment in women.1 89 92 93 94 95 In geriatric patients, clearance is similar in men and women, and dosage is not gender specific.1 89 92 93 (See Special Populations: Absorption, under Pharmacokinetics; see CNS Depression and Next-day Impairment under Cautions; and see Dosage under Dosage and Administration.)

In geriatric patients receiving zolpidem as conventional or extended-release tablets, half-life is 2.9 hours.1 89 Half-life in geriatric patients reportedly is increased by 32% (for conventional tablets) or unchanged (for sublingual tablets [Intermezzo]) compared with younger adults.1 94

In patients with cirrhosis receiving zolpidem as conventional tablets, half-life is about 9.9 hours.1 89 Extended-release tablets not studied to date in patients with hepatic impairment.89

In nondialyzed patients with chronic renal disease and in patients undergoing periodic dialysis, slower elimination rates reported with IV zolpidem (not commercially available in the US).2 3 81 No substantial pharmacokinetic alterations reported with oral zolpidem in patients with end-stage renal failure undergoing hemodialysis.1 89 Extended-release tablets not studied to date in patients with renal impairment.89

Not removed by hemodialysis.1 89

• Importance of providing patients a copy of the medication guide and discussing the contents with every patient prior to initiation of therapy.1 89 92 93 94 95 Importance of patients reading the medication guide prior to initiation of therapy and each time the prescription is refilled.1 89 92 93 94 95

• Importance of informing patients and their families of the benefits and risks of zolpidem therapy.1 89 92 93 94 95

• Importance of informing all patients (men and women) of the potential for next-day impairment, that the risk is increased if dosing instructions are not carefully followed, and that impairment may be present despite feeling fully awake.1 89 92 93 94 95

• Importance of administering immediate-release zolpidem preparations intended for bedtime administration (conventional tablets, oral spray, 5- and 10-mg sublingual tablets [Edluar]) immediately before getting into bed, at least 7–8 hours before being active again.1 92 93 Wait ≥8 hours after taking the drug before driving or engaging in other activities requiring full mental alertness.1 92 93

• Importance of administering extended-release zolpidem immediately before getting into bed, at least 7–8 hours before being active again.89 Avoid driving or engaging in other activities requiring complete mental alertness the day after taking this preparation.89

• Importance of administering the 1.75- or 3.5-mg sublingual tablets (Intermezzo) in bed, only once per night as needed, if middle-of-the-night awakening is followed by difficulty returning to sleep, and only if ≥4 hours remain before planned time of awakening.94 Wait ≥4 hours after taking this preparation and until feeling fully awake before driving or engaging in other activities requiring full mental alertness.94

• Potential risk of abnormal thinking and behavioral changes, including sleep-driving and other complex behaviors (e.g., preparing and eating food, making phone calls, having sex) while not being fully awake; importance of immediately informing clinician if any such changes occur.1 89 91

• Importance of immediately informing clinician of any suicidal thoughts or memory impairment.1 89

• Potential risk of severe anaphylactic and anaphylactoid reactions; importance of immediately seeking medical attention if manifestations of such reactions occur.1 89

• Importance of taking zolpidem only as prescribed; do not increase dosage unless otherwise instructed by a clinician; inform clinician if the drug is not effective.1 89 92 93 94 95

• Risk of withdrawal symptoms following abrupt discontinuance or rapid reduction in dosage.1 89 Importance of informing clinician of any tolerance or dependence/withdrawal symptoms.1 89

• Importance of not taking zolpidem with or immediately after a meal.1 89 92 93 94

• Importance of placing the zolpidem sublingual tablet (Edluar) under the tongue and allowing it to disintegrate; do not swallow or take with water.93

• Importance of placing the zolpidem sublingual tablet (Intermezzo) under the tongue and allowing it to disintegrate completely before swallowing; do not swallow whole.94 Remove the tablet from the pouch just prior to dosing.94

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses, particularly depression.1 89

• Importance of not taking zolpidem after consuming alcohol in the evening or before bedtime.1 89 92 93 94

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 89 92 93 94

• Importance of informing patients of other important precautionary information.1 89 92 93 94 (See Cautions.)