Generic Name: Zolpidem Tartrate
Class: Anxiolytics, Sedatives, and Hypnotics; Miscellaneous
VA Class: CN309
Chemical Name: Imidazo(1,2 - a)pyridine - 3 - acetamide,N,N,6 - trimethyl - 2 - (4 - methylphenyl) - ,(R - (R*,R*)) - 2,3 - dihydroxybutanedioate (2:1)
Molecular Formula: C19H21N3O•½C4H6O
CAS Number: 103188-50-7

Introduction

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

Uses for Ambien

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

Slideshow: Insomnia Treatment with Non-Benzodiazepines Ambien, Lunesta & Sonata

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

Ambien Dosage and Administration

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.)

Conventional Tablets

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

Extended-release Tablets

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

Oral Spray

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.)

Sublingual Tablets (Edluar)

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

Sublingual Tablets (Intermezzo)

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

Insomnia
Difficulty with Sleep Initiation
Oral (Conventional Tablets, Oral Spray) or Sublingual (Edluar Sublingual Tablets)

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.)

Difficulty with Sleep Initiation or Sleep Maintenance
Oral (Extended-release Tablets)

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.)

Middle-of-the-Night Awakening
Sublingual (Intermezzo Sublingual Tablets)

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

Insomnia
Difficulty with Sleep Initiation
Oral (Conventional Tablets, Oral Spray) or Sublingual (Edluar Sublingual Tablets)

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

Difficulty with Sleep Initiation or Sleep Maintenance
Oral (Extended-release Tablets)

Maximum 12.5 mg once daily immediately before bedtime.89

Middle-of-the-Night Awakening
Sublingual (Intermezzo Sublingual Tablets)

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

Cautions for Ambien

Contraindications

Warnings/Precautions

CNS Depression and Next-day Impairment

CNS depressant; may impair daytime function in some patients even when used as prescribed.1 89 92 93 94 95 96

Zolpidem blood concentrations >50 ng/mL may impair driving to a degree that increases risk of a motor vehicle accident.95 Concentrations >50 ng/mL reported at 8 hours after a dose in 15% of women and 3% of men receiving 10 mg (as conventional tablets); in 33% of women and 25% of men receiving 12.5 mg (as extended-release tablets); and in 15% of nongeriatric women, 5% of nongeriatric men, and 10% of both geriatric men and women receiving 6.25 mg (as extended-release tablets).95 Some patients had concentrations ≥90 or ≥100 ng/mL.95 Because of these findings, bedtime dosages currently recommended by the manufacturers and FDA are lower than original labeled dosages.95 96

Impaired driving reported when driving test administered to healthy individuals <4 hours after a 3.5-mg sublingual dose;94 potential driving impairment at 4 hours after recommended 1.75-mg dose in women or 3.5-mg dose in men cannot be completely excluded.94

Use smallest effective dose to decrease potential risk of next-day impairment.95 (See Dosage under Dosage and Administration.)

Monitor patients for excessive CNS depression; however, impairment may occur in the absence of symptoms and may not be reliably detected by ordinary clinical examination (i.e., formal psychomotor testing may be required).89

Concurrent use of other CNS depressants (e.g., alcohol, benzodiazepines, opiates, tricyclic antidepressants) increases risk of CNS depression.1 89 92 93 94 Dosage adjustments of zolpidem and concurrent CNS depressants may be necessary.1 89 92 93 94 (See Specific Drugs under Interactions.)

Use with other sedatives and hypnotics (including other zolpidem-containing preparations) at bedtime or in middle of the night is not recommended.1 89 92 93 94

Women appear to be more susceptible to next-day psychomotor impairment because zolpidem clearance is slower in women than in men.95 (See Elimination: Special Populations, under Pharmacokinetics.)

Administration as extended-release tablets increases risk of next-day impairment.89 Extended-release zolpidem may not be an appropriate treatment choice for patients who need to drive or perform activities that require full alertness the next morning.95 Drug concentrations may remain high enough the next day to impair performance.89 96 (See Advice to Patients.)

Risk of next-day impairment is increased if preparations intended for bedtime administration (e.g., conventional or extended-release tablets, oral spray, 5- or 10-mg sublingual tablets) are administered with less than 7–8 hours of sleep time remaining, if preparations intended for middle-of-the-night administration (1.75- or 3.5-mg sublingual tablets) are administered with <4 hours of sleep time remaining; if higher than recommended dose is administered; or if used concomitantly with other CNS depressants or drugs that increase zolpidem concentrations.1 89 92 93 94

Adequate Patient Evaluation

Insomnia may be a manifestation of an underlying physical and/or psychiatric disorder; carefully evaluate patient before providing symptomatic treatment.1 23 79 89

Failure of insomnia to remit after 7–10 days of treatment, worsening of insomnia, or emergence of new thinking or behavioral abnormalities may indicate the presence of an underlying psychiatric and/or medical condition that requires evaluation.1 89

Sensitivity Reactions

Angioedema involving the tongue, glottis, or larynx reported following initial or subsequent doses of sedative and hypnotic drugs, including zolpidem; may result in airway obstruction and death.1 89 91 Anaphylaxis also reported.1 89 91

Do not rechallenge with the drug if angioedema occurs.1 89 91

Abnormal Thinking and Behavioral Changes

Abnormal thinking and behavioral changes (e.g., decreased inhibition, aggressiveness, uncharacteristic extroversion, bizarre behavior, agitation, depersonalization, visual and auditory hallucinations) reported in patients receiving sedative and hypnotic drugs, including zolpidem.1 4 89 Amnesia, anxiety, and other neuropsychiatric symptoms may occur.1 89

Complex behaviors such as sleep-driving (i.e., driving while not fully awake after ingesting a sedative and hypnotic drug, with no memory of the event), preparing and eating food, making phone calls, or having sex while not fully awake after taking a sedative and hypnotic drug, and usually with no memory of the event, reported.1 89 91

Complex behaviors may occur in sedative and hypnotic drug-naive or drug-experienced patients.1 89 91

Increased risk of complex behaviors with concomitant use of alcohol and other CNS depressants or use of the drug at doses exceeding the maximum recommended dose; however, may occur with the drug alone at therapeutic doses.1 89 91

Strongly consider discontinuing drug in patients who report a sleep-driving episode because of the risk to the patient and community.1 89 91

Carefully and immediately evaluate any new concerning behavioral sign or symptom.1 89

Depression

Worsening of depression and suicidal thoughts and actions (including completed suicides) reported in primarily depressed patients receiving sedatives and hypnotics.1 89 Suicidal tendencies may be present; intentional overdosage more frequent in such patients.1 89 Protective measures may be required.1 89 Prescribe and dispense drug in the smallest feasible quantity.1 89

Respiratory Depression

No respiratory depressant effects reported following 10-mg doses in healthy individuals or patients with mild to moderate COPD; 1 85 89 however, decreased oxygen saturation reported in patients with mild to moderate sleep apnea.1 86 89 Respiratory insufficiency reported, mostly in patients with preexisting respiratory impairment.1 89

Use with caution in patients with compromised respiratory function; sedatives and hypnotics may depress respiratory drive.1 89

Consider risk of respiratory depression prior to use in patients with respiratory impairment (e.g., sleep apnea, myasthenia gravis).1 89

Withdrawal Effects

Signs and symptoms of withdrawal reported following rapid dosage reduction or abrupt discontinuance; monitor patients for tolerance and dependence.1 89

Abuse Potential

Zolpidem tartrate 40 mg and diazepam 20 mg (as single doses) had similar effects in former drug abusers; effects of zolpidem tartrate 10 mg and placebo were difficult to distinguish.1 89 Monitor patients for abuse.1 89

Increased risk for misuse and abuse of and addiction to zolpidem in patients with a history of addiction to or abuse of drugs or alcohol; carefully monitor such patients.1 89

Specific Populations

Pregnancy

Category C.1 89 90 92 93 94

No established use in labor and delivery.1 89 92 93

Lactation

Distributed into milk in small amounts;1 84 89 92 93 94 100 potential effects on nursing infants are not known.94 100 Use with caution in nursing women.1 89 92 93 Closely monitor infant for increased sedation, lethargy, and changes in feeding habits.100

Pediatric Use

Not recommended in pediatric patients.1 89 92 93 94

Safety and efficacy not established in pediatric patients <18 years of age.1 89 92 93 94 Dizziness, headache, and hallucinations reported.1 89

Geriatric Use

Pharmacokinetic changes in geriatric patients compared with younger adults.1 (See Absorption: Special Populations and also Elimination: Special Populations, under Pharmacokinetics.)

Potential increased sensitivity to zolpidem.1 89 92 93 94 Adverse effects tend to be dose related, 1 2 4 9 82 89 particularly in geriatric patients.1 2 9 Adverse effect profile in patients ≥65 years of age receiving 6.25-mg dose (as extended-release tablets) similar to that in younger adults receiving 12.5-mg dose.89

Use reduced dose to minimize adverse effects related to impaired motor and/or cognitive performance and unusual sensitivity to sedative and hypnotic drugs.1 89 92 93 94 (See Geriatric Patients under Dosage and Administration.)Sedatives may cause confusion and oversedation in geriatric patients; observe closely.94

Hepatic Impairment

Prolonged elimination; reduce dose.1 81 89 92 93 94 (See Hepatic Impairment under Dosage and Administration and also see Elimination: Special Populations and Absorption: Special Populations, under Pharmacokinetics.)

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 however, some clinicians recommend that dosage reduction be considered.2 3 81

Common Adverse Effects

Drowsiness,1 92 93 dizziness,1 89 92 93 headache,89 94 drugged feeling,1 92 93 next-day somnolence,89 fatigue,94 nausea,94 diarrhea.1 92 93

Interactions for Ambien

Metabolized principally by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6.88

Drugs Affecting Hepatic Microsomal Enzymes

Some drugs that inhibit CYP3A may increase systemic exposure to zolpidem.1 89

Effect of inhibitors of other CYP isoenzymes on pharmacokinetics (e.g., systemic exposure) of zolpidem not known.1 89

Specific Drugs

Drug

Interaction

Comments

Chlorpromazine

Pharmacokinetic interactions unlikely; however, additive effects in reducing alertness and psychomotor performance1 89

Cimetidine

No effect on zolpidem pharmacokinetics or pharmacodynamics1 89

CNS depressants (e.g., alcohol, benzodiazepines, opiates, tricyclic antidepressants)

Increased risk of CNS depression1 89

Extended-release zolpidem: Additive effects with concomitant use, including daytime use, of other CNS depressants89

Alcohol: Additive adverse effect on psychomotor performance1 89

Use not recommended with other sedatives and hypnotics (including other zolpidem-containing preparations) at bedtime or in middle of the night1 89

Dosage adjustment of zolpidem and concomitant CNS depressants may be necessary1 89 92 93 94

When zolpidem used for middle-of-the-night awakening, recommended dose in men or women receiving concomitant CNS depressants is 1.75 mg; dosage adjustment of concomitant CNS depressant may be necessary94

Digoxin

No effect on digoxin pharmacokinetics1 89

Fluoxetine

Clinically important pharmacokinetic or pharmacodynamic (e.g., psychomotor function) interactions not observed in healthy individuals1 89 102 103

Haloperidol

No effect on zolpidem pharmacokinetics or pharmacodynamics following single dose; does not exclude effect following chronic use1 89

Imipramine

Decreased imipramine peak concentration but no other pharmacokinetic interactions; however, additive effect in reducing alertness1 89

Itraconazole

Increased zolpidem AUC, but no changes in psychomotor performance, postural sway, or self-perceived drowsiness1 89 104

Ketoconazole

Increased peak concentration, AUC, elimination half-life, and pharmacodynamic effects of zolpidem; possible increased hypnotic effects1 89

Consider lower dose of zolpidem1 89

Ranitidine

No effect on zolpidem pharmacokinetics or pharmacodynamics1 89

Rifampin

Decreased AUC, peak concentration, half-life, and pharmacodynamic effects of zolpidem; possible decreased hypnotic efficacy1 89 101

Sertraline

Earlier and higher peak zolpidem concentrations; possible earlier hypnotic onset and greater hypnotic effect1 89 105

No clinically important effects on pharmacokinetics of sertraline or N-desmethylsertraline1 89 105

Warfarin

No effect on PT in healthy individuals1 89

Ambien Pharmacokinetics

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

Stability

Storage

Oral

Conventional Tablets

20–25°C.1

Extended-release Tablets

15–25°C (may be exposed to temperatures up to 30°C).89

Oral Spray

25°C (may be exposed to 15–30°C); avoid prolonged exposure to temperatures >30°C.92 Store upright.92 Do not freeze.92

Sublingual

Sublingual Tablets (Edluar)

20–25°C.93 Protect from light and moisture.93

Sublingual Tablets (Intermezzo)

20–25°C (may be exposed to 15–30°C).94 Protect from moisture.94

Store tablet in pouch until just prior to administration.94

Actions

  • Interacts with the CNS GABA-benzodiazepine-chloride ionophore receptor complex.1 2 3 89

  • Selectivity for the type 1 benzodiazepine (BZ1) receptor not absolute, but may account for the decreased muscle relaxant, anxiolytic, and anticonvulsant effects compared with benzodiazepines reported in animal studies,1 2 3 4 6 7 89 as well as the preservation of deep sleep (stages 3 and 4) reported in human studies.1 4 89

Advice to Patients

  • 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.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.1 89 92 93 94

Zolpidem Tartrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

5 mg/metered spray

Zolpimist (C-IV)

ECR

Tablets, extended-release, film-coated

6.25 mg

Ambien CR (C-IV)

Sanofi-Aventis

Zolpidem Tartrate Extended-release Tablets (C-IV)

12.5 mg

Ambien CR (C-IV)

Sanofi-Aventis

Zolpidem Tartrate Extended-release Tablets (C-IV)

Tablets, film-coated

5 mg

Ambien (C-IV)

Searle

Zolpidem Tartrate Tablets (C-IV)

10 mg

Ambien (C-IV)

Searle

Zolpidem Tartrate Tablets (C-IV)

Sublingual

Tablets

1.75 mg

Intermezzo (C-IV)

Purdue

3.5 mg

Intermezzo (C-IV)

Purdue

5 mg

Edluar (C-IV)

Meda

10 mg

Edluar (C-IV)

Meda

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Ambien 10MG Tablets (SANOFI-AVENTIS U.S.): 30/$209.98 or 90/$599.98

Ambien 5MG Tablets (SANOFI-AVENTIS U.S.): 30/$203.64 or 90/$582.16

Ambien CR 12.5MG Controlled-release Tablets (SANOFI-AVENTIS U.S.): 30/$190.99 or 90/$549.97

Ambien CR 6.25MG Controlled-release Tablets (SANOFI-AVENTIS U.S.): 30/$193.99 or 90/$555.97

Edluar 10MG Sublingual Tablets (MEDA PHARMACEUTICALS): 30/$179.99 or 90/$525.99

Edluar 5MG Sublingual Tablets (MEDA PHARMACEUTICALS): 30/$179.99 or 90/$519.96

Zolpidem Tartrate 10MG Tablets (MYLAN): 30/$17.99 or 90/$45.97

Zolpidem Tartrate 12.5MG Controlled-release Tablets (WINTHROP US): 30/$155.99 or 90/$439.99

Zolpidem Tartrate 5MG Tablets (SANDOZ): 30/$17.99 or 90/$45.97

Zolpidem Tartrate 6.25MG Controlled-release Tablets (WINTHROP US): 30/$155.99 or 60/$299.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 22, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Sanofi-Aventis. Ambien (zolpidem tartrate) tablet prescribing information. Bridgewater, NJ; 2013 Apr.

2. Langtry HD, Benfield P. Zolpidem: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential. Drugs. 1990; 40:291-313. [PubMed 2226217]

3. Fullerton T, Frost M. Focus on zolpidem: a novel agent for the treatment of insomnia. Hosp Formul. 1992; 27:773-91.

4. Anon. Zolpidem for insomnia. Med Lett Drugs Ther. 1993; 35:35-6. [PubMed 8386301]

5. Cavallaro R, Regazzetti MG, Covelli G et al. Tolerance and withdrawal with zolpidem. Lancet. 1993; 342:374- 5. [IDIS 318718] [PubMed 8101619]

6. Perrault G, Morel E, Sanger DJ et al. Differences in the pharmacological profiles of a new generation of benzodiazepine and non-benzodiazepine hypnotics. Eur J Pharmacol. 1990; 187:487-94. [PubMed 1981555]

7. Perrault G, Morel E, Sanger DJ et al. Lack of tolerance and physical dependence upon repeated treatment with the novel hypnotic zolpidem. J Pharmacol Exp Ther. 1992; 263:298-303. [PubMed 1403792]

8. Griffiths RR, Sannerud CA, Ator NA et al. Zolpidem behavioral pharmacology in baboons: self-injection, discrimination, tolerance and withdrawal. J Pharmacol Exp Ther. 1992; 260:1199-208. [PubMed 1312162]

9. Scharf MB, Mayleben DW, Kaffeman M et al. Dose response effects of zolpidem in normal geriatric subjects. J Clin Psychiatry. 1991; 52:77-83. [IDIS 278622] [PubMed 1993640]

10. Bensimon G, Foret J, Warot D et al. Daytime wakefulness following a bedtime oral dose of zolpidem 20 mg, flunitrazepam 2 mg and placebo. Br J Clin Pharmacol. 1990; 30:463-9. [IDIS 272319] [PubMed 2223425]

11. Fairweather DB, Kerr JS, Hindmarch I. The effects of acute and repeated doses of zolpidem on subjective sleep, psychomotor performance and cognitive function in elderly volunteers. Eur J Clin Pharmacol. 1992; 43:597-601. [IDIS 310281] [PubMed 1493840]

12. Brunner DP, Dijk DJ, Münch M et al. Effect of zolpidem on sleep and sleep EEG spectra in healthy young men. Psychopharmacology (Berl). 1991; 104:1-5. [PubMed 1881993]

13. Sicard BA, Trocherie S, Moreau J et al. Evaluation of zolpidem on alertness and psychomotor abilities among aviation ground personnel and pilots. Aviat Space Environ Med. 1993; 64:371-5. [PubMed 8503809]

14. Roger M, Attali P, Coquelin JP. Multicenter, double- blind, controlled comparison of zolpidem and triazolam in elderly patients with insomnia. Clin Ther. 1993; 15:127-36. [PubMed 8458042]

15. Jonas JM, Coleman BS, Sheridan AQ et al. Comparative clinical profiles of triazolam versus other shorter-acting hypnotics. J Clin Psychiatr. 1992; 53(Suppl):19-31.

16. Byrnes JJ, Greenblatt DJ, Miller LG. Benzodiazepine receptor binding of nonbenzodiazepines in vivo: alpidem, zolpidem and zopiclone. Brain Res Bull. 1992; 29:905- 8. [PubMed 1361878]

17. Benavides J, Peny B, Durand A et al. Comparative in vivo and in vitro regional selectivity of central omega (benzodiazepine) site ligands in inhibiting [3H]flumazenil binding in the rat central nervous system. J Pharmacol Exp Ther. 1992; 263:884-96. [PubMed 1331419]

18. Perrault G, Morel E, Sanger DJ et al. Lack of tolerance and physical dependence upon repeated treatment with the novel hypnotic zolpidem. J Pharmacol Exp Ther. 1992; 263:298-303. [PubMed 1403792]

19. Lader M. Rebound insomnia and newer hypnotics. Psychopharmacology (Berl). 1992; 108:248-55. [PubMed 1523276]

20. Maarek L, Cramer P, Attali P et al. The safety and efficacy of zolpidem in insomniac patients: a long-term open study in general practice. J Int Med Res. 1992; 20:162-70. [PubMed 1521672]

21. Wheatley D. Prescribing short-acting hypnosedatives: current recommendations from a safety perspective. Drug Saf. 1992; 7:106-15. [PubMed 1605897]

22. Kryger MH, Steljes D, Pouliot Z et al. Subjective versus objective evaluation of hypnotic efficacy: experience with zolpidem. Sleep. 1991; 14:399-407. [PubMed 1759092]

23. The Upjohn Company. Halcion (triazolam) tablets prescribing information, dated 1991 Dec. In: Physicians’ desk reference. 46th ed. Montvale, NJ: Medical Economics Company Inc; 1992(Suppl A):A127-30.

24. Greenblatt DJ, Shader RI, Abernethy DR. Drug therapy: current status of benzodiazepines (first of two parts). N Engl J Med. 1983; 309:354-8. [IDIS 173691] [PubMed 6135156]

25. Greenblatt DJ, Shader RI, Abernethy DR. Drug therapy: current status of benzodiazepines (second of two parts). N Engl J Med. 1983; 309:410-6. [IDIS 174051] [PubMed 6135990]

26. Anon. Choice of benzodiazepines. Med Lett Drugs Ther. 1988; 30:26-8. [PubMed 2893246]

27. National Institutes of Health. Drugs and insomnia: the use of medications to promote sleep. Consensus Development Conference. JAMA. 1984; 251:2410-4. [PubMed 6142971]

28. Kales A, Soldatos CR, Kales JD. Sleep disorders: insomnia, sleepwalking, night terrors, nightmares, and enuresis. Ann Intern Med. 1987; 106:582-92. [PubMed 3548525]

29. Greenblatt DJ, Harmatz JS, Zinny MA et al. Effect of gradual withdrawal on the rebound sleep disorder after discontinuation of triazolam. N Engl J Med. 1987; 317:722-8. [IDIS 233512] [PubMed 3306380]

30. Kales A, Soldatos CR, Bixler EO et al. Early morning insomnia with rapidly eliminated benzodiazepines. Science. 1983; 20:95-7.

31. Kales A, Scharf MB, Kales JD et al. Rebound insomnia. Science. 1980; 208:424. [PubMed 17843621]

32. Bixler EO, Kales JD, Kales A et al. Rebound insomnia and elimination half-life: assessment of individual subject response. J Clin Pharmacol. 1985; 25:115-24. [IDIS 197633] [PubMed 2859304]

33. Gillin JC, Spinweber CL, Johnson LC. Rebound insomnia: a critical review. J Clin Psychopharmacol. 1989; 9:161-72. [IDIS 254724] [PubMed 2567741]

34. Kales A, Kales JD. Sleep laboratory studies of hypnotic drugs: efficacy and withdrawal effects. J Clin Psychopharmacol. 1983; 3:140-50. [IDIS 168418] [PubMed 6132933]

35. Kales A, Soldatos CR, Bixler EO et al. Midazolam: dose-response studies of effectiveness and rebound insomnia. Pharmacology. 1983; 26:138-49. [PubMed 6132414]

36. Kales A, Soldatos CR, Bixler EO et al. Rebound insomnia and rebound anxiety: a review. Pharmacology. 1983; 26:121-37. [PubMed 6132413]

37. Kales A, Scharf MB, Kales JD et al. Rebound insomnia: a potential hazard following withdrawal of certain benzodiazepines. JAMA. 1979; 241:1692-5. [IDIS 94542] [PubMed 430730]

38. Kales A, Scharf MB, Kales JD. Rebound insomnia: a new clinical syndrome. Science. 1978; 201:1039-41. [PubMed 684426]

39. Kales A, Bixler EO, Kales JD et al. Comparative effectiveness of nine hypnotic drugs: sleep laboratory studies. J Clin Pharmacol. 1977; 17:207-13. [PubMed 321488]

40. Vogel GW, Barker K, Gibbons P et al. A comparison of the effects of flurazepam 30 mg and triazolam 0.5 mg on the sleep of insomniacs. Psychopharmacologia. 1976; 47:81-6.

41. Murphy P, Hindmarch I, Hyland CM. Aspects of short-term use of two benzodiazepine hypnotics in the elderly. Age Ageing. 1982; 11:222-8. [PubMed 6129788]

42. Ogura C, Nakazawa K, Majima K et al. Residual effects of hypnotics: triazolam, flurazepam, and nitrazepam. Psychopharmacology (Berl). 1980; 68:61-5. [PubMed 6104840]

43. Morgan K, Oswald I. Anxiety caused by a short-life hypnotic. BMJ. 1982; 284:942. [IDIS 148143] [PubMed 6121606]

44. Larson EB, Kukull WA, Buchner D et al. Adverse drug reactions associated with global cognitive impairment in elderly persons. Ann Intern Med. 1987; 107:169-73. [IDIS 233222] [PubMed 2886086]

45. Bixler EO, Kales A, Brubaker BH et al. Adverse reactions to benzodiazepine hypnotics: spontaneous reporting system. Pharmacology. 1987; 35:286-300. [PubMed 2892212]

46. Juhl RP, Daugherty VM, Kroboth PD. Incidence of next-day anterograde amnesia caused by flurazepam hydrochloride and triazolam. Clin Pharm. 1984; 3:622-5. [IDIS 193408] [PubMed 6150782]

47. Kales A, Bixler EO, Vela-Bueno A et al. Comparison of short and long half-life benzodiazepine hypnotics: triazolam and quazepam. Clin Pharmacol Ther. 1986; 40:378-86. [IDIS 222121] [PubMed 3530586]

48. Jerram T. Hypnotics and sedatives. In: Dukes MNG, ed. Meyler’s side effects of drugs. 10th ed. New York: Elsevier; 1984:81-108.

49. Jerram T. Hypnotics and sedatives. In: Dukes MNG, ed. Side effects of drugs. Annual 11. New York: Elsevier; 1987:37-43.

50. Regestein QR, Reich P. Agitation observed during treatment with newer hypnotics. J Clin Psychiatry. 1985; 46:280-3. [IDIS 203334] [PubMed 2861195]

51. Adam K, Oswald I. Can a rapidly-eliminated hypnotic cause daytime anxiety? Pharmacopsychiatry. 1989; 22:115-9.

52. Kales A, Soldatos CR, Bixler EO et al. Diazepam: effects on sleep and withdrawal phenomena. J Clin Psychopharmacol. 1988; 8:340-6. [IDIS 246932] [PubMed 3183072]

53. Baker Cummins Pharmaceuticals, Inc. Doral (quazepam) prescribing information. Miami, FL; 1990 May.

54. Ankier SI, Goa KL. Quazepam: a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in insomnia. Drugs. 1988; 35:42-62. [IDIS 238596] [PubMed 2894293]

55. Baker Cummins Pharmaceuticals, Inc. Doral (quazepam) drug reference. Miami, FL; 1989 Jul.

56. Baker Cummins Pharmaceuticals, Inc. Doral (quazepam) receptor-selective benzodiazepine hypnotic monograph. Miami, FL; 1990 Feb.

57. Rall TW. Hypnotics and sedatives; ethanol: benzodiazepines and management of insomnia. In: Gilman AG, Rall TW, Nies AS et al. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990:346-58,369-70.

58. Kales A, Bixler EO, Soldatos CR et al. Quazepam and flurazepam: long-term use and extended withdrawal. Clin Pharmacol Ther. 1982; 32:781-8. [IDIS 161844] [PubMed 7140142]

59. Kales A, Scharf MB, Soldatos CR et al. Quazepam, a new benzodiazepine hypnotic: intermediate-term sleep laboratory evaluation. J Clin Pharmacol. 1980; 20:184-92. [IDIS 112918] [PubMed 6103903]

60. Anon. Quazepam: a new hypnotic. Med Lett Drugs Ther. 1990; 32:39-40. [PubMed 1970112]

61. Kales A, Bixler EO, Soldatos CR et al. Quazepam and temazepam: effects of short- and intermediate-term use and withdrawal. Clin Pharmacol Ther. 1986; 39:345-52. [IDIS 213997] [PubMed 2868823]

62. Lee A, Lader M. Tolerance and rebound during and after short-term administration of quazepam, triazolam and placebo to healthy human volunteers. Int Clin Psychopharmacol. 1988; 3:31-47. [PubMed 2895786]

63. Mamelak M, Csima A, Price V. A comparative 25-night sleep laboratory study on the effects of quazepam and triazolam on chronic insomniacs. J Clin Pharmacol. 1984; 24:65-75. [IDIS 183605] [PubMed 6143767]

64. Mamelak M, Csima A, Price V. Effects of quazepam and triazolam on the sleep of chronic insomniacs: a comparative 25-night sleep laboratory study. Clin Neuropharmacol. 1985; 8(Suppl 1):S63-73. [PubMed 3837688]

65. Kales A, Scharf MB, Bixler EO et al. Dose-response studies of quazepam. Clin Pharmacol Ther. 1981; 30:194-200. [IDIS 136583] [PubMed 6113910]

66. Bixler EO, Kales JD, Kales A et al. Rebound insomnia and elimination half-life: assessment of individual subject response. J Clin Pharmacol. 1985; 25:115-24. [IDIS 197633] [PubMed 2859304]

67. Aden GC, Thatcher C. Quazepam in the short-term treatment of insomnia in outpatients. J Clin Psychiatry. 1983; 44:454-6. [IDIS 179748] [PubMed 6361006]

68. Kales JD, Kales A, Soldatos CR. Quazepam: sleep laboratory studies of effectiveness and withdrawal. Clin Neuropharmacol. 1985; 8(Suppl 1):S55-62.

69. Mendels J, Stern S. Evaluation of the short-term treatment of insomnia in out-patients with 15 milligrams of quazepam. J Int Med Res. 1983; 11:155-61. [PubMed 6347747]

70. Abbott. ProSom prescribing information. North Chicago, IL; 1990 Dec.

71. Abbott. Product information form for American Hospital Formulary Service on ProSom. North Chicago, IL; 1991 May.

72. Scharf MB, Roth PB, Dominguez RA. Estazolam and flurazepam: a multicenter, placebo-controlled comparative study in outpatients with insomnia. J Clin Pharmacol. 1990; 30:461-7. [IDIS 266288] [PubMed 1971831]

73. Lamphere J, Roehrs T, Zorick F et al. Chronic hypnotic efficacy of estazolam. Drugs Exp Clin Res. 1986; 12:687-91. [PubMed 2875857]

74. Dominguez RA, Goldstein BJ, Jacobson AF et al. Comparative efficacy of estazolam, flurazepam, and placebo in outpatients with insomnia. J Clin Psychiatry. 1986; 47:362-5. [IDIS 218982] [PubMed 2873132]

75. Greenblatt DJ, Miller LG, Shader RI. Neurochemical and pharmacokinetic correlates of the clinical action of benzodiazepine hypnotic drugs. Am J Med. 1990; 88(Suppl 3A):18-24S.

76. Roehrs T. Rebound insomnia: its determinants and significance. Am J Med. 1990; 88(Suppl 3A):39-42S.

77. Greenblatt DJ, Harmatz JS, Zinny MA et al. Effect of gradual withdrawal on the rebound sleep disorder after discontinuation of triazolam. N Engl J Med. 1987; 317:722-8. [IDIS 233512] [PubMed 3306380]

78. Kales A, Manfredi RL, Vgontzas AN et al. Rebound insomnia after only brief and intermittent use of rapidly eliminated benzodiazepines. Clin Pharmacol Ther. 1991; 49:468- 76. [IDIS 281235] [PubMed 2015735]

79. National Institutes of Health. Drugs and insomnia: the use of medications to promote sleep. Consensus Conference. JAMA. 1984; 251:2410-4. [PubMed 6142971]

80. Fillastre JP, Geffroy-Josse S, Etienne I et al. Pharmacokinetics and pharmacodynamics of zolpidem following repeated doses in hemodialyzed uraemic patients. Fundam Clin Pharmacol. 1993; 7:1-9. [PubMed 8458597]

81. Bianchetti G, Dubruc C, Thiercelin JF et al. Clinical pharmacokinetics of zolpidem an various physiological and pathological conditions. In: Sauvenet JP, Langer SZ, Morselli PL, eds. Imidazopyridines in sleep disorders. New York: Raven Press; 1988:155-63.

82. Hoehns JD, Perry PJ. Zolpidem: a nonbenzodiazepine hypnotic for treatment of insomnia. Clin Pharm. 1993; 12:814-28. [IDIS 321040] [PubMed 8275648]

83. Ansseau M, Pitchot W, Hansenne M et al. Psychotic reactions to zolpidem. Lancet. 1992; 339:809. [IDIS 293659] [PubMed 1347827]

84. Pons G, Francoual C, Guillet P et al. Zolpidem excretion in breast milk. Eur J Clin Pharmacol. 1989; 37:245-8. [IDIS 260022] [PubMed 2612539]

85. George CFP. Perspectives on the management of insomnia in patients with chronic respiratory disorders. Sleep. 2000; 23(Suppl 1): S1-31-7.

86. Searle, Skokie, IL: Personal communication.

87. Salva P, Costa J. Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications. Clin Pharmacokinet. 1995; 29:142-53. [PubMed 8521677]

88. Pichard L, Gillet G, Bonfils C et al. Oxidative metabolism of zolpidem by human liver cytochrome P450S. Drug Metab Dispos. 1995; 23:1253-62. [PubMed 8591727]

89. Sanofi-Aventis. Ambien CR (zolpidem tartrate) extended-release tablet prescribing information. Bridgewater, NJ; 2013 Apr.

90. Sanofi-Aventis, New York, NY: Personal communication.

91. Greene D. Dear healthcare professional letter regarding important updated prescribing information for Ambien (zolpidem tartrate) tablets and Ambien CR (zolpidem tartrate) extended-release tablets. Bridgewater, NJ: Sanofi-Aventis US; 2007 Mar.

92. ECR Pharmaceuticals. Zolpimist (zolpidem tartrate) oral spray prescribing information. Richmond, VA; 2013 May.

93. Meda Pharmaceuticals Inc. Edluar (zolpidem tartrate) sublingual tablets prescribing information. Somerset, NJ: 2013 Apr.

94. Purdue Pharma L.P. Intermezzo (zolpidem tartrate) sublingual tablets prescribing information. Stamford, CT: 2013 Mar.

95. Food and Drug Administration. FDA drug safety communication: Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, Zolpimist). Rockville, MD; 2013 Jan 10. From FDA website.

96. Food and Drug Administration. FDA drug safety communication: FDA approves new label changes and dosing for zolpidem products and a recommendation to avoid driving the day after using Ambien CR. Rockville, MD; 2013 May 14. From FDA website.

97. Krystal AD, Erman M, Zammit GK et al. Long-term efficacy and safety of zolpidem extended-release 12.5 mg, administered 3 to 7 nights per week for 24 weeks, in patients with chronic primary insomnia: a 6-month, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Sleep. 2008; 31:79-90. [PubMed 18220081]

98. Roth T, Hull SG, Lankford DA et al. Low-dose sublingual zolpidem tartrate is associated with dose-related improvement in sleep onset and duration in insomnia characterized by middle-of-the-night (MOTN) awakenings. Sleep. 2008; 31:1277-84. [PubMed 18788653]

99. Roth T, Krystal A, Steinberg FJ et al. Novel sublingual low-dose zolpidem tablet reduces latency to sleep onset following spontaneous middle-of-the-night awakening in insomnia in a randomized, double-blind, placebo-controlled, outpatient study. Sleep. 2013; 36:189-96. [PubMed 23372266]

100. Zolpidem. In: Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 9th ed. Philadelphia: Lippincott Williams & Wilkins; 2011:1611-3.

101. Villikka K, Kivistö KT, Luurila H et al. Rifampin reduces plasma concentrations and effects of zolpidem. Clin Pharmacol Ther. 1997; 62:629-34. [PubMed 9433391]

102. Allard S, Sainati S, Roth-Schechter B et al. Minimal interaction between fluoxetine and multiple-dose zolpidem in healthy women. Drug Metab Dispos. 1998; 26:617-22. [PubMed 9660843]

103. Piergies AA, Sweet J, Johnson M et al. The effect of co-administration of zolpidem with fluoxetine: pharmacokinetics and pharmacodynamics. Int J Clin Pharmacol Ther. 1996; 34:178-83. [PubMed 8861737]

104. Luurila H, Kivistö KT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zolpidem. Eur J Clin Pharmacol. 1998; 54:163-6. [PubMed 9626922]

105. Allard S, Sainati SM, Roth-Schechter BF. Coadministration of short-term zolpidem with sertraline in healthy women. J Clin Pharmacol. 1999; 39:184-91. [PubMed 11563412]

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