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Zolpidem Tartrate Monograph for Professionals

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7/16/2014
12:40 | Author: David Perry

Zolpidem tartrate
Zolpidem Tartrate Monograph for Professionals

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.).

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

Men: Initially, 6.25 or 12.5 mg. 89 95.

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.

No effect on zolpidem pharmacokinetics or pharmacodynamics 1 89 Rifampin.

No clinically important effects on pharmacokinetics of sertraline or N -desmethylsertraline 1 89 105 Warfarin.

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

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

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.

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

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

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

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.

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

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.

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

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.

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

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

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.

Women: Maximum 1.75 mg once per night. 94.

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.).

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.

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

Decreased AUC, peak concentration, half-life, and pharmacodynamic effects of zolpidem; possible decreased hypnotic efficacy 1 89 101 Sertraline.

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.

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.

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

Decreased imipramine peak concentration but no other pharmacokinetic interactions; however, additive effect in reducing alertness 1 89 Itraconazole.

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.).

Pharmacokinetic interactions unlikely; however, additive effects in reducing alertness and psychomotor performance 1 89 Cimetidine.

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

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.

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

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

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.

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.).

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

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

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

Extended-release zolpidem: Additive effects with concomitant use, including daytime use, of other CNS depressants 89.

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

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.

Consider lower dose of zolpidem 1 89 Ranitidine.

Earlier and higher peak zolpidem concentrations; possible earlier hypnotic onset and greater hypnotic effect 1 89 105.

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.

No effect on zolpidem pharmacokinetics or pharmacodynamics 1 89.

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

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

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

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.

Maximum 12.5 mg once daily immediay before bedtime. 89.

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

Women: Initially, 5 mg. 1 92 93 95.

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.).

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.

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.

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

Known hypersensitivity to zolpidem. 1 89 90 92 93 94.

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.

Use smallest effective dose. 1 89 92 93 95.

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

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

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

Women: Initially, 6.25 mg. 89 95.

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.

Increased peak concentration, AUC, elimination half-life, and pharmacodynamic effects of zolpidem; possible increased hypnotic effects 1 89.

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.

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.

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.

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

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.).

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.

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 compley excluded. 94.

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.

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

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

Women: 1.75 mg. 94.

Increased zolpidem AUC, but no changes in psychomotor performance, postural sway, or self-perceived drowsiness 1 89 104 Ketoconazole.

Not recommended in pediatric patients. 1 89 92 93 94.

No effect on digoxin pharmacokinetics 1 89 Fluoxetine.

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.

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.

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

Men: 3.5 mg. 94.

Remove tablet from pouch just prior to administration. 94.

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

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

Increased risk of CNS depression 1 89.

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

Alcohol: Additive adverse effect on psychomotor performance 1 89.

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

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.).

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: 6.25 mg once daily immediay before bedtime. 89.

Category C. 1 89 90 92 93 94.

No effect on PT in healthy individuals 1 89.

Dosage adjustment of zolpidem and concomitant CNS depressants may be necessary 1 89 92 93 94.

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

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

Clinically important pharmacokinetic or pharmacodynamic (e.g., psychomotor function) interactions not observed in healthy individuals 1 89 102 103 Haloperidol.

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

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

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 necessary 94 Digoxin.

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.

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.

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

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

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.

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.

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: C 19 H 21 N 3 O•½C 4 H 6 O CAS Number: Brands: Ambien, Ambien CR, Edluar, Intermezzo, Zolpimist.

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

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.).

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

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.

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

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.

No effect on zolpidem pharmacokinetics or pharmacodynamics following single dose; does not exclude effect following chronic use 1 89 Imipramine.

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.

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.

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

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

Men: Maximum 3.5 mg once per night. 94.

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

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


Zolpidem tartrate