Zolpidem (Lexi-Drugs)

Pronunciation

(zole PI dem)

Brand Names: US

Ambien; Ambien CR; Edluar; Intermezzo; Zolpimist

Brand Names: Canada

APO-Zolpidem ODT; PMS-Zolpidem ODT; Sublinox

Pharmacologic Category

Hypnotic, Miscellaneous

Dosing: Adult

Insomnia: Oral: Note: The lowest effective dose should be used; higher doses may be more likely to impair next morning activities.

Immediate release tablet, spray: 5 mg (females) or 5 to 10 mg (males) immediately before bedtime; maximum dose: 10 mg daily

Extended release tablet: 6.25 mg (females) or 6.25 to 12.5 mg (males) immediately before bedtime; maximum dose: 12.5 mg daily

Sublingual tablet:

Edluar, Sublinox [Canadian product]: 5 mg (females) or 5 to 10 mg (males) immediately before bedtime; if 5 mg dose is ineffective may increase to 10 mg (maximum dose: 10 mg daily)

Intermezzo: Note: Take in bed only if ≥4 hours left before waking and there is difficulty in returning to sleep

Females: 1.75 mg once per night as needed (maximum: 1.75 mg/night)

Males: 3.5 mg once per night as needed (maximum: 3.5 mg/night)

Dosage adjustment with concomitant CNS depressants: Females and males: 1.75 mg once per night as needed; dose adjustment of concomitant CNS depressant(s) may be necessary.

Debilitated patients:

Immediate release tablet, spray: 5 mg immediately before bedtime

Sublingual tablet:

Edluar, Sublinox [Canadian product]: 5 mg immediately before bedtime

Extended release tablet: 6.25 mg immediately before bedtime

Dosing: Geriatric

Oral:

Immediate release tablet, spray: 5 mg immediately before bedtime

Sublingual tablet:

Edluar, Sublinox [Canadian product]: 5 mg immediately before bedtime

Intermezzo: Females and males: 1.75 mg once per night as needed (maximum: 1.75 mg/night). Note: Take in bed only if ≥4 hours left before waking and there is difficulty in returning to sleep.

Extended release tablet: 6.25 mg immediately before bedtime

Dosing: Renal Impairment: Adult

No dosage adjustment necessary.

Hemodialysis: Not dialyzable

Dosing: Hepatic Impairment: Adult

Immediate release tablet:

Mild to moderate impairment: 5 mg immediately before bedtime

Severe impairment: Avoid use

Extended release tablet:

Mild to moderate impairment: 6.25 mg immediately before bedtime

Severe impairment: Avoid use

Oral spray: 5 mg immediately before bedtime

Sublingual tablet:

Edluar: 5 mg immediately before bedtime

Intermezzo: Females and males: 1.75 mg once per night as needed. Note: Take in bed only if ≥4 hours left before waking and there is difficulty in returning to sleep.

Sublinox [Canadian product]:

Mild to moderate impairment: 5 mg immediately before bedtime

Severe impairment: Use is contraindicated.

Dosing: Pediatric

Note: The lowest effective dose should be used; higher doses may be more likely to impair next-morning activities.

Insomnia:

Children and Adolescents ≤17 years: Limited data available; efficacy results variable and have not been demonstrated in randomized placebo-controlled trials (Anand 2017). Oral: Immediate-release tablets: Usual reported dose: 0.25 mg/kg at bedtime; maximum dose: 10 mg/dose (Blumer 2008; Blumer 2009; Hanna 2018); dosing based on reported experience from an open-label, dose escalation pharmacokinetic evaluation showed zolpidem was well-tolerated in pediatric patients 2 to 18 years of age and recommended a dose of 0.25 mg/kg at bedtime for evaluation in future efficacy trials (Blumer 2008). However, zolpidem has not been shown to be effective in a randomized placebo-controlled trial (n=201) of children aged 6 to 17 years with ADHD-associated insomnia; zolpidem 0.25 mg/kg/dose (maximum dose: 10 mg) administered nightly did not decrease sleep latency; in addition, hallucinations occurred in 7.4% of patients (Blumer 2009). A comparative, randomized controlled trial of zolpidem and haloperidol in pediatric burn patients (n=40, mean age: 9.4 ± 0.7 years) showed zolpidem dosed at 0.5 mg/kg nightly for 1 week (maximum dose: 20 mg) minimally increased Stage 3/4 sleep and REM but not total sleep time; the authors no longer use zolpidem to try to improve sleep in their pediatric burn patients (Armour 2008). A retrospective study compared effectiveness of zolpidem (no dose noted in study) in pediatric burn patients (n=46, mean age: 11 ± 3.7 years) with and without ADHD and found that sleep dysfunction was similar between the groups and those with ADHD required a sleep medication change sooner, concluding that zolpidem was not an effective drug in managing sleep in pediatric burn patients with or without ADHD (Cronin 2015). A prospective, randomized double-blind clinical trial of children between ages 2 to 9 years reported that zolpidem at 0.25 mg/kg (maximum dose: 10 mg/dose) was similar to midazolam with regards to anxiety scoring and inferior with regard to mask acceptance score when used as premedication for perioperative anxiety (Hanna 2018).

Adolescents ≥18 years (non-debilitated patients): Note: The lowest effective dose should be used; higher doses may be more likely to impair next morning activities.

Oral:

Immediate-release tablet (eg, Ambien), spray (Zolpimist): 5 mg (females) or 5 to 10 mg (males) immediately before bedtime; maximum dose: 10 mg/dose

Extended-release tablet (eg, Ambien CR): 6.25 mg (females) or 6.25 to 12.5 mg (males) immediately before bedtime; maximum dose: 12.5 mg/dose

Sublingual tablet:

Edluar: 5 mg (females) or 5 to 10 mg (males) immediately before bedtime; maximum daily dose: 10 mg/day

Intermezzo: Note: Should be taken if patient awakens in middle of night, has difficulty returning to sleep, and has at least 4 hours left before waking.

Females: 1.75 mg once per night as needed; maximum dose: 1.75 mg/night

Males: 3.5 mg once per night as needed; maximum dose: 3.5 mg/night

Dosage adjustment with concomitant CNS depressants: Females and males: 1.75 mg once per night as needed; dose adjustment of concomitant CNS depressant(s) may be necessary

Dosing: Renal Impairment: Pediatric

There are no pediatric-specific recommendations; based on experience in adult patients, no adjustment may be necessary.

Hemodialysis: Not dialyzable.

Dosing: Hepatic Impairment: Pediatric

Adolescents ≥ 18 years:

Immediate-release tablet:

Mild to moderate impairment: 5 mg immediately before bedtime

Severe impairment: Avoid use

Extended-release tablet:

Mild to moderate impairment: 6.25 mg immediately before bedtime

Severe impairment: Avoid use

Oral spray: 5 mg immediately before bedtime

Sublingual tablet:

Edluar: 5 mg immediately before bedtime

Intermezzo: Females and males: 1.75 mg once per night as needed. Note: Take in bed only if ≥4 hours left before waking and there is difficulty in returning to sleep.

Use: Labeled Indications

Insomnia:

Immediate release and sublingual tablets (Edluar only) and oral spray: Short-term treatment of insomnia with difficulty of sleep onset

Extended release tablet: Treatment of insomnia with difficulty of sleep onset and/or sleep maintenance

Sublingual tablet (Intermezzo only): “As needed” treatment of insomnia when middle-of-the-night awakening is followed by difficulty returning to sleep and the patient has ≥4 hours of sleep time remaining

Sublingual tablet (Sublinox only [Canadian product]): Short-term treatment of insomnia (with difficulty of sleep onset, frequent awakenings, and/or early awakenings)

Clinical Practice Guidelines

Insomnia:

American Academy of Sleep Medicine (AASM), “Clinical Practice Guidelines for the Pharmacologic Treatment of Chronic Insomnia in Adults, An American Academy of Sleep Medicine Clinical Practice Guideline” 2017

Administration: Oral

Administer immediately before bedtime due to rapid onset of action. Regardless of dosage form, do not administer with or immediately after a meal (may delay onset). With the exception of Intermezzo, zolpidem should be taken as a single dose at bedtime with at least 7 to 8 hours remaining before planned time of awakening and should not be readministered during the same night. Intermezzo should be taken in bed if patient awakes in the middle of the night (ie, if ≥4 hours left before waking) and there is difficulty in returning to sleep.

Extended release tablet: Swallow tablet whole; do not divide, crush, or chew.

Sublingual tablet: Place sublingual tablet under the tongue and allow to disintegrate; do not swallow or administer Edluar or Sublinox with water.

Oral spray: Spray directly into the mouth over the tongue. Prior to initial use, prime pump by spraying 5 times. If pump is not used for at least 14 days, reprime pump with 1 spray.

Administration: Pediatric

Oral:

All formulations: Regardless of dosage form, do not administer with or immediately after a meal (may delay onset). With the exception of Intermezzo, zolpidem should be taken as a single dose immediately before bedtime (due to rapid onset) with at least 7 to 8 hours remaining before planned time of awakening and should not be readministered during the same night. Intermezzo should be taken in bed if patient awakens in the middle of the night (ie, if ≥4 hours left before waking) and there is difficulty in returning to sleep.

Extended-release tablets (Ambien CR): Swallow whole; do not divide, crush, or chew.

Sublingual tablets (Edluar, Intermezzo): Examine blisterpack before use; do not use if blisters are broken, torn, or missing. Separate individual blisters at perforation; peel off top layer of paper; push tablet through foil. Place under the tongue and allow to disintegrate; do not swallow or administer with water.

Oral spray (Zolpimist): Spray directly into the mouth over the tongue. Prior to initial use, pump should be primed by spraying 5 times. If pump is not used for at least 14 days, reprime pump with 1 spray.

Dietary Considerations

Do not administer with or immediately after a meal (may delay onset).

Storage/Stability

Immediate release and sublingual tablets: Store at 20°C to 25°C (68°F to 77°F). Protect sublingual tablets from light and moisture.

Extended release tablet: Store at 15°C to 25°C (59°F to 77°F); limited excursions permitted up to 30°C (86°F).

Oral spray: Store upright at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze. Avoid prolonged exposure to temperatures >30°C (86°F).

Sublingual tablet (Sublinox [Canadian product]): Store at 15°C to 30°C (59°F to 86°F); protect from light and moisture.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, fatigue, headache, nausea, or diarrhea. Have patient report immediately to prescriber mood changes, behavioral changes, depression, suicidal ideation, hallucinations, confusion, impaired thinking, difficulty breathing, slow breathing, shallow breathing, change in balance, vision changes, memory impairment, or severe loss of strength and energy (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  Geriatric Patients: High-Risk Medication:
  International issues:
Medication Guide and/or Vaccine Information Statement (VIS)
Contraindications

Hypersensitivity to zolpidem or any component of the formulation

Canadian labeling: Additional contraindications (not in US labeling): Significant obstructive sleep apnea syndrome and acute and/or severe impairment of respiratory function; myasthenia gravis; severe hepatic impairment; personal or family history of sleepwalking

Warnings/Precautions

Concerns related to adverse effects:

• Abnormal thinking/behavioral changes: Hypnotics/sedatives have been associated with abnormal thinking and behavior changes including decreased inhibition (eg, aggressiveness and extroversion that seemed out of character), bizarre behavior, agitation, visual and auditory hallucinations, and depersonalization. These changes may occur unpredictably and may indicate previously unrecognized psychiatric disorders; evaluate appropriately.

• CNS depression: May cause CNS depression impairing physical and mental capabilities; patients must be cautioned about performing tasks which require mental alertness (operating machinery or driving). An increased risk of next-day psychomotor impairment is increased if patient is unable to stay in bed for a full night of sleep (7 to 8 hours); if coadministered with other CNS depressants and/or taken with other drugs that increase blood levels of zolpidem; or if a higher than recommended dose is taken. Dose adjustment may be necessary if taking concomitant CNS depressants; use with alcohol is not recommended.

• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis as well as angioedema, have been reported after taking the first or subsequent doses. Do not rechallenge patient if such reactions occur.

• Sleep-related activities: An increased risk for hazardous sleep-related activities such as sleep-driving, preparing and eating food, making phone calls, or having sex while asleep have also been noted; amnesia, anxiety, and other neuropsychiatric symptoms may also occur. Patients usually do not remember these events. The use of alcohol, other CNS depressants, and exceeding the recommended maximum dose may increase the risk of these activities. Discontinue treatment in patients who report any sleep-driving episodes.

Disease-related concerns:

• Depression: Use with caution in patients with depression; worsening of depression, including suicide or suicidal ideation has been reported with the use of hypnotics. Intentional overdose may be an issue in this population. The minimum dose that will effectively treat the individual patient should be used. Prescriptions should be written for the smallest quantity consistent with good patient care.

• Drug abuse: Use with caution in patients with a history of drug dependence. Risk of abuse is increased in patients with a history or family history of alcohol or drug abuse or mental illness.

• Hepatic impairment: GABA agonists, including zolpidem, have been associated with precipitation of hepatic encephalopathy in patients with hepatic impairment. Patients with hepatic impairment do not clear zolpidem as rapidly as patients with normal hepatic function. Use with caution in patients with mild to moderate hepatic impairment; dose adjustment recommended. Avoid use of immediate and extended-release tablets in patients with severe hepatic impairment; may result in encephalopathy.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis.

• Respiratory disease: Use with caution in patients with respiratory compromise, COPD, or sleep apnea.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Debilitated: Use with caution in debilitated patients; potential for oversedation, impaired coordination, and confusion with use; dosage adjustment recommended.

• Elderly: Use with caution in elderly patients; dose adjustment recommended. Monitor for impaired cognitive and/or motor performance, confusion, and potential for falling.

• Females: Dosage adjustment is recommended for females; pharmacokinetic studies involving zolpidem showed a significant increase in maximum concentration and exposure in females compared to males at the same dose.

• Pediatric: When studied for the unapproved use of insomnia associated with ADHD in children, a higher incidence (~7%) of hallucinations was reported. In addition, sleep latency did not decrease compared to placebo.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.

Other warnings/precautions:

• Appropriate use: Symptomatic treatment of insomnia should be initiated only after careful evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve after 7 to 10 days may indicate the need for psychiatric and/or medical illness reevaluation.

• Rapid onset: Because of the rapid onset of action, administer Intermezzo immediately prior to bedtime, after the patient has gone to bed and is having difficulty falling asleep, or during the middle of the night when at least 4 hours are left before waking.

• Withdrawal: Abrupt discontinuance or rapid dose decrease may lead to withdrawal symptoms.

Geriatric Considerations

Refer to Medication Safety Issues for Beers Criteria information.

In doses >5 mg, there was subjective evidence of impaired sleep on the first post-treatment night. There have been reports of increased hypotension and/or falls in the elderly with this drug. With Ambien CR, the adverse event profile of 6.25 mg in elderly patients was similar to the 12.5 mg dose in younger adults. Use with caution in the elderly. For Intermezzo, it may be advisable to avoid this formulation since elderly patients may not realize if they have >4 more hours to sleep.

Warnings: Additional Pediatric Considerations

The most common adverse effects observed in children include the following: Dizziness, headache, hallucinations, affect lability, enuresis, gastroenteritis, and anxiety (Blumer 2009).

Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Pregnancy Considerations

Zolpidem crosses the placenta (Juric 2009).

Severe neonatal respiratory depression and sedation have been reported when zolpidem was used at the end of pregnancy, especially when used concurrently with other CNS depressants. Children born of mothers taking sedative/hypnotics may be at risk for withdrawal; neonatal flaccidity has been reported in infants following maternal use of sedative/hypnotics during pregnancy. Additional adverse effects to the fetus/newborn have been noted in some studies (Sharma 2011; Wang 2010; Wikner 2011). Exposed neonates should be monitored for excess sedation, hypotonia, and respiratory depression.

Breast-Feeding Considerations

Zolpidem is present in breast milk (Pons 1989).

A single oral dose of immediate release zolpidem 20 mg was administered to 5 breastfeeding women; the amount of zolpidem recovered in milk samples 3 hours postadministration ranged from 0.76 to 3.88 mcg (0.004% to 0.019% of the administered maternal dose). Zolpidem was undetectable at 13 and 16 hours postadministration in all women (Pons 1989).

Excess sedation in breastfed infants has been reported. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Monitor the infant for excess sedation, hypotonia, and respiratory depression. Consider interrupting pumping and discarding breast milk during treatment and for 23 hours after the last dose to minimize exposure to the infant.

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

As reported with oral administration, unless otherwise noted.

>10%: Central nervous system: Headache (oral: 7% to 19%; sublingual: 3%), drowsiness (2% to 15%), dizziness (1% to 12%)

1% to 10%:

Cardiovascular: Palpitations (2%), chest discomfort (1%), chest pain (1%), increased blood pressure (1%), edema (≤1%), hypertension (≤1%), orthostatic hypotension (≤1%), syncope (≤1%), tachycardia (≤1%)

Central nervous system: Anxiety (2% to 6%), hallucination (≤4%), disorientation (3%), drugged feeling (3%), fatigue (oral: 3%; sublingual: 1%), lethargy (3%), memory impairment (3%), equilibrium disturbance (2%), psychomotor retardation (2%), vertigo (2%), hypoesthesia (≤2%), lack of concentration (≤2%), depression (2%), confusion (>1%), insomnia (>1%), abnormal dreams (1%), amnesia (1%), ataxia (1%), disinhibition (1%), eating disorder (1%; binge eating), euphoria (1%), increased body temperature (1%), sleep disorder (1%), stress (1%), agitation (≤1%), apathy (≤1%), cerebrovascular disease (≤1%), cognitive dysfunction (≤1%), depersonalization (≤1%), dysarthria (≤1%), emotional lability (≤1%), falling (≤1%), illusion (≤1%), malaise (≤1%), migraine (≤1%), nervousness (≤1%), paresthesia (≤1%), speech disturbance (≤1%), stupor (≤1%)

Dermatologic: Skin rash (1% to 2%), diaphoresis (≤1%), pallor (≤1%), pruritus (≤1%), urticaria (≤1%), wrinkling of skin (1%)

Endocrine & metabolic: Hypermenorrhea (1%), hyperglycemia (≤1%), increased thirst (≤1%), menstrual disease (≤1%)

Gastrointestinal: Nausea (7%), xerostomia (3%), diarrhea (1% to 3%), constipation (2%), dyspepsia (>1%), hiccups (>1%), abdominal distress (1%), abdominal tenderness (1%), change in appetite (1%), frequent bowel movements (1%), gastroesophageal reflux disease (1%), anorexia (≤1%), dysgeusia (≤1%), flatulence (≤1%), gastroenteritis (≤1%), vomiting (≤1%)

Genitourinary: Urinary tract infection (>1%), cystitis (≤1%), dysuria (≤1%), urinary incontinence (≤1%), vaginitis (≤1%)

Hematologic & oncologic: Bruise (1%)

Hepatic: Abnormal hepatic function tests (≤1%), increased serum ALT (≤1%)

Hypersensitivity: Hypersensitivity reaction (4%)

Infection: Influenza (3%), infection (≤1%)

Neuromuscular & skeletal: Myalgia (4%), back pain (3% to 4%), neck pain (2%), arthralgia (>1%), weakness (1%), arthritis (≤1%), leg cramps (≤1%), tremor (≤1%)

Ophthalmic: Visual disturbance (1% to 3%; including altered depth perception), blurred vision (2%), eye redness (2%), diplopia (>1%), asthenopia (1%), eye irritation (≤1%), eye pain (≤1%), scleritis (≤1%)

Otic: Labyrinthitis (1%), tinnitus (≤1%)

Respiratory: Sinusitis (4%), pharyngitis (3%), flu-like symptoms (1% to 2%), lower respiratory tract infection (>1%), upper respiratory tract infection (>1%), throat irritation (1%), bronchitis (≤1%), cough (≤1%), dyspnea (≤1%), rhinitis (≤1%)

Miscellaneous: Fever (≤1%), trauma (≤1%)

<1%, postmarketing, and/or case reports: Abnormal gait, abnormal lacrimation, abnormality in thinking, abscess, accommodation disturbance, acne vulgaris, acute renal failure, aggressive behavior, alteration of saliva, altered sense of smell, anaphylactic shock, anaphylaxis, anemia, angina pectoris, angioedema (including tongue, glottis, larynx), arteritis, behavioral changes, breast fibroadenosis, breast neoplasm, bronchospasm, bullous rash, cardiac arrhythmia, circulatory shock, conjunctivitis, corneal ulcer, decreased libido, delusions, dementia, dental caries, dermatitis, drug tolerance, dysphagia, dysphasia, enteritis, epistaxis, eructation, esophageal spasm, exacerbation of hypertension, extrasystoles, facial edema, furunculosis, gastritis, glaucoma, gout, hemorrhoids, hepatic encephalopathy (in patients with hepatic insufficiency), hepatitis (mixed pattern, hepatocellular, and cholestatic; with or without jaundice), herpes simplex infection, herpes zoster, hot flash, hyperbilirubinemia, hypercholesteremia, hyperhemoglobinemia, hyperlipidemia, hypokinesia, hypotension, hypotonia, hypoxia, hysteria, impotence, increased appetite, increased blood urea nitrogen, increased erythrocyte sedimentation rate, increased serum alkaline phosphatase, increased serum AST, inflammation at injection site, intestinal obstruction, intoxicated feeling, laryngitis, leukopenia, lymphadenopathy, macrocytic anemia, manic reaction, mastalgia, myasthenia, myocardial infarction, neuralgia, neuritis, neuropathy, nocturia, numbness of tongue, oral bullae (sublingual tablet), oral inflammation (sublingual tablet), oral mucosa ulcer (sublingual tablet), osteoarthritis, pain, otitis externa, otitis media, panic disorder, paresis, periorbital edema, personality disorder, phlebitis, photopsia, pneumonia, polyuria, psychoneurosis, pulmonary edema, pulmonary embolism, purpura, pyelonephritis, rectal hemorrhage, renal pain, respiratory depression, restless leg syndrome, rigors, sciatica, skin photosensitivity, sleep driving, somnambulism, strange feeling, suicidal ideation, suicidal tendencies, tendonitis, tenesmus, tetany, thrombosis, urinary frequency, urinary retention, varicose veins, ventricular tachycardia, weight loss, yawning

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2C19 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions 

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants.Risk D: Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

CarBAMazepine: Zolpidem may enhance the CNS depressant effect of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Zolpidem. Management: Monitor zolpidem response closely. Reduce the Intermezzo brand sublingual zolpidem dose to 1.75 mg for men who are also receiving carbamazepine. No such dose change is recommended for women. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Ciprofloxacin (Systemic): May increase the serum concentration of Zolpidem. Management: Consider avoiding the combination of ciprofloxacin and zolpidem if possible. If combined, monitor for signs of zolpidem toxicity (eg, somnolence, dizziness, lethargy). Risk D: Consider therapy modification

CNS Depressants: May enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Zolpidem. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Zolpidem. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Zolpidem. Risk C: Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

FluvoxaMINE: May enhance the CNS depressant effect of Zolpidem. FluvoxaMINE may increase the serum concentration of Zolpidem. Risk C: Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.Risk D: Consider therapy modification

Itraconazole: May increase the serum concentration of Zolpidem. Risk C: Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Ketoconazole (Systemic): May increase the serum concentration of Zolpidem. Management: Consider using a lower starting dose of zolpidem in patients receiving ketoconazole and monitor for increased zolpidem effects/toxicities if these agents are combined. Risk D: Consider therapy modification

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Risk D: Consider therapy modification

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Melatonin: May enhance the sedative effect of Hypnotics (Nonbenzodiazepine). Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Risk D: Consider therapy modification

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

RifAMPin: May decrease the serum concentration of Zolpidem. Risk X: Avoid combination

Ritonavir: May increase the serum concentration of Zolpidem. Risk C: Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Sodium Oxybate: Hypnotics (Nonbenzodiazepine) may enhance the CNS depressant effect of Sodium Oxybate. Risk X: Avoid combination

St John’s Wort: May decrease the serum concentration of Zolpidem. Risk X: Avoid combination

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Food Interactions

Maximum plasma concentration and bioavailability are decreased with food; time to peak plasma concentration is increased; half-life remains unchanged. Management: Do not administer with (or immediately after) a meal.

Test Interactions

Increased aminotransferase [ALT/AST], bilirubin (S); decreased RAI uptake

Monitoring Parameters

Daytime alertness; fall risk, respiratory rate (patients with compromised respiration); behavior profile; tolerance, abuse, and dependence; reevaluate if insomnia persists after 7 to 10 days of use.

Advanced Practitioners Physical Assessment/Monitoring

For short-term use. Assess for history of addiction; long-term use can result in dependence, abuse, or tolerance; behaviors that patient has no memory of performing after taking (driving, preparing food, or eating); periodically evaluate need for continued use. Monitor for CNS depression. For inpatient use, institute safety measures to prevent falls.

Nursing Physical Assessment/Monitoring

For short-term use. Assess for history of addiction; long-term use can result in dependence, abuse, or tolerance; behaviors that patient has no memory of performing after taking (driving, preparing food, or eating); periodically evaluate need for continued use. Monitor for CNS depression. For inpatient use, institute safety measures to prevent falls.

Controlled Substance

C-IV

Dosage Forms Considerations

Zolpimist oral spray 4.5 mL containers contain 30 actuations and 7.7 mL containers contain 60 actuations.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Oral, as tartrate:

Zolpimist: 5 mg/actuation (7.7 mL [DSC]) [contains benzoic acid, propylene glycol]

Zolpimist: 5 mg/actuation (4.5 mL, 7.7 mL) [contains benzoic acid, propylene glycol; cherry flavor]

Tablet, Oral, as tartrate:

Ambien: 5 mg [contains fd&c red #40, polysorbate 80]

Ambien: 10 mg

Generic: 5 mg, 10 mg

Tablet Extended Release, Oral, as tartrate:

Ambien CR: 6.25 mg

Ambien CR: 12.5 mg [contains fd&c blue #2 (indigotine)]

Generic: 6.25 mg, 12.5 mg

Tablet Sublingual, Sublingual, as tartrate:

Edluar: 5 mg, 10 mg [contains saccharin sodium]

Intermezzo: 1.75 mg, 3.5 mg

Generic: 1.75 mg, 3.5 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Sublingual, Sublingual, as tartrate:

Sublinox: 5 mg, 10 mg [contains SACCHARIN SODIUM]

Generic: 5 mg, 10 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • N05CF02
Generic Available (US)

May be product dependent

Pricing: US

Solution (Zolpimist Oral)

5 mg/ACT (per mL): $87.87

Sublingual (Edluar Sublingual)

5 mg (per each): $14.84

10 mg (per each): $14.84

Sublingual (Intermezzo Sublingual)

1.75 mg (per each): $14.89

3.5 mg (per each): $14.89

Sublingual (Zolpidem Tartrate Sublingual)

1.75 mg (per each): $10.04

3.5 mg (per each): $10.04

Tablet, controlled release (Ambien CR Oral)

6.25 mg (per each): $20.20

12.5 mg (per each): $20.20

Tablet, controlled release (Zolpidem Tartrate ER Oral)

6.25 mg (per each): $1.61 – $6.12

12.5 mg (per each): $1.61 – $6.12

Tablets (Ambien Oral)

5 mg (per each): $20.20

10 mg (per each): $20.20

Tablets (Zolpidem Tartrate Oral)

5 mg (per each): $0.10 – $5.14

10 mg (per each): $0.11 – $5.14

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Zolpidem, an imidazopyridine hypnotic that is structurally dissimilar to benzodiazepines, enhances the activity of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), via selective agonism at the benzodiazepine-1 (BZ1) receptor; the result is increased chloride conductance, neuronal hyperpolarization, inhibition of the action potential, and a decrease in neuronal excitability leading to sedative and hypnotic effects. Because of its selectivity for the BZ1 receptor site over the BZ2 receptor site, zolpidem exhibits minimal anxiolytic, myorelaxant, and anticonvulsant properties (effects largely attributed to agonism at the BZ2 receptor site).

Pharmacodynamics/Kinetics

Onset of action: Immediate release: 30 minutes

Duration: Immediate release: 6 to 8 hours

Absorption: Cmax and AUC is increased by ~45% in females compared to male subjects

Immediate release and sublingual: Rapid

Extended release: Biphasic absorption; rapid initial absorption (similar to immediate release product); then provides extended concentrations in the plasma beyond 3 hours postadministration

Distribution: Vd:

Children 2 to 6 years: 1.8 ± 0.8 L/kg (Blumer 2008)

Children >6 to 12 years: 2.2 ± 1.7 L/kg (Blumer 2008)

Adolescents: 1.2 ± 0.4 L/kg (Blumer 2008)

Adults: 0.54 L/kg after an IV dose (Holm 2000)

Protein binding: ~93%

Metabolism: Hepatic methylation and hydroxylation via CYP3A4 (~60%), CYP2C9 (~22%), CYP1A2 (~14%), CYP2D6 (~3%), and CYP2C19 (~3%) to 3 inactive metabolites (Holm 2000)

Bioavailability: Immediate release: 70% (Holm 2000)

Half-life elimination:

Children 2 to 6 years: Immediate release: 1.8 hours (Blumer 2008)

Children >6 years and Adolescents: Immediate release: 2.3 hours (Blumer 2008)

Adults:

Immediate release, Extended release: ~2.5 hours (range: 1.4 to 4.5 hours); Cirrhosis: Up to 9.9 hours; Elderly: Prolonged up to 32%

Spray: ~3 hours (range: 1.7 to 8.4)

Sublingual tablet: ~3 hours (range: 1.4 to 6.7 hours)

Time to peak, plasma:

Children 2 to 6 years: Immediate release: 0.9 hours (Blumer 2008)

Children >6 to 12 years: Immediate release: 1.1 hours (Blumer 2008)

Adolescents: Immediate release: 1.3 hours (Blumer 2008)

Adults:

Immediate release: 1.6 hours; 2.2 hours with food

Extended release: 1.5 hours; 4 hours with food

Spray: ~0.9 hours

Sublingual tablet: Edluar: ~1.4 hours, ~1.8 hours with food; Intermezzo: 0.6 to 1.3 hours, ~3 hours with food

Excretion: Urine (48% to 67%, primarily as metabolites); feces (29% to 42%, primarily as metabolites)

Clearance, apparent:

Children 2 to 6 years: 11.7 ± 7.9 mL/minute/kg (Blumer 2008)

Children >6 to 12 years: 9.7 ± 10.3 mL/minute/kg (Blumer 2008)

Adolescents: 4.8 ± 2 mL/minute/kg (Blumer 2008)

Adults: Intermezzo: Males: 4 mL/minute/kg; Females: 2.7 mL/minute/kg

Pharmacodynamics/Kinetics: Additional Considerations

Hepatic function impairment: Cmax and AUC were found to be 2 and 5 times higher, respectively, in hepatically compromised patients. The mean half-life in cirrhotic patients of 9.9 hours was greater than that observed in normal subjects of 2.2 hours.

Geriatric:

Immediate release: Cmax, half-life, and AUC were significantly increased when compared with results in younger adults.

Extended release: Mean Cmax and mean AUC are 70.6 ng/mL and 413 ng•h/mL, respectively, while the median Tmax is 2 hours.

Gender: Cmax and AUC were higher when comparing the same dose in women with men. Women clear zolpidem from the body at a lower rate than men. In geriatric patients, clearance is similar between men and women..

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health Professional Considerations

An adult companion should accompany the patient to and from dental office.

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation) (see Dental Health Professional Considerations)

Effects on Bleeding

No information available to require special precautions

Index Terms

Zolpidem Tartrate

FDA Approval Date
December 16, 1992
References

Alade SL, Brown RE, Paquet A Jr. Polysorbate 80 and E-Ferol toxicity. Pediatrics. 1986;77(4):593-597.[PubMed 3960626]

Ambien (zolpidem tartrate tablet) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; February 2019.

Ambien CR (zolpidem tartrate tablet) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; February 2019.

American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227-2246. doi:10.1111/jgs.13702[PubMed 26446832]

Blumer JL, Reed MD, Steinberg F, et al, “Potential Pharmacokinetic Basis for Zolpidem Dosing in Children With Sleep Difficulties,” Clin Pharmacol Ther, 2008, 83(4):551-8.[PubMed 17957186]

Centers for Disease Control (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199.http://www.cdc.gov/mmwr/preview/mmwrhtml/00000319.htm[PubMed 6423951]

Durand A, Thénot JP, Bianchetti G, et al, “Comparative Pharmacokinetic Profile of Two Imidazopyridine Drugs: Zolpidem and Alpidem,” Drug Metab Rev, 1992, 24(2):239-66.[PubMed 1576937]

Edluar (zolpidem tartrate sublingual tablet) [prescribing information]. Somerset, NJ: Meda Pharmaceuticals; December 2018.

Edluar (zolpidem tartrate tablet) [prescribing information]. Somerset, NJ: Meda Pharmaceuticals; October 2018.

Holm KJ and Goa KL, “Zolpidem: An Update of Its Pharmacology, Therapeutic Efficacy and Tolerability in the Treatment of Insomnia,” Drugs, 2000, 59(4):865-89.[PubMed 10804040]

Intermezzo (zolpidem tartrate tablet) [prescribing information]. Stamford, CT: Purdue Pharma L.P.; December 2018.

Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-313.[PubMed 12534540]

Juric S, Newport DJ, Ritchie JC, et al, “Zolpidem (Ambien) in Pregnancy: Placental Passage and Outcome,” Arch Womens Ment Health, 2009, 12(6):441-6.[PubMed 19657707]

Lange CL, “Medication-Associated Somnambulism,” J Am Acad Child Adolesc Psychiatry, 2005, 44(3):211-2.[PubMed 15725964]

Langtry HD and Benfield P, “Zolpidem: A Review of Its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Potential,” Drugs, 1990, 40(2):291-313.[PubMed 2226217]

Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172.[PubMed 10985636]

Pharmacy Quality Alliance. Use of high-risk medications in the elderly (HRM). http://pqaalliance.org/images/uploads/files/HRM2015.pdf. Published 2015. Accessed October 26, 2015.

Pons G, Francoual C, Guillet P, et al. Zolpidem excretion in breast milk. Eur J Clin Pharmacol. 1989;37(3):245-248.[PubMed 2612539]

Salva P and Costa J, “Clinical Pharmacokinetics and Pharmacodynamics of Zolpidem. Therapeutic Implications,” Clin Pharmacokinet, 1995, 29(3):142-53.[PubMed 8521677]

Sanger DJ, “The Pharmacology and Mechanisms of Action of New Generation, Non-Benzodiazepine Hypnotic Agents,” CNS Drugs, 2004, 18 (Suppl 1):9-15.[PubMed 15291009]

Sharma A, Sayeed N, Khees CR, Akhtar S. High dose zolpidem induced fetal neural tube defects. Curr Drug Saf. 2011;6(2):128-129.[PubMed 21385155]

Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8960):1312-1313.[PubMed 7746084]

Sublinox (zolpidem) [product monograph]. Laval, Quebec, Canada: Meda Valeant Pharma Canada Inc; December 2014.

Taylor JR, Vazquez CM, and Campbell KM, “Pharmacologic Management of Chronic Insomnia,” South Med J, 2006, 99(12):1373-7.[PubMed 17233194]

Wang LH, Lin HC, Lin CC, et al, “Increased Risk of Adverse Pregnancy Outcomes in Women Receiving Zolpidem During Pregnancy,” Clin Pharmacol Ther, 2010, 88(3):369-74.[PubMed 20686480]

Wikner BN and Källén B, “Are Hypnotic Benzodiazepine Receptor Agonists Teratogenic in Humans?” J Clin Psychopharmacol, 2011, 31(3):356-9.[PubMed 21508851]

Zolpimist oral spray (zolpidem tartrate) [prescribing information]. Englewood, CO: Aytu BioScience, Inc.; February 2019.

Brand Names: International

Adormix (CL); Ambien (BB, BM, BS, BZ, GY, JM, PR, SR, TT); Ambien CR (AR, IL); Ambulax-2 (IN); Conyx (KR); Dactive (PH); Dalparan (ES); Dormeben (CO); Dormizol (AU); Flazinil (EC); Fulsadem (AR); Hypnogen (EE); Ivadal (AT); Jonfa (VN); Lioram (BR); Nidraj (BD); Niotal (IT); Nitrest (BD, IN); Nocte (CR, DO, GT, HN, LK, NI, PA, SV); Nocte Sublingual (AR); Nuo Bin (CN); Nytamel (IE); Sanval (RU); Sleepman (TW); Slepzol (ID); Somidem (AU, MY); Somit (AR, PY, UY); Somnil (CO); Somno (PE); Sove (LK); Stildem (AU); Stilnix (IL); Stilnoct (BE, DK, FI, GB, IE, IS, LU, NL, NO, SE); Stilnox (AU, BF, BG, BJ, BR, CH, CI, CL, CN, CO, CR, CY, CZ, DE, DO, EE, ES, ET, FR, GH, GM, GN, GR, GT, HK, HN, HU, ID, IT, JO, KE, KR, KW, LB, LR, LT, LV, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NI, PA, PE, PH, PK, PL, PT, PY, QA, RO, SA, SC, SD, SK, SL, SN, SV, TN, TR, TW, TZ, UG, VE, VN, ZA, ZM); Stilnox CR (AU, BR, CO, CR, DO, GT, HK, HN, KR, MY, NI, PA, SG, SV); Sucedal (EC); Vicknox (HK); Ziohex (PH); Zodenox (MY); Zodium (EG); Zodorm (IL); Zoldem (AT, BD, DE, IE); Zoldox (TW); Zoliprex (LK); Zolmia (ID); Zolnod (IE); Zolnox (PY, UY); Zolpibell (AU); Zolpicin (TW); Zolpid (BD, KR); Zolpihexal (ZW); Zolpinox (DE); Zolpirest (PH); Zolpista (EG); Zolpitop (BE); Zolsana (BG); Zopidem (TW); Zopim (MY, TW); Zorimin (TW)

Zolpidem (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(zole PI dem)

Brand Names: US

Ambien; Ambien CR; Edluar; Intermezzo; Zolpimist

Brand Names: Canada

Sublinox

What is this drug used for?
  • It is used to treat sleep problems.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to zolpidem or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have liver disease.
  • If you are taking any other drugs that can make you sleepy. There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.
  • If you are taking any of these drugs: Rifampin or St. John’s wort.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • All products:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • This drug may be habit-forming with long-term use.
  • When sleep drugs are used nightly for more than a few weeks, they may not work as well to help sleep problems. This is known as tolerance. Only use sleep drugs for a short time. If sleep problems last, call the doctor.
  • Do not take naps.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Avoid alcohol while taking this drug. Do not take this drug if you drank alcohol that evening or before bed.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • Some people have done certain tasks or actions while they were not fully awake like driving, making and eating food, and having sex. Most of the time, people do not remember doing these things. Tell your doctor if this happens to you.
  • This drug may cause sleepiness or lower alertness. This may lead to falls and injuries that may be very bad. Very bad injuries like broken hips and bleeding in the brain have happened. Talk with the doctor.
  • If you are a woman, use this drug with care. You could have more side effects.
  • If you are 60 or older, use this drug with care. You could have more side effects.
  • This drug is not approved for use in children. The chance of side effects like dizziness and hallucinations may be raised in children. However, your child’s doctor may decide the benefits of taking this drug may outweigh the risks. Talk with the doctor if you have questions about giving this drug to your child.
  • Tell your doctor if you are pregnant, plan on getting pregnant, or are breast-feeding. You will need to talk about the benefits and risks to you and the baby.
  • Taking this drug in the third trimester of pregnancy may lead to some health problems in the newborn. Talk with the doctor.
  • Extended-release tablets:
  • You may not be alert. Do not drive or do other tasks or actions that call for you to be alert on the day after you take this drug.
  • All other products:
  • Avoid driving and doing other tasks or actions that call for you to be alert after you take this drug. You may still feel sleepy the day after you take this drug. Avoid these tasks or actions until you feel fully awake.
  • Under the tongue (sublingual) tablet:
  • If you have phenylketonuria (PKU), talk with your doctor. Some products have phenylalanine.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • New or worse behavior or mood changes like depression or thoughts of killing yourself.
  • Hallucinations (seeing or hearing things that are not there).
  • Feeling confused.
  • Not thinking clearly.
  • Trouble breathing, slow breathing, or shallow breathing.
  • Change in balance.
  • Change in eyesight.
  • Memory problems or loss.
  • Feeling very tired or weak.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Dizziness.
  • Feeling sleepy the next day.
  • Headache.
  • Upset stomach.
  • Diarrhea.
  • Feeling tired or weak.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • If you still have trouble sleeping after 7 to 10 days, call your doctor.
  • Take this drug at bedtime.
  • Take this drug only 1 time per night.
  • Take on an empty stomach.
  • Do not take with or right after a meal.
  • Tablets:
  • Take this drug right before you get into bed.
  • Do not take this drug unless you can get a full night’s sleep (at least 7 to 8 hours) before you need to be active again.
  • Extended-release tablets:
  • Take this drug right before you get into bed.
  • Swallow whole. Do not chew, break, or crush.
  • Do not take this drug unless you can get a full night’s sleep (at least 7 to 8 hours) before you need to be active again.
  • Spray:
  • Take this drug right before you get into bed.
  • Spray into mouth over the tongue.
  • Prime pump before first use.
  • Prime pump by spraying it 5 times.
  • If you have not used the spray for more than 14 days, you will need to prime the pump with 1 spray or until you see a fine mist.
  • Do not take this drug unless you can get a full night’s sleep (at least 7 to 8 hours) before you need to be active again.
  • Under the tongue (sublingual) tablet:
  • Be sure your hands are dry before you touch this drug.
  • Place under tongue and let dissolve all the way. Do not chew, suck or swallow tablet.
  • Do not eat, drink, or smoke while the tablet is dissolving.
  • Edluar:
  • Take this drug right before you get into bed.
  • Do not take this drug unless you can get a full night’s sleep (at least 7 to 8 hours) before you need to be active again.
  • Intermezzo®:
  • Take only as needed if you wake up in the middle of the night and have trouble going back to sleep. Only take a dose if you have 4 or more hours of bedtime left. Do not take more than 1 dose per night.
  • Only keep 1 pouch with this drug in it at your bedside. Store all other pouches away from your bedside. Do not remove the drug from the pouch until you are ready to take a dose. After you take this drug, leave the empty pouch where you can see it. This will help remind you that you have taken your dose.
What do I do if I miss a dose?
  • All products other than Intermezzo:
  • If you take this drug on a regular basis, take a missed dose as soon as you think about it.
  • If you will not be able to get a full night’s sleep (at least 7 hours) after taking the missed dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • Do not take more than 1 dose of this drug in the same day.
  • Many times this drug is taken on an as needed basis. Do not take more often than told by the doctor.
  • Intermezzo®:
  • If you take this drug on a regular basis, take a missed dose as soon as you think about it.
  • If you will not be able to get 4 or more hours of sleep after taking the missed dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • Do not take more than 1 dose of this drug in the same day.
  • Many times this drug is taken on an as needed basis. Do not take more often than told by the doctor.
How do I store and/or throw out this drug?
  • All products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
  • Spray:
  • Store upright with the cap on.
  • Do not freeze.
  • Throw away after the stated number of sprays have been used, even if it feels like there is more drug left.
  • All other products:
  • Protect from light.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Zolpidem (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(zole PI dem)

Brand Names: US

Ambien; Ambien CR; Edluar; Intermezzo; Zolpimist

Brand Names: Canada

Sublinox

What is this drug used for?
  • It is used to treat sleep problems.
  • This drug is not approved for use in children. The chance of side effects like dizziness and hallucinations may be raised in children. However, your child’s doctor may decide the benefits of taking this drug may outweigh the risks. Talk with the doctor if you have questions about giving this drug to your child.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has liver disease.
  • If your child is taking any other drugs that can make your child sleepy. There are many drugs that can do this. Ask your child’s doctor or pharmacist if you are not sure.
  • If your child is taking any of these drugs: Rifampin or St. John’s wort.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • All products:
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • This drug may be habit-forming with long-term use.
  • When sleep drugs are used nightly for more than a few weeks, they may not work as well to help your child sleep. This is known as tolerance. Only give your child sleep drugs for a short time. If your child’s sleep problems last, call the doctor.
  • Do not let your child take naps.
  • To lower the chance of feeling dizzy or passing out, have your child rise slowly if your child has been sitting or lying down. Have your child be careful going up and down stairs.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • Talk with your child’s doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • Some people have done certain tasks or actions while they were not fully awake like driving, and making and eating food. Most of the time, people do not remember doing these things. Tell the doctor if this happens to your child.
  • This drug may cause sleepiness or lower alertness. This may lead to falls and injuries that may be very bad. Very bad injuries like broken hips and bleeding in the brain have happened. Talk with the doctor.
  • If your child is a female, give this drug with care. She could have more side effects.
  • If your child is pregnant or breast-feeding a baby:
  • Talk with the doctor if your child is pregnant, becomes pregnant, or is breast-feeding a baby. You will need to talk about the benefits and risks to your child and the baby.
  • Taking this drug in the third trimester of pregnancy may lead to some health problems in the newborn. Talk with the doctor.
  • Extended-release tablets:
  • Your child may not be alert. Have your child avoid tasks or actions that call for alertness on the day after your child takes this drug.
  • All other products:
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles. Your child may still feel sleepy the day after taking this drug. Have your child avoid these tasks or actions until your child feels fully awake.
  • Under the tongue (sublingual) tablet:
  • If your child has phenylketonuria (PKU), talk with your child’s doctor. Some products have phenylalanine.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • New or worse behavior or mood changes like depression or thoughts of killing him/herself.
  • Hallucinations (seeing or hearing things that are not there).
  • Feeling confused.
  • Not thinking clearly.
  • Trouble breathing, slow breathing, or shallow breathing.
  • Change in balance.
  • Change in eyesight.
  • Memory problems or loss.
  • Feeling very tired or weak.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Dizziness.
  • Feeling sleepy the next day.
  • Headache.
  • Upset stomach.
  • Diarrhea.
  • Feeling tired or weak.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • If your child still has trouble sleeping after 7 to 10 days, call your child’s doctor.
  • Give at bedtime.
  • Give this drug only 1 time per night.
  • Give on an empty stomach.
  • Do not give with or right after a meal.
  • Tablets:
  • Give this drug right before your child gets into bed.
  • Do not give this drug unless your child can get a full night’s sleep (at least 7 to 8 hours) before needing to be active again.
  • Extended-release tablets:
  • Give this drug right before your child gets into bed.
  • Have your child swallow whole. Do not let your child chew, break, or crush.
  • Do not give this drug unless your child can get a full night’s sleep (at least 7 to 8 hours) before needing to be active again.
  • Spray:
  • Give this drug right before your child gets into bed.
  • Spray into mouth over the tongue.
  • Prime pump before first use.
  • Prime pump by spraying it 5 times.
  • If you have not used the spray for more than 14 days, you will need to prime the pump with 1 spray or until you see a fine mist.
  • Do not give this drug unless your child can get a full night’s sleep (at least 7 to 8 hours) before needing to be active again.
  • Under the tongue (sublingual) tablet:
  • Be sure your hands are dry before you touch this drug.
  • Place under your child’s tongue and let dissolve all the way before swallowing. Do not let your child chew, suck, or swallow the tablet.
  • Do not let your child eat, drink, or smoke while the tablet is dissolving.
  • Edluar:
  • Give this drug right before your child gets into bed.
  • Do not give this drug unless your child can get a full night’s sleep (at least 7 to 8 hours) before needing to be active again.
  • Intermezzo®:
  • Give only as needed if your child wakes up in the middle of the night and has trouble going back to sleep. Only give a dose if your child has 4 or more hours of bedtime left. Do not give more than 1 dose per night.
  • Only keep 1 pouch with this drug in it at the bedside. Store all other pouches away from the bedside. Do not remove the drug from the pouch until you are ready to give a dose. After you give this drug, leave the empty pouch where you can see it. This will help remind you that you have given the dose to your child.
What do I do if my child misses a dose?
  • All products other than Intermezzo:
  • If your child takes this drug on a regular basis, give a missed dose as soon as you think about it.
  • If your child will not be able to get a full night’s sleep (at least 7 hours) after taking the missed dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
  • Do not give more than 1 dose of this drug in the same day.
  • Many times this drug is given on an as needed basis. Do not give to your child more often than told by the doctor.
  • Intermezzo®:
  • If your child takes this drug on a regular basis, give a missed dose as soon as you think about it.
  • If your child will not be able to get 4 or more hours of sleep after taking the missed dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
  • Do not give more than 1 dose of this drug in the same day.
  • Many times this drug is given on an as needed basis. Do not give to your child more often than told by the doctor.
How do I store and/or throw out this drug?
  • All products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
  • Spray:
  • Store upright with the cap on.
  • Do not freeze.
  • Throw away after the stated number of sprays have been used, even if it feels like there is more drug left.
  • All other products:
  • Protect from light.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.