Zolpidem (Ambien) is a sleeping pill (hypnotic drug) that is different than the commonly prescribed medicines belonging to the benzodiazepine class like alprazolam and clonazepam. It has got little anxiolytic effects and does not possess anti-convulsant or myorelaxant properties.

It is used in the treatment of Insomnia:

• • Sublingual tablets (Edluar only), oral spray, and immediate-release tablets:

    • It is used for short-term treatment of insomnia with difficulty of sleep onset

  • Extended-release tablet:

    • It is used for the treatment of insomnia with difficulty of sleep onset and/or sleep maintenance

  • Sublingual tablet (Intermezzo only):

    • It is used for "As needed" treatment of insomnia when a 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]):

    • It is used for short-term treatment of insomnia (with difficulty of sleep onset, frequent awakenings, and/or early awakenings)

Zolpidem (Ambien) Dose in Adults

Zolpidem (Ambien) dosage in the treatment of Insomnia:

• The lowest effective dose is 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 given before bedtime
    • the maximum dose is 10 mg daily

  • Extended-release tablet:

    • 6.25 mg (females) or 6.25 to 12.5 mg (males) immediately given before bedtime
    • the maximum dose is 12.5 mg daily

• Sublingual tablet:

  • Edluar, Sublinox [Canadian product]:

    • 5 mg (females) or 5 to 10 mg (males) immediately given before bedtime;
    • if 5 mg dose is ineffective may be increased to 10 mg (maximum dose: 10 mg daily)

  • Intermezzo: Note:

    • Use in bed only if ≥4 hours left before waking and there is difficulty in returning to sleep
    • Females:
      • 75 mg once per night as needed is given (maximum: 1.75 mg/night)
    • Males:
      • 5 mg once per night as needed is given (maximum: 3.5 mg/night)

• Dosage adjustment with concomitant CNS depressants:

  • Females and males:
    • 1.75 mg once per night as needed is given
    • dose adjustment of concomitant CNS depressant(s) might be necessary.

Zolpidem (Ambien) dosage in Debilitated patients:

• Immediate release tablet, spray:

  • 5 mg immediately given before bedtime

• Sublingual tablet:

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

• Extended release tablet:

  • 25 mg immediately given before bedtime

Zolpidem (Ambien) Dose in Children

Zolpidem (Ambien ) dose in the treatment of Insomnia:

• Children and Adolescents ≤17 years: .

  • Immediate-release tablets:

    • Usual reported dose is 0.25 mg/kg orally at bedtime to a maximum dose of 10 mg/dose.

• Adolescents ≥18 years (non-debilitated patients):

  • • Immediate-release tablet (eg, Ambien), spray (Zolpimist):

      • 5 mg (females) or 5 to 10 mg (males) orally immediately is given before bedtime
      • the maximum dose is 10 mg/dose

    • The extended-release tablet (eg, Ambien CR):

      • 25 mg (females) or 6.25 to 12.5 mg (males) orally given immediately before bedtime
      • the maximum dose is 12.5 mg/dose

    • Sublingual tablet:

      • Edluar:
        • 5 mg (females) or 5 to 10 mg (males) immediately given before bedtime
        • the maximum daily dose is 10 mg/day
• Intermezzo: Note:
  • It should be used if the patient awakens in the middle of the night, has difficulty returning to sleep, and has at least 4 hours left before waking.

    • Females:

      • 75 mg orally once per night as needed is given ;
      • Its maximum dose is 1.75 mg/night

    • Males:

      • 5 mg orally once per night as needed is given ;
      • Its maximum dose: 3.5 mg/night

• Dosage adjustment with concomitant CNS depressants:

  • Females and males:
    • 1.75 mg once per night as needed is given
    • dose adjustment of concomitant CNS depressant(s) might be necessary

Zolpidem (Ambien) Pregnancy Risk Factor: C

• Breast milk contains Zolpidem.
• Breastfed infants have been shown to experience excessive sedation.
• According to the manufacturer the decision to breastfeed while on therapy should consider the risks to infants, the benefits to breastfeeding to infants, and the benefits to mother during treatment.
• Assess the infant for excessive sedation, hypotonia and respiratory depression.
• You might consider stopping pumping and dumping breast milk during treatment, and up to 23 hours after the last dose.

Use Zolpidem while breastfeeding

• Breast milk contains Zolpidem.
• Breastfed infants have been shown to experience excessive sedation.
• According to the manufacturer the decision to breastfeed while on therapy should consider the risks to infants, the benefits to breastfeeding to infants, and the benefits to mother during treatment.
• Assess the infant for excessive sedation, hypotonia and respiratory depression.
• You might consider stopping pumping and dumping breast milk during treatment, and up to 23 hours after the last dose

Zolpidem (Ambien) dose in Kidney disease:

No dosage adjustment is necessary.

• Hemodialysis: It is not dialyzable

Zolpidem (Ambien) dose in Liver disease:

• Tablet immediately available for release

  • Mild to moderate impairmentTake 5mg immediately before bedtime
  • Severe impairmentUse caution

• Extended-release tablet

  • Mild to moderate impairment25mg taken immediately before bedtime
  • Severe impairmentUse caution
• Oral spray: 5mg immediately before bedtime

  • Sublingual tablet

    • Edluar

      • Take 5mg immediately before bedtime

    • Intermezzo

      • Males and females receive 1.75 mg each night as needed.

    • Sublinox:

      • Mild to moderate impairmentTake 5mg immediately before bedtime
      • Severe impairmentContraindicated.

Common Side Effects of Zolpidem (Ambien) Include:

• Central nervous system:

  • Headache
  • Drowsiness
  • Dizziness

Less Common Side Effects of Zolpidem (Ambien) Include:

• Cardiovascular:

  • Palpitations
  • Chest Discomfort
  • Chest Pain
  • Increased Blood Pressure
  • Edema
  • Hypertension
  • Orthostatic Hypotension
  • Syncope
  • Tachycardia

• Central Nervous System:

  • Anxiety
  • Hallucination
  • Disorientation
  • Drugged Feeling
  • Fatigue
  • Lethargy
  • Memory Impairment
  • Equilibrium Disturbance
  • Psychomotor Retardation
  • Vertigo
  • Hypoesthesia
  • Lack Of Concentration
  • Depression
  • Confusion
  • Insomnia
  • Abnormal Dreams
  • Amnesia
  • Ataxia
  • Disinhibition
  • Eating Disorder
  • Euphoria
  • Increased Body Temperature
  • Sleep Disorder
  • Stress
  • Agitation
  • Apathy
  • Cerebrovascular Disease
  • Cognitive Dysfunction
  • Depersonalization
  • Dysarthria
  • Emotional Lability
  • Falling
  • Illusion
  • Malaise
  • Migraine
  • Nervousness
  • Paresthesia
  • Speech Disturbance
  • Stupor

• Dermatologic:

  • Skin Rash
  • Diaphoresis
  • Pallor
  • Pruritus
  • Urticaria
  • Wrinkling Of Skin

• Endocrine & Metabolic:

  • Hypermenorrhea
  • Hyperglycemia
  • Increased Thirst
  • Menstrual Disease

• Gastrointestinal:

  • Nausea
  • Xerostomia
  • Diarrhea
  • Constipation
  • Dyspepsia
  • Hiccups
  • Abdominal Distress
  • Abdominal Tenderness
  • Change In Appetite
  • Frequent Bowel Movements
  • Gastroesophageal Reflux Disease
  • Anorexia
  • Dysgeusia
  • Flatulence
  • Gastroenteritis
  • Vomiting

• Genitourinary:

  • Urinary Tract Infection
  • Cystitis
  • Dysuria
  • Urinary Incontinence
  • Vaginitis

• Hematologic & Oncologic:

  • Bruise

• Hepatic:

  • Abnormal Hepatic Function Tests
  • Increased Serum ALT

• Hypersensitivity:

  • Hypersensitivity Reaction

• Infection:

  • Influenza
  • Infection

• Neuromuscular & Skeletal:

  • Myalgia
  • Back Pain
  • Neck Pain
  • Arthralgia
  • Weakness
  • Arthritis
  • Leg Cramps
  • Tremor

• Ophthalmic:

  • Visual Disturbance
  • Blurred Vision
  • Eye Redness
  • Diplopia
  • Asthenopia
  • Eye Irritation
  • Eye Pain
  • Scleritis

• Otic:

  • Labyrinthitis
  • Tinnitus

• Respiratory:

  • Sinusitis
  • Pharyngitis
  • Flu-Like Symptoms
  • Lower Respiratory Tract Infection
  • Upper Respiratory Tract Infection
  • Throat Irritation
  • Bronchitis
  • Cough
  • Dyspnea
  • Rhinitis

• Miscellaneous:

  • Fever
  • Trauma

Contraindication to Zolpidem (Ambien) Include:

• Hypersensitivity to zolpidem or any part of the formulation
• Significant obstructive sleep apnea syndrome and acute and/or severe impairment of respiratory function
• myasthenia gravis
• severe hepatic derangement
• personal or family history of sleepwalking

Warnings and Precautions

• Abnormal behavior/thinking:
  • Hypnotics/sedatives can cause abnormal thinking and behavior changes, such as decreased inhibition (e.g. aggressiveness and extroversion which seemed out of character), agitation and bizarre behavior, auditory and visual hallucinations and depersonalization.
  • These changes may be unpredicted and could indicate previously unrecognized mental disorders. Get evaluated accordingly.
• Depression in the CNS:
  • It can lead to CNS depression, which can impair physical and mental abilities.
  • Patients who perform tasks that require mental alertness, such as driving or operating machinery, should be advised to take the drug with caution.
  • If the patient cannot stay in bed for 7 to 8 hours, or if they take zolpidem with other CNS depressants or other drugs that increase blood levels, then there is an increased risk of next-day psychological impairment.
  • If you are taking CNS depressants with concomitant CNS medications, dosage adjustment may be required. Alcohol is not recommended.
• Hypersensitivity reactions
  • After taking the first or second dose, hypersensitivity reactions such as anaphylaxis and angioedema have been reported.
  • If such reactions occur, do not restart the patient.
• Activities that are sleep-related:​​​​​​​​​​​​​​
  • There has been an increase in the risk of hazardous sleep-related activities like driving, cooking and eating, as well as making phone calls or having sex while you sleep.
  • Anxiety, amnesia and other neuropsychiatric symptoms may also be present.
  • Most patients forget the events.
  • Drinking alcohol or other CNS depressants can increase your risk.
  • Stop treating patients who have reported any episodes of sleep-driving.
• ​​​​​​​​​​​​​​Depression
  • Patients with depression should be cautious when using hypnotics.
  • There have been cases of suicide attempts or worsening depression due to the use of these hypnotics.
  • This population can become a problem if they accidentally overdose.
  • It is important to only give the minimum amount that can effectively treat a patient.
  • For good patient care, prescriptions should only be given for the minimum amount.
• ​​​​​​​​​​​​​​Use of drugs:
  • Patients with a history or drug dependence should be cautious.
  • Patients with a family history of drug abuse or mental illness or a history of alcohol abuse are at greater risk.
• ​​​​​​​​​​​​​​Hepatic impairment​​​​​​​
  • GABA agonists such as zolpidem have been shown to cause hepatic dysfunction in patients with hepatic impairment.
  • Patients with impaired hepatic function do not get zolpidem as quickly as patients with normal hepatic function.
  • Patients with mild or moderate hepatic impairment should be cautious; dosage adjustment is recommended.
  • Patients with severe hepatic impairment should not use this product as it can cause encephalopathy.
• ​​​​​​​​​​​​​​Myasthenia gravis
  • Patients with myasthenia gravis should be treated with caution.
• ​​​​​​​​​​​​​​Respiratory disease
  • Patients with COPD, respiratory compromise, sleep apnea, or COPD should be cautious.

Zolpidem: Drug Interaction

Monitor:

• Daytime alertness; fall risk
• respiratory rate (patients with compromised respiration)
• behavior profile
• tolerance, abuse, and dependence
• reevaluate the patient if insomnia persists after a week or more of its use.

How to administer Zolpidem (Ambien)?

Oral:

• Due to the rapid onset, give immediately before bedtime
• Do not give the medication with or immediately following a meal, regardless of its dosage form. This may delay the onset.
• Except for Intermezzo, zolpidem must be taken at bedtime in a single dose. There should be at least 7 to 8 hours before the scheduled time of awakening. It should not be administered twice during the night.
• Intermezzo should only be administered in bed when the patient wakes up in the middle or late of the night, and there is difficulty returning to sleep.

Extended-release tablet:

• Take the entire tablet and swallow it
• Do not chop, break, or chew.

Sublingual tablet

• Place a sublingual tablet underneath the tongue, and let it dissolve
• Do not drink water with Edluar and Sublinox.

Oral spray:

• Spray directly onto the tongue and into the mouth.
• Prime the pump 5 times before first use. After 14 days of inactivity, prime the pump again with one spray

Mechanism of action of Zolpidem (Ambien):

• Zolpidem is an imidazopyridine hypnotic which is structurally different to benzodiazepines. It enhances the activity the inhibitory neurotransmitter g-aminobutyric Acid (GABA) via selective agonism at benzodiazepine-1(BZ ).
• This causes an increase in chloride conductance, neuronal overpolarization, and inhibition of the action pot. It also results in sedative and/or hypnotic effects.
• Zolpidem has minimal anxiolytic and myorelaxant and anticonvulsant qualities.

The onset of action:

• Immediate release in 30 minutes

Duration

• : Immediate release up to 6 to 8 hours

Absorption:

• C and AUC is increased by almost 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: V :

• Children 2 to 6 years: 1.8 ± 0.8 L/kg
• Children >6 to 12 years: 2.2 ± 1.7 L/kg
• Adolescents: 1.2 ± 0.4 L/kg
• Adults: 0.54 L/kg after an IV dose

Protein binding: 

• almost93%

Metabolism:

It goes through Hepatic methylation and hydroxylation via CYP3A4 (~60%), CYP2C9 (~22%), CYP1A2 (~14%), CYP2D6 (~3%), and CYP2C19 (~3%) to 3 inactive metabolites

Bioavailability:

• Immediate release: 70%

Half-life elimination

• Children 2 to 6 years: Immediate release in 1.8 hours
• Children >6 years and Adolescents: Immediate release in 2.3 hours
• Adults:
  • Immediate release, Extended-release: almost 2.5 hours (range: 1.4 to 4.5 hours); Cirrhosis: Up to 9.9 hours; Elderly: Prolonged up to 32%
  • Spray: almost 3 hours (range: 1.7 to 8.4)
  • Sublingual tablet: almost 3 hours (range: 1.4 to 6.7 hours)

Time to peak, plasma:

• Children 2 to 6 years: Immediate release: 0.9 hours
• Children >6 to 12 years: Immediate release: 1.1 hours
• Adolescents: Immediate release: 1.3 hours
• Adults:
  • Immediate release: 1.6 hours; 2.2 hours with food
  • Extended-release: 1.5 hours; 4 hours with food
  • Spray: almost 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:

• Mostly 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
• Children >6 to 12 years: 9.7 ± 10.3 mL/minute/kg
• Adolescents: 4.8 ± 2 mL/minute/kg
• Adults: Intermezzo: Males: 4 mL/minute/kg; Females: 2.7 mL/minute/kg  

International Brands of Zolpidem:

• Adormix
• Ambien
• Ambien CR
• Ambulax-2
• Conyx
• Dactive
• Dalparan
• Dormeben
• Dormizol
• Flazinil
• Fulsadem
• Hypnogen
• Ivadal
• Jonfa
• Lioram
• Nidraj
• Niotal
• Nitrest
• Nocte
• Nocte Sublingual
• Nuo Bin
• Nytamel
• Sanval
• Sleepman
• Slepzol
• Somidem
• Somit
• Somnil
• Somno
• Sove
• Stildem
• Stilnix
• Stilnoct
• Stilnox
• Stilnox CR
• Sucedal
• Vicknox
• Ziohex
• Zodenox
• Zodium
• Zodorm
• Zoldem
• Zoldox
• Zoliprex
• Zolmia
• Zolnod
• Zolnox
• Zolpibell
• Zolpicin
• Zolpid
• Zolpihexal
• Zolpinox
• Zolpirest
• Zolpista
• Zolpitop
• Zolsana
• Zopidem
• Zopim
• Zorimin
• Ambien
• Ambien CR
• Edluar
• Intermezzo
• Zolpimist
• APO-Zolpidem ODT
• PMS-Zolpidem ODT
• Sublinox

Zolpidem Brands in Pakistan: