Zolpidem Tartrate

Trade Names:
Ambien
- Tablets 5 mg
- Tablets 10 mg

Trade Names:
Ambien CR
- Tablets, extended-release 6.25 mg
- Tablets, extended-release 12.5 mg

Trade Names:
Tovalt ODT
- Tablets, orally disintegrating 5 mg
- Tablets, orally disintegrating 10 mg

Pharmacology

Mechanism is unknown but may involve subunit modulation of the GABA _A receptor chloride channel macromolecular complex.

Pharmacokinetics

Absorption

Rapid absorption from the GI tract. T _max is 1.6 h (immediate-release). C _max (5 mg tablet) is about 29 to 113 ng/mL; C _max (10 mg tablet) is about 58 to 272 ng/mL.

Mean C _max and AUC are 134 ng/mL and 740 ng•h/mL, respectively, while median T _max is 1.5 h.

Mean C _max is 101.68 ng/mL and T _max is 1.75 h.

Distribution

Protein binding is about 92.5%.

Metabolism

Zolpidem is converted to inactive metabolites.

Elimination

Primarily excreted in the urine.

The t _½ (5 mg tablet) is 2.6 h; the t _½ (10 mg tablet) is 2.5 h; the t _½ (ER tablet) is 2.8 h; the t _½ (orally disintegrating tablet) is 3.5 h.

Special Populations

No dosage adjustment is necessary.

C _max and AUC were found to be 2 times and 5 times higher, respectively, in hepatically compromised patients. Modify dosing accordingly in patients with hepatic function impairment.

C _max , t _½ , and AUC were significantly increased when compared with results in younger adults.

Mean C _max and mean AUC are 70.6 ng/mL and 413 ng•h/mL, respectively, while the median T _max is 2 h.

Indications and Usage

Short-term treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.

Contraindications

Standard considerations.

Dosage and Administration

PO 10 mg immediately before bedtime. Max dose is no more than 10 mg.

An initial 5 mg dose is recommended.

PO 12.5 mg immediately before bedtime.

An initial 6.25 mg dose is recommended.

General Advice

• Administer immediately before bedtime.
• Administer on an empty stomach for fast sleep onset. Administer with food if GI upset occurs. Do not administer with or immediately after a meal.
• Instruct patient receiving orally disintegrating tablet to place tablet in the mouth, where it will dissolve in seconds and then be swallowed with saliva.
• Orally disintegrating tablet may be taken with or without water.
• Instruct patient receiving ER or orally disintegrating tablet not to chew, crush, or split the tablet.

Storage/Stability

Store immediate-release or orally disintegrating tablets at controlled room temperature (68° to 77°F). Store ER tablets at controlled room temperature (59° to 77°F), with limited excursions up to 86°F permissible.

Drug Interactions

Zolpidem plasma levels may be increased.

Possible additive or potentiation of CNS depressant effects.

Reduces absorption of zolpidem.

May reverse the sedative/hypnotic effects of zolpidem.

Zolpidem plasma levels may be reduced, decreasing the pharmacologic effects.

Possible severe sedation and respiratory depression.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Palpitation (2%); BP increased (1%).

CNS

Headache (19%); somnolence (15%); dizziness (12%); drowsiness (8%); hallucinations (4%); anxiety, disorientation, drugged feeling, fatigue, lethargy, memory disorders (3%); balance disorder, depression, disturbance in attention, hypoesthesia, light-headedness, psychomotor retardation, vertigo (2%); asthenia, ataxia, confusion, euphoria, insomnia, vertigo (more than 1%); abnormal dreams, amnesia, binge eating, depersonalization, disinhibition, mood swings, nervousness, paresthesia, sleep disorder, stress symptoms (1%).

Dermatologic

Rash (2%); skin wrinkling, urticaria (1%).

EENT

Sinusitis (4%); visual disturbance (3%); eye redness, vision blurred (2%); abnormal vision, diplopia (more than 1%); altered depth perception, asthenopia, labyrinthitis, throat irritation, rhinitis, tinnitus (1%).

GI

Nausea (7%); dyspepsia (5%); diarrhea, dry mouth (3%); abdominal pain, constipation (2%); hiccup (more than 1%); abdominal discomfort/tenderness, anorexia, appetite disorder, frequent bowel movements, gastroenteritis, gastroesophageal reflux disease, vomiting (1%).

Genitourinary

UTI (2%); menorrhagia (1%).

Musculoskeletal

Myalgia (7%); arthralgia, back pain (4%).

Respiratory

Upper respiratory tract infection (5%); pharyngitis (3%).

Miscellaneous

Allergy (4%); influenza (3%); influenza-like symptoms (2%); body temperature increase, chest discomfort, chest pain, contusion, exposure to poisonous plant, infection, neck pain (1%).

Precautions

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Recommended immediate-release dose is 5 mg and recommended ER dose is 6.25 mg to decrease possibility of adverse reactions; closely monitor elderly or debilitated patients.

Renal Function

Monitor patient closely.

Hepatic Function

Initiate treatment with 5 mg immediate-release or 6.25 mg ER tablets and closely monitor patient.

Hazardous Tasks

May impair judgment, thinking, or motor skills.

Abrupt discontinuation

Abrupt discontinuation associated with withdrawal symptoms similar to those associated with other CNS depressant drugs.

Abuse/Dependence

Use with caution in patients with history of drug or alcohol abuse, depression, or suicidal tendencies.

Anaphylactic/Anaphylactoid reactions

Rare cases of angioedema involving the larynx, glottis, or tongue have been reported with the first or subsequent doses. Additional symptoms suggesting anaphylaxis have included dyspnea, nausea, throat closing, and vomiting.

CNS effects

A variety of abnormal thinking and behavior changes (eg, decreased inhibition, visual and auditory hallucinations) have been reported to occur in association with use of sedative/hypnotics. Worsening of insomnia or emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder, an adverse reaction of therapy, or spontaneous origin. Emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation.

Complex behavior

Patients driving their car while not fully awake and with no memory of the event has been reported in patients taking sedative/hypnotics.

Concomitant illness

Use with caution in patients with conditions or diseases that could affect metabolism or hemodynamic responses.

Depression

Use with caution in patients exhibiting signs or symptoms of depression; may worsen depression.

Duration of therapy

Generally limit to 7 to 10 days; reevaluate patient if to be taken for more than 2 to 3 wk.

Psychiatric/Physical disorder

Before initiating symptomatic treatment, carefully evaluate patient for psychiatric and/or physical disorders that could cause sleep disturbance.

Respiratory depression

Use with caution in patients with compromised respiratory function.

Suicide

Suicidal tendencies may be present; take protective measures. Prescribe the smallest quantity feasible in order to reduce the risk of overdose.

Overdosage

Symptoms

CV compromise, light coma, respiratory compromise, somnolence.

Patient Information

• Advise patient to read patient information leaflet carefully before starting therapy and to reread and check for new information each time the medication is refilled.
• Review lifestyle changes that may improve sleep (eg, avoidance of caffeine and nicotine, quiet and dark environment, relaxation techniques, warm water bath).
• Advise patient to take prescribed dose immediately before going to bed.
• Advise patient taking ER or orally disintegrating zolpidem not to crush, chew, or break the tablet.
• Advise patient to take on an empty stomach but to take with food if stomach upset occurs.
• Instruct patient receiving orally disintegrating tablet to place tablet in the mouth, where it will dissolve in seconds and then be swallowed with saliva.
• Orally disintegrating tablet may be taken with or without water.
• Caution patient not to take zolpidem unless planning to get 7 to 8 h of sleep before being active again. Advise patient that taking zolpidem with less than 7 to 8 h of sleep may result in daytime drowsiness, amnesia, or memory problems.
• Review safety precautions with regard to falls, especially for elderly and debilitated patients.
• Caution patient that medication may be habit forming and to take as prescribed. Caution patient not to change the dose unless advised by health care provider.
• Advise patient that sleep may be disturbed for 1 or 2 nights following discontinuation of zolpidem therapy.
• Advise patient that if medication needs to be discontinued after 2 or more weeks of nightly use, it will be slowly withdrawn unless safety concerns (eg, rash) require a more rapid withdrawal.
• Instruct patient to avoid alcoholic beverages and other depressants while taking this medication.
• Instruct patient to contact health care provider if sleep problems do not appear to be getting better, are getting worse, or if bothersome adverse reactions (eg, daytime drowsiness, dizziness, incoordination, memory problems, changes in thinking or behavior) occur. Caution patient not to increase the dose if sleep problems do not appear to be improving.
• Advise patient that drug may have a carryover effect the next day and to use extreme care while driving or performing other tasks requiring mental alertness and coordination until tolerance is determined.

Link to Page

Print Page

Email Page

Add to List