Zolpidem tartate

Category:

Sedative-hypnotic

Indications

Insomnia (treatment)—Zolpidem is indicated for short-term treatment of insomnia. A decrease in sleep

latency and increase in the duration of sleep for up to 5 weeks have been demonstrated in controlled clinical
studies with zolpidem. Failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence
of a primary psychiatric or medical illness. Worsening of insomnia or the emergence of new abnormalities of
thinking or behavior may be the consequence of an unrecognized psychiatric or physical disorder.

Onset of action:

Rapid 

Time to peak concentration:

30 minutes to 2 hours ; may be longer if zolpidem is taken with food.

Precautions to Consider

Carcinogenicity/Tumorigenicity

No evidence of carcinogenic potential was observed in mice administered zolpidem in doses of 4, 18, and 80
mg per kg of body weight (mg/kg) per day (26 to 520 times the recommended human dose of 10 mg per day
on a mg/kg basis) for 2 years. In rats administered zolpidem in doses of 4, 18, and 80 mg/kg per day (43 to
876 times the recommended human dose on a mg/kg basis) for 2 years, the incidences of lipoma and
liposarcoma were comparable to those seen in historical controls.

Mutagenicity

Zolpidem showed no evidence of mutagenicity based on unscheduled DNA synthesis in rat hepatocytes in
vitro , the Ames test, or the micronucleus test in mice. Zolpidem showed no evidence of genotoxicity in
mouse lymphoma cells in vitro ; and caused no chromosomal aberrations in cultured human lymphocytes.

Pregnancy/Reproduction
Fertility
In rats given daily oral doses of 4 to 100 mg/kg of zolpidem base (5 to 130 times the recommended human
dose in mg per square meter of body surface area [mg/m 2]), neither male nor female fertility was
affected {01}. However, female rats receiving 100 mg/kg of zolpidem base per day displayed irregular estrus
cycles and prolonged precoital intervals. The significance to humans is not known.

Pregnancy
Zolpidem has not been studied in pregnant women.

No frank teratogenicity was seen in rat and rabbit studies. Rats administered 20 and 100 mg/kg of zolpidem
base (25 to 125 times the recommended human dose in mg/m 2) showed maternal lethargy and ataxia as well
as a dose-related trend toward incomplete ossification of fetal skull bones, which was believed to be
secondary to delayed maturation. Rabbits administered 16 mg/kg of zolpidem base (28 times the
recommended human dose in mg/m 2) showed an increase in postimplantation fetal loss and
underossification of fetal sternebrae. These effects were believed to be secondary to decreased maternal
weight gain.

Postpartum
Studies of children whose mothers received zolpidem during pregnancy have not been conducted. However,
flaccidity and withdrawal symptoms have been reported in neonates born to mothers receiving other
sedative-hypnotics during pregnancy.

Breast-feeding

One study in 5 nursing mothers showed <0.02% of a single oral dose of zolpidem was distributed into breast
milk. The effect of zolpidem on the infant is not known.

Pediatrics

Appropriate studies on the relationship of age to the effects of zolpidem have not been performed in children
up to 18 years of age. Safety and efficacy have not been established.

Geriatrics

Studies have shown zolpidem to have an increased half-life, peak plasma concentration, and area under the
plasma concentration time curve in geriatric patients. Elderly patients may be more likely to experience
confusion or falls while taking zolpidem . A reduced starting dosage and careful monitoring are
recommended. In addition, geriatric patients are more likely to have age-related renal function impairment,
which may require dosage reductions.
Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential
clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive

Note Combinations containing any of the following medications, depending on the amount present, may also
interact with this medication.

 Alcohol or CNS depression–producing medications   (concurrent use may increase the CNS depressant

effects of either these medications or zolpidem; caution is recommended, and dosage of one or both agents
should be reduced)

Chlorpromazine    (concurrent use may prolong elimination half-life of chlorpromazine)

Imipramine    (concurrent use may increase drowsiness and incidence of anterograde amnesia, and decrease
peak concentrations of imipramine )

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential
clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive.

Risk-benefit should be considered when the following medical problems exist

 Alcohol intoxication, acute, with depressed vital signs    (additive CNS depression may occur)

Alcohol or drug abuse or dependence, history of    (predisposition to habituation and dependence may exist)

Hepatic function impairment    (zolpidem elimination may be prolonged due to biphasic elimination with

prolonged terminal half-life)

Mental depression  (condition may be exacerbated)

Pulmonary disease, severe chronic obstructive (ventilatory failure may be exacerbated)

Renal function impairment    (zolpidem elimination may be prolonged)

Sensitivity to zolpidem
Sleep apnea, established or suspected    (condition may be exacerbated )
Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance
(possible signs and symptoms in parentheses where appropriate) not necessarily inclusive.

Those indicating need for medical attention

Incidence less frequent
    
Ataxia (clumsiness or unsteadiness)
    
confusion—higher incidence in the elderly
    
mental depression

Incidence rare
    
Allergic reaction or rash}
    
anaphylaxis (fast heartbeat; swelling of face; wheezing or difficulty in breathing)
    
falling—higher incidence in the elderly
    
hypotension (dizziness, lightheadedness, or fainting)
    
paradoxical reactions, including agitation (unusual excitement or nervousness), or irritability
hallucinations (seeing, hearing, or feeling things that are not there), or insomnia (trouble in sleeping)

Clinical effects of overdose

The following effects have been selected on the basis of their potential clinical significance (possible signs and
symptoms in parentheses where appropriate)—not necessarily inclusive:
    
Ataxia, severe (clumsiness or unsteadiness)
    
cardiovascular compromise (slow heartbeat)
    
diplopia (double vision), or disturbed vision
    
dizziness, severe
    
drowsiness, severe
    
nausea, severe
    
respiratory problems (troubled breathing)
    
unconsciousness
    
vomiting, severe
Treatment of overdose
Treatment is essentially symptomatic and supportive, possibly including:

To decrease absorption:
Inducing emesis or performing gastric lavage  as appropriate.

To enhance elimination:
Administering activated charcoal to increase clearance and decrease absorption of zolpidem.

Zolpidem is not dialyzable.

Specific treatment:
Withholding sedating drugs even if excitation occurs.

Flumazenil may be useful in reversing zolpidem's sedative and respiratory depressant effects.