Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

ZOLPIDEM

NFPA

PRODUCT USE

Hypnotic; selective benzodiazepine receptor agonist not related chemically to the
benzodiazepines. Controlled substance. Subunit modulation of the GABAa receptor chloride
channel macromolecular complex is thought to be responsible for the sedative,
anticonvulsive anxiolytic and myorelaxant properties of certain drugs. The major
modulatory site of the GABAa receptor complex is located on its alpha subunit and is
referred to as the benzodiazepine (BZ) or omega receptor. At least three subtypes of the
omega receptor have been identified. Zolpidem interacts with this receptor and shares some
of the pharmacological properties of benzodiazepines. In contrast to the benzodiazepines,
which bind non- selectively to and activate all three omega receptor subtypes zolpidem, in
vitro, binds preferentially, although not absolutely, to the omega 1 subtype. Selective
binding may explain the relative absence of myorelaxant and anticonvulsant effects in
animal studies as well as preservation of deep sleep in human studies when zolpidem is
given at hypnotic doses. WARNING: Exposed individuals should be warned against engaging in
duties which involve metal alertness or motor coordination such as operating machinery or
driving a motor vehicle.

SYNONYMS

C38-H42-N6-O2, "imidazo[1, 2-a]pyridine-3-acetamide, N, N, 6-trimethyl-2-(4-
methylphenyl)-, ", "imidazo[1, 2-a]pyridine-3-acetamide, N, N, 6-trimethyl-2-(4-
methylphenyl)-, ", "N, N, 6-trimethyl-2-(4-methylphenyl)imidazo[1, 2-a]pyridine-3-
acetamide", "N, N, 6-trimethyl-2-(4-methylphenyl)imidazo[1, 2-a]pyridine-3-acetamide", "N,
N, 6-trimethyl-2-p-tolylimidazo[1, 2-a]pyridine-3-acetamide", "N, N, 6-trimethyl-2-p-
tolylimidazo[1, 2-a]pyridine-3-acetamide", SL-80.0750, "hypnotic/ tranquiliser/
antidepressant/ anxiolytic"

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

None

EMERGENCY OVERVIEW

RISK

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  Accidental ingestion of the material may be damaging to the health of the individual.  Central nervous system (CNS) depression may include general discomfort, symptoms of giddiness, headache, dizziness, nausea, anaesthetic effects, slowed reaction time, slurred speech and may progress to unconsciousness. Serious poisonings may result in respiratory depression and may be fatal.  Persons exposed to this material at work are liable to the same side effects as those taking this material in supervised conditions. Persons with a psychiatric history taking drugs should be monitored carefully as they are more prone to dependence and addiction. Side effects of sleeping medication include drowsiness, dizziness, light-headedness and inco-ordination and alcohol can increase them. Drug dependency can occur after a few weeks of nightly administration. Withdrawal of the drug is associated with a range of unpleasant effects and severity; it can also cause rebound insomnia where the symptoms are worse than before. Rarely, behavior changes may follow administration of sleeping drugs. If used late in pregnancy it can sedate the fetus.  

EYE

  Although the material is not thought to be an irritant, direct contact with the eye may cause transient discomfort characterized by tearing or conjunctival redness (as with windburn). Slight abrasive damage may also result. The material may produce foreign body irritation in certain individuals.  

SKIN

  The material is not thought to produce adverse health effects or skin irritation following contact (as classified using animal models). Nevertheless, good hygiene practice requires that exposure be kept to a minimum and that suitable gloves be used in an occupational setting.  Entry into the blood-stream, through, for example, cuts, abrasions or lesions, may produce systemic injury with harmful effects. Examine the skin prior to the use of the material and ensure that any external damage is suitably protected.  

INHALED

  Inhalation may produce health damage*.  Inhalation of dusts, generated by the material during the course of normal handling, may be damaging to the health of the individual.  The material is not thought to produce respiratory irritation (as classified using animal models). Nevertheless inhalation of dusts, or fume, especially for prolonged periods, may produce respiratory discomfort and occasionally, distress.  Persons exposed to this material at work are liable to the same side effects as those taking this material in supervised conditions. Persons with a psychiatric history taking drugs should be monitored carefully as they are more prone to dependence and addiction. Side effects of sleeping medication include drowsiness, dizziness, light-headedness and inco-ordination and alcohol can increase them. Drug dependency can occur after a few weeks of nightly administration. Withdrawal of the drug is associated with a range of unpleasant effects and severity; it can also cause rebound insomnia where the symptoms are worse than before. Rarely, behavior changes may follow administration of sleeping drugs. If used late in pregnancy it can sedate the fetus.  

CHRONIC HEALTH EFFECTS

  Long term exposure to high dust concentrations may cause changes in lung function i.e. pneumoconiosis; caused by particles less than 0.5 micron penetrating and remaining in the lung. Prime symptom is breathlessness; lung shadows show on X-ray.  There is limited evidence that, skin contact with this product is more likely to cause a sensitization reaction in some persons compared to the general population.  Based on experience with animal studies, there is a possibility that exposure to the material may result in toxic effects to the development of the fetus, at levels which do not cause significant toxic effects to the mother.  Babies born to mothers taking sedatives/hypnotics may show withdrawal symptoms from the drug in the weeks after birth. Loss of muscle tone in these babies has also been noted.  In rats receiving up to 115 times the maximum human dose (mg/kg basis)  for 2 years, renal liposarcomas were seen in 4 of 100 rats receiving the  highest dose rate and a renal lipoma was seen in one male rat receiving  18 mg/kg/day. Incidences for lipoma and liposarcoma were comparable in  those seen in historical controls and tumour findings were thought to be  a spontaneous occurrence. Treated mice receiving doses up to 520 times the  maximum human dose (on a mg/kg basis) showed no evidence of carcinogenic  activity. Zolpidem did not exhibit mutagenicity in the Ames test,  genotoxicity in mouse lymphoma cells in vitro, chromosomal aberrations in  cultured human lymphocytes, unscheduled DNA synthesis in rat hepatocytes  in vivo, and the micronucleus test in mice.  In a rat reproduction study the highest dose (100 mg base/ kg) produced  irregular oestrus cycles and prolonged precoital intervals but there was  no effect on male or female fertility after daily doses of 4 to 100 mg/kg  (5 to 130 times the maximum recommended human dose (mg/m2)).  Teratology studies with rats receiving 20 to 100 mg/kg base/kg showed  adverse maternal and foetal effects. Underossification of foetal bones  indicated a delay in maturation and is often seen in rats treated with  sedative/ hypnotic drugs. There were no teratogenic effects after  zolpidem administration. The no-effect dose for maternal and foetal  toxicity was 4 mg/kg base or 5 times the maximum human dose (mg/m2 basis).  In rabbits, dose-related maternal sedation and decreased weight gain  occurred at all doses tested. At the high dose (16 mg/base/kg) there was  an increase in postimplantation foetal loss and underossification of  sternebrae in viable foetuses. Foetal findings in rabbits were often  secondary to reduction in maternal body weight gain. There were no frank  teratogenic effects. The no-effect dose for foetal toxicity was  4 mg base/mg (7 times the maximum human dose on a mg/m3 basis).  In a rat study, zolpidem inhibited the secretion of milk in lactating  mothers. The no-effect dose was the 6 times the recommended dose (in  mg/m3).