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>I wish I had more info on Ambien (Zolpidem). zolpidem / Ambien(R) SEDATIVE / Sleeping Description: Zolpidem tartrate is a non-benzodiazepine sedative-hypnotic fo= r the short-term treatment of insomnia. Although chemically unrelated to othe= r hypnotics such as the benzodiazepines or barbiturates, zolpidem does share some pharmacological actions with these drugs. Unlike the benzodiazepines, zolpidem produces muscle relaxation and anticonvulsant effects only at dose= s much higher than the hypnotic dose. Zolpidem has a short half-life and no active metabolites. This reduces the possibility of residual next-day effects from excessive sedation, and CNS depression with impairment of cognitive and motor function, commonly seen with barbiturates or long-actin= g benzodiazepines in the treatment for insomnia. A next-day "hangover" effect and CNS depression are less for zolpidem than the barbiturates. Zolpidem ha= s a rapid onset of action and should only be taken immediately before retiring. Treatment of insomnia with zolpidem should be restricted to a period of 7-10 days. Rebound insomnia or signs of withdrawal have not been significantly greater than placebo after discontinuation of treatment when zolpidem was administered at the recommended dose of 10 mg. Zolpidem received FDA approval in 1993. Mechanism of Action: Zolpidem tartrate is highly specific for the gamma-aminobutyric acid (GABA)-chloride channel complex within type 1 benzodiazepine receptors in the CNS. Benzodiazepines, in contrast, bind als= o to type 2 and peripheral type 3 benzodiazepine receptors. The selectivity o= f zolpidem for the type 1 receptor may explain its lack of muscle relaxant, anticonvulsant, and anxiolytic effects, relative to the benzodiazepines. Zolpidem induces sedation by modulation of the actions of GABA. The site of action is located within the GABA-A receptor complex on the =F0 subunit, whic= h is known as the benzodiazepine (BZ) or omega receptor. The omega receptor can be subdivided into at least three types, and the omega-1 receptor has been identified as the site of action of zolpidem. Flumazenil, a benzodiazepine antagonist, can also antagonize the sedative actions of zolpidem. Zolpidem appears to modestly reduce time spent in REM sleep, however, no conclusions can be made regarding the dose-response nature of this effect.=A5 Nonspecific modulation of the GABA-A receptor chloride channel macromolecular complex are thought to be responsible for sedative, anticonvulsant, anxiolytic, and myorelaxant properties. GABA mediates the inhibitory actions of local interneurons in the brain. Inhibition of the GABA-ergic pathways may be partially responsible for reduced muscle hypertonia and spread of seizure activity. Pharmacokinetics: Zolpidem is administered orally and is rapidly absorbed from the GI tract. The presence of food reduces the amount of absorption an= d increases the time taken to achieve maximum concentration, delaying sleep onset slightly. Zolpidem pharmacokinetics follow a linear profile in the dosage range 5-20 mg. Pharmacokinetic parameters in patients with end-stage renal failure undergoing hemodialysis, are not significantly different from healthy patients. Zolpidem is about 92% bound to plasma protein. Metabolism produces inactive metabolites that are primarily excreted in the urine. The elimination half-life is about 2.6 hours in patients with normal hepatic and renal function. The mean half-life in healthy patients is 2.2 hours, increased to 2.9 hours in elderly patients and to 9.9 hours for thos= e with chronic hepatic impairment, allowing use of reduced dosage in the elderly and hepatically impaired. Zolpidem is not removed by hemodialysis. Patients with hepatic insufficiency do not clear the drug as rapidly as normals. CONTRAINDICATIONS/PRECAUTIONS: Zolpidem is only recommended for use in the short-term treatment of insomnia. Problems associated with abrupt discontinuation of hypnotic drugs are more likely to occur following chronic therapy. There is no reliable data documenting the occurrence of withdrawal symptoms following discontinuation of zolpidem, but evidence of fatigue, nausea/vomiting, flushing, lightheadedness, inconsolable crying, stomach cramps, panic attack, nervousness, and abdominal discomfort may constitute a withdrawal syndrome. Withdrawal of some hypnotics also precipitates a rebound insomnia= . If therapy is continued for more than 2 weeks the possibility of a withdrawal syndrome should be considered and abrupt discontinuation of therapy avoided. The possibility of physical and psychological dependence t= o zolpidem requires close monitoring. Zolpidem should be used cautiously in patients with a history of substance abuse. Sleep disturbance may indicate an underlying physical or psychiatric problem. Thus, zolpidem should be used cautiously in patients with major depression. These patients may become more susceptible to suicidal ideation= . Elderly and/or debilitated patients may be more sensitive to the effects of zolpidem. The impairment of cognitive and motor function may be more marked in this patient group and lower initial dosage is recommended together with close monitoring. Zolpidem should be administered cautiously to patients with severe hepatic disease because the elimination half-life of the drug can be prolonged, wit= h possible resultant toxicity. Patients with hepatic disease should receive a lower initial dosage to avoid adverse CNS reactions. Zolpidem is classified as pregnancy category B. Animal studies have shown n= o evidence of teratogenicity. However lack of information on the effects of zolpidem in pregnant women precludes its use unless clearly needed. There i= s some risk that babies born to mothers taking sedatives may suffer withdrawa= l symptoms and possible neonatal flaccidity. Small amounts of zolpidem are excreted into breast milk. Since the effects on the infant have not been evaluated, the use of zolpidem in breast-feeding women is not recommended. Safe use of zolpidem in children under age 18 years has not been evaluated. Zolpidem should be used with caution in patients with pre-existing respiratory depression, pulmonary disease such as severe COPD (chronic obstructive pulmonary disease), or sleep apnea to avoid the risk of depressing ventilatory function. Although evidence to date does not indicate any need to use lower doses of zolpidem in patients with renal disease, chronic renal impairment may reduc= e clearance of zolpidem. These patients should be closely monitored for drug accumulation and changes in pharmacokinetic parameters. DRUG INTERACTIONS: Evidence of drug interactions between zolpidem and other CNS agents is limited. Some single-dose interactions have been studied but reactions may differ during chronic therapy. Single-dose results indicate that haloperido= l has no effect on the pharmacokinetics or pharmacodynamics of zolpidem. Ethanol has an additive effect on psychomotor performance when given with zolpidem. Other CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with zolpidem. Zolpidem reduced peak serum concentrations of imipramine by 20%, but other pharmacokinetic parameters were not affected. Loss of alertness was exacerbated when the drugs were administered concurrently. Interactions wit= h other tricyclic antidepressants have not been studied, but additive drowsiness is also possible. Chlorpromazine and zolpidem together produced no change in pharmacokinetic parameters, but had an additive effect on loss of mental alertness and psychomotor function. Concurrent use of zolpidem with chlorpromazine or other phenothiazines should be undertaken with caution. Flumazenil, a benzodiazepine antagonist, can reverse the sedative/hypnotic effects of zolpidem. Flumazenil and zolpidem are pharmacological opposites. Thus, this represents a pharmacodynamic interaction and not a pharmacokinetic one. Some studies of possible interaction between zolpidem and other drugs have been undertaken. Cimetidine or ranitidine did not affect the pharmacokinetics or pharmacodynamics of zolpidem. Concurrent use of digoxin showed no effect on the pharmacokinetics of digoxin or zolpidem. Concurrent use of zolpidem with warfarin did not affect prothrombin time. Long term studies have not been undertaken and concurrent use of any drug during chronic therapy may produce different results. ADVERSE REACTIONS: Most of the adverse effects associated with zolpidem therapy are dose-dependent and CNS-related. The most frequently reported are headache, drowsiness, dizziness, amnesia, lethargy and a drugged feeling, although in one study of elderly volunteers, headache was reported by equal numbers of subjects taking placebo as those taking 20 mg doses of zolpidem.=A5 According to the manufacturer, the incidence of headache, dizziness, drowsiness, and diarrhea were greater for zolpidem (short-term treatment with up to 10 mg/day) as compared to placebo. During long-term (28-35 nights) treatment with doses up to 10 mg/day, the only adverse effects that were significantl= y different from placebo were dizziness and drugged feelings. Symptoms of CNS stimulation including euphoria, hallucination, agitation, nightmares and hyperactivity are paradoxical effects that can occur with zolpidem therapy. If there is evidence of CNS stimulation zolpidem should be discontinued. Gastrointestinal adverse events resulting from zolpidem use also appear to be dose related, most commonly observed were diarrhea and nausea/vomiting. Dyspepsia and constipation have been reported. Sedatives and hypnotics have been implicated in producing signs of withdrawal following abrupt discontinuation of treatment. Reliable determinations regarding possible drug dependancy on zolpidem have not been undertaken. There is some evidence that symptoms of fatigue, nausea/vomiting, flushing, lightheadedness, inconsolable crying, stomach cramps, panic attack, nervousness, and abdominal discomfort that may constitute a withdrawal syndrome. Drug dependency may be related to dosage and duration of treatment. A dosage-tapering schedule may be adopted if dru= g dependency is suspected. Withdrawal of some hypnotics can precipitate a rebound insomnia and elderly patients may be more susceptible to sleep impairment following discontinuation of therapy, especially at doses above = 5 mg of zolpidem. PATIENT INFORMATION: What do zolpidem tablets do? ZOLPIDEM (Ambien(R)) helps to relieve insomnia (sleeplessness) which can be= : trouble falling asleep, waking up too early in the morning, or waking up to= o often during the night. Zolpidem helps people with temporary sleep problems and should not be taken for long periods, except on your doctor's advice. Zolpidem belongs to a group of medicines known as sedatives/hypnotics. Federal law prohibits the transfer of zolpidem to any person other than the patient for whom it was prescribed. Do not share your medicine with anyone else. Generic zolpidem tablets are not yet available. What should my doctor, dentist, or pharmacist know before I take zolpidem? They need to know if you have any of these conditions: *an alcohol or drug abuse problem *liver disease *lung or respiratory disease (breathing difficulties) *mental depression *an unusual or allergic reaction to zolpidem, other medicines, foods, dyes, or preservatives *breast-feeding How should I take this medicine? Take zolpidem tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. It is better to take zolpidem on an empty stomach (without food) and only when you are ready for bed. Do not take your medicine more often than directed. Special precautions for use in children: This medicine is not for children under 18 years old. Elderly patients over age 65 years may have a stronger reaction to this medicine and need smaller doses. What if I miss a dose? This does not apply. Zolpidem should only be taken immediately before getting into bed (or in bed). Do not take double or extra doses. What other medicines can interact with zolpidem? *alcohol *flumazenil Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines. What side effects may I notice from taking zolpidem? Serious side effects with zolpidem include: *lightheadedness or fainting spells *confusion *hallucinations (seeing, hearing, or feeling things that are not really there) *mental depression *slurred speech *unusual weakness *staggering, tremors *blurred vision *hostility, restlessness, excitability Call your doctor as soon as you can if you get any of these side effects. Minor side effects with zolpidem include: *dizziness, drowsiness "hangover" effect *nightmares *stomach upset *diarrhea *loss of memory Let your doctor know about these side effects if they do not go away or if they annoy you. What do I need to watch for while I take zolpidem? Visit your doctor for regular checks on your progress. If sleep medicine is taken every night for a long time it may no longer help you to sleep. In most cases zolpidem should only be taken for a few days and for not longer than 1 or 2 weeks. Consult your doctor if you still have difficulty in sleeping. If you have been taking zolpidem regularly and suddenly stop taking it, you may get unpleasant withdrawal symptoms. Your doctor may want to gradually reduce the dose. Do not stop taking except on your doctor's advice. After you stop taking zolpidem you may get rebound insomnia. This means that for a few nights you may have trouble sleeping, but this usually goes away after 1 or 2 nights. You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how zolpidem affects you. To reduce dizzy or fainting spells, do not sit or stand up quickly, especially if you are an older patient. Alcohol can increase possible unpleasant effects. Avoid alcoholic drinks. If you are going to have surgery, tell your doctor or dentist that you are taking zolpidem. Ronald Vetter 1936, dz PD 1984, carbidopa/levodopa, Mirapex, selegiline [log in to unmask] Ridgecrest, California http://www.ridgecrest.ca.us/~rfvetter