Zolpidem tartrate

457.48

764.353333

200-659-6

2933996500

152.67000

1.12620

196 °C

48.2 °F

Solubility in water (20 °C): 23 mg/ml

2-8°C

pKa = 6.2 /Zolpidem/

White to off-white crystalline powder that is sparingly soluble in alcohol and propylene glycol /Tartrate/

UN1230 - class 3 - PG 2 - Methanol, solution

36/37/38-39/23/24/25-23/24/25-11

26-36-45-36/37-16-7

Xi,T,F

P210-P260-P280-P301 + P310-P311

H225-H301 + H311 + H331-H370

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Schedule IV includes zolpidem, DEA Code #2783; Drug class: depressants.|The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl zolpidem tartrate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H302 (99.05%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P273, P301+P312, P330, P391, and P501|Aggregated GHS information provided by 105 companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chlorpromazine, haloperidol, imipramine, & cimetidine have little effect on zolpidem toxicokinetics, although potentiation of the sedative effect of zolpidem was observed when it was given in combination with chlorpromazine & imipramine. No pharmacodynamic interactions have been observed with concomitant admin of cimetidine or ranitidine. /Salt not specified/|This study was undertaken to determine whether there are pharmacokinetic (PK) interactions between zolpidem, a hypnotic, & sertraline, an antidepressant. 28 healthy female volunteers received a single dose of zolpidem alone & 5 consecutive dose(s) of zolpidem 10 mg in the presence of chronic doses (19 days) of sertraline 50 mg. Using HPLC, plasma levels of zolpidem, sertraline, & N-desmethylsertraline were determined at different times throughout the study & PK parameters derived. Compared to zolpidem alone, the /half life/ of the first dose of zolpidem in the presence of sertraline was reduced, the Cmax of the fifth zolpidem dose in the presence of sertraline was significantly increased, & its Tmax was significantly reduced. After 5 doses of zolpidem, the AUC of sertraline (-60%) & the Cmax of N-desmethylsertraline (+13%) were changed. There were no next-day effects of zolpidem on the Digit Symbol Substitution Test, & both drugs were well tolerated. Overall, coadministration of sertraline 50 mg & zolpidem 10 mg appears to be safe in healthy females but could result in a shortened onset of action & increased effect of zolpidem. /Salt not specified/|... The inhibitory effect of ritonavir on the biotransformation of the hypnotic agents triazolam & zolpidem was tested in vitro using human liver microsomes. In a double-blind clinical study, volunteer study subjects received 0.125 mg triazolam or 5.0 mg zolpidem concurrent with low-dose ritonavir (4 doses of 200 mg), or with placebo. ... Ritonavir was a potent in vitro inhibitor of triazolam hydroxylation but was less potent as an inhibitor of zolpidem hydroxylation. In the clinical study, ritonavir reduced triazolam clearance to <4% of control values (p<.005), prolonged elimination half-life (41 versus 3 hrs; p<.005), & magnified benzodiazepine agonist effects such as sedation & performance impairment. In contrast, ritonavir reduced zolpidem clearance to 78% of control values (p<.08), & slightly prolonged elimination half-life (2.4 versus 2.0 hrs; NS). Benzodiazepine agonist effects of zolpidem were not altered by ritonavir. ... Short-term low-dose admin of ritonavir produces a large & significant impairment of triazolam clearance & enhancement of clinical effects. In contrast, ritonavir produced small & clinically unimportant reductions in zolpidem clearance. The findings are consistent with the complete dependence of triazolam clearance on CYP3A activity, compared with the partial dependence of zolpidem clearance on CYP3A. /Salt not specified/|The objective was to evaluate possible pharmacokinetic & pharmacodynamic interactions for repeated nightly zolpidem dosing with fluoxetine. 29 healthy female volunteers (mean age, 25.6 yrs) received zolpidem (10 mg) & fluoxetine (20 mg) in the following open design: zolpidem on night 1 followed by 1 washout day, a daily morning dose of fluoxetine on days 3-27, & a morning dose of fluoxetine plus an evening dose of zolpidem on days 28-32. Plasma levels of zolpidem, fluoxetine, & norfluoxetine were determined at the transitions from one regimen to the next. Morning psychomotor tests were performed on days 1, 2, 28, 29, & 33. Steady-state plasma concns of fluoxetine/norfluoxetine were reached by day 24 of fluoxetine dosing. No significant differences in any pharmacokinetic parameters for fluoxetine & norfluoxetine were observed between day 27 & day 32. There were no significant differences in AUC, maximal plasma concn, or time to maximal concn parameters for zolpidem plasma concns among nights 1, 28, & 32. There was a statistically significantly increased /half life/ for zolpidem on night 32, compared with night 28 (3.64 & 3.29 hr, respectively). There were no significant differences in the next-morning Digit Symbol Substitution Test performance at any time in the study. Both zolpidem & fluoxetine were well tolerated alone or during coadministration. These findings indicate the absence of clinically significant pharmacokinetic or pharmacodynamic interactions between fluoxetine & zolpidem (5 consecutive doses) when the drugs are coadministered to healthy women. Therefore, based on these observations, short-term cotherapy with fluoxetine (20 mg) & zolpidem (10 mg) appears safe. /Salt not specified/|For more Interactions (Complete) data for ZOLPIDEM TARTRATE (14 total), please visit the HSDB record page.

The excretion of zolpidem in breast milk represents 0.004 to 0.019% of an admin dose. /Salt not specified/

This report describes two cases of acute zolpidem overdose. The decedent in the first case was a 36-yr-old female .... zolpidem concns: blood (subclavian), 4.5 mg/l; blood (iliac), 7.7 mg/l; vitreous humor, 1.6 mg/l; bile, 8.9 mg/l; urine, 1.2 mg/l; liver, 22.6 mg/kg; & gastric contents, 42 mg. The second case involved a 58-yr old female, also found dead ... Zolpidem concns were as follows: blood (iliac), 1.6 mg/l; vitreous humor, 0.52 mg/l; bile, 2.6 mg/l; liver, 12 mg/kg; & gastric contents, 0.9 mg. The zolpidem blood concns of these cases are consistent with those of the previously published fatalities. The blood/vitreous humor ratios of zolpidem were 2.81 (subclavian) & 4.81 (iliac) in the first case & 3.08 (iliac) in the second case. ... /Salt not specified/

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. /Included in US product labeling/ /Salt not specified/|Selective benzodiazepine receptor agonist not related chemically to benzodiazepines; sedative; hypnotic. /Salt not specified/|... A case of antipsychotic-induced parkinsonism that was managed with zolpidem /was reported/. ... A 34-yr-old white man who had had antipsychotic-induced parkinsonism with symptoms of repetitive persistent gross tremors of the hands for numerous years was unresponsive to traditional antiparkinsonian medications. With the initiation of zolpidem ... the tremors decreased significantly. ... When zolpidem was started ..., the motor exam score on the Unified Parkinson's Disease Rating Scale decreased from 29 at baseline to a score of 9 after one month of use. After 4 months of zolpidem use, the patient's mental status decompensated, & clozapine was initiated. As the patient experienced excessive sedation, zolpidem was discontinued while clozapine was maintained to help with the psychosis &, potentially, the tremors. The tremors reemerged with a motor exam score of 30. Zolpidem was reinitiated ..., & the patient's tremors have been stable for 2 years. ... Further investigation is needed to study the use of nontraditional medications in patients requiring ...antipsychotic medication who have refractory parkinsonian symptoms. /Salt not specified/|1. A new imidazo-pyridine hypnotic (zolpidem 10 mg and 20 mg) was compared with placebo as premedication before general anaesthesia in female patients undergoing minor gynaecological surgery. Efficacy and tolerance before and after anaesthesia were assessed. Psychomotor testing was used to study recovery from anaesthesia. 2 Both doses of zolpidem produced good sedation pre-operatively but only the higher dose was associated with anterograde amnesia. 3 Premorbid anxiety scores were low in the group of patients studied and were unaffected by either dose of zolpidem. 4 There were no significant effects on the course of anaesthesia. However, postoperatively there was a tendency for wake-up to be delayed in those patients who received either dose of zolpidem. 5 Postoperative recovery, as indicated by tests of psychomotor performance, was noticeably delayed with a dose of 20 mg compared with placebo whilst psychomotor performance had returned towards baseline levels 3 h after wake-up in those patients who had received placebo. The zolpidem 10 mg group was intermediate. 6 Zolpidem may be a suitable premedicant when hypnosis and amnesia only are required. /Salt not specified/|For more Therapeutic Uses (Complete) data for ZOLPIDEM TARTRATE (8 total), please visit the HSDB record page.

Its half-life in plasma is approx 2 hr in individuals with normal hepatic blood flow or function. This value may be increased twofold or more in those with cirrhosis, & it also tends to be greater in older patients; adjustment of dosage often is necessary in both categories of patients. ... The elimination of the drug is slower in patients with chronic renal insufficiency, largely owing to an incr in its apparent volume of distribution. /Salt not specified/|Headache, drowsiness, and dizziness were the most frequent adverse nervous system effects of zolpidem during short-term (up to 10 days) treatment or prolonged therapy (45 weeks) with the drug at recommended doses in clinical trials, and among the most frequent adverse effects requiring discontinuance of the drug. Headache occurred in 7% of patients receiving short-term (up to 10 days) treatment with zolpidem at recommended doses and 6% of those receiving placebo, and in 19% of those receiving prolonged therapy (45 weeks) with the drug at recommended doses and 22% of those receiving placebo. ... Drowsiness occurred in 2% of patients receiving short-term (up to 10 days) treatment with zolpidem at recommended doses, in 8% of patients receiving prolonged therapy (45 weeks) with the drug at recommended doses, and in 5% of those receiving placebo. ... Dizziness occurred in 1% of patients receiving short-term (up to 10 days) treatment with zolpidem at recommended doses, in 5% of patients receiving prolonged therapy (45 weeks) with the drug at recommended doses, and in 1% of those receiving placebo. /Salt not specified/|Diarrhea was one of the most frequent adverse effects of short-term (up to 10 days) treatment with zolpidem at recommended doses in clinical trials, occurring in 1% of patients. Diarrhea occurred in 3% of patients receiving prolonged therapy (4-5 weeks) with zolpidem at recommended doses in clinical trials and in 2% of those receiving placebo. Nausea occurred in 2 and 6% of patients receiving short-term (up to 10 days) treatment or prolonged therapy (4-5 weeks), respectively, with zolpidem at recommended doses in clinical trials, and in 3 and 6%, respectively, of those receiving placebo. Dry mouth occurred in 3% of patients receiving prolonged therapy (4-5 weeks) with zolpidem at recommended doses in clinical trials and in 1% of those receiving placebo. ... Vomiting occurred in 1% of patients receiving prolonged therapy (4-5 weeks) with zolpidem at recommended doses in clinical trials, the same frequency as in those receiving placebo ... /Salt not specified/|Palpitation was reported in 2% of patients receiving prolonged therapy (4-5 weeks) with zolpidem at recommended doses in clinical trials. Cerebrovascular disorder, hypertension, postural hypotension, edema, chest pain, syncope, and tachycardia have been reported in 0.1-1% of patients, and arrhythmia, ventricular tachycardia, extrasystoles, arteritis, circulatory failure, hypotension, flushing, aggravated hypertension, angina pectoris, myocardial infarction, phlebitis, pulmonary embolism, pulmonary or facial edema, and varicose veins have been reported in <0.1% of patients receiving zolpidem. /Salt not specified/|For more Drug Warnings (Complete) data for ZOLPIDEM TARTRATE (16 total), please visit the HSDB record page.

Endogenous compounds and drugs that bind to and activate GABA-A RECEPTORS. (See all compounds classified as GABA-A Receptor Agonists.)|Drugs used to induce SLEEP, prevent SLEEPLESSNESS, or treat SLEEP INITIATION AND MAINTENANCE DISORDERS. (See all compounds classified as Sleep Aids, Pharmaceutical.)

A peak blood level of 200 ng/mL was reached 30 min after oral admin of 20 mg zolpidem. After oral admin zolpidem is rapidly & completely absorbed from the GI tract. Although some first-pass biotransformation of the drug results in a bioavailability of about 70%, after doses of 7-20 mg, zolpidem is 92% bound to plasma proteins. The apparent volume of distribution after a 5 mg iv dose was 0.5 L/kg. Brain concns reach one third to one half of those achieved in the plasma. Zolpidem is completely metabolized. <1% of an admin dose is excreted unchanged in the urine. Three metabolites have been identified but have no pharmacologic activity after an 8 mg iv dose. Systemic clearance of zolpidem was 0.26 L/kg/g & the elimination half-life was 1.5 hr. /Salt not specified/|The excretion of zolpidem in breast milk represents 0.004 to 0.019% of an admin dose. /Salt not specified/|Zolpidem is eliminated almost entirely by conversion to inactive products in the liver, largely through oxidation of the methyl groups on the phenyl & imidazopyridine rings to the corresponding carboxylic acids. Its half-life in plasma is approx 2 hr in individuals with normal hepatic blood flow or function. This value may be increased twofold or more in those with cirrhosis, & it also tends to be greater in older patients; adjustment of dosage often is necessary in both categories of patients. Although little or no unchanged zolpidem is found in the urine, the elimination of the drug is slower in patients with chronic renal insufficiency, largely owing to an incr in its apparent volume of distribution. /Salt not specified/|Solid dispersions & physical mixtures of Zolpidem in polyethylene glycol 4000 (PEG 4000) & 6000 (PEG 6000) were prepared with the aim to incr its aqueous solubility. ... Physical determinations/revealed/ no drug-polymer interactions ... Both solubility & dissolution rate of the drug in these formulations were increased. Each individual dissolution profile of PEG based formulation fitted Baker-Lonsdale & first order kinetic models. Finally, significant differences in ataxic induction time were observed between Zolpidem orally administered as suspension of drug alone & as solid dispersion or physical mixture. These formulations, indeed, showed almost 2- to 3-fold longer ataxic induction times suggesting that, in the presence of PEG, the intestinal membrane permeability is probably the rate-limiting factor of the absorption process. /Salt not specified/|For more Absorption, Distribution and Excretion (Complete) data for ZOLPIDEM TARTRATE (6 total), please visit the HSDB record page.

... Zopiclone & zolpidem are used primarily as hypnotics. Both are extensively metabolized; N-demethylation, N-oxidation, & decarboxylation of zopiclone occur, & zolpidem undergoes oxidation of methyl groups & hydroxylation of a position on the imidazolepyridine ring system. ... Since CYP3A4 has been reported to play an important role in metab of zolpidem, possible interactions with drugs which are substrates &/or inhibitors of that CYP isozyme should be considered. /Salt not specified/

Its half-life in plasma is approx 2 hr in individuals with normal hepatic blood flow or function. This value may be increased twofold or more in those with cirrhosis, & it also tends to be greater in older patients ... . /Salt not specified/|Nursing mothers: Studies in lactating mothers indicate that the half-life of zolpidem is similar to that in young normal volunteers (2.6 + or - 0.3 hr). /Salt not specified/|Carvedilol ... has a terminal half-life of 7-10 hr, but most of the drug is eliminated with a half-life of about 2 hr.

Imidazopyridines are thought to interact with the same GABA receptor/chloride channel complex as the benzodiazepines by high affinity with the "central-type" benzodiazepine receptors. Like the benzodiazepine hypnotic drugs, zolpidem appears to potentiate GABAergic transmission, thus increasing the frequency of chloride channel opening, resulting in the inhibition of neuronal excitation. Zolpidem appears to cause only sedation, but is devoid of significant myorelaxant, anxiolytic, & anticonvulsant activity. It also appears to be free of monoaminergic & histaminergic activity. Benzodiazepines exert both their clinical & side effects through nonselective interaction with a family of benzodiazepine recognition sites on neuronal membranes. One of these sites, the so-called benzodiazepine or omega site, appears to mediate sedation, whereas other sites may mediate anticonvulsant anxiolytic & other effects. Zolpidem appears to be relatively selective for the omega site. /Salt not specified/|Mutagenesis: Zolpidem did not have mutagenic activity in several tests including the Ames test, genotoxicity in mouse lymphoma cells in vitro, chromosomal aberrations in cultured human lymphocytes, unscheduled DNA synthesis in rat hepatocytes in vitro, and the micronucleus test in mice. /Salt not specified/|... Whereas in the recommended dose range zolpidem almost exclusively binds to the alpha(1) subunit of the GABA(A) receptor associated with sleep promotion, in higher doses it also binds the alpha(2), alpha(3) & alpha(5) subunits typically targeted by benzodiazepines & associated with anxiolytic effects. ... /Salt not specified/

Treatment should be largely symptomatic & supportive, similar to that following a benzodiazepine overdose. ... Tracheal protection must be provided. Activated charcoal was used in one patient, but there are no systematic studies supporting its use. Extracorporeal methods of treatment (hemodialysis, hemoperfusion) would probably not be useful in the clinical setting (high protein binding, rapid onset of action & elimination, availability of an effective antidote). In a controlled study flumazenil ... rapidly reversed the decr in alertness, psychometricity, & electroencephalographic changes induced by zolpidem. In one overdose patient who had ingested 300 mg of zolpidem followed by coma, pinpoint pupils, & respiratory depression requiring assisted ventilation, iv flumazenil ... was followed by arousal of the patient, correction of the miosis, & normalization of the respiratory pattern & blood gas analysis. Naloxone appears to be ineffective in diminishing coma or respiratory acidosis. Repeated doses of flumazenil may be required. /Salt not specified/

/SIGNS AND SYMPTOMS/ Coma, pinpoint pupils & respiratory depression have been described /in cases of overdose/. Somnolence, vertigo, & vomiting may be observed. In one patient ingestion of 39 tablets was not followed by coma, even though treatment was not begun for 6 hr. Hand, limb, & perioral tremor, muscle twitching, myoclonic jerks, diplopia, gastric & abdominal pain, & swallowing difficulties have been reported. Seizures may follow withdrawal. /Salt not specified/|/CASE REPORTS/ This report describes two cases of acute zolpidem overdose. The decedent in the first case was a 36-yr-old female .... She had a history of psychiatric illness, including paranoid disorder, depression with panic episodes, & post-traumatic stress disordER ... She was treated with risperidone & sertraline. Nine months prior to her death, the decedent was also prescribed zolpidem (Ambien). The postmortem exam revealed white foam within the larynx & upper trachea, which is indicative of pulmonary edema. Toxicological analyses of the urine showed the presence of caffeine, risperidone, & zolpidem. Subsequent quantitation of postmortem iliac serum revealed 5.6 microg/l of 9-hydroxyrisperidone & the following zolpidem concns: blood (subclavian), 4.5 mg/l; blood (iliac), 7.7 mg/l; vitreous humor, 1.6 mg/l; bile, 8.9 mg/l; urine, 1.2 mg/l; liver, 22.6 mg/kg; & gastric contents, 42 mg. The second case involved a 58-yr old female, also found dead ... with white foam around her mouth. The decedent had a 25-yr history of hypertension & mental illness--manic depression & schizophrenia. She was medicated with carbamazepine, naproxen, risperidone, & zolpidem. The postmortem exam revealed cardiomegaly, pulmonary edema, hepatomegaly, mild coronary atherosclerosis, & no signs of trauma. Toxicological analyses of the urine showed the presence of zolpidem & carbamazepine & metabolite. Zolpidem concns were as follows: blood (iliac), 1.6 mg/l; vitreous humor, 0.52 mg/l; bile, 2.6 mg/l; liver, 12 mg/kg; & gastric contents, 0.9 mg. The zolpidem blood concns of these cases are consistent with those of the previously published fatalities. The blood/vitreous humor ratios of zolpidem were 2.81 (subclavian) & 4.81 (iliac) in the first case & 3.08 (iliac) in the second case. These ratios, along with the sampling times of blood & vitreous humor for both cases, are not conclusive to indicate a definitive presence or absence of postmortem drug redistribution of zolpidem. The cause of death for both cases was determined to be acute zolpidem overdose ... /Salt not specified/

Ambien

The main ingredient in the drug Ambien ... (tablets)|Ivadal; Niotal; Stilnoct; Stilnox

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients