Linked Life Data

Ambien CR (Tablet, Coated)

Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/983

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Ambien CR (Tablet, Coated)
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The dose of Ambien CR should be individualized. Ambien CR is available as extended-release tablets containing 6.25 mg or 12.5 mg of zolpidem tartrate for oral administration. Ambien CR extended-release tablets should be swallowed whole, and not be divided, crushed, or chewed. The effect of Ambien CR may be slowed by ingestion with or immediately after a meal. The recommended dose of Ambien CR for adults is 12.5 mg immediately before bedtime. Elderly or debilitated patients may be especially sensitive to the effects of zolpidem. Patients with hepatic insufficiency do not clear the drug as rapidly as normal subjects. The recommended dose of Ambien CR in these patients is 6.25 mg immediately before bedtime (see Precautions).
dailymed-instance:descripti...
Ambien CR contains zolpidem tartrate, a non-benzodiazepine hypnotic of the imidazopyridine class. Ambien CR (zolpidem tartrate extended-release tablets) is available in 6.25-mg and 12.5-mg strength tablets for oral administration. Chemically, zolpidem tartrate is N,N,6-trimethyl-2-p-tolylimidazo[1,2-a] pyridine-3-acetamide L-(+)-tartrate (2:1). It has the following structure: Zolpidem tartrate is a white to off-white crystalline powder that is sparingly soluble in water, alcohol, and propylene glycol. It has a molecular weight of 764.88. Ambien CR consists of a coated two-layer tablet: one layer that releases its drug content immediately and another layer that allows a slower release of additional drug content. The 6.25-mg Ambien CR tablet contains the following inactive ingredients: colloidal silicon dioxide, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, potassium bitartrate, red ferric oxide, sodium starch glycolate, and titanium dioxide. The 12.5-mg Ambien CR tablet contains the following inactive ingredients: colloidal silicon dioxide, FD&C Blue #2, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, potassium bitartrate, sodium starch glycolate, titanium dioxide, and yellow ferric oxide.
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Pharmacodynamics: Subunit modulation of the GABAreceptor chloride channel macromolecular complex is hypothesized to be responsible for sedative, anticonvulsant, anxiolytic, and myorelaxant drug properties. The major modulatory site of the GABAreceptor complex is located on its alpha (��) subunit and is referred to as the benzodiazepine (BZ) receptor. Zolpidem, the active moiety of zolpidem tartrate, is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, pyrrolopyrazines, pyrazolopyrimidines, or other drugs with known hypnotic properties. In contrast to the benzodiazepines, which nonselectively bind to and activate all BZ receptor subtypes, zolpidem in vitro binds the BZreceptor preferentially with a high affinity ratio of the alpha/alphasubunits. The BZreceptor is found primarily on the Lamina IV of the sensorimotor cortical regions, substantia nigra (pars reticulata), cerebellum molecular layer, olfactory bulb, ventral thalamic complex, pons, inferior colliculus, and globus pallidus. This selective binding of zolpidem on the BZreceptor is not absolute, but it may explain the relative absence of myorelaxant and anticonvulsant effects in animal studies as well as the preservation of deep sleep (stages 3 and 4) in human studies of zolpidem at hypnotic doses.<br/>Pharmacokinetics: Ambien CR exhibits biphasic absorption characteristics, which results in rapid initial absorption from the gastrointestinal tract similar to zolpidem tartrate immediate-release, then provides extended plasma concentrations beyond three hours after administration. A study in 24 healthy male subjects was conducted to compare mean zolpidem plasma concentration-time profiles obtained after single oral administration of Ambien CR (12.5 mg) and of an immediate-release formulation of zolpidem tartrate (10 mg). The terminal elimination half-life observed with Ambien CR (12.5 mg) was similar to that obtained with immediate-release zolpidem tartrate (10 mg). The mean plasma concentration time profiles for Ambien CR (12.5 mg) and for zolpidem tartrate (10 mg) are shown below: In adult and elderly patients treated with Ambien CR, there was no evidence of accumulation after repeated once-daily dosing for up to two weeks.<br/>Absorption: Following administration of Ambien CR, administered as a single 12.5-mg dose in healthy male adult subjects, the mean peak concentration (C) of zolpidem was 134 ng/mL (range: 68.9 to 197 ng/ml) occurring at a median time (T) of 1.5 hours. The mean AUC of zolpidem was 740 ng���hr/mL (range: 295 to 1359 ng���hr/mL). A food-effect study in 45 healthy subjects compared the pharmacokinetics of Ambien CR 12.5 mg when administered while fasting or within 30 minutes after a meal. Results demonstrated that with food, mean AUC and Cwere decreased by 23% and 30%, respectively, while median Twas increased from 2 hours to 4 hours. The half-life was not changed. These results suggest that, for faster sleep onset, Ambien CR should not be administered with or immediately after a meal.<br/>Distribution: Total protein binding was found to be 92.5��0.1% and remained constant, independent of concentration between 40 and 790 ng/mL.<br/>Metabolism: Zolpidem is converted to inactive metabolites that are eliminated primarily by renal excretion.<br/>Elimination: Ambien CR administered as a single 12.5 mg dose in healthy male adult subjects, the mean zolpidem elimination half-life was 2.8 hours (range: 1.62 to 4.05 hr).<br/>Special Populations:<br/>Controlled trials supporting safety and efficacy: Ambien CR was evaluated in two placebo-controlled studies for the treatment of patients with chronic primary insomnia (as defined in the APA Diagnostic and Statistical Manual of Mental Disorders, DSM IV). Adult outpatients (18���64 years) with primary insomnia (N=212) were evaluated in a double-blind, randomized, parallel-group, 3-week trial comparing Ambien CR 12.5 mg and placebo. Ambien CR 12.5 mg decreased wake time after sleep onset (WASO) for the first 7 hours during the first 2 nights and for the first 5 hours after 2 weeks of treatment. Ambien CR 12.5 mg was superior to placebo on objective measures (polysomnography recordings) of sleep induction (by decreasing latency to persistent sleep [LPS]) during the first 2 nights of treatment and after 2 weeks of treatment. Ambien CR 12.5 mg was also superior to placebo on the patient reported global impression regarding the aid to sleep after the first 2 nights and after 3 weeks of treatment. Elderly outpatients (���65 years) with primary insomnia (N=205) were evaluated in a double-blind, randomized, parallel-group, 3-week trial comparing Ambien CR 6.25 mg and placebo. Ambien CR 6.25 mg decreased wake time after sleep onset (WASO) for the first 6 hours during the first 2 nights and the first 4 hours after 2 weeks of treatment. Ambien CR 6.25 mg was superior to placebo on objective measures (polysomnography recordings) of sleep induction (by decreasinglatency to persistent sleep [LPS]) during the first 2 nights of treatment and after 2 weeks on treatment. Ambien CR 6.25 mg was superior to placebo on the patient reported global impression regarding the aid to sleep after the first 2 nights and after 3 weeks of treatment. In both studies, in patients treated with Ambien CR, polysomnography showed increased wakefulness at the end of the night compared to placebo-treated patients.<br/>Studies Pertinent To Safety Concerns For Sedative/Hypnotic Drugs:
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Ambien CR is contraindicated in patients with known hypersensitivity to zolpidem tartrate or to any of the inactive ingredients in the formulation.
dailymed-instance:supply
Ambien CR 6.25 mg tablets are composed of two layersand are coated, pink, round, bi-convex, debossed with A~ on one side and supplied as: NDC Number Size 0024-5501-31 bottle of 1000024-5501-50 bottle of 5000024-5501-10 carton of 30 unit dose0024-5501-34 carton of 100 unit dose Ambien CR 12.5-mg tablets are composed of two layersand are coated, blue, round, bi-convex, debossed with A~ on one side and supplied as: NDC Number Size 0024-5521-31 bottle of 1000024-5521-50 bottle of 5000024-5521-10 carton of 30 unit dose0024-5521-34 carton of 100 unit dose Store between 15�����25��C (59�����77��F). Limited excursions permissible up to 30��C (86��F).
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Signs and symptoms: In postmarketing experience of overdose with zolpidem tartrate alone, or in combination with CNS-depressant agents, impairment of consciousness ranging from somnolence to coma, cardiovascular and/or respiratory compromise, and fatal outcomes have been reported.<br/>Recommended treatment: General symptomatic and supportive measures should be used along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. Flumazenil may be useful; however, flumazenil administration may contribute to the appearance of neurological symptoms (convulsions). As in all cases of drug overdose, respiration, pulse, blood pressure, and other appropriate signs should be monitored and general supportive measures employed. Hypotension and CNS depression should be monitored and treated by appropriate medical intervention. Sedating drugs should be withheld following zolpidem tartrate overdosage, even if excitation occurs. The value of dialysis in the treatment of overdosage has not been determined, although hemodialysis studies in patients with renal failure receiving therapeutic doses have demonstrated that zolpidem is not dialyzable.<br/>Poison control center: As with the management of all overdosage, the possibility of multiple drug ingestion should be considered. The physician may wish to consider contacting a poison control center for up-to-date information on the management of hypnotic drug product overdosage.
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zolpidem tartrate
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Ambien CR (Tablet, Coated)
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Clinical trial experience:<br/>Associated with discontinuation of treatment: In clinical trials with Ambien CR, 3.5% of 201 patients receiving 6.25-mg or 12.5-mg of Ambien CR discontinued treatment because of an adverse event. Events most commonly associated with discontinuation were somnolence (1.0%) and dizziness (1.0%). Data from a clinical study in which selective serotonin reuptake inhibitor (SSRI)-treated patients were given immediate-release zolpidem tartrate revealed that four of the seven discontinuations during double-blind treatment with zolpidem (n=95) were associated with impaired concentration, continuing or aggravated depression, and manic reaction; one patient treated with placebo (n =97) was discontinued afteran attempted suicide.<br/>Most commonly observed adverse events in controlled trials: During treatment with Ambien CR in adults and elderly at daily doses of 12.5 mg and 6.25 mg, respectively, each for three weeks, the most commonly observed adverse events associated with the use of Ambien CR were headache, somnolence, and dizziness.<br/>Adverse events observed at an incidence of���1% in controlled trials of Ambien CR: The following tables enumerate treatment-emergent adverse event frequencies that were observed at an incidence equal to 1% or greater among patients with insomnia who received Ambien CR in placebo-controlled trials. Events reported by investigators were classified utilizing the MedDRA dictionary for the purpose of establishing event frequencies. The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice in which patient characteristics and other factors differ from those that prevailed in these clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigators involving related drug products and uses, since each group of drug trials is conducted under a different set of conditions. However, the cited figures provide the physician with a basis for estimating the relative contribution of drug and nondrug factors to the incidence of side effects in the population studied. The following tables were derived from results of two placebo-controlled efficacy trials involving Ambien CR. These trials involved patients with primary insomnia who were treated for 3 weeks with Ambien CR at doses of 12.5 mg (Table 1) or 6.25 mg (Table 2), respectively. The tables include only adverse events occurring at an incidence of at least 1% for Ambien CR patients and with an incidence greater than that seen in the placebo patients.<br/>Dose relationship for adverse events: There is evidence from dose comparison trials suggesting a dose relationship for many of the adverse events associated with zolpidem use, particularly for certain CNS and gastrointestinal adverse events.<br/>Other adverse events observed during the premarketing evaluation of Ambien CR: Other treatment-emergent adverse events associated with participation in Ambien CR studies (those reported at frequencies of<1%) were not different in nature or frequency to those seen in studies with immediate-release zolpidem tartrate, which are listed below.<br/>Adverse events observed during the premarketing evaluation of immediate-release zolpidem tartrate: Immediate-release zolpidem tartrate, was administered to 3,660 subjects in clinical trials throughout the U.S., Canada, and Europe. Treatment-emergent adverse events associated with clinical trial participation were recorded by clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals experiencing treatment-emergent adverse events, similar types of untoward events were grouped into a smaller number of standardized event categories and classified utilizing a modified World Health Organization (WHO) dictionary of preferred terms. The frequenciespresented, therefore, represent the proportions of the 3,660 individuals exposed to zolpidem, at all doses, who experienced an event of the type cited on at least one occasion while receiving immediate-release zolpidem. All reported treatment-emergent adverse events are included, except those coding terms that are so general as to be uninformative and those events where a drug cause was remote. It is important to emphasize that, although the events reported did occur during treatment with immediate-release zolpidem, they were not necessarily caused by it. Adverse events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in greater than 1/100 subjects; infrequent adverse events are those occurring in 1/100 to 1/1,000 patients; rare events are those occurring in less than 1/1,000 patients. Autonomic nervous system: Frequent: dry mouth. Infrequent: increased sweating, pallor, postural hypotension, syncope. Rare: abnormal accommodation, altered saliva, flushing, glaucoma, hypotension, impotence, increased saliva, tenesmus. Body as a whole: Frequent: allergy, asthenia, back pain, influenza-like symptoms. Infrequent: chest pain, edema, falling, fatigue, fever, malaise, trauma. Rare: allergic reaction, allergy aggravated, anaphylactic shock, face edema, hot flashes, increased ESR, pain, restless legs, rigors, tolerance increased, weight decrease. Cardiovascular system: Frequent: palpitation. Infrequent: cerebrovascular disorder, hypertension, tachycardia. Rare: angina pectoris, arrhythmia, arteritis, circulatory failure, extrasystoles, hypertension aggravated, myocardial infarction, phlebitis, pulmonary embolism, pulmonary edema, varicose veins, ventricular tachycardia. Central and peripheral nervous system: Frequent: ataxia, confusion, depression, dizziness, drowsiness, drugged feeling, euphoria, headache, insomnia, lethargy, lightheadedness, vertigo. Infrequent: abnormal dreams, agitation, amnesia, anxiety, decreased cognition, detached, difficulty concentrating, dysarthria, emotional lability, hallucination, hypoesthesia, illusion, leg cramps, migraine, nervousness, paresthesia, sleep disorder, sleeping (after daytime dosing), speech disorder, stupor, tremor. Rare: abnormal gait, abnormal thinking, aggressive reaction, apathy, appetite increased,decreased libido, delusion, dementia, depersonalization, dysphasia, feeling strange, hypokinesia, hypotonia, hysteria, intoxicated feeling, manic reaction, neuralgia, neuritis, neuropathy, neurosis, panic attacks, paresis, personality disorder, somnambulism, suicide attempts, tetany, yawning. Gastrointestinal system: Frequent: abdominal pain, diarrhea, dyspepsia, hiccup, nausea. Infrequent: anorexia, constipation, dysphagia, flatulence, gastroenteritis, vomiting. Rare: enteritis, eructation, esophagospasm, gastritis, hemorrhoids, intestinal obstruction, rectal hemorrhage, tooth caries. Hematologic and lymphatic system: Rare: anemia, hyperhemoglobinemia, leukopenia, lymphadenopathy, macrocytic anemia, purpura, thrombosis. Immunologic system: Infrequent: infection. Rare: abscess, herpes simplex, herpes zoster, otitis externa, otitis media. Liver and biliary system: Infrequent: abnormal hepatic function, increased SGPT. Rare: bilirubinemia, increased SGOT. Metabolic and nutritional: Infrequent: hyperglycemia, thirst. Rare: gout, hypercholesteremia, hyperlipidemia, increased alkaline phosphatase, increased BUN, periorbital edema. Musculoskeletal system: Frequent: arthralgia, myalgia. Infrequent: arthritis. Rare: arthrosis, muscle weakness, sciatica, tendinitis. Reproductive system: Infrequent: menstrual disorder, vaginitis. Rare: breast fibroadenosis, breast neoplasm, breast pain. Respiratory system: Frequent: pharyngitis, sinusitis, upper respiratory infection. Infrequent: bronchitis, coughing, dyspnea, rhinitis. Rare: bronchospasm, epistaxis, hypoxia, laryngitis, pneumonia. Skin and appendages: Frequent: rash. Infrequent: pruritus. Rare: acne, bullous eruption, dermatitis, furunculosis, injection-site inflammation, photosensitivity reaction, urticaria. Special senses: Frequent: diplopia, vision abnormal. Infrequent: eye irritation, eye pain, scleritis, taste perversion, tinnitus. Rare: conjunctivitis, corneal ulceration, lacrimation abnormal, parosmia, photopsia. Urogenital system: Frequent: urinary tract infection. Infrequent: cystitis, urinary incontinence. Rare: acute renal failure, dysuria, micturition frequency, nocturia, polyuria, pyelonephritis, renal pain, urinary retention.<br/>Postmarketing Experience: In addition to adverse events reported in clinical trials, angioneurotic edema has been reported spontaneously in postmarketing experience with zolpidem tartrate.
dailymed-instance:indicatio...
Ambien CR (zolpidem tartrate extended-release tablets) is indicated for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance (as measured by wake time after sleep onset). (See Clinical Pharmacology: Controlled trials supporting safety and efficacy.) The clinical trials performed in support of efficacy were both 3 weeks in duration, although the final formal assessments of sleep latency and maintenance were performed after 2 weeks of treatment.
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Ambien CR