What Other Drugs Have The Same Makeup Of 12.5 Zolpidem

What is Ambien CR and how is it used?

Ambien CR (zolpidem tartrate) is a sedative-hypnotic drug used to treat patients with indisposition and other problems with sleeping similar maintaining slumber. The CR means extended release. Ambien CR is available in generic form.

What are side effects of Ambien CR?

Mutual side effects of Ambien CR include:

daytime drowsiness,
headache,
dizziness,
weakness,
feeling "drugged,"
lightheadedness,
tired feeling,
loss of coordination,
stuffy olfactory organ,
dry mouth,
olfactory organ or throat irritation,
nausea,
constipation,
diarrhea,
upset stomach,
muscle pain,
depression, and
unusual thinking, including thoughts of self-injury, anxiety, aggression, and risk-taking.

Tell your doctor if you take any infrequent but severe side effects of Ambien CR including:

allergic reactions,
chest pain,
irregular heartbeats,
dementia,
blood clots, and
skin reactions.

Unusual and dangerous "sleep driving" has occurred with a few patients.

Description

AMBIEN CR contains zolpidem tartrate, a gamma-aminobutyric acid (GABA) A agonist 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 is Northward,Due north,6-trimethyl-2-p-tolylimidazo[1,2-a] pyridine-3-acetamide L-(+)tartrate (2:1). Information technology has the following structure:

AMBIEN CR® (zolpidem tartrate) Structural Formula Illustration

Zolpidem tartrate is a white to off-white crystalline pulverisation that is sparingly soluble in h2o, alcohol, and propylene glycol. It has a molecular weight of 764.88. AMBIEN CR consists of a coated two-layer tablet: ane layer that releases its drug content immediately and another layer that allows a slower release of additional drug content. The half dozen.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 Blueish #2, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, potassium bitartrate, sodium starch glycolate, titanium dioxide, and yellow ferric oxide.

INDICATIONS

AMBIEN CR (zolpidem tartrate extended-release tablets) is indicated for the handling of insomnia characterized by difficulties with sleep onset and/or sleep maintenance (as measured by wake fourth dimension after slumber onset).

The clinical trials performed in back up of efficacy were up to 3 weeks (using polysomnography measurement up to two weeks in both adult and elderly patients) and 24 weeks (using patient-reported assessment in developed patients merely) in duration [see Clinical Studies].

DOSAGE AND Assistants

Dosage In Adults

Utilise the lowest effective dose for the patient. The recommended initial dose is 6.25 mg for women and either 6.25 or 12.5 mg for men, taken only one time per night immediately before bedtime with at to the lowest degree 7-eight hours remaining before the planned time of awakening. If the vi.25 mg dose is not effective, the dose can exist increased to 12.5 mg. In some patients, the higher morning blood levels post-obit apply of the 12.v mg dose increment the risk of adjacent day damage of driving and other activities that require total alertness [see WARNINGS AND PRECAUTIONS]. The total dose of AMBIEN CR should non exceed 12.5 mg in one case daily immediately before bedtime. Ambien CR should be taken as a single dose and should not exist readministered during the same night.

The recommended initial doses for women and men are different considering zolpidem clearance is lower in women.

Special Populations

Elderly or debilitated patients may be especially sensitive to the effects of zolpidem tartrate. The recommended dose of AMBIEN CR in these patients is 6.25 mg once daily immediately before bedtime [encounter WARNINGS AND PRECAUTIONS, Apply in Specific Populations].

Patients with balmy to moderate hepatic impairment exercise non clear the drug as rapidly as normal subjects. The recommended dose of AMBIEN CR in these patients is half-dozen.25 mg in one case daily immediately before bedtime. Avoid AMBIEN CR use in patients with astringent hepatic impairment as information technology may contribute to encephalopathy [meet WARNINGS AND PRECAUTIONS, Use in Specific Populations, CLINICAL PHARMACOLOGY].

Use With CNS Depressants

Dosage adjustment may be necessary when AMBIEN CR is combined with other CNS depressant drugs because of the potentially additive effects [see WARNINGS AND PRECAUTIONS].

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 past ingestion with or immediately after a repast.

HOW SUPPLIED

Dosage Forms And Strengths

AMBIEN CR is bachelor as extended-release tablets containing half-dozen.25 mg or 12.5 mg of zolpidem tartrate for oral administration. Tablets are non scored.

AMBIEN CR half-dozen.25 mg tablets are pink, round, bi-convex, and debossed with A~ on 1 side.

AMBIEN CR 12.v mg tablets are blue, circular, bi-convex, and debossed with A~ on 1 side.

Storage And Handling

AMBIEN CR half dozen.25 mg tablets are composed of 2 layers* and are coated, pinkish, round, biconvex, debossed with A~ on one side and supplied as:

NDC Number	Size
0024-5501-31	bottle of 100

AMBIEN CR 12.5 mg tablets are composed of two layers* and are coated, blue, round, arched, debossed with A~ on 1 side and supplied as:

NDC Number	Size
0024-5521-31	bottle of 100
0024-5521-50	bottle of 500
0024-5521-ten	carton of 30 unit of measurement dose

*Layers are covered past the coating and are duplicate.

Store between 15°-25° C (59°-77°F). Limited excursions permissible up to thirty° C (86°F)

sanofi-aventis U.S. LLC Bridgewater, NJ 08807 A SANOFI Company. Revised: Dec 2016

SLIDESHOW

Sleep Disorders: Foods That Aid Sleep or Keep You Awake See Slideshow

SIDE Effects

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

CNS-depressant furnishings and adjacent-day impairment [see WARNINGS AND PRECAUTIONS]
Serious anaphylactic and anaphylactoid reactions [see WARNINGS AND PRECAUTIONS]
Abnormal thinking and behavior changes, and complex behaviors [run across WARNINGS AND PRECAUTIONS]
Withdrawal effects [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Associated With Discontinuation Of Treatment

In 3-week clinical trials in adults and elderly patients ( > 65 years), 3.5% (7/201) patients receiving AMBIEN CR 6.25 or 12.v mg discontinued handling due to an adverse reaction as compared to 0.ix% (2/216) of patients on placebo. The reaction most commonly associated with discontinuation in patients treated with AMBIEN CR was somnolence (one%).

In a 6-month report in adult patients (18-64 years of age), eight.5% (57/669) of patients receiving AMBIEN CR 12.five mg as compared to four.6% on placebo (xvi/349) discontinued treatment due to an agin reaction. Reactions almost commonly associated with discontinuation of AMBIEN CR included anxiety (anxiety, restlessness or agitation) reported in 1.5% (10/669) of patients every bit compared to 0.three% (1/349) of patients on placebo, and low (depression, major depression or depressed mood) reported in one.5% (ten/669) of patients as compared to 0.3% (1/349) of patients on placebo.

Data from a clinical study in which selective serotonin reuptake inhibitor-(SSRI-) treated patients were given zolpidem revealed that four of the 7 discontinuations during double-bullheaded treatment with zolpidem (due north=95) were associated with impaired concentration, continuing or aggravated low, and manic reaction; ane patient treated with placebo (north =97) was discontinued after an attempted suicide.

Most Ordinarily Observed Agin Reactions In Controlled Trials

During handling with AMBIEN CR in adults and elderly at daily doses of 12.five mg and vi.25 mg, respectively, each for 3 weeks, the nigh commonly observed adverse reactions associated with the use of AMBIEN CR were headache, side by side-day somnolence, and dizziness.

In the vi-month trial evaluating AMBIEN CR 12.five mg, the agin reaction contour was consequent with that reported in short-term trials, except for a higher incidence of anxiety (6.3% for AMBIEN CR versus 2.6% for placebo).

Adverse Reactions Observed At An Incidence Of ≥ 1% In Controlled Trials

The post-obit tables enumerate treatment-emergent adverse reaction frequencies that were observed at an incidence equal to 1% or greater amongst 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 outcome frequencies. The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the grade 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 exist compared with figures obtained from other clinical investigators involving related drug products and uses, since each group of drug trials is conducted nether a different set of conditions. However, the cited figures provide the dr. with a basis for estimating the relative contribution of drug and nondrug factors to the incidence of side furnishings 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 chief insomnia who were treated for 3 weeks with AMBIEN CR at doses of 12.5 mg (Table one) or half-dozen.25 mg (Tabular array two), respectively. The tables include only adverse reactions occurring at an incidence of at least one% for AMBIEN CR patients and with an incidence greater than that seen in the placebo patients.

Table ane: Incidences of Treatment-Emergent Adverse Reactions in a 3-Week Placebo-Controlled Clinical Trial in Adults (percentage of patients reporting)

Trunk Arrangement/ Adverse Reaction *	AMBIEN CR 12.5 mg (N = 102)	Placebo (N = 110)
Infections and infestations
Influenza	3	0
Gastroenteritis	1	0
Labyrinthitis	i	0
Metabolism and diet disorders
Appetite disorder	1	0
Psychiatric disorders
Hallucinations **	iv	0
Disorientation	3	2
Anxiety	ii	0
Low	ii	0
Psychomotor retardation	2	0
Binge eating	1	0
Depersonalization	ane	0
Disinhibition	1	0
Euphoric mood	1	0
Mood swings	1	0
Stress symptoms	1	0
Nervous system disorders
Headache	19	16
Somnolence	xv	2
Dizziness	12	5
Retentiveness disorders ***	3	0
Remainder disorder	2	0
Disturbance in attention	2	0
Hypoesthesia	2	1
Ataxia	1	0
Paresthesia	1	0
Center disorders
Visual disturbance	3	0
Centre redness	2	0
Vision blurred	2	1
Altered visual depth perception	one	0
Asthenopia	1	0
Ear and labyrinth disorders
Vertigo	2	0
Tinnitus	1	0
Respiratory, thoracic and mediastinal disorders
Throat irritation	1	0
Gastrointestinal disorders
Nausea	7	four
Constipation	2	0
Abdominal discomfort	1	0
Abdominal tenderness	1	0
Frequent bowel movements	1	0
Gastroesophageal reflux illness	1	0
Airsickness	1	0
Skin and subcutaneous tissue disorders
Rash	ane	0
Skin wrinkling	1	0
Urticaria	i	0
Musculoskeletal and connective tissue disorders
Back pain	four	3
Myalgia	4	0
Neck hurting	1	0
Reproductive system and chest disorders
Menorrhagia	one	0
General disorders and administration site conditions
Fatigue	3	2
Asthenia	1	0
Chest discomfort	1	0
Investigations
Claret pressure increased	1	0
Body temperature increased	1	0
Injury, poisoning and procedural complications
Contusion	1	0
Social circumstances
Exposure to poisonous institute	1	0
Reactions reported by at least i% of patients treated with AMBIEN CR and at greater frequency than in the placebo group. Hallucinations included hallucinations NOS too as visual and hypnogogic hallucinations. **Retention disorders include: retention impairment, amnesia, anterograde amnesia.

Table ii: Incidences of Treatment-Emergent Adverse Reactions in a iii-Calendar week Placebo-Controlled Clinical Trial in Elderly (percentage of patients reporting)

Torso Organization/ Adverse Reaction *	AMBIEN CR 6.25 mg (North=99)	Placebo (Northward=106)
Infections and infestations
Nasopharyngitis	6	iv
Lower respiratory tract infection	ane	0
Otitis externa	i	0
Upper respiratory tract infection	one	0
Psychiatric disorders
Feet	3	ii
Psychomotor retardation	2	0
Apathy	1	0
Depressed mood	1	0
Nervous system disorders
Headache	14	11
Dizziness	viii	3
Somnolence	six	v
Burning sensation	1	0
Dizziness postural	one	0
Memory disorders **	1	0
Musculus contractions involuntary	1	0
Paresthesia	1	0
Tremor	one	0
Cardiac disorders
Palpitations	2	0
Respiratory, thoracic and mediastinal disorders
Dry pharynx	ane	0
Gastrointestinal disorders
Flatulence	1	0
Airsickness	1	0
Peel and subcutaneous tissue disorders
Rash	1	0
Urticaria	1	0
Musculoskeletal and connective tissue disorders
Arthralgia	ii	0
Musculus cramp	two	1
Neck pain	2	0
Renal and urinary disorders
Dysuria	i	0
Reproductive system and breast disorders
Vulvovaginal dryness	i	0
General disorders and administration site conditions
Influenza like illness	ane	0
Pyrexia	ane	0
Injury, poisoning and procedural complications
Neck injury	1	0
Reactions reported by at least 1% of patients treated with AMBIEN CR and at greater frequency than in the placebo group. *Retention disorders include: memory impairment, amnesia, anterograde amnesia.

Dose Relationship For Adverse Reactions

At that place is testify from dose comparison trials suggesting a dose human relationship for many of the adverse reactions associated with zolpidem use, particularly for certain CNS and gastrointestinal agin events.

Other Agin Reactions Observed During The Premarketing Evaluation Of AMBIEN CR

Other treatment-emergent adverse reactions associated with participation in AMBIEN CR studies (those reported at frequencies of < 1%) were not unlike in nature or frequency to those seen in studies with immediate-release zolpidem tartrate, which are listed below.

Adverse Events Observed During The Premarketing Evaluation Of Firsthand-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 agin events associated with clinical trial participation were recorded past clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals experiencing treatment-emergent agin events, like types of untoward events were grouped into a smaller number of standardized result categories and classified utilizing a modified World Wellness Organisation (WHO) lexicon of preferred terms.

The frequencies presented, therefore, represent the proportions of the iii,660 individuals exposed to zolpidem, at all doses, who experienced an event of the type cited on at least ane occasion while receiving zolpidem. All reported treatment-emergent agin events are included, except those already listed in the table above of adverse events in placebo-controlled studies, 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 AMBIEN, they were not necessarily caused by it.

Adverse events are further classified within trunk system categories and enumerated in social club of decreasing frequency using the post-obit definitions: frequent adverse events are defined equally those occurring in greater than 1/100 subjects; infrequent agin events are those occurring in 1/100 to 1/i,000 patients; rare events are those occurring in less than 1/i,000 patients.

Autonomic nervous organization: Frequent: dry mouth. Infrequent: increased sweating, pallor, postural hypotension, syncope. Rare: aberrant accommodation, altered saliva, flushing, glaucoma, hypotension, impotence, increased saliva, tenesmus.

Body as a whole: Frequent: asthenia. Infrequent: chest hurting, edema, falling, fever, malaise, trauma. Rare: allergic reaction, allergy aggravated, anaphylactic daze, confront edema, hot flashes, increased ESR, pain, restless legs, rigors, tolerance increased, weight decrease.

Cardiovascular system: Exceptional: 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.

Fundamental and peripheral nervous system: Frequent: ataxia, confusion, drowsiness, drugged feeling, euphoria, insomnia, lethargy, lightheadedness, vertigo. Infrequent: agitation, decreased cognition, discrete, difficulty concentrating, dysarthria, emotional lability, hallucination, hypoesthesia, illusion, leg cramps, migraine, nervousness, paresthesia, sleeping (subsequently daytime dosing), spoken communication disorder, stupor, tremor. Rare: abnormal gait, abnormal thinking, ambitious 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 organization: Frequent: diarrhea, dyspepsia, hiccup. Infrequent: anorexia, constipation, dysphagia, flatulence, gastroenteritis. 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: Exceptional: infection. Rare: abscess canker simplex herpes zoster, otitis externa, otitis media.

Liver and biliary system: Infrequent: abnormal hepatic role, 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: Infrequent: arthritis. Rare: arthrosis, muscle weakness, sciatica, tendinitis.

Reproductive organisation: Infrequent: menstrual disorder, vaginitis. Rare: breast fibroadenosis, breast neoplasm, breast hurting.

Respiratory organization: Frequent: sinusitis. Infrequent: bronchitis, cough, dyspnea. Rare: bronchospasm, respiratory depression, epistaxis, hypoxia, laryngitis, pneumonia.

Pare and appendages: Infrequent: pruritus. Rare: acne, bullous eruption, dermatitis, furunculosis, injection-site inflammation, photosensitivity reaction, urticaria.

Special senses: Frequent: diplopia, vision aberrant. Infrequent: eye irritation, eye pain, scleritis, taste perversion, tinnitus. Rare: conjunctivitis, corneal ulceration, lacrimation abnormal, parosmia, photopsia.

Urogenital arrangement: Frequent: urinary tract infection. Infrequent: cystitis, urinary incontinence. Rare: acute renal failure, dysuria, micturition frequency, nocturia, polyuria, pyelonephritis, renal pain, urinary retention.

Postmarketing Experience

The following adverse reactions accept been identified during post-approval apply of AMBIEN CR. Considering these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably guess their frequency or establish a causal relationship to drug exposure.

Liver and biliary organisation: acute hepatocellular, cholestatic or mixed liver injury with or without jaundice (i.eastward., bilirubin > 2x ULN, alkali metal phosphatase ≥ 2x ULN, transaminase ≥ 5x ULN).

DRUG INTERACTIONS

CNS-active Drugs

Co-administration of zolpidem with other CNS depressants increases the risk of CNS low. Concomitant apply of zolpidem with these drugs may increase drowsiness and psychomotor impairment, including impaired driving ability. [see WARNINGS AND PRECAUTIONS]. Zolpidem tartrate was evaluated in salubrious volunteers in unmarried-dose interaction studies for several CNS drugs.

Imipramine, Chlorpromazine

Imipramine in combination with zolpidem produced no pharmacokinetic interaction other than a 20% decrease in elevation levels of imipramine, but there was an additive effect of decreased alertness. Similarly, chlorpromazine in combination with zolpidem produced no pharmacokinetic interaction, only there was an additive effect of decreased alertness and psychomotor performance [meet CLINICAL PHARMACOLOGY].

Haloperidol

A study involving haloperidol and zolpidem revealed no effect of haloperidol on the pharmacokinetics or pharmacodynamics of zolpidem. The lack of a drug interaction post-obit single-dose administration does not predict the absence of an effect following chronic assistants [encounter CLINICAL PHARMACOLOGY].

Alcohol

An additive adverse effect on psychomotor performance between alcohol and oral zolpidem was demonstrated [encounter WARNINGS AND PRECAUTIONS].

Sertraline Concomitant administration of zolpidem and sertraline increases exposure to zolpidem [see CLINICAL PHARMACOLOGY].

Fluoxetine

After multiple doses of zolpidem tartrate and fluoxetine an increase in the zolpidem half-life (17%) was observed. There was no bear witness of an additive effect in psychomotor performance [see CLINICAL PHARMACOLOGY].

Drugs That Affect Drug Metabolism Via Cytochrome P450

Some compounds known to induce or inhibit CYP3A may affect exposure to zolpidem. The effect of drugs that induce or inhibit other P450 enzymes on the exposure to zolpidem is not known.

CYP3A4 Inducers

Rifampin, a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects of zolpidem. Use of CYP3A4 inducers in combination with zolpidem may decrease the efficacy of zolpidem [run into CLINICAL PHARMACOLOGY].

CYP3A4 Inhibitors

Ketoconazole, a strong CYP3A4 inhibitor, increased the exposure to and pharmacodynamic furnishings of zolpidem. Consideration should be given to using a lower dose of zolpidem when a potent CYP3A4 inhibitor and zolpidem are given together [see CLINICAL PHARMACOLOGY].

Drug Abuse And Dependence

Controlled Substance

Zolpidem tartrate is classified as a Schedule IV controlled substance by federal regulation.

Abuse

Abuse and addiction are separate and singled-out from physical dependence and tolerance. Abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances. Tolerance is a state of accommodation in which exposure to a drug induces changes that result in a diminution of ane or more of the drug effects over time. Tolerance may occur to both desired and undesired effects of drugs and may develop at different rates for unlike furnishings.

Addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: dumb control over drug employ, compulsive use, continued use despite harm, and craving. Drug habit is a treatable illness, using a multidisciplinary arroyo, but relapse is common.

Studies of abuse potential in erstwhile drug abusers establish that the furnishings of single doses of zolpidem tartrate 40 mg were like, merely non identical, to diazepam 20 mg, while zolpidem tartrate 10 mg furnishings were difficult to distinguish from placebo.

Considering persons with a history of addiction to, or abuse of, drugs or booze are at increased gamble for misuse, corruption and habit of zolpidem, they should be monitored carefully when receiving zolpidem or any other hypnotic.

Dependence

Concrete dependence is a state of accommodation that is manifested past a specific withdrawal syndrome that can exist produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.

Allaying/hypnotics take produced withdrawal signs and symptoms following abrupt discontinuation. These reported symptoms range from mild dysphoria and indisposition to a withdrawal syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions. The post-obit agin events, which are considered to run across the DSMIII-R criteria for uncomplicated sedative/hypnotic withdrawal, were reported during U.S. clinical trials following placebo commutation occurring inside 48 hours following last zolpidem treatment: fatigue, nausea, flushing, lightheadedness, uncontrolled crying, emesis, stomach cramps, panic assault, nervousness, and intestinal discomfort. These reported adverse events occurred at an incidence of one% or less. However, available data cannot provide a reliable estimate of the incidence, if any, of dependence during treatment at recommended doses. Mail-marketing reports of corruption, dependence and withdrawal accept been received.

WARNINGS

Included equally part of the PRECAUTIONS section.

PRECAUTIONS

CNS Depressant Effects And Adjacent-Day Harm

AMBIEN CR is a central nervous arrangement (CNS) depressant and tin impair daytime function in some patients even when used every bit prescribed. Prescribers should monitor for excess depressant furnishings, but impairment can occur in the absence of subjective symptoms, and may not be reliably detected by ordinary clinical examination (i.due east. less than formal psychomotor testing). While pharmacodynamic tolerance or adaptation to some adverse depressant effects of AMBIEN CR may develop, patients using AMBIEN CR should exist cautioned against driving or engaging in other chancy activities or activities requiring complete mental alertness the day later use.

Condiment effects occur with concomitant use of other CNS depressants (e.g. benzodiazepines, opioids, tricyclic antidepressants, booze), including daytime use. Downwards dose aligning of AMBIEN CR and concomitant CNS depressants should be considered [see DOSAGE AND ADMINISTRATION].

The use of AMBIEN CR with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the dark is non recommended.

The run a risk of next-day psychomotor impairment is increased if AMBIEN CR is taken with less than a full night of sleep remaining (7 to 8 hours); if higher than the recommended dose is taken; if co-administered with other CNS depressants or alcohol; or co-administered with other drugs that increase the blood levels of zolpidem. Patients should be warned against driving and other activities requiring complete mental alertness if Ambien CR is taken in these circumstances [run across DOSAGE AND Administration and Clinical Studies].

Vehicle drivers and machine operators should exist warned that, as with other hypnotics, there may be a possible gamble of agin reactions including drowsiness, prolonged reaction time, dizziness, sleepiness, blurred/double vision, reduced alertness and dumb driving the morning after therapy. In order to minimize this risk a full dark of slumber (vii-8 hours) is recommended.

Need To Evaluate For Co-morbid Diagnoses

Considering slumber disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated simply afterward a careful evaluation of the patient. The failure of insomnia to remit after 7 to ten days of treatment may indicate the presence of a primary psychiatric and/or medical affliction that should be evaluated. Worsening of insomnia or the emergence of new thinking or beliefs abnormalities may be the outcome of an unrecognized psychiatric or physical disorder. Such findings have emerged during the grade of treatment with sedative/hypnotic drugs, including zolpidem.

Astringent Anaphylactic And Anaphylactoid Reactions

Cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the offset or subsequent doses of sedative-hypnotics, including zolpidem. Some patients have had additional symptoms such as dyspnea, throat closing or nausea and vomiting that suggest anaphylaxis. Some patients accept required medical therapy in the emergency section. If angioedema involves the pharynx, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with zolpidem should non be rechallenged with the drug.

Abnormal Thinking And Behavioral Changes

Abnormal thinking and beliefs changes have been reported in patients treated with sedative/hypnotics, including AMBIEN CR. Some of these changes included decreased inhibition (e.chiliad. aggressiveness and extroversion that seemed out of grapheme), bizarre behavior, agitation and depersonalization. Visual and auditory hallucinations take been reported.

In controlled trials, < one% of adults with insomnia reported hallucinations. In a clinical trial, 7% of pediatric patients treated with AMBIEN 0.25 mg/kg taken at bedtime reported hallucinations versus 0% treated with placebo [see Use in Specific Populations].

Complex behaviors such equally "sleep-driving" (i.eastward., driving while non fully awake afterwards ingestion of a allaying-hypnotic, with amnesia for the event) have been reported in sedative-hypnotic-naive equally well every bit in sedative-hypnotic-experienced persons. Although behaviors such every bit "sleep-driving" have occurred with AMBIEN CR alone at therapeutic doses, the co-administration of alcohol and other CNS depressants increases the risk of such behaviors, as does the use of AMBIEN CR at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of AMBIEN CR should exist strongly considered for patients who report a "slumber-driving" episode.

Other complex behaviors (e.g., preparing and eating nutrient, making phone calls, or having sex) have been reported in patients who are not fully awake later on taking a sedative-hypnotic. Every bit with "sleep-driving", patients usually do not remember these events. Amnesia, anxiety and other neuro-psychiatric symptoms may too occur.

It tin rarely be determined with certainty whether a particular instance of the abnormal behaviors listed above is drug induced, spontaneous in origin, or a result of an underlying psychiatric or physical disorder. Nonetheless, the emergence of whatsoever new behavioral sign or symptom of business organization requires careful and firsthand evaluation.

Employ In Patients With Low

In primarily depressed patients treated with sedative-hypnotics, worsening of depression, and suicidal thoughts and actions (including completed suicides), accept been reported. Suicidal tendencies may exist present in such patients and protective measures may be required. Intentional overdosage is more common in this group of patients; therefore, the lowest number of tablets that is feasible should exist prescribed for the patient at any ane fourth dimension.

Respiratory Low

Although studies with ten mg zolpidem tartrate did not reveal respiratory depressant effects at hypnotic doses in good for you subjects or in patients with mild-to-moderate chronic obstructive pulmonary illness (COPD), a reduction in the Total Arousal Index, together with a reduction in everyman oxygen saturation and increase in the times of oxygen desaturation below 80% and 90%, was observed in patients with mild-to-moderate sleep apnea when treated with zolpidem compared to placebo. Since sedative-hypnotics accept the chapters to depress respiratory drive, precautions should be taken if AMBIEN CR is prescribed to patients with compromised respiratory part. Post-marketing reports of respiratory insufficiency in patients receiving x mg of zolpidem tartrate, about of whom had pre-existing respiratory impairment, have been reported. The hazard of respiratory depression should be considered prior to prescribing AMBIEN CR in patients with respiratory impairment including slumber apnea and myasthenia gravis.

Precipitation Of Hepatic Encephalopathy

GABA agonists such every bit zolpidem tartrate have been associated with precipitation of hepatic encephalopathy in patients with hepatic insufficiency. In add-on, patients with hepatic insufficiency do not clear zolpidem tartrate equally speedily as patients with normal hepatic function. Avoid AMBIEN CR utilise in patients with severe hepatic harm every bit it may contribute to encephalopathy [see DOSAGE AND Assistants, Use in Specific Populations, CLINICAL PHARMACOLOGY].

Withdrawal Effects

There have been reports of withdrawal signs and symptoms following the rapid dose decrease or precipitous discontinuation of zolpidem. Monitor patients for tolerance, abuse, and dependence [see Drug Abuse and Dependence].

Severe Injuries

Zolpidem can cause drowsiness and a decreased level of consciousness, which may pb to falls and consequently to severe injuries. Astringent injuries such equally hip fractures and intracranial hemorrhage take been reported.

Patient Counseling Information

Propose patients to read the FDA-canonical patient labeling (Medication Guide). Inform patients and their families about the benefits and risks of treatment with AMBIEN CR. Inform patients of the availability of a Medication Guide and instruct them to read the Medication Guide prior to initiating handling with AMBIEN CR and with each prescription refill. Review the AMBIEN CR Medication Guide with every patient prior to initiation of treatment. Instruct patients or caregivers that AMBIEN CR should be taken but as prescribed.

CNS Depressant Effects And Next-Day Harm

Tell patients that AMBIEN CR tin cause next-mean solar day harm fifty-fifty when used as prescribed, and that this risk is increased if dosing instructions are not carefully followed. Caution patients against driving and other activities requiring complete mental alertness the day after utilise. Inform patients that harm can be present despite feeling fully awake.

Astringent Anaphylactic And Anaphylactoid Reactions

Inform patients that severe anaphylactic and anaphylactoid reactions take occurred with zolpidem. Draw the signs/symptoms of these reactions and propose patients to seek medical attention immediately if any of them occur.

Sleep-driving And Other Complex Behaviors

Instruct patients and their families that allaying hypnotics can cause aberrant thinking and behavior change, including "slumber driving" and other complex behaviors while not being fully awake (preparing and eating nutrient, making phone calls, or having sex). Tell patients to telephone call you immediately if they develop any of these symptoms.

Suicide

Tell patients to immediately written report any suicidal thoughts.

Alcohol And Other Drugs

Ask patients about alcohol consumption, medicines they are taking, and drugs they may exist taking without a prescription. Advise patients not to apply AMBIEN CR if they drank alcohol that evening or before bed.

Tolerance, Abuse, And Dependence

Tell patients non to increase the dose of AMBIEN CR on their own, and to inform yous if they believe the drug "does not piece of work".

Administration Instructions

Patients should be counseled to take AMBIEN CR correct before they get into bed and merely when they are able to stay in bed a full dark (seven-8 hours) before being active again. AMBIEN CR tablets should not exist taken with or immediately afterwards a repast. Advise patients Non to take AMBIEN CR if they drank alcohol that evening.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Zolpidem was administered to mice and rats for 2 years at oral doses of 4, 18, and 80 mg base/kg. In mice, these doses are approximately 2, 9, and 40 times the maximum recommended human being dose (MRHD) of 12.5 mg/day (10 mg zolpidem base) on mg/m² ground. In rats, these doses are approximately 4, eighteen, and 80 times the MRHD on a mg/m² basis. No bear witness of carcinogenic potential was observed in mice. In rats, renal tumors (lipoma, liposarcoma) were seen at the mid-and loftier doses.

Mutagenesis

Zolpidem was negative in in vitro (bacterial reverse mutation, mouse lymphoma, and chromosomal aberration) and in vivo (mouse micronucleus) genetic toxicology assays.

Damage Of fertility

Oral administration of zolpidem (doses of 4, 20, and 100 mg base/kg/24-hour interval) to rats prior to and during mating, and continuing in females through postpartum day 25, resulted in irregular estrus cycles and prolonged precoital intervals at the highest dose tested. The no-effect dose for these findings is approximately 20 times the MRHD on a mg/m² basis. There was no harm of fertility at any dose tested.

Employ In Specific Populations

Pregnancy

Pregnancy Category C

There are no acceptable and well-controlled studies of AMBIEN CR in pregnant women. Studies in children to appraise the effects of prenatal exposure to zolpidem take not been conducted; notwithstanding, cases of severe neonatal respiratory depression have been reported when zolpidem was used at the end of pregnancy, specially when taken with other CNS depressants. Children born to mothers taking sedative-hypnotic drugs may be at risk for withdrawal symptoms during the postnatal period. Neonatal flaccidity has too been reported in infants born to mothers who received sedative-hypnotic drugs during pregnancy. AMBIEN CR should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.

Administration of zolpidem to significant rats and rabbits resulted in adverse furnishings on offspring development at doses greater than the AMBIEN CR maximum recommended human being dose (MRHD) of 12.v mg/solar day (approximately 10 mg/day zolpidem base); withal, teratogenicity was not observed.

When zolpidem was administered at oral doses of 4, xx, and 100 mg base/kg/day to significant rats during the period of organogenesis, dose-related decreases in fetal skull ossification occurred at all but the everyman dose, which is approximately 4 times the MRHD on a mg/m² ground. In rabbits treated during organogenesis with zolpidem at oral doses of 1, 4, and sixteen mg base/kg/day, increased embryo-fetal expiry and incomplete fetal skeletal ossification occurred at the highest dose. The no-effect dose for embryo-fetal toxicity in rabbits is approximately 8 times the MRHD on a mg/g² basis. Administration of zolpidem to rats at oral doses of 4, 20, and 100 mg base of operations/kg/day during the latter office of pregnancy and throughout lactation produced decreased offspring growth and survival at all merely the lowest dose, which is approximately four times the MRHD on a mg/chiliad² footing.

Labor And Delivery

AMBIEN CR has no established utilise in labor and delivery [see Pregnancy].

Nursing Mothers

Zolpidem is excreted in homo milk. Caution should be exercised when AMBIEN CR is administered to a nursing adult female.

Pediatric Use

AMBIEN CR is not recommended for use in children. Safety and effectiveness of zolpidem in pediatric patients below the age of 18 years have not been established.

In an 8-week study in pediatric patients (aged six-17 years) with indisposition associated with attention-deficit/hyperactivity disorder (ADHD) an oral solution of zolpidem tartrate dosed at 0.25 mg/kg at bedtime did not subtract sleep latency compared to placebo. Psychiatric and nervous organisation disorders comprised the most frequent ( > five%) treatment emergent adverse reactions observed with zolpidem versus placebo and included dizziness (23.5% vs. i.v%), headache (12.5% vs. 9.2%), and hallucinations were reported in vii% of the pediatric patients who received zolpidem; none of the pediatric patients who received placebo reported hallucinations [see WARNINGS AND PRECAUTIONS]. Ten patients on zolpidem (7.4%) discontinued treatment due to an agin reaction.

FDA has not required pediatric studies of AMBIEN CR in the pediatric population based on these efficacy and safety findings.

Geriatric Apply

A full of 99 elderly ( ≥ 65 years of historic period) received daily doses of 6.25 mg AMBIEN CR in a 3week placebo-controlled study. The adverse reaction profile of AMBIEN CR half dozen.25 mg in this population was similar to that of AMBIEN CR 12.5 mg in younger adults ( ≤ 64 years of age). Dizziness was reported in 8% of AMBIEN CR-treated patients compared with 3% of those treated with placebo.

The dose of AMBIEN CR in elderly patients is 6.25 mg to minimize adverse effects related to impaired motor and/or cognitive operation and unusual sensitivity to sedative/hypnotic drugs [run into WARNINGS AND PRECAUTIONS].

Gender Departure In Pharmacokinetics

Women clear zolpidem tartrate from the body at a lower rate than men. Cmax and AUC parameters of zolpidem from AMBIEN CR were, respectively, approximately l% and 75% college at the same dose in developed female subjects compared to developed male subjects. Betwixt six and 12 hours later dosing, zolpidem concentrations were 2-to 3 fold higher in adult female compared to adult male subjects. Given the higher claret levels of zolpidem tartrate in women compared to men at a given dose, the recommended initial dose of AMBIEN CR for developed women is 6.25 mg, and the recommended dose for adult men is six.25 or 12.5 mg.

In geriatric patients, clearance of zolpidem is similar in men and women. The recommended dose of AMBIEN CR in geriatric patients is 6.25 mg regardless of gender.

Hepatic Impairment

The recommended dose of AMBIEN CR in patients with balmy to moderate hepatic impairment is 6.25 mg once daily immediately before bedtime. Avoid AMBIEN CR use in patients with astringent hepatic impairment as it may contribute to encephalopathy [see DOSAGE AND Administration, WARNINGS AND PRECAUTIONS, CLINICAL PHARMACOLOGY].

Overdosage & Contraindications

OVERDOSE

Signs And Symptoms

In postmarketing experience of overdose with zolpidem tartrate alone, or in combination with CNS-depressant agents, damage of consciousness ranging from somnolence to coma, cardiovascular and/or respiratory compromise and fatal outcomes take been reported.

Recommended Treatment

Full general symptomatic and supportive measures should exist used along with immediate gastric lavage where appropriate. Intravenous fluids should exist administered every bit needed. Zolpidem's sedative hypnotic event was shown to exist reduced by flumazenil and therefore may be useful; however, flumazenil assistants may contribute to the advent of neurological symptoms (convulsions). As in all cases of drug overdose, respiration, pulse, claret force per unit area, and other appropriate signs should exist monitored and full general supportive measures employed. Hypotension and CNS depression should exist monitored and treated past appropriate medical intervention. Sedating drugs should be withheld following zolpidem overdosage, even if excitation occurs. The value of dialysis in the handling of overdosage has not been determined, although hemodialysis studies in patients with renal failure receiving therapeutic doses have demonstrated that zolpidem is not dialyzable.

As with the management of all overdosage, the possibility of multiple drug ingestion should be considered. The physician may wish to consider contacting a poisonous substance control center for upwards-todate information on the management of hypnotic drug product overdosage.

CONTRAINDICATIONS

AMBIEN CR is contraindicated in patients with known hypersensitivity to zolpidem. Observed reactions include anaphylaxis and angioedema [come across WARNINGS AND PRECAUTIONS].

CLINICAL PHARMACOLOGY

Mechanism Of Action

Zolpidem, the active moiety of zolpidem tartrate, is a hypnotic amanuensis with a chemic structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties. It interacts with a GABA-BZ receptor complex and shares some of the pharmacological properties of the benzodiazepines. In contrast to the benzodiazepines, which non-selectively demark to and activate all BZ receptor subtypes, zolpidem in vitro binds the BZ1 receptor preferentially with a high affinity ratio of the α1/α5 subunits. This selective binding of zolpidem on the BZ1 receptor is non absolute, but it may explain the relative absence of myorelaxant and anticonvulsant effects in animal studies besides equally the preservation of deep sleep (stages 3 and 4) in human being studies of zolpidem tartrate at hypnotic doses.

Pharmacokinetics

AMBIEN CR exhibits biphasic absorption characteristics, which results in rapid initial assimilation from the gastrointestinal tract similar to zolpidem tartrate immediate-release, then provides extended plasma concentrations beyond iii hours after administration. A report in 24 good for you male subjects was conducted to compare mean zolpidem plasma concentration-fourth dimension profiles obtained after unmarried oral administration of AMBIEN CR 12.5 mg and of an immediate-release conception of zolpidem tartrate (10 mg). The terminal elimination one-half-life observed with AMBIEN CR (12.5 mg) was like to that obtained with immediate-release zolpidem tartrate (ten mg). The mean plasma concentration-time profiles are shown in Effigy 1.

Figure 1: Mean plasma concentration-time profiles for AMBIEN CR (12.5 mg) and immediate-release zolpidem tartrate (ten mg)

Mean plasma concentration-time profiles - Illustration

In adult and elderly patients treated with AMBIEN CR, there was no prove of accumulation later repeated once-daily dosing for up to ii weeks.

Absorption

Following administration of AMBIEN CR, administered equally a single 12.five mg dose in healthy male adult subjects, the mean peak concentration (Cmax) of zolpidem was 134 ng/mL (range: 68.9 to 197 ng/ml) occurring at a median time (Tmax) of 1.v hours. The mean AUC of zolpidem was 740 ng•hr/mL (range: 295 to 1359 ng•60 minutes/mL).

A food-issue written report in 45 healthy subjects compared the pharmacokinetics of AMBIEN CR 12.5 mg when administered while fasting or inside 30 minutes subsequently a repast. Results demonstrated that with nutrient, hateful AUC and Cmax were decreased by 23% and 30%, respectively, while median Tmax was increased from 2 hours to 4 hours. The half-life was non changed. These results suggest that, for faster slumber onset, AMBIEN CR should not be administered with or immediately after a meal.

Distribution

Full protein binding was found to be 92.v ± 0.one% and remained constant, contained of concentration between 40 and 790 ng/mL.

Metabolism

Zolpidem is converted to inactive metabolites that are eliminated primarily by renal excretion.

Elimination

When AMBIEN CR was administered as a unmarried 12.five mg dose in healthy male person adult subjects, the hateful zolpidem elimination half-life was 2.8 hours (range: 1.62 to 4.05 hr).

Special Populations

Elderly

In 24 elderly ( ≥ 65 years) good for you subjects administered a single 6.25 mg dose of AMBIEN CR, the mean pinnacle concentration (Cmax) of zolpidem was 70.6 (range: 35.0 to 161) ng/mL occurring at a median time (Tmax) of two.0 hours. The mean AUC of zolpidem was 413 ng•hr/mL (range: 124 to 1190 ng•hr/mL) and the hateful elimination one-half-life was 2.ix hours (range: i.59 to 5.50 hours).

Hepatic Damage

AMBIEN CR was non studied in patients with hepatic impairment. The pharmacokinetics of an immediate-release conception of zolpidem tartrate in 8 patients with chronic hepatic insufficiency were compared to results in salubrious subjects. Post-obit a single 20-mg oral zolpidem tartrate dose, mean Cmax and AUC were found to exist two times (250 vs. 499 ng/mL) and five times (788 vs. four,203 ng•hr/mL) higher, respectively, in hepatically compromised patients. Tmax did not change. The hateful half-life in cirrhotic patients of 9.9 60 minutes (range: 4.1 to 25.viii hr) was greater than that observed in normal subjects of 2.two hr (range: 1.6 to 2.4 60 minutes) [see DOSAGE AND Administration, WARNINGS AND PRECAUTIONS, Use in Specific Populations].

Renal Harm

AMBIEN CR was not studied in patients with renal impairment. The pharmacokinetics of an immediate-release formulation of zolpidem tartrate were studied in xi patients with stop-stage renal failure (mean ClCr = 6.5 ± 1.5 mL/min) undergoing hemodialysis three times a calendar week, who were dosed with zolpidem tartrate ten mg orally each day for xiv or 21 days. No statistically pregnant differences were observed for Cmax, Tmax, half-life, and AUC between the get-go and terminal 24-hour interval of drug administration when baseline concentration adjustments were fabricated. Zolpidem was not hemodialyzable. No accumulation of unchanged drug appeared after fourteen or 21 days. Zolpidem pharmacokinetics were non significantly different in renally-dumb patients. No dosage adjustment is necessary in patients with compromised renal role.

Drug Interactions

CNS-depressants

Co-administration of zolpidem with other CNS depressants increases the take chances of CNS depression [see WARNINGS AND PRECAUTIONS]. Zolpidem tartrate was evaluated in salubrious volunteers in single-dose interaction studies for several CNS drugs. Imipramine in combination with zolpidem produced no pharmacokinetic interaction other than a 20% decrease in peak levels of imipramine, but at that place was an additive issue of decreased alertness. Similarly, chlorpromazine in combination with zolpidem produced no pharmacokinetic interaction, simply in that location was an additive result of decreased alacrity and psychomotor performance.

A study involving haloperidol and zolpidem revealed no issue of haloperidol on the pharmacokinetics or pharmacodynamics of zolpidem. The lack of a drug interaction following single-dose administration does not predict the absence of an issue following chronic administration.

An additive adverse issue on psychomotor performance between alcohol and oral zolpidem was demonstrated [meet WARNINGS AND PRECAUTIONS].

Following five consecutive nightly doses at bedtime of oral zolpidem tartrate 10 mg in the presence of sertraline l mg (17 sequent daily doses, at 7:00 am, in good for you female person volunteers), zolpidem Cmax was significantly higher (43%) and Tmax was significantly decreased (-53%). Pharmacokinetics of sertraline and N-desmethylsertraline were unaffected by zolpidem.

A unmarried-dose interaction study with zolpidem tartrate 10 mg and fluoxetine xx mg at steady-country levels in male volunteers did non demonstrate any clinically significant pharmacokinetic or pharmacodynamic interactions. When multiple doses of zolpidem and fluoxetine were given at steady state and the concentrations evaluated in healthy females, an increase in the zolpidem half-life (17%) was observed. There was no evidence of an condiment effect in psychomotor performance.

Drugs That Touch Drug Metabolism Via Cytochrome P450

Some compounds known to inhibit CYP3A may increase exposure to zolpidem. The effect of inhibitors of other P450 enzymes on the pharmacokinetics of zolpidem is unknown.

A single-dose interaction study with zolpidem tartrate 10 mg and itraconazole 200 mg at steady-state levels in male volunteers resulted in a 34% increase in AUC0-∞of zolpidem tartrate. There were no pharmacodynamic effects of zolpidem detected on subjective drowsiness, postural sway, or psychomotor operation.

A single-dose interaction written report with zolpidem tartrate 10 mg and rifampin 600 mg at steady-country levels in female subjects showed meaning reductions of the AUC (-73%), Cmax (-58%), and T½ (-36 %) of zolpidem together with significant reductions in the pharmacodynamic effects of zolpidem tartrate. Rifampin, a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects of zolpidem [see DRUG INTERACTIONS].

A single-dose interaction study with zolpidem tartrate 5 mg and ketoconazole, a potent CYP3A4 inhibitor, given as 200 mg twice daily for ii days increased Cmax of zolpidem (xxx%) and the full AUC of zolpidem (70%) compared to zolpidem solitary and prolonged the elimination half-life (30 %) along with an increment in the pharmacodynamic effects of zolpidem [see DRUG INTERACTIONS].

Additionally, fluvoxamine (a strong inhibitor of CYP1A2 and a weak inhibitor of CYP3A4 and CYP2C9) and ciprofloxacin (a stiff inhibitor of CYP1A2 and a moderate inhibitor of CYP3A4) are also probable to inhibit zolpidem's metabolic pathways, potentially leading to an increase in zolpidem exposure.

Other Drugs With No Interactions With Zolpidem

A study involving cimetidine/zolpidem tartrate and ranitidine/zolpidem tartrate combinations revealed no effect of either drug on the pharmacokinetics or pharmacodynamics of zolpidem.

Zolpidem tartrate had no consequence on digoxin pharmacokinetics and did not affect prothrombin time when given with warfarin in salubrious subjects.

Clinical Studies

Controlled Clinical Trials

AMBIEN CR was evaluated in three placebo-controlled studies for the handling 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 indisposition (N=212) were evaluated in a double-blind, randomized, parallel-grouping, iii-week trial comparing AMBIEN CR 12.5 mg and placebo. AMBIEN CR 12.5 mg decreased wake time later sleep onset (WASO) for the start vii hours during the first 2 nights and for the first five hours afterwards 2 weeks of treatment. AMBIEN CR 12.5 mg was superior to placebo on objective measures (polysomnography recordings) of slumber consecration (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 likewise superior to placebo on the patient reported global impression regarding the help to slumber later the get-go 2 nights and after 3 weeks of treatment.

Elderly outpatients ( ≥ 65 years) with chief indisposition (North=205) were evaluated in a double-bullheaded, randomized, parallel-group, 3-week trial comparison AMBIEN CR half-dozen.25 mg and placebo. AMBIEN CR 6.25 mg decreased wake time after sleep onset (WASO) for the kickoff 6 hours during the start two nights and the beginning 4 hours after 2 weeks of treatment. AMBIEN CR 6.25 mg was superior to placebo on objective measures (polysomnography recordings) of slumber consecration (by decreasing LPS) during the outset 2 nights of treatment and after ii weeks on handling. AMBIEN CR 6.25 mg was superior to placebo on the patient reported global impression regarding the assist to sleep subsequently the first 2 nights and subsequently three weeks of treatment.

In both studies, in patients treated with AMBIEN CR, polysomnography showed increased wakefulness at the cease of the dark compared to placebo-treated patients.

In a 24-week double-bullheaded, placebo controlled, randomized study in adult outpatients (18-64 years) with primary insomnia (N=1025), AMBIEN CR 12.5 mg administered every bit needed (iii to 7 nights per calendar week) was superior to placebo over 24 weeks, on patient global impression regarding aid to sleep, and on patient-reported specific slumber parameters for slumber induction and slumber maintenance with no significant increased frequency of drug intake observed over time.

Studies Pertinent To Safety Concerns For Sedative/Hypnotic Drugs

Side by side-day Balance Effects

In five clinical studies [three controlled studies in adults (eighteen-64 years of age) administered AMBIEN CR 12.five mg and ii controlled studies in the elderly ( ≥ 65 years of historic period) administered AMBIEN CR 6.25 mg or 12.v mg], the upshot of AMBIEN CR on vigilance, retention, or motor function were assessed using neurocognitive tests. In these studies, no significant decrease in operation was observed eight hours after a night dose. In addition, no evidence of next-solar day residual effects was detected with AMBIEN CR 12.5 mg and 6.25 mg using self-ratings of sedation.

During the iii-week studies, next-24-hour interval somnolence was reported by 15% of the adult patients who received 12.5 mg AMBIEN CR versus 2% of the placebo group; side by side-day somnolence was reported by vi% of the elderly patients who received half-dozen.25 mg AMBIEN CR versus 5% of the placebo group [see ADVERSE REACTIONS]. In a 6-month written report, the overall incidence of adjacent-twenty-four hour period somnolence was 5.7% in the AMBIEN CR group as compared to ii% in the placebo group.

Rebound Effects

Rebound insomnia, defined every bit a dose-dependent worsening in sleep parameters (latency, sleep efficiency, and number of awakenings) compared with baseline following discontinuation of handling, is observed with short-and intermediate-interim hypnotics. In the 2 3-week placebo-controlled studies in patients with primary insomnia, a rebound effect was merely observed on the first night after abrupt discontinuation of AMBIEN CR. On the second night, there was no worsening compared to baseline in the AMBIEN CR group.

In a six-calendar month placebo-controlled written report in which AMBIEN CR was taken as needed (3 to 7 nights per week), within the showtime calendar month a rebound outcome was observed for Total Sleep Time (not for WASO) during the get-go night off medication. After this kickoff calendar month menstruation, no further rebound insomnia was observed. After last treatment discontinuation no rebound was observed.

PATIENT INFORMATION

AMBIEN CR®
(am'be-en run across ahr)
(zolpidem tartrate) Extended-release Tablets

Read the Medication Guide that comes with AMBIEN CR earlier you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider nearly your medical condition or treatment.

What is the well-nigh important information I should know about AMBIEN CR?

Do not take more AMBIEN CR than prescribed.
Practice not accept AMBIEN CR unless you are able to stay in bed a total night (7 to 8 hours) before yous must be active again.
Accept AMBIEN CR right before you get in bed, not sooner.

AMBIEN CR may crusade serious side effects that yous may not know are happening to you. These side effects include:

sleepiness during the day
not thinking conspicuously
deed strangely, confused, or upset
"sleep-walking" or doing other activities when y'all are asleep like:
- eating
- talking
- having sexual practice
- driving a auto

Telephone call your healthcare provider right abroad if you observe out that you accept done any of the above activities subsequently taking AMBIEN CR.

Yous should not bulldoze a car or do things that require clear thinking the day subsequently you have AMBIEN CR.

Practise not accept AMBIEN CR if you lot:

drank booze that evening or before bed
take other medicines that can brand you sleepy. Taking AMBIEN CR with other drugs can cause side furnishings. Talk to your healthcare provider about all of your medicines. Your healthcare provider volition tell you if yous can take AMBIEN CR with your other medicines.
cannot go a full night'south sleep

What is AMBIEN CR?

AMBIEN CR is a sedative-hypnotic (sleep) medicine. AMBIEN CR is used in adults for the handling of a sleep problem chosen indisposition. Symptoms of insomnia include:

trouble falling comatose
waking up oftentimes during the night

It is not known if AMBIEN CR is prophylactic and effective in children nether the age of xviii years.

AMBIEN CR is a federally controlled substance (C-Iv) considering information technology can be abused or lead to dependence. Keep AMBIEN CR in a prophylactic place to prevent misuse and abuse. Selling or giving abroad AMBIEN CR may harm others, and is against the law. Tell your healthcare provider if yous have ever abused or have been dependent on alcohol, prescription medicines or street drugs.

Who should not take AMBIEN CR?

Do not take AMBIEN CR if y'all are allergic to zolpidem or whatsoever other ingredients in AMBIEN CR. See the end of this Medication Guide for a complete list of ingredients in AMBIEN CR.
Do not have AMBIEN CR if you have had an allergic reaction to drugs containing zolpidem, such equally Ambien, Edluar, Zolpimist, or Intermezzo.

Symptoms of a serious allergic reaction to zolpidem can include:

swelling of your face, lips, and throat that may crusade difficulty breathing or swallowing

What should I tell my healthcare provider before taking AMBIEN CR?

AMBIEN CR may not be right for you lot. Earlier starting AMBIEN CR, tell your healthcare provider about all of your health atmospheric condition, including if you:

take a history of depression, mental illness, or suicidal thoughts
have a history of drug or booze abuse or habit
accept kidney or liver disease
have a lung disease or breathing problems
are pregnant, planning to become pregnant. It is not known if AMBIEN CR will harm your unborn infant.
are breastfeeding or plan to breastfeed. AMBIEN CR can pass into your chest milk. It is not known if AMBIEN CR will impairment your baby. Talk to your healthcare provider about the best way to feed your infant while you take AMBIEN CR.

Tell your healthcare provider about all of the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements.

Medicines can interact with each other, sometimes causing serious side effects. Exercise not accept AMBIEN CR with other medicines that tin can make you sleepy unless your healthcare provider tells y'all to.

Know the medicines you accept. Go on a listing of your medicines with you to show your healthcare provider and pharmacist each time yous get a new medicine.

How should I take AMBIEN CR?

Come across "What is the most of import information I should know about AMBIEN CR?"
Take AMBIEN CR exactly every bit prescribed. Just have 1 AMBIEN CR tablet a night if needed.
Exercise not have AMBIEN CR if you drank alcohol that evening or before bed.
Y'all should not have AMBIEN CR with or right after a meal. AMBIEN CR may aid you lot autumn asleep faster if y'all have information technology on an empty tum.
Take AMBIEN CR Tablets whole. Do not intermission, beat out, dissolve or chew AMBIEN CR tablets before swallowing. If you cannot swallow AMBIEN CR tablets whole, tell your healthcare provider. You may need a different medicine.
Phone call your healthcare provider if your insomnia worsens or is non better within 7 to x days. This may hateful that there is another condition causing your sleep problems.
If yous take as well much AMBIEN CR or overdose, get emergency treatment.

What are the possible side effects of AMBIEN CR?

AMBIEN CR may crusade serious side effects including:

getting out of bed while not being fully awake and doing an activity that you lot do not know you lot are doing. (Come across "What is the nigh important information I should know nigh AMBIEN CR?")
abnormal thoughts and behavior. Symptoms include more outgoing or aggressive behavior than normal, confusion, agitation, hallucinations, worsening of depression, and suicidal thoughts or actions.
memory loss
anxiety
severe allergic reactions. Symptoms include swelling of the natural language or throat, trouble breathing, and nausea and airsickness. Get emergency medical help if you go these symptoms later taking AMBIEN CR.
falls, which may lead to astringent injuries

Call your healthcare provider right abroad if you have whatsoever of the in a higher place side effects or any other side effects that worry you lot while using AMBIEN CR.

The nearly mutual side effects of AMBIEN CR are:

headache
sleepiness
dizziness
drowsiness the adjacent mean solar day after you accept AMBIEN CR

Later you cease taking a sleep medicine, y'all may have symptoms for i to 2 days such every bit:

trouble sleeping
nausea
flushing
lightheadedness
uncontrolled crying
vomiting
tummy cramps
panic assail
nervousness
stomach area pain

These are non all the side furnishings of AMBIEN CR. Ask your healthcare provider or pharmacist for more information.

Call your healthcare provider for medical advice about side furnishings. You may report side effects to FDA at 1-800-FDA-1088.

How should I store AMBIEN CR?

Shop AMBIEN CR at room temperature, 59°F to 77°F (15°C to 25° C).

Keep AMBIEN CR and all medicines out of reach of children.

Full general Data about the safe and effective utilize of AMBIEN CR

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not utilize AMBIEN CR for a condition for which it was not prescribed. Practice not share AMBIEN CR with other people, even if you lot recall they accept the same symptoms that you lot have. Information technology may harm them and it is against the law.

This Medication Guide summarizes the almost important data nearly AMBIEN CR. If y'all would like more information, talk with your healthcare provider. You lot tin can ask your healthcare provider or pharmacist for information about AMBIEN CR that is written for healthcare professionals.

For more information, get to www.ambiencr.com or call i-800-633-1610.

What are the ingredients in AMBIEN CR?

Active Ingredient: Zolpidem tartrate

Inactive Ingredients:

The 6.25 mg tablets contain: 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 tablets incorporate: 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.

This Medication Guide has been approved by the U.S. Food and Drug Assistants.