Ambien CR

Name: Ambien CR

What is zolpidem, and how does it work (mechanism of action)?

  • Zolpidem belongs to a class of drugs called sedatives or hypnotics. Zolpidem shares some characteristics of a family of sedatives called benzodiazepines. Benzodiazepines cause sedation, muscle relaxation, act as anti-convulsants (anti-seizure medications), and reduce anxiety. Zolpidem has selectivity in that it has little of the muscle relaxant and anti-seizure effects and more of the sedative effect. Therefore, it is used primarily as a medication for sleep. The oral spray form of zolpidem, Zolpimist, has more rapid absorption than the tablet form because it is absorbed through the lining of the mouth.

The FDA approved zolpidem in December 1992.

Uses of Ambien CR

Ambien CR is a prescription medicine used in adults for the treatment of a sleep problem called insomnia (difficulty falling asleep or staying asleep). It slows brain activity to allow sleep.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Ambien CR Drug Class

Ambien CR is part of the drug class:

  • Benzodiazepine related drugs

Ambien CR Usage

Take Ambien CR exactly as prescribed. Do not take more Ambien CR than prescribed for you.

  • Take Ambien CR right before you get into bed.
  • Do not take Ambien CR unless you are able to stay in bed a full night (7–8 hours) before you must be active again.
  • Ambien CR should be taken without food. The effect of Ambien CR may be slowed if taken with or immediately after a meal
  • Swallow Ambien CR whole. Do not crush, divide or chew Ambien CR tablets.
  • Call your doctor if your insomnia worsens or is not better within 7 to 10 days. This may mean that there is another condition causing your sleep problem.

How is this medicine (Ambien CR) best taken?

Use Ambien CR as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Use this medicine only for short periods of time (7 to 10 days).
  • If you still have trouble sleeping after 7 to 10 days, call your doctor.
  • Take Ambien CR (zolpidem extended-release tablets) at bedtime.
  • Take this medicine only 1 time per night.
  • Take on an empty stomach.
  • Take Ambien CR right before you get into bed.
  • Swallow whole. Do not chew, break, or crush.
  • Do not take this medicine unless you can get a full night's sleep (at least 7 to 8 hours) before you need to be active again.

What do I do if I miss a dose?

  • If you take Ambien CR on a regular basis, take a missed dose as soon as you think about it.
  • If you will not be able to get a full night's sleep (at least 7 hours) after taking the missed dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • Do not take more than 1 dose of this medicine in the same day.
  • Many times Ambien CR is taken on an as needed basis. Do not take more often than told by the doctor.

Ambien CR Dosage and Administration

Dosage in Adults

Use 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 once per night immediately before bedtime with at least 7–8 hours remaining before the planned time of awakening. If the 6.25 mg dose is not effective, the dose can be increased to 12.5 mg. In some patients, the higher morning blood levels following use of the 12.5 mg dose increase the risk of next day impairment of driving and other activities that require full alertness [see Warnings and Precautions (5.1)]. The total dose of Ambien CR should not exceed 12.5 mg once daily immediately before bedtime. Ambien CR should be taken as a single dose and should not be readministered during the same night.

The recommended initial doses for women and men are different because 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 [see Warnings and Precautions (5.1), Use in Specific Populations (8.5)].

Patients with mild to moderate hepatic impairment do not clear the drug as rapidly as normal subjects. The recommended dose of Ambien CR in these patients is 6.25 mg once daily immediately before bedtime. Avoid Ambien CR use in patients with severe hepatic impairment as it may contribute to encephalopathy [see Warnings and Precautions (5.7), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

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 (5.1)].

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.

Contraindications

Ambien CR is contraindicated in patients with known hypersensitivity to zolpidem. Observed reactions include anaphylaxis and angioedema [see Warnings and Precautions (5.3)].

Warnings and Precautions

CNS Depressant Effects and Next-Day Impairment

Ambien CR is a central nervous system (CNS) depressant and can impair daytime function in some patients even when used as prescribed. Prescribers should monitor for excess depressant effects, but impairment can occur in the absence of subjective symptoms, and may not be reliably detected by ordinary clinical exam (i.e. 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 be cautioned against driving or engaging in other hazardous activities or activities requiring complete mental alertness the day after use.

Additive effects occur with concomitant use of other CNS depressants (e.g. benzodiazepines, opioids, tricyclic antidepressants, alcohol), including daytime use. Downward dose adjustment of Ambien CR and concomitant CNS depressants should be considered [see Dosage and Administration (2.3)].

The use of Ambien CR with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended.

The 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 [see Dosage and Administration (2) and Clinical Studies (14.2)].

Vehicle drivers and machine operators should be warned that, as with other hypnotics, there may be a possible risk of adverse reactions including drowsiness, prolonged reaction time, dizziness, sleepiness, blurred/double vision, reduced alertness and impaired driving the morning after therapy. In order to minimize this risk a full night of sleep (7-8 hours) is recommended.

Need to Evaluate for Co-morbid Diagnoses

Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. Such findings have emerged during the course of treatment with sedative/hypnotic drugs, including zolpidem.

Severe Anaphylactic and Anaphylactoid Reactions

Cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first 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 have required medical therapy in the emergency department. If angioedema involves the throat, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with zolpidem should not be rechallenged with the drug.

Abnormal Thinking and Behavioral Changes

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

In controlled trials, <1% 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 (8.4)].

Complex behaviors such as "sleep-driving" (i.e., driving while not fully awake after ingestion of a sedative-hypnotic, with amnesia for the event) have been reported in sedative-hypnotic-naive as well as in sedative-hypnotic-experienced persons. Although behaviors such as "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 be strongly considered for patients who report a "sleep-driving" episode.

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

It can 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 any new behavioral sign or symptom of concern requires careful and immediate evaluation.

Use in Patients with Depression

In primarily depressed patients treated with sedative-hypnotics, worsening of depression, and suicidal thoughts and actions (including completed suicides), have been reported. Suicidal tendencies may be 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 be prescribed for the patient at any one time.

Respiratory Depression

Although studies with 10 mg zolpidem tartrate did not reveal respiratory depressant effects at hypnotic doses in healthy subjects or in patients with mild-to-moderate chronic obstructive pulmonary disease (COPD), a reduction in the Total Arousal Index, together with a reduction in lowest 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 have the capacity to depress respiratory drive, precautions should be taken if Ambien CR is prescribed to patients with compromised respiratory function. Post-marketing reports of respiratory insufficiency in patients receiving 10 mg of zolpidem tartrate, most of whom had pre-existing respiratory impairment, have been reported. The risk of respiratory depression should be considered prior to prescribing Ambien CR in patients with respiratory impairment including sleep apnea and myasthenia gravis.

Precipitation of Hepatic Encephalopathy

GABA agonists such as zolpidem tartrate have been associated with precipitation of hepatic encephalopathy in patients with hepatic insufficiency. In addition, patients with hepatic insufficiency do not clear zolpidem tartrate as rapidly as patients with normal hepatic function. Avoid Ambien CR use in patients with severe hepatic impairment as it may contribute to encephalopathy [see Dosage and Administration (2.2), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

Withdrawal Effects

There have been reports of withdrawal signs and symptoms following the rapid dose decrease or abrupt discontinuation of zolpidem. Monitor patients for tolerance, abuse, and dependence [see Drug Abuse and Dependence (9.2) and (9.3)].

Severe Injuries

Zolpidem can cause drowsiness and a decreased level of consciousness, which may lead to falls and consequently to severe injuries. Severe injuries such as hip fractures and intracranial hemorrhage have been reported.

Ambien CR 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 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.

How Supplied/Storage and Handling

Ambien CR 6.25 mg tablets are composed of two layers1 and are coated, pink, round, bi-convex, 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 layers1 and are coated, blue, round, bi-convex, debossed with A~ on one side and supplied as:

NDC Number Size
0024-5521-31 bottle of 100
0024-5521-50 bottle of 500
0024-5521-10 carton of 30 unit dose
1 Layers are covered by the coating and are indistinguishable.

Store between 15°–25° C (59°–77°F). Limited excursions permissible up to 30° C (86°F)

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

What is zolpidem (ambien, ambien cr, edluar, intermezzo, zolpimist)?

Zolpidem is a sedative, also called a hypnotic. It affects chemicals in your brain that may become unbalanced and cause sleep problems (insomnia).

Zolpidem is used to treat insomnia. The immediate-release forms of zolpidem are Ambien, Intermezzo,Edluar, and Zolpimist, which are used to help you fall asleep. The extended-release form of zolpidem is Ambien CR, which has a first layer that dissolves quickly to help you fall asleep, and a second layer that dissolves slowly to help you stay asleep.

Ambien, Edluar, and Zolpimist are used to help you fall asleep when you first go to bed. Intermezzo, is used to help you fall back to sleep if you wake up in the middle of the night and then have trouble sleeping.

Your doctor will determine which form of zolpidem is best for you.

Zolpidem may also be used for purposes not listed in this medication guide.

Before taking this medicine

Some people using this medicine have engaged in activity such as driving, eating, walking, making phone calls, or having sex and later having no memory of the activity. If this happens to you, stop taking Ambien CR and talk with your doctor about another treatment for your sleep disorder.

You should not use this medicine if you are allergic to Ambien CR. This medicine tablets may contain lactose. Use caution if you are sensitive to lactose.

To make sure Ambien CR is safe for you, tell your doctor if you have:

  • kidney disease;

  • liver disease;

  • lung disease such as asthma, bronchitis, emphysema, or chronic obstructive pulmonary disease (COPD);

  • sleep apnea (breathing stops during sleep);

  • myasthenia gravis;

  • a history of depression, mental illness, or suicidal thoughts; or

  • a history of drug or alcohol addiction.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Zolpidem can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

The sedative effects of Ambien CR may be stronger in older adults.

Ambien CR is not approved for use by anyone younger than 18 years old.

It is dangerous to try and purchase Ambien CR on the Internet or from vendors outside of the United States. Medications distributed from Internet sales may contain dangerous ingredients, or may not be distributed by a licensed pharmacy. Samples of this medicine purchased on the Internet have been found to contain haloperidol (Haldol), a potent antipsychotic drug with dangerous side effects. For more information, contact the U.S. Food and Drug Administration (FDA) or visit www.fda.gov/buyonlineguide.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of Ambien CR can be fatal, especially when it is taken together with other medications that can cause drowsiness.

Overdose symptoms may include sleepiness, confusion, shallow breathing, feeling light-headed, fainting, or coma.

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