Ambien CR Side Effects
Generic Name: zolpidem
Please note - some side effects for Ambien CR may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).
Side Effects of Ambien CR - for the Consumer
Ambien CR Extended-Release Tablets
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Ambien CR Extended-Release Tablets:
Seek medical attention right away if any of these SEVERE side effects occur when using Ambien CR Extended-Release Tablets:Dizziness; drowsiness (including daytime drowsiness); "drugged" feeling; dry mouth; headache; muscle aches; nausea; nose or throat irritation; sluggishness; stomach upset.
TopSevere allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the hands, legs, mouth, face, lips, eyes, throat, or tongue; unusual hoarseness); abnormal thinking; behavior changes; chest pain; confusion; decreased coordination; difficulty swallowing or breathing; fainting; fast or irregular heartbeat; hallucinations; memory problems (eg, memory loss); mental or mood changes (eg, aggression, agitation, anxiety, depression); severe dizziness; shortness of breath; suicidal thoughts or actions; vision changes.
Ambien CR Side Effects - for the Professional
Ambien CR
The following serious adverse reactions are discussed in greater detail in other sections of the labeling:
- Serious anaphylactic and anaphylactoid reactions [see Warnings and Precautions (5.2)]
- Abnormal thinking, behavior changes, and complex behaviors [see Warnings and Precautions (5.3)]
- Withdrawal effects [see Warnings and Precautions (5.4)]
- CNS-depressant effects [see Warnings and Precautions (5.5)]
6.1 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 12.5 mg discontinued treatment due to an adverse reaction as compared to 0.9% (2/216) of patients on placebo. The reaction most commonly associated with discontinuation in patients treated with Ambien CR was somnolence (1%).
In a 6-month study in adult patients (18–64 years of age), 8.5% (57/669) of patients receiving Ambien CR 12.5 mg as compared to 4.6% on placebo (16/349) discontinued treatment due to an adverse reaction. Reactions most commonly associated with discontinuation of Ambien CR included anxiety (anxiety, restlessness or agitation) reported in 1.5% (10/669) of patients as compared to 0.3% (1/349) of patients on placebo, and depression (depression, major depression or depressed mood) reported in 1.5% (10/669) 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 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 after an attempted suicide.
Most commonly observed adverse reactions 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 reactions associated with the use of Ambien CR were headache, next-day somnolence, and dizziness.
In the 6-month trial evaluating Ambien CR 12.5 mg, the adverse reaction profile was consistent 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 following tables enumerate treatment-emergent adverse reaction 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 reactions occurring at an incidence of at least 1% for Ambien CR patients and with an incidence greater than that seen in the placebo patients.
| Body System/Adverse Reaction * | Ambien CR 12.5 mg |
Placebo |
|---|---|---|
| (N = 102) | (N = 110) | |
| Infections and infestations | ||
| Influenza | 3 | 0 |
| Gastroenteritis | 1 | 0 |
| Labyrinthitis | 1 | 0 |
| Metabolism and nutrition disorders | ||
| Appetite disorder | 1 | 0 |
| Psychiatric disorders | ||
| Hallucinations † | 4 | 0 |
| Disorientation | 3 | 2 |
| Anxiety | 2 | 0 |
| Depression | 2 | 0 |
| Psychomotor retardation | 2 | 0 |
| Binge eating | 1 | 0 |
| Depersonalization | 1 | 0 |
| Disinhibition | 1 | 0 |
| Euphoric mood | 1 | 0 |
| Mood swings | 1 | 0 |
| Stress symptoms | 1 | 0 |
| Nervous system disorders | ||
| Headache | 19 | 16 |
| Somnolence | 15 | 2 |
| Dizziness | 12 | 5 |
| Memory disorders ‡ | 3 | 0 |
| Balance disorder | 2 | 0 |
| Disturbance in attention | 2 | 0 |
| Hypoesthesia | 2 | 1 |
| Ataxia | 1 | 0 |
| Paresthesia | 1 | 0 |
| Eye disorders | ||
| Visual disturbance | 3 | 0 |
| Eye redness | 2 | 0 |
| Vision blurred | 2 | 1 |
| Altered visual depth perception | 1 | 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 | 4 |
| Constipation | 2 | 0 |
| Abdominal discomfort | 1 | 0 |
| Abdominal tenderness | 1 | 0 |
| Frequent bowel movements | 1 | 0 |
| Gastroesophageal reflux disease |
1 | 0 |
| Vomiting | 1 | 0 |
| Skin and subcutaneous tissue disorders | ||
| Rash | 1 | 0 |
| Skin wrinkling | 1 | 0 |
| Urticaria | 1 | 0 |
| Musculoskeletal and connective tissue disorders | ||
| Back pain | 4 | 3 |
| Myalgia | 4 | 0 |
| Neck pain | 1 | 0 |
| Reproductive system and breast disorders | ||
| Menorrhagia | 1 | 0 |
| General disorders and administration site conditions | ||
| Fatigue | 3 | 2 |
| Asthenia | 1 | 0 |
| Chest discomfort | 1 | 0 |
| Investigations | ||
| Blood pressure increased | 1 | 0 |
| Body temperature increased | 1 | 0 |
| Injury, poisoning and procedural complications | ||
| Contusion | 1 | 0 |
| Social circumstances | ||
| Exposure to poisonous plant | 1 | 0 |
| Body System/Adverse Reaction * | Ambien CR | Placebo |
|---|---|---|
| 6.25 mg (N=99) |
(N=106) | |
| Infections and infestations | ||
| Nasopharyngitis | 6 | 4 |
| Lower respiratory tract infection | 1 | 0 |
| Otitis externa | 1 | 0 |
| Upper respiratory tract infection | 1 | 0 |
| Psychiatric disorders | ||
| Anxiety | 3 | 2 |
| Psychomotor retardation | 2 | 0 |
| Apathy | 1 | 0 |
| Depressed mood | 1 | 0 |
| Nervous system disorders | ||
| Headache | 14 | 11 |
| Dizziness | 8 | 3 |
| Somnolence | 6 | 5 |
| Burning sensation | 1 | 0 |
| Dizziness postural | 1 | 0 |
| Memory disorders † | 1 | 0 |
| Muscle contractions involuntary | 1 | 0 |
| Paresthesia | 1 | 0 |
| Tremor | 1 | 0 |
| Cardiac disorders | ||
| Palpitations | 2 | 0 |
| Respiratory, thoracic and mediastinal disorders | ||
| Dry throat | 1 | 0 |
| Gastrointestinal disorders | ||
| Flatulence | 1 | 0 |
| Vomiting | 1 | 0 |
| Skin and subcutaneous tissue disorders | ||
| Rash | 1 | 0 |
| Urticaria | 1 | 0 |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 2 | 0 |
| Muscle cramp | 2 | 1 |
| Neck pain | 2 | 0 |
| Renal and urinary disorders | ||
| Dysuria | 1 | 0 |
| Reproductive system and breast disorders | ||
| Vulvovaginal dryness | 1 | 0 |
| General disorders and administration site conditions | ||
| Influenza like illness | 1 | 0 |
| Pyrexia | 1 | 0 |
| Injury, poisoning and procedural complications | ||
| Neck injury | 1 | 0 |
Dose relationship for adverse reactions: There is evidence from dose comparison trials suggesting a dose relationship for many of the adverse reactions associated with zolpidem use, particularly for certain CNS and gastrointestinal adverse events.
Other adverse 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 different 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 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 frequencies presented, 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 zolpidem. All reported treatment-emergent adverse 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 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: asthenia. Infrequent: chest pain, edema, falling, 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: 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, drowsiness, drugged feeling, euphoria, insomnia, lethargy, lightheadedness, vertigo. Infrequent: agitation, decreased cognition, detached, difficulty concentrating, dysarthria, emotional lability, hallucination, hypoesthesia, illusion, leg cramps, migraine, nervousness, paresthesia, 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: 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: 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: Infrequent: arthritis. Rare: arthrosis, muscle weakness, sciatica, tendinitis.
Reproductive system: Infrequent: menstrual disorder, vaginitis. Rare: breast fibroadenosis, breast neoplasm, breast pain.
Respiratory system: Frequent: sinusitis. Infrequent: bronchitis, coughing, dyspnea. Rare: bronchospasm, epistaxis, hypoxia, laryngitis, pneumonia.
Skin and appendages: 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.
TopSide Effects by Body System
General
In general, zolpidem is well-tolerated and causes little or no residual daytime effects in most young adult volunteers. Additionally, zolpidem does not significantly alter sleep architecture at recommended doses.
General side effects including fatigue have been reported.
Nervous system
Chronic use in high doses and subsequent withdrawal may induce grand mal seizures. Cases of falls have been reported in elderly patients.
Nervous system side effects most frequently have included visual disturbances, ataxia, and dizziness. Headache, drugged feeling, confusion, anterograde amnesia, excessive sedation, lightheadedness, delirium, nightmares, hallucinations, nervousness, and agitation have also been reported.
Hypersensitivity
Hypersensitivity side effects including rare 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.
Gastrointestinal
Gastrointestinal side effects have included nausea, vomiting, dyspepsia, anorexia, and diarrhea. In clinical studies on the sublingual tablet, one patient developed transient sublingual erythema and another patient developed transient paresthesia of the tongue.
Other
Other side effects including tolerance to the pharmacologic effects of zolpidem have been reported rarely. Withdrawal symptoms after either abrupt cessation or fast tapering may occur. Withdrawal symptoms may include agitation, restlessness, anxiety, depression, insomnia, tremor, nausea, abdominal discomfort, and sweating.
A case of sleep driving has also been reported.
Psychiatric
Psychiatric side effects including cases of psychotic reactions have been reported in association with zolpidem therapy.
Respiratory
Zolpidem-induced respiratory depression may be responsive to flumazenil. Zolpidem-induced respiratory depression is generally not clinically significant at the usual hypnotic doses even in patients with impaired respiratory function.
One study has suggested that zolpidem doses of 20 mg (twice the usual dose) may cause apneic episodes in patients with obstructive sleep apnea.
Respiratory side effects have included respiratory depression which may occur at high doses. Upper respiratory infection and rhinitis have also been reported.
Cardiovascular
Cardiovascular side effects including palpitations have been reported in patients taking zolpidem.
Genitourinary
Genitourinary side effects including urinary incontinence and urinary tract infection have been reported.
Hepatic
Hepatic side effects include one case of hepatotoxicity associated with zolpidem given alone at therapeutic doses.
Immunologic
Immunologic side effects including infection have been reported infrequently.
Musculoskeletal
Musculoskeletal side effects including arthralgia and myalgia have been reported.
TopMore Ambien CR resources
- Ambien CR Prescribing Information (FDA)
- Ambien CR Extended-Release Tablets Medfacts Consumer Leaflet (Wolters Kluwer)
- Ambien CR Advanced Consumer (Micromedex) - Includes Dosage Information
- Zolpidem Prescribing Information (FDA)
- Ambien Prescribing Information (FDA)
- Ambien Medfacts Consumer Leaflet (Wolters Kluwer)
- Ambien Detailed Consumer Information (PDR)
- Ambien Consumer Overview
- Edluar Medfacts Consumer Leaflet (Wolters Kluwer)
- Edluar Consumer Overview
- Edluar Prescribing Information (FDA)
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