Estazolam
Tablet · Oral
Uses
Estazolam tablets, USP are indicated for the short-term management of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. Both outpatient studies and a sleep laboratory study have shown that estazolam administered at bedtime improved sleep induction and sleep maintenance (see CLINICAL PHARMACOLOGY ). Because insomnia is often transient and intermittent, the prolonged administration of estazolam is generally neither necessary nor recommended. Since insomnia may be a symptom of several other disorders, the possibility that the complaint may be related to a condition for which there is a more specific treatment should be considered. There is evidence to support the ability of estazolam to enhance the duration and quality of sleep for intervals up to 12 weeks (see CLINICAL PHARMACOLOGY ).
Dosage and administration
The recommended initial dose for adults is 1 mg at bedtime; however, some patients may need a 2 mg dose. In healthy elderly patients, 1 mg is also the appropriate starting dose, but increases should be initiated with particular care. In small or debilitated older patients, a starting dose of 0.5 mg, while only marginally effective in the overall elderly population, should be considered. Discontinuation or Dosage Reduction of Estazolam To reduce the risk of withdrawal reactions, use a gradual taper to discontinue estazolam or reduce the dosage. If a patient develops withdrawal reactions, consider pausing the taper or increasing the dosage to the previous tapered dosage level. Subsequently decrease the dosage more slowly (see WARNINGS , Dependence and Withdrawal Reactions and DRUG ABUSE AND DEPENDENCE, Dependence ).
Contraindications
Estazolam is contraindicated with ketoconazole and itraconazole, since these medications significantly impair oxidative metabolism mediated by CYP3A (see WARNINGS and PRECAUTIONS, Drug Interactions ).
Warnings
Risks from Concomitant Use with Opioids Concomitant use of benzodiazepines, including estazolam, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe estazolam concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. In patients already receiving an opioid analgesic, prescribe a lower initial dose of estazolam than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking estazolam, prescribe a lower initial dose of the opioid and titrate based upon clinical response. Advise both patients and caregivers about the risks of respiratory depression and sedation when estazolam is used with opioids. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined (see PRECAUTIONS , Drug Interactions ). Abuse, Misuse, and Addiction The use of benzodiazepines, including estazolam, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death (see DRUG ABUSE AND DEPENDENCE , Abuse ) . Before prescribing estazolam and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of estazolam, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of estazolam along with monitoring for signs and symptoms of abuse, misuse, and addiction. Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. If a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate. Dependence and Withdrawal Reactions To reduce the risk of withdrawal reactions, use a gradual taper to discontinue estazolam or reduce the dosage (a patient-specific plan should be used to taper the dose) (see DOSAGE AND ADMINISTRATION , Discontinuation or Dosage Reduction of Estazolam ). Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use. Acute Withdrawal Reactions The continued use of benzodiazepines, including estazolam, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of estazolam after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) (see DRUG ABUSE AND DEPENDENCE , Dependence ) . Protracted Withdrawal Syndrome In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see DRUG ABUSE AND DEPENDENCE , Dependence ). 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. Because some of the important adverse effects of sedative-hypnotics appear to be dose-related (see PRECAUTIONS and DOSAGE AND ADMINISTRATION ), it is important to use the smallest possible effective dose, especially in the elderly. 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. These events can occur in sedative-hypnotic-naïve as well as in sedative-hypnotic-experienced persons. Although behaviors such as sleep driving may occur with sedative-hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with sedative-hypnotics appears to increase the risk of such behaviors, as does the use of sedative-hypnotics at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of sedative-hypnotics 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. Because sedative-hypnotics can cause drowsiness and a decreased level of consciousness, patients, particularly the elderly, are at higher risk of falls.
Precautions
General Impaired motor and/or cognitive performance attributable to the accumulation of benzodiazepines and their active metabolites following several days of repeated use at their recommended doses is a concern in certain vulnerable patients (e.g., those especially sensitive to the effects of benzodiazepines or those with a reduced capacity to metabolize and eliminate them) (see DOSAGE AND ADMINISTRATION ). Elderly or debilitated patients and those with impaired renal or hepatic function should be cautioned about these risks and advised to monitor themselves for signs of excessive sedation or impaired conditions. Estazolam appears to cause dose-related respiratory depression that is ordinarily not clinically relevant at recommended doses in patients with normal respiratory function. However, patients with compromised respiratory function may be at risk and should be monitored appropriately. As a class, benzodiazepines have the capacity to depress respiratory drive; there are insufficient data available, however, to characterize their relative potency in depressing respiratory drive at clinically recommended doses. As with other benzodiazepines, estazolam should be administered with caution to patients exhibiting signs or symptoms of depression. 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 least amount of drug that is feasible should be prescribed for the patient at any one time. Information for Patients Advise the patient to read the FDA-approved patient labeling (Medication Guide). Risks from Concomitant Use with Opioids Advise both patients and caregivers about the risks of potentially fatal respiratory depression and sedation when estazolam is used with opioids and not to use such drugs concomitantly unless supervised by a health care provider. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined (see WARNINGS : Risks from Concomitant Use with Opioids and PRECAUTIONS , Drug Interactions ). Abuse, Misuse, and Addiction Inform patients that the use of estazolam, even at recommended dosages, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose and death, especially when used in combination with other medications (e.g., opioid analgesics), alcohol, and/or illicit substances. Inform patients about the signs and symptoms of benzodiazepine abuse, misuse, and addiction; to seek medical help if they develop these signs and/or symptoms; and on the proper disposal of unused drug (see WARNINGS , Abuse, Misuse, and Addiction and DRUG ABUSE AND DEPENDENCE ). Withdrawal Reactions Inform patients that the continued use of estazolam may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction of estazolam may precipitate acute withdrawal reactions, which can be life-threatening. Inform patients that in some cases, patients taking benzodiazepines have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months. Instruct patients that discontinuation or dosage reduction of estazolam may require a slow taper (see WARNINGS , Dependence and Withdrawal Reactions and DRUG ABUSE AND DEPENDENCE ). “Sleep-Driving” and Other Complex Behaviors There have been reports of people getting out of bed after taking a sedative-hypnotic and driving their cars while not fully awake, often with no memory of the event. If a patient experiences such an episode, it should be reported to his or her doctor immediately, since “sleep-driving” can be dangerous. This behavior is more likely to occur when sedative-hypnotics are taken with alcohol or other central nervous system depressants (see WARNINGS ). 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. Inform your physician about any alcohol consumption and medicine you are taking now, including drugs you may buy without a prescription. Alcohol should not be used during treatment with hypnotics. Inform your physician if you are planning to become pregnant, if you are pregnant, or if you become pregnant while you are taking this medicine. You should not take this medicine if you are nursing, as the drug may be excreted in breast milk. Until you experience the way this medicine affects you, do not drive a car, operate potentially dangerous machinery, or engage in hazardous occupations requiring complete mental alertness after taking this medicine. Advise patients that increased drowsiness and decreased consciousness may increase the risk of falls in some patients. Pregnancy Advise pregnant females that use of estazolam late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in newborns (see WARNINGS: Neonatal Sedation and Withdrawal Syndrome and PRECAUTIONS: Pregnancy ). Instruct patients to inform their healthcare provider if they are pregnant. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to estazolam during pregnancy (see PRECAUTIONS, Pregnancy ). Nursing Advise patients that breastfeeding is not recommended during treatment with estazolam (see PRECAUTIONS: Nursing Mothers ) . Laboratory Tests Laboratory tests are not ordinarily required in otherwise healthy patients. When treatment with estazolam is protracted, periodic blood counts, urinalyses, and blood chemistry analyses are advisable.
Side effects
Commonly Observed The most commonly observed adverse events associated with the use of estazolam, not seen at an equivalent incidence among placebo-treated patients were somnolence, hypokinesia, dizziness, and abnormal coordination. A ssociated with Discontinuation of Treatment Approximately 3% of 1277 patients who received estazolam in U.S. premarketing clinical trials discontinued treatment because of an adverse clinical event. The only event commonly associated with discontinuation, accounting for 1.3% of the total, was somnolence. Incidence in Controlled Clinical Trials The table below enumerates adverse events that occurred at an incidence of 1% or greater among patients with insomnia who received estazolam in 7-night, placebo-controlled trials. Events reported by investigators were classified into standard dictionary (COSTART) terms to establish event frequencies. Event frequencies reported were not corrected for the occurrence of these events at baseline. The frequencies were obtained from data pooled across six studies: estazolam, N = 685; placebo, N = 433. 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 six 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 was conducted under a different set of conditions. However, the cited figures provide the physician with a basis of estimating the relative contribution of drug and nondrug factors to the incidence of side effects in the population studied. INCIDENCE OF ADVERSE EXPERIENCES IN PLACEBO-CONTROLLED CLINICAL TRIALS (Percentage of Patients Reporting) Estazolam Placebo Body System/Adverse Event* (N=685) (N=433) Body as a Whole Headache 16 27 Asthenia 11 8 Malaise 5 5 Lower extremity pain 3 2 Back pain 2 2 Body pain 2 2 Abdominal pain 1 2 Chest pain 1 1 Digestive System Nausea 4 5 Dyspepsia 2 2 Musculoskeletal System Stiffness 1 -- Nervous System Somnolence 42 27 Hypokinesia 8 4 Nervousness 8 11 Dizziness 7 3 Coordination abnormal 4 1 Hangover 3 2 Confusion 2 -- Depression 2 3 Dream abnormal 2 2 Thinking abnormal 2 1 Respiratory System Cold symptoms 3 5 Pharyngitis 1 2 Skin and Appendages Pruritus 1 -- * Events reported by at least 1% of estazolam patients. Other Adverse Events During clinical trials, some of which were not placebo-controlled, estazolam was administered to approximately 1300 patients. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals experiencing adverse events, similar types of untoward events must be grouped into a smaller number of standardized event categories. In the tabulations that follow, a standard COSTART dictionary terminology has been used to classify reported adverse events. The frequencies presented, therefore, represent the proportion of the 1277 individuals exposed to estazolam who experienced an event of the type cited on at least one occasion while receiving estazolam. All reported events are included except those already listed in the previous table, those COSTART terms too general to be informative, and those events where a drug cause was remote. 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 on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in less than 1/1000 patients. It is important to emphasize that, although the events reported did occur during treatment with estazolam, they were not necessarily caused by it. Body as a Whole - Infrequent: allergic reaction, chills, fever, neck pain, upper extremity pain; Rare: edema, jaw pain, swollen breast. Cardiovascular System - Infrequent: flushing, palpitation; Rare: arrhythmia, syncope. Digestive System - Frequent: constipation, dry mouth; Infrequent: decreased appetite, flatulence, gastritis, increased appetite, vomiting; Rare: enterocolitis, melena, ulceration of the mouth. Endocrine System - Rare: thyroid nodule. Hematologic and Lymphatic System - Rare: leukopenia, purpura, swollen lymph nodes. Metabolic/Nutritional Disorders - Infrequent: thirst; Rare: increased SGOT, weight gain, weight loss. Musculoskeletal System - Infrequent: arthritis, muscle spasm, myalgia; Rare: arthralgia. Nervous System - Frequent: anxiety; Infrequent: agitation, amnesia, apathy, emotional lability, euphoria, hostility, paresthesia, seizure, sleep disorder, stupor, twitch; Rare: ataxia, circumoral paresthesia, decreased libido, decreased reflexes, hallucinations, neuritis, nystagmus, tremor. Minor changes in EEG patterns, usually low-voltage fast activity, have been observed in patients during estazolam therapy or withdrawal and are of no known clinical significance. Respiratory System - Infrequent: asthma, cough, dyspnea, rhinitis, sinusitis; Rare: epistaxis, hyperventilation, laryngitis. Skin and Appendages - Infrequent: rash, sweating, urticaria; Rare: acne, dry skin. Special Senses - Infrequent: abnormal vision, ear pain, eye irritation, eye pain, eye swelling, perverse taste, photophobia, tinnitus; Rare: decreased hearing, diplopia, scotomata. Urogenital System - Infrequent: frequent urination, menstrual cramps, urinary hesitancy, urinary urgency, vaginal discharge/itching; Rare: hematuria, nocturia, oliguria, penile discharge, urinary incontinence. Postintroduction Reports - Voluntary reports of non-U.S.
Overdosage
Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory depression and coma. Overdosage of benzodiazepines in combination with other CNS depressants (including alcohol and opioids) may be fatal (see WARNINGS: Dependence and Withdrawal Reactions ). Markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raise the concern that additional drugs and/or alcohol are involved in the overdosage. In managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway management. Flumazenil, a specific benzodiazepine receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines in the management of benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures, particularly in the context of mixed overdosage with drugs that increase seizure risk (e.g., tricyclic and tetracyclic antidepressants) and in patients with long-term benzodiazepine use and physical dependency. The risk of withdrawal seizures with flumazenil use may be increased in patients with epilepsy. Flumazenil is contraindicated in patients who have received a benzodiazepine for control of a potentially life-threatening condition (e.g., status epilepticus). If the decision is made to use flumazenil, it should be used as an adjunct to, not as a substitute for, supportive management of benzodiazepine overdosage. See the flumazenil injection Prescribing Information. Consider contacting a poison center (1-800-222-1222), poisoncontrol.org, or a medical toxicologist for additional overdosage management recommendations.
Description
Estazolam, USP, a triazolobenzodiazepine derivative, is an oral hypnotic agent. Estazolam occurs as a fine, white, odorless powder that is soluble in alcohol and practically insoluble in water. The chemical name for estazolam is 8-chloro-6-phenyl-4 H - s -triazolo[4,3-α][1,4]benzodiazepine. The structural formula is represented as follows: C 16 H 11 ClN 4 M. W. 294.75 Each tablet, for oral administration, contains either 1 mg or 2 mg of estazolam, USP. In addition, each tablet contains the following inactive ingredients: docusate sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, sodium benzoate, sodium starch glycolate and stearic acid. The 2 mg tablets also contain FD&C Red #40 Aluminum Lake. Estazolam Structural Formula
How supplied
Estazolam tablets USP, 1 mg are white, scored, diamond-shaped tablets, debossed with 744 above the score and 1 below the score on one side, and WATSON on the other side, supplied in bottles of 100 (NDC 0591-0744-01). Estazolam tablets USP, 2 mg are dark pink, scored, diamond-shaped tablets, debossed with 745 above the score and 2 below the score on one side, and WATSON on the other side, supplied in bottles of 100 (NDC 0591-0745-01). Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required). Manufactured In India By: Watson Pharma Private Limited Verna, Salcette Goa 403 722 INDIA Manufactured For: Teva Pharmaceuticals Parsippany, NJ 07054 Rev. G 6/2024
Label text from the FDA structured product label by Actavis Pharma, Inc. (revised Jun 30, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Estazolam in 6 products
Estazolam NDC products (6)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0591-0744 | Estazolam 1 mg/1 Tablet | Actavis Pharma, Inc. | ANDA · DEA CIV |
| 0591-0745 | Estazolam 2 mg/1 Tablet | Actavis Pharma, Inc. | ANDA · DEA CIV |
| 75907-028 | Estazolam 1 mg/1 Tablet | Dr. Reddy's Labratories Inc. | ANDA · DEA CIV |
| 75907-029 | Estazolam 2 mg/1 Tablet | Dr. Reddy's Labratories Inc. | ANDA · DEA CIV |
| 70954-480 | Estazolam 1 mg/1 Tablet | Novitium Pharma LLC | ANDA · DEA CIV |
| 70954-481 | Estazolam 2 mg/1 Tablet | Novitium Pharma LLC | ANDA · DEA CIV |
Frequently asked questions
What is Estazolam used for?
Estazolam tablets, USP are indicated for the short-term management of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. Both outpatient studies and a sleep laboratory study have shown that estazolam administered at bedtime improved sleep induction and sleep maintenance (see CLINICAL PHARMACOLOGY ). Because insomnia is often…
What are the side effects of Estazolam?
Commonly Observed The most commonly observed adverse events associated with the use of estazolam, not seen at an equivalent incidence among placebo-treated patients were somnolence, hypokinesia, dizziness, and abnormal coordination. A ssociated with Discontinuation of Treatment Approximately 3% of 1277 patients who received estazolam in U.S. premarketing clinical trials discontinued treatment… See the full label for the complete list.
Who makes Estazolam?
Estazolam is listed by 3 labelers in the FDA NDC directory, including Actavis Pharma, Inc., Dr. Reddy's Labratories Inc., Novitium Pharma LLC.