Estazolam

>10%

Somnolence (42%)

Headache (16%)

Asthenia (11%)

Neuromuscular & skeletal weakness

1-10%

Dizziness (7-8%)

Hypokinesia (7-8%)

Abnormal coordination (4%)

Hangover (3%)

Abnormal thinking (2%)

Flushing palpitation

Hangover effect

Euphoria

Hostility

Seizure

Sleep disorder

Rash

Urticaria

<1%

Angioedema

Sleep-driving (sleep-cooking, sleep eating, etc) may occur

Muscle spasm

Fever

Neck pain

Myalgia

Drug dependence may occur

Benzodiazepine, sedative and hypnotic.e

Pharmacokinetics

Absorption

Estazolam tablets have been found to be equivalent in absorption to an orally administered solution of Estazolam. In healthy subjects who received up to three times the recommended dose of Estazolam, peak Estazolam plasma concentrations occurred within two hours after dosing (range 0.5 to 6.0 hours) and were proportional to the administered dose, suggesting linear pharmacokinetics over the dosage range tested.

Distribution

Independent of concentration, Estazolam in plasma is 93% protein bound.

Metabolism

Estazolam is extensively metabolized. Only two metabolites (1-oxo-Estazolam & 4-hydroxy-Estazolam) were detected in human plasma up to 18 hrs.

The pharmacologic activity of Estazolam is primarily from the parent drug. The elimination of the parent drug takes place via hepatic metabolism of Estazolam to hydroxylated and other metabolites that are eliminated largely in the urine both free and conjugated. In humans, greater than 70% of a single dose of Estazolam was recovered in the urine as metabolites. Less than 5% of a 2 mg dose of Estazolam was excreted unchanged in the urine, with only 4% of the dose appearing in the feces. The principal urinary excretion product is an unidentified metabolite, presumed to be a metabolic product of 4-hydroxy-Estazolam, accounting for at least 27% of the administered dose. 4-hydroxy-Estazolam is the major metabolite in plasma, with concentrations approaching 12% of those of the parent eight hours after administration. Urinary 4-hydroxy-Estazolam and 1-oxo-Estazolam account for 11.9% and 4.4% of the dose respectively. In vitro studies with human liver microsomes indicate that the biotransformation of Estazolam to the major circulating metabolite 4-hydroxy-Estazolam is mediated by cytochrome P450 3A (CYP3A). While 4-hydroxy-Estazolam and the lesser metabolite, 1-oxo-Estazolam, have some pharmacologic activity, their low potencies and low concentrations preclude any significant contribution to the hypnotic effect of Estazolam.

Elimination

The range of estimates for the mean elimination half-life of Estazolam varied from 10 to 24 hours. Radiolabel mass balance studies indicate that the main route of excretion is via the kidneys. After 5 days, 87% of the administered radioactivity was excreted in human urine. Less than 4% of the dose was excreted unchanged. Eleven metabolites were found in urine. Four metabolites were identified as 1-oxo-Estazolam, 4'-hydroxy-Estazolam, 4-hydroxy-Estazolam, and benzophenone, as free metabolites and glucuronides. The predominant metabolite in urine (17% of the administered dose) has not been identified, but is likely to be a metabolite of 4-hydroxy-Estazolam.

Special Populations

In a small study (N = 8) using various doses in older subjects (59 to 68 years), peak Estazolam concentrations were found to be similar to those observed in younger subjects with a mean elimination half-life of 18.4 hours (range 13.5 to 34.6 hours). The influence of hepatic or renal impairment on the pharmacokinetics of Estazolam has not been studied.

Pediatrics

The pharmacokinetics of Estazolam have not been studied in pediatric patients.

Race

The influence of race on the pharmacokinetics of Estazolam has not been studied.

Gender

The gender-effect on the pharmacokinetics of Estazolam has not been investigated.

Cigarette smoking

The clearance of benzodiazepines is accelerated in smokers compared to nonsmokers, and there is evidence that this occurs with Estazolam. This decrease in half-life, presumably due to enzyme induction by smoking, is consistent with other drugs with similar hepatic clearance characteristics. In all subjects and at all doses, the mean elimination half-life appeared to be independent of the dose.

Drug-drug interaction

The metabolism of Estazolam to the major circulating metabolite 4-hydroxy-Estazolam is catalyzed by CYP3A. While no in vivo drug-drug interaction studies were conducted between Estazolam and inhibitors/inducers of CYP3A, compounds that are potent CYP3A inhibitors (such as ketoconazole, itraconazole, nefazodone, fluvoxamine, and erythromycin) would be expected to increase plasma Estazolam concentrations and CYP3A inducers (such as carbamazepine, phenytoin, rifampin and barbiturates) would be expected to decrease Estazolam concentrations.

Drug interaction with fluoxetine

A multiple-dose study was conducted to assess the effect of fluoxetine 20 mg BID on the pharmacokinetics of Estazolam 2 mg QHS after seven days. The pharmacokinetics of Estazolam (Cmax and AUC) were not affected during multiple-dose fluoxetine, suggesting no clinically significant pharmacokinetic interaction.

The ability of Estazolam to induce or inhibit human enzyme systems

The results from in vitro human liver microsomal studies suggest that at therapeutic concentrations, Estazolam has no significant inhibitory effect on the major human cytochrome P450 enzyme activities (i.e., CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A). The ability of Estazolam to induce human hepatic enzyme systems has not been determined.

Pharmacodynamics

Postulated relationship between elimination rate of benzodiazepine hypnotics and their profile of common untoward effects: The type and duration of hypnotic effects and the profile of unwanted effects during administration of benzodiazepine drugs may be influenced by the biologic half-life of administered drug and any active metabolites formed. If half-lives are long, drug or metabolites may accumulate during periods of nightly administration and may be associated with impairments of cognitive and/or motor performance during waking hours; the possibility of interaction with other psychoactive drugs or alcohol will be increased. In contrast, if half-lives are short, drug and metabolites will be cleared before the next dose is ingested, and carry-over effects related to excessive sedation or CNS depression should be minimal or absent. However, during nightly use for an extended period, pharmacodynamic tolerance or adaptation to some effects of benzodiazepine hypnotics may develop. If the drug has a short elimination half-life, it is possible that a relative deficiency of the drug or its active metabolites (i.e., in relationship to the receptor site) may occur at some point in the interval between each night's use. This sequence of events may account for two clinical findings reported to occur after several weeks of nightly use of rapidly eliminated benzodiazepine hypnotics, namely, increased wakefulness during the last third of the night and increased daytime anxiety in selected patients.

Controlled Trials Supporting Efficacy: In three 7 night, double-blind, parallel-group trials comparing Estazolam 1 mg and/or 2 mg with placebo in adult outpatients with chronic insomnia, Estazolam 2 mg was consistently superior to placebo in subjective measures of sleep induction (latency) and sleep maintenance (duration, number of awakenings, depth and quality of sleep); Estazolam 1 mg was similarly superior to placebo on all measures of sleep maintenance, however, it significantly improved sleep induction in only one of two studies. In a similarly designed trial comparing Estazolam 0.5 mg and 1 mg with placebo in geriatric outpatients with chronic insomnia, only the 1 mg Estazolam dose was consistently superior to placebo in sleep induction (latency) and in only one measure of sleep maintenance (i.e., duration of sleep).

In a single-night, double-blind, parallel-group trial comparing Estazolam 2 mg and placebo in patients admitted for elective surgery and requiring sleep medications, Estazolam was superior to placebo in subjective measures of sleep induction and maintenance.

In a 12 week, double-blind, parallel-group trial including a comparison of Estazolam 2 mg and placebo in adult outpatients with chronic insomnia, Estazolam was superior to placebo in subjective measures of sleep induction (latency) and maintenance (duration, number of awakenings, total wake time during sleep) at week 2, but produced consistent improvement over 12 weeks only for sleep duration and total wake time during sleep. Following withdrawal at week 12, rebound insomnia was seen at the first withdrawal week, but there was no difference between drug and placebo by the second withdrawal week in all parameters except latency, for which normalization did not occur until the fourth withdrawal week.

Adult outpatients with chronic insomnia were evaluated in a sleep laboratory trial comparing four doses of Estazolam (0.25, 0.5, 1 and 2 mg) and placebo, each administered for 2 nights in a crossover design. The higher Estazolam doses were superior to placebo in most EEG measures of sleep induction and maintenance, especially at the 2 mg dose, but only for sleep duration in subjective measures of sleep.

Benzodiazepines may cause fetal damage when administered during pregnancy. An increased risk of congenital malformations associated with the use of diazepam and chlordiazepoxide during the first trimester of pregnancy has been suggested in several studies. Transplacental distribution has resulted in neonatal CNS depression and also withdrawal phenomena following the ingestion of therapeutic doses of a benzodiazepine hypnotic during the last weeks of pregnancy.

Estazolam is contraindicated in pregnant women. If there is a likelihood of the patient becoming pregnant while receiving Estazolam she should be warned of the potential risk to the fetus and instructed to discontinue the drug prior to becoming pregnant. The possibility that a woman of childbearing potential is pregnant at the time of institution of therapy should be considered.

Estazolam is contraindicated with ketoconazole and itraconazole, since these medications significantly impair oxidative metabolism mediated by CYP3A (see WARNINGS and PRECAUTIONS, Drug Interactions ).

WARNINGS

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 for use 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 Drug Interactions].

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.

Severe Anaphylactic and Anaphylactoid Reactions

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 Estazolam. 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 tongue, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with Estazolam should not be rechallenged with the drug.

Estazolam, like other benzodiazepines, has CNS depressant effects. For this reason, patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness, such as operating machinery or driving a motor vehicle, after ingesting the drug, including potential impairment of the performance of such activities that may occur the day following ingestion of Estazolam. Patients should also be cautioned about possible combined effects with alcohol and other CNS depressant drugs.

As with all benzodiazepines, amnesia, paradoxical reactions (e.g., excitement, agitation, etc.), and other adverse behavioral effects may occur unpredictably.

There have been reports of withdrawal signs and symptoms of the type associated with withdrawal from CNS depressant drugs following the rapid decrease or the abrupt discontinuation of benzodiazepines (see DRUG ABUSE AND DEPENDENCE).

Estazolam Interaction With Drugs That Inhibit Metabolism via Cytochrome P450 3A (CYP3A)

The metabolism of Estazolam to the major circulating metabolite 4-hydroxy-Estazolam and the metabolism of other triazolobenzodiazepines is catalyzed by CYP3A. Consequently, Estazolam should be avoided in patients receiving ketoconazole and itraconazole, which are very potent inhibitors of CYP3A (see CONTRAINDICATIONS). With drugs inhibiting CYP3A to a lesser, but still significant degree, Estazolam should be used only with caution and consideration of appropriate dosage reduction. The following are examples of drugs known to inhibit the metabolism of other related benzodiazepines, presumably through inhibition of CYP3A: nefazodone, fluvoxamine, cimetidine, diltiazem, isoniazide, and some macrolide antibiotics.

While no in vivo drug-drug interaction studies were conducted between Estazolam and inducers of CYP3A, compounds that are potent CYP3A inducers (such as carbamazepine, phenytoin, rifampin, and barbiturates) would be expected to decrease Estazolam concentrations.

NDC 51862-070-01

Estazolam
Tablets
2 mg

CIV

PHARMACIST: Dispense the accompanying
Medication Guide to each patient.

Rx only

100 TABLETS

(es TA zoe lam)

• ProSom

Variable

Half-Life Elimination

10 to 24 hours

Protein Binding

93%

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Analgesics (Opioid): CNS Depressants may enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CloZAPine: Benzodiazepines may enhance the adverse/toxic effect of CloZAPine. Management: Consider decreasing the dose of (or possibly discontinuing) benzodiazepines prior to initiating clozapine. Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Estazolam. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Fosphenytoin: Benzodiazepines may increase the serum concentration of Fosphenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Itraconazole: May increase the serum concentration of Estazolam. Avoid combination

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Ketoconazole (Systemic): May increase the serum concentration of Estazolam. Avoid combination

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Macrolide Antibiotics: May increase the serum concentration of Estazolam. Management: Consider an alternative less likely to interact. Azithromycin is likely a lower-risk macrolide, and benzodiazepines less dependent on CYP3A metabolism (e.g., lorazepam, oxazepam) are similarly less likely to interact. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Melatonin: May enhance the sedative effect of Benzodiazepines. Monitor therapy

Methadone: Benzodiazepines may enhance the CNS depressant effect of Methadone. Avoid combination

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

OLANZapine: May enhance the adverse/toxic effect of Benzodiazepines. Management: Avoid concomitant use of parenteral benzodiazepines and IM olanzapine due to risks of additive adverse events (e.g., cardiorespiratory depression). Olanzapine prescribing information provides no specific recommendations regarding oral administration. Avoid combination

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Phenytoin: Benzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Ritonavir: May increase the serum concentration of Estazolam. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Sodium Oxybate: Benzodiazepines may enhance the CNS depressant effect of Sodium Oxybate. Avoid combination

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Teduglutide: May increase the serum concentration of Benzodiazepines. Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Theophylline Derivatives: May diminish the therapeutic effect of Benzodiazepines. Consider therapy modification

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

>10%: Central nervous system: Drowsiness (42%)

1% to 10%:

Central nervous system: Dizziness (7%), ataxia (4%), hangover effect (3%), abnormality in thinking (2%), confusion (2%), anxiety (≥1%)

Dermatologic: Pruritus (1%)

Gastrointestinal: Constipation (≥1%), xerostomia (≥1%)

Neuromuscular & skeletal: Hypokinesia (8%), leg pain (3%), stiffness (1%)

<1% (Limited to important or life-threatening): Acne vulgaris, adenopathy, agitation, agranulocytosis, amnesia, apathy, arm pain, arthralgia, arthritis, asthma, auditory impairment, breast swelling, cardiac arrhythmia, chills, cough, decreased appetite, decreased libido, diaphoresis, diplopia, dysgeusia, dyspnea, edema, emotional lability, enterocolitis, epistaxis, euphoria, eye irritation, eye pain, fever, flatulence, flushing, gastritis, genital discharge, hallucination, hematuria, hostility, hypersensitivity reaction, hyperventilation, hyporeflexia, increased appetite, increased serum AST, increased thirst, jaw pain, laryngitis, leukopenia, melena, muscle spasm, myalgia, neck pain, neuritis, nocturia, nystagmus, oliguria, oral mucosa ulcer, oral paresthesia, otalgia, palpitations, paresthesia, pelvic cramps (menstrual cramps), photophobia, polyuria, purpura, rhinitis, scotoma, seizure, sinusitis, skin photosensitivity, skin rash, sleep disorder, Stevens-Johnson syndrome, stupor, swelling of eye, syncope, thyroid nodule, tinnitus, tremor, twitching, urinary hesitancy, urinary incontinence, urinary urgency, urticaria, visual disturbance, vomiting, vulvovaginal pruritus, weight gain, weight loss, xeroderma

Applies to estazolam: oral tablet

General

The most commonly reported side effects were somnolence, hypokinesia, dizziness, and abnormal coordination.[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Allergic reaction[Ref]

Psychiatric

Very common (10% or more): Somnolence (42%)
Common (1% to 10%): Anxiety, depression, abnormal dream, abnormal thinking
Uncommon (0.1% to 1%): Agitation, apathy, emotional lability, euphoria, hostility, sleep disorder
Rare (less than 0.1%): Hallucinations[Ref]

Nervous system

Very common (10% or more): Headache (16%)
Common (1% to 10%): Hypokinesia, nervousness, dizziness, abnormal coordination, hangover, confusion
Uncommon (0.1% to 1%): Amnesia, paresthesia, seizure, stupor, twitch
Rare (less than 0.1%): Ataxia, circumoral paresthesia, decreased reflexes, neuritis, nystagmus, tremor
Frequency not reported: Minor changes in EEG patterns[Ref]

Hepatic

Rare (less than 0.1%): Increased SGOT[Ref]

Other

Very common (10% or more): Asthenia (11%)
Common (1% to 10%): Malaise, body pain
Uncommon (0.1% to 1%): Chills, fever, ear pain, perverse taste, tinnitus
Rare (less than 0.1%): Edema, decreased hearing[Ref]

Respiratory

Common (1% to 10%): Cold symptoms, pharyngitis
Uncommon (0.1% to 1%): Asthma, cough, dyspnea, rhinitis, sinusitis
Rare (less than 0.1%): Epistaxis, hyperventilation, laryngitis[Ref]

Gastrointestinal

Common (1% to 10%): Constipation, dry mouth, nausea, dyspepsia
Uncommon (0.1% to 1%): Decreased appetite, flatulence, gastritis, increased appetite, vomiting
Rare (less than 0.1%): Enterocolitis, melena, ulceration of the mouth[Ref]

Cardiovascular

Uncommon (0.1% to 1%): Flushing, palpitation
Rare (less than 0.1%): Arrhythmia, syncope[Ref]

Dermatologic

Uncommon (0.1% to 1%): Rash, sweating, urticaria
Rare (less than 0.1%): Acne, dry skin
Postmarketing reports: Stevens-Johnson syndrome, photosensitivity[Ref]

Endocrine

Rare (less than 0.1%): Thyroid nodule[Ref]

Genitourinary

Uncommon (0.1% to 1%): Frequent urination, menstrual cramps, urinary hesitancy, urinary urgency, vaginal discharge/itching
Rare (less than 0.1%): Swollen breast, decreased libido, hematuria, nocturia, oliguria, penile discharge, urinary incontinence[Ref]

Hematologic

Rare (less than 0.1%): Leukopenia, purpura, swollen lymph nodes
Postmarketing reports: Agranulocytosis[Ref]

Metabolic

Uncommon (0.1% to 1%): Thirst
Rare (less than 0.1%): Weight gain, weight loss[Ref]

Musculoskeletal

Common (1% to 10%): Lower extremity pain, back pain, stiffness
Uncommon (0.1% to 1%): Neck pain, upper extremity pain, arthritis, muscle spasm, myalgia
Rare (less than 0.1%): Jaw pain, arthralgia[Ref]

Ocular

Uncommon (0.1% to 1%): Abnormal vision, eye irritation, eye pain, eye swelling, photophobia
Rare (less than 0.1%): Diplopia, scotomata[Ref]

Some side effects of estazolam may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.