Estazolam (Estazolam) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

Commonly Observed: The most commonly observed adverse events associated with the use of estazolam, not seen at an equivalent incidence amoung placebo-treated patients were somnolence, hypokinesia, dizziness, and abnormal coordination.

Associated with Discontinuation of Treatment: Approximately 3% of 1277 patients who received estazolam in US 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)
* Events reported by at least 1% of estazolam patients.
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	--

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-US postmarketing experience with estazolam have included rare occurrences of photosensitivity, Stevens-Johnson syndrome, and agranulocytosis. Because of the uncontrolled nature of these spontaneous reports, a causal relationship to estazolam treatment has not been determined.

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO ESTAZOLAM

Possible Estazolam side effects / adverse reactions in 54 year old male

Reported by a individual with unspecified qualification from Japan on 2007-01-04

Patient: 54 year old male

Reactions: Locked-in Syndrome, Hyponatraemia, Neuroleptic Malignant Syndrome, Blood Glucose Increased, Ileus Paralytic, Loss of Consciousness, Pallanaesthesia

Adverse event resulted in: hospitalization

Suspect drug(s):
Biperiden Hydrochloride TAB
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Biperiden Hydrochloride TAB
    Indication: Insomnia

Biperiden Hydrochloride TAB
    Indication: Irritability

Biperiden Hydrochloride TAB
    Indication: Mental Disorder

Carbamazepine
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Carbamazepine
    Indication: Insomnia

Carbamazepine
    Indication: Irritability

Carbamazepine
    Indication: Mental Disorder

Chlorpromazine
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Chlorpromazine
    Indication: Insomnia

Chlorpromazine
    Indication: Irritability

Chlorpromazine
    Indication: Mental Disorder

Estazolam
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Estazolam
    Indication: Insomnia

Estazolam
    Indication: Irritability

Estazolam
    Indication: Mental Disorder

Haloperidol
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Haloperidol
    Indication: Insomnia

Haloperidol
    Indication: Irritability

Haloperidol
    Indication: Mental Disorder

Other drugs received by patient: Anti-Diabetics; Insulin Human; Laxatives

Possible Estazolam side effects / adverse reactions in 54 year old male

Reported by a individual with unspecified qualification from Japan on 2007-01-19

Patient: 54 year old male

Reactions: Neuroleptic Malignant Syndrome, Ileus Paralytic

Adverse event resulted in: hospitalization

Suspect drug(s):
Biperiden Hydrochloride TAB
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Biperiden Hydrochloride TAB
    Indication: Insomnia

Biperiden Hydrochloride TAB
    Indication: Irritability

Biperiden Hydrochloride TAB
    Indication: Mental Disorder

Carbamazepine
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Carbamazepine
    Indication: Insomnia

Carbamazepine
    Indication: Irritability

Carbamazepine
    Indication: Mental Disorder

Chlorpromazine
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Chlorpromazine
    Indication: Insomnia

Chlorpromazine
    Indication: Irritability

Chlorpromazine
    Indication: Mental Disorder

Estazolam
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Estazolam
    Indication: Insomnia

Estazolam
    Indication: Irritability

Estazolam
    Indication: Mental Disorder

Haloperidol
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Haloperidol
    Indication: Insomnia

Haloperidol
    Indication: Irritability

Haloperidol
    Indication: Mental Disorder

Other drugs received by patient: Anti-Diabetics; Insulin Human; Laxatives

Possible Estazolam side effects / adverse reactions in 54 year old male

Reported by a individual with unspecified qualification from Japan on 2007-02-20

Patient: 54 year old male

Reactions: Neuroleptic Malignant Syndrome, Ileus Paralytic

Adverse event resulted in: hospitalization

Suspect drug(s):
Biperiden Hydrochloride TAB
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Biperiden Hydrochloride TAB
    Indication: Insomnia

Biperiden Hydrochloride TAB
    Indication: Irritability

Biperiden Hydrochloride TAB
    Indication: Mental Disorder

Carbamazepine
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Carbamazepine
    Indication: Insomnia

Carbamazepine
    Indication: Irritability

Carbamazepine
    Indication: Mental Disorder

Chlorpromazine
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Chlorpromazine
    Indication: Insomnia

Chlorpromazine
    Indication: Irritability

Chlorpromazine
    Indication: Mental Disorder

Estazolam
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Estazolam
    Indication: Insomnia

Estazolam
    Indication: Irritability

Estazolam
    Indication: Mental Disorder

Haloperidol
    Administration route: Oral
    Indication: Alcoholic Psychosis
    End date: 2004-06-01

Haloperidol
    Indication: Insomnia

Haloperidol
    Indication: Irritability

Haloperidol
    Indication: Mental Disorder

Other drugs received by patient: Anti-Diabetics; Insulin Human; Laxatives