Halcion (Triazolam) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

During placebo-controlled clinical studies in which 1,003 patients received HALCION Tablets, the most troublesome side effects were extensions of the pharmacologic activity of triazolam, eg, drowsiness, dizziness, or light-headedness.

The figures cited below are estimates of untoward clinical event incidence among subjects who participated in the relatively short duration (i.e., 1 to 42 days) placebo-controlled clinical trials of HALCION. The figures cannot be used to predict precisely the incidence of untoward events in the course of usual medical practice where patient characteristics and other factors often differ from those in clinical trials. These figures cannot be compared with those obtained from other clinical studies involving related drug products and placebo, as each group of drug trials is conducted under a different set of conditions.

Comparison of the cited figures, however, can provide the prescriber with some basis for estimating the relative contributions of drug and nondrug factors to the untoward event incidence rate in the population studied. Even this use must be approached cautiously, as a drug may relieve a symptom in one patient while inducing it in others. (For example, an anticholinergic, anxiolytic drug may relieve dry mouth [a sign of anxiety] in some subjects but induce it [an untoward event] in others.)

	HALCION	PLACEBO
Number of Patients	1003	997
% Patients Reporting:
Central Nervous System
Drowsiness	14.0	6.4
Headache	9.7	8.4
Dizziness	7.8	3.1
Nervousness	5.2	4.5
Light-headedness	4.9	0.9
Coordination disorders/ataxia	4.6	0.8
Gastrointestinal
Nausea/vomiting	4.6	3.7

In addition to the relatively common (i.e., 1% or greater) untoward events enumerated above, the following adverse events have been reported less frequently (i.e., 0.9% to0.5%): euphoria, tachycardia, tiredness, confusional states/memory impairment, cramps/pain, depression, visual disturbances.

Rare (i.e., less than 0.5%) adverse reactions included constipation, taste alterations, diarrhea, dry mouth, dermatitis/allergy, dreaming/nightmares, insomnia, paresthesia, tinnitus, dysesthesia, weakness, congestion, death from hepatic failure in a patient also receiving diuretic drugs.

In addition to these untoward events for which estimates of incidence are available, the following adverse events have been reported in association with the use of HALCION and other benzodiazepines: amnestic symptoms (anterograde amnesia with appropriate or inappropriate behavior), confusional states (disorientation, derealization, depersonalization, and/or clouding of consciousness), dystonia, anorexia, fatigue, sedation, slurred speech, jaundice, pruritus, dysarthria, changes in libido, menstrual irregularities, incontinence, and urinary retention. Other factors may contribute to some of these reactions, eg, concomitant intake of alcohol or other drugs, sleep deprivation, an abnormal premorbid state, etc.

Other events reported include: paradoxical reactions such as stimulation, mania, an agitational state (restlessness, irritability, and excitation), increased muscle spasticity, sleep disturbances, hallucinations, delusions, aggressiveness, falling, somnambulism, syncope, inappropriate behavior and other adverse behavioral effects. Should these occur, use of the drug should be discontinued.

The following events have also been reported: chest pain, burning tongue/glossitis/stomatitis.

Laboratory analyses were performed on all patients participating in the clinical program for HALCION. The following incidences of abnormalities were observed in patients receiving HALCION and the corresponding placebo group. None of these changes were considered to be of physiological significance.

	HALCION		PLACEBO
Number of Patients	380		361
% of Patients Reporting:	Low	High	Low	High
Hematology
Hematocrit	1
Hemoglobin
Total WBC count	1.7	2.1		1.3
Neutrophil count	1.5	1.5	3.3	1.0
Lymphocyte count	2.3	4.0	3.1	3.8
Monocyte count	3.6		4.4	1.5
Eosinophil count	10.2	3.2	9.8	3.4
Basophil count	1.7	2.1		1.8
Urinalysis
Albumi	—	1.1	—
Sugar	—		—
RBC/HPF	—	2.9	—	2.9
WBC/HPF	—	11.7	—	7.9
Blood chemistry
Creatinine	2.4	1.9	3.6	1.5
Bilirubin		1.5	1.0
SGOT		5.3		4.5
Alkaline phosphatase		2.2		2.6

When treatment with HALCION is protracted, periodic blood counts, urinalysis, and blood chemistry analyses are advisable.

Minor changes in EEG patterns, usually low-voltage fast activity, have been observed in patients during therapy with HALCION and are of no known significance.

REPORTS OF SUSPECTED HALCION SIDE EFFECTS / ADVERSE REACTIONS

Possible Halcion side effects / adverse reactions in 63 year old female

Reported by a pharmacist from Japan on 2011-10-04

Patient: 63 year old female

Reactions: Abnormal Behaviour, Cognitive Disorder, Nervousness

Suspect drug(s):
Lyrica
    Dosage: 25mg
    Administration route: Oral
    Start date: 2011-09-14

Halcion
    Dosage: 0.25mg daily
    Administration route: Oral

Possible Halcion side effects / adverse reactions in 53 year old female

Reported by a pharmacist from Italy on 2011-10-04

Patient: 53 year old female

Reactions: Bradykinesia, Suicide Attempt, Bradyphrenia

Adverse event resulted in: hospitalization

Suspect drug(s):
Halcion
    Dosage: 1250 ug, single
    Administration route: Oral
    Start date: 2011-08-31
    End date: 2011-08-31

Amitriptyline Hydrochloride
    Dosage: 125 mg, single
    Administration route: Oral
    Start date: 2011-08-31
    End date: 2011-08-31

Diazepam
    Dosage: 30 drops daily
    Administration route: Oral
    Start date: 2011-08-31
    End date: 2011-08-31

Possible Halcion side effects / adverse reactions in 60 year old male

Reported by a physician from Japan on 2011-10-05

Patient: 60 year old male

Reactions: Road Traffic Accident, Dizziness, Loss of Consciousness

Suspect drug(s):
Aspirin
    Dosage: unk
    Administration route: Oral

Januvia
    Dosage: unk
    Administration route: Oral

Omeprazole
    Dosage: unk
    Administration route: Oral

Micardis
    Dosage: unk
    Administration route: Oral

Isosorbide Dinitrate
    Dosage: unk

Varenicline Tartrate
    Dosage: 0.5 mg, 2x/day
    Administration route: Oral
    Start date: 2011-06-04
    End date: 2011-06-07

Varenicline Tartrate
    Dosage: 1 mg, 2x/day
    Administration route: Oral
    Start date: 2011-06-08
    End date: 2011-08-24

Crestor
    Dosage: unk
    Administration route: Oral

Plavix
    Dosage: unk
    Administration route: Oral

Varenicline Tartrate
    Dosage: 0.5 mg, 1x/day
    Administration route: Oral
    Indication: Smoking Cessation Therapy
    Start date: 2011-06-01
    End date: 2011-06-03

Levothyroxine Sodium
    Dosage: unk
    Administration route: Oral

Halcion
    Dosage: unk
    Administration route: Oral
    Indication: Insomnia