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
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.)
|Number of Patients % Patients Reporting:
|Central Nervous System
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
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
The following events have also been reported: chest pain,
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.
|Number of Patients % of Patients Reporting:
|T otal WBC count
|WBC/HPF Blood chemistry
|* Less than 1%
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.
Drug Abuse And Dependence
Abuse and addiction are separate and distinct from
physical dependence and tolerance. Abuse is characterized by misuse of the drug
for non-medical purposes, often in combination with other psychoactive
substances. Physical dependence is a state of adaptation that is manifested by
a specific withdrawal syndrome that can be produced by abrupt cessation, rapid
dose reduction, decreasing blood level of the drug and/or administration of an
antagonist. Tolerance is a state of adaptation in which exposure to a drug
induces changes that result in a diminution of one or more of the drug's
effects over time. Tolerance may occur to both the desired and undesired
effects of drugs and may develop at different rates for different effects.
Addiction is a primary, chronic, neurobiological disease
with genetic, psychosocial, and environmental factors influencing its
development and manifestations. It is characterized by behaviors that include
one or more of the following: impaired control over drug use, compulsive use,
continued use despite harm, and craving. Drug addiction is a treatable disease,
utilizing a multidisciplinary approach, but relapse is common.
Triazolam is a controlled substance under the Controlled
Substance Act, and HALCION Tablets have been assigned to Schedule IV.
Abuse, Dependence And Withdrawal
Withdrawal symptoms, similar in character to those noted
with barbiturates and alcohol (convulsions, tremor, abdominal and muscle
cramps, vomiting, sweating, dysphoria, perceptual disturbances and insomnia),
have occurred following abrupt discontinuance of benzodiazepines, including
HALCION. The more severe symptoms are usually associated with higher dosages
and longer usage, although patients at therapeutic dosages given for as few as
1-2 weeks can also have withdrawal symptoms and in some patients there may be
withdrawal symptoms (daytime anxiety, agitation) between nightly doses (see CLINICAL
PHARMACOLOGY). Consequently, abrupt discontinuation should be avoided and a
gradual dosage tapering schedule is recommended in any patient taking more than
the lowest dose for more than a few weeks. The recommendation for tapering is
particularly important in any patient with a history of seizure.
The risk of dependence is increased in patients with a
history of alcoholism, drug abuse, or in patients with marked personality
disorders. Such dependence-prone individuals should be under careful surveillance
when receiving HALCION. As with all hypnotics, repeat prescriptions should be
limited to those who are under medical supervision.