ADVERSE REACTIONS During placebo-controlled clinical studies in which 1,003 patients received triazolam tablets, the most troublesome side effects were extensions of the pharmacologic activity of triazolam, e.g., 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 triazolam tablets. 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.) Triazolam Placebo Number of Patients 1,003 997 % 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% to 0.5%): 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 triazolam tablets 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, e.g., 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 triazolam tablets. The following incidences of abnormalities were observed in patients receiving triazolam tablets and the corresponding placebo group. None of these changes were considered to be of physiological significance. Triazolam Placebo Number of Patients 380 361 % of Patients Reporting Low High Low High Hematology Hematocrit * * * * 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 Albumin - 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 *Less than 1% When treatment with triazolam tablets 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 triazolam tablets and are of no known significance.