Common side effects include: Coordination problems, dizziness, drowsiness, headache, light-headedness, nausea/vomiting, nervousness
Traveler's amnesia" has been reported by patients who took Halcion to induce sleep while traveling. To avoid this condition, it is recommended to not take Halcion on an overnight flight of less than 7 to 8 hours.
Halcion’s high complaint rate not unique to America
French and Italian regulators forced the half-milligram from their market
Upjohn voluntarily lowered the recommended starting dose from a half milligram to a quarter in the U.S. and under FDA pressure, the company also acknowledged a revised package insert (“bizarre or abnormal behavior, agitation and hallucinations”)
Concern with what level of sedation is being achieved with this new technique
Anxiolysis - Drug induced state of consciousness in which a patient still has the capability to respond to verbal command with a sustained cognitive function.
Conscious Sedation – A minimally depressed level of consciousness retaining the patient’s ability to independently and continuously maintain an airway and respond appropriately to physical stimulation.
Main Concerns of Dental Organizations and Regulatory Agencies
“ Sleep dentistry” was either misleading advertising or promoted unlawful drug administration
Weekend courses largely devoted to marketing have resulted in inadequately educated clinicians
Giving additional doses before the full effects of the first dose have occurred may result in oversedation
“ Titration of oral medication for the purposes of sedation is unpredictable. Repeated dosing of orally administered sedative agents may result in an alteration of the state of consciousness beyond the intent of the practitioner.” ( ADA Guidelines )
In an estimated representation of plasma concentrations, with stacked dosing every 30 minutes, presented data to suggest a plasma concentration that would increase approximately two-fold (ng/mL) with each 0.25mg dose
The terminal peak plasma level of the stacked dose, when compared with the single dose technique, suggests a plasma level difference at an estimated increase of approximately 4ng/mL
Source: Greenblatt et al: J Pharmacol Exp Ther 293:435-43, 2000.
Time (hr) Stacked oral dosing (0.25 mg) every 30 min Triazolam (ng/mL)
Recommended initial dose of Romazicon is 0.2 mg administered intravenously over 15 seconds. If the desired level of consciousness is not obtained after waiting an additional 45 seconds, a second dose of 0.2 mg can be injected and repeated at 60-second intervals where necessary (up to a maximum of 4 additional times) to a maximum total dose of 1 mg (10 mL). The dosage should be individualized based on the patient’s response.
Source: Morgan GE, Mikhail MS, Murray MJ. Clinical Anesthesiology, ed. 3. New York; McGraw-Hill, 2002.
To evaluate the CNS depression evoked by the repeated dosing of sublingual triazolam, to a total dose of 1.0 mg, in healthy adults,
To determine the time-dependent plasma concentrations of triazolam in a repeated dosing paradigm,
To compare the efficacy of a single intraoral submucosal (SL, tongue), intramuscular (IM), and intravenous (IV) injection of flumazenil (0.2 mg) at reversing the sedative effects of triazolam.
Study Design and Measures 0.2 mg 0.25 mg 0.5 mg 0.25 mg Jackson et al: J Clin Psychopharmacol 26:4-8, 2006
Observer’s Assessment of Alertness/Sedation (OA/AS) Scale Jackson et al: J Clin Psychopharmacol 26:4-8, 2006 1 Marked ptosis Marked relaxation No words No response to prodding/shaking 2 Marked ptosis Marked relaxation Few words recognizable Responds after mild prodding 3 Marked ptosis Marked relaxation Slurring Responds after loud calling 4 Glazed Mild relaxation Mild slurring Lethargic 5 No ptosis Normal Normal Readily/ Normal tone Score Eyes Facial Expression Speech Responsiveness
Clinical Interpretation of Bispectral Analysis BIS Score Clinical State 100 0 60 40 awake sedated moderate hypnotic level deep hypnotic level isoelectric EEG, total suppression Rosow C - Anesthesiol Clin North America - 01-DEC-2001; 19(4): 947-66, xi
Observer Rating of Sedation During Incremental Triazolam Dosing by Subject
Bispectral Analysis During Incremental Triazolam Dosing by Subject
Time-Dependent Changes in Plasma Concentrations of Triazolam by Subject
Observer Rating of Sedation Post Flumazenil (0.2 mg) Administration Time (minutes post-1st SL triazolam dose) Sedation Score flumazenil admin. 240 210 180 150 1 2 3 4 5 Tongue (n=5) IM (n=3) IV (n=2)
“ Given the considerable inter-subject variability in triazolam concentrations and effects, additional research is needed to assess this multidosing strategy before it can be endorsed as a useful and safe sedation sedation technique for managing fearful and anxious patients in dental practice.”