Remimazolam

Source: UK SPC (eMC) for Byfavo 20 mg powder for solution for injection, §4.2 (https://www.medicines.org.uk/emc/product/12746/smpc). ELDERLY >= 65 years and/or ASA-PS III-IV and/or body weight < 50 kg: with an opioid — initial dose 2.5 to 5 mg (1 to 2 mL) over 1 minute after the opioid (waiting 1 to 2 minutes), then maintenance/titration 1.25 to 2.5 mg (0.5 to 1 mL) over 15 seconds; without an opioid — induction 2.5 to 5 mg (1 to 2 mL) over 1 minute, then 1.25 to 2.5 mg (0.5 to 1 mL) over 15 seconds. The opioid example given is 50 micrograms fentanyl, or a suitably reduced dose for elderly or debilitated patients. Dosing should be individually titrated to an effective dose that provides the desired level of sedation and minimises adverse reactions. Onset and offset are fast: in clinical trials peak sedation occurred 3 to 3.5 minutes after the initial bolus and patients became fully alert 12 to 14 minutes from the last dose. Opioids are known to increase the sedative effect and to depress the ventilatory response to carbon dioxide stimulation. ADMINISTRATION SAFETY REQUIREMENTS (§4.2): remimazolam must only be administered by healthcare professionals experienced in sedation; the patient must be monitored throughout by a separate healthcare professional not involved in the procedure whose sole task is monitoring, trained in detecting and managing airway obstruction, hypoventilation and apnoea including maintaining a patent airway, supportive ventilation and cardiovascular resuscitation; respiratory and cardiac function must be continuously monitored; resuscitative medicinal products and age- and size-appropriate equipment for restoring airway patency and bag/valve/mask ventilation must be immediately available; flumazenil (benzodiazepine reversal) must be immediately available. HEPATIC IMPAIRMENT: no dose adjustment for mild (Child-Pugh 5-6) or moderate (Child-Pugh 7-9); in severe hepatic impairment (Child-Pugh 10-15, data from only 3 subjects) effects may be more pronounced and last longer — no dose adjustment is required but careful attention should be paid to the timing of titration doses and remimazolam should be carefully titrated to effect. PAEDIATRIC (non-numeric, so no structured paedDose): 'The safety and efficacy of remimazolam in children and adolescents aged 0 to <18 years have not yet been established. No data are available.' COVERAGE NOTE for this ICU-specialty page: the fetched SPC covers PROCEDURAL SEDATION only. It contains NO regimen for continuous-infusion sedation of mechanically ventilated ICU patients (no mg/kg/h or micrograms/kg/min rate is stated anywhere in this source), so any ICU continuous-sedation dosing must be sourced separately and must not be inferred from the procedural bolus doses above. The US label in this bundle (BYFAVO) is likewise procedural sedation only, with the same 5 mg induction / 2.5 mg supplemental doses and 2.5 to 5 mg induction / 1.25 to 2.5 mg supplemental doses for ASA III-IV.