Byfavo

Remimazolam must only be administered by healthcare professionals experienced in sedation. The patient should be monitored throughout by a separate healthcare professional, who is not involved in the conduct of the procedure, and whose sole task is to monitor the patient.

This personnel must be trained in the detection and management of airway obstruction, hypoventilation and apnoea, including the maintenance of a patent airway, supportive ventilation and cardiovascular resuscitation. The patient´s 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. A benzodiazepine reversal medicinal product (flumazenil) must be immediately available for use.

Posology Remimazolam dosing should be individually titrated to an effective dose which provides the desired level of sedation and minimises adverse reactions (see Table 1). Additional doses can be administered as needed to induce or maintain the desired level of sedation.

At least 2 minutes should elapse prior to administration of any supplemental dose in order to fully assess the sedative effect. If 5 doses of remimazolam within 15 minutes do not result in the desired level of sedation then an additional or another sedative should be considered.

Remimazolam is associated with fast onset and offset of sedation. 5 minutes after the initial bolus and patients became fully alert 12-14 minutes from last dose of remimazolam. 5). 5 mg (1 mL) over 15 sec Maximal total dose administrated in the clinical trials was 33 mg.

5 mg. 5 mg (1 mL) over 15 sec Maximal total dose administrated in the clinical trials was 33 mg. 5 mg. 4. g. 50 micrograms fentanyl or a suitably reduced dose for elderly or debilitated patients. 1. # American Society of Anesthesiologists Physical Status Special populations Elderly, American Society of Anesthesiologists Physical Status (ASA-PS) III-IV patients and patients with body weight < 50 kg Elderly patients and patients with ASA-PS III-IV may be more sensitive to the effects of sedatives.

4). Renal impairment No dosage adjustment is required in any grade of renal impairment (including patients with glomerular filtration rate [GFR] < 15 mL/min). 2). No dose adjustment is recommended for patients with mild (Child-Pugh scores 5 and 6) or moderate (Child-Pugh scores 7 to 9) hepatic impairment.

In patients with severe hepatic impairment (Child-Pugh scores 10 to 15; data from only 3 subjects in clinical trials), the clinical effects may be more pronounced and last longer than in healthy subjects. 4). 4 Paediatric population The safety and efficacy of remimazolam in children and adolescents aged 0 to ˂18 years have not yet been established.

8%). 4). Tabulated list of adverse reactions Adverse reactions associated with intravenous remimazolam observed in controlled clinical trials in procedural sedation and the postmarketing setting are tabulated below in Table 2 according to the MedDRA system organ classification and frequency.

Within each frequency grouping, adverse 7 reactions are presented in order of decreasing seriousness.. Frequency groupings are as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); and not known (cannot be estimated from available data).

Table 2:

Tabulated list of adverse reactions Immune system disorders Not known Anaphylactic reaction Nervous system disorders Common Common Uncommon Headache Dizziness Somnolence Cardiac disorders Common Bradycardia1* Vascular disorders Very common Hypotension2* Respiratory, thoracic and mediastinal disorders Very common Uncommon Respiratory depression3* Hiccups Gastrointestinal disorders Common Common Nausea Vomiting General disorders and administration site conditions Uncommon Uncommon Chills Feeling cold 1 Bradycardia covers the following identified events: bradycardia, sinus bradycardia, and heart rate decreased.

2 Hypotension covers the following identified events: hypotension, diastolic hypotension, blood pressure decreased, blood pressure decreased systolic, and blood pressure decreased diastolic. 3 Respiratory depression covers the following identified events: hypoxia, respiratory rate decreased, respiratory acidosis, bradypnoea, dyspnoea, oxygen saturation decreased, breath sounds abnormal, hypopnoea, respiratory depression, and respiratory distress.

0%) than patients below 65 years old. 8%) than patients with ASA- PS I-II. Older age and higher ASA-PS were not associated with a higher frequency of bradycardia. 4. Patients with hepatic impairment Respiratory depression (hypoxia/oxygen saturation decreased) was reported in 2 of 8 subjects with moderate hepatic impairment, and 1 of 3 with severe hepatic impairment enrolled in a dedicated trial assessing remimazolam in hepatic impairment.

Cardiorespiratory adverse reactions Cardiorespiratory adverse reactions have been reported with the use of remimazolam, including respiratory depression, bradycardia and hypotension. Remimazolam administration can be associated with a transient increase in heart rate (10-20 beats per minute) starting as early as 30 seconds after the start of dosing (corresponding to the time of maximum concentration of remimazolam) before resolving within about 30 minutes after the end of administration.

This increase in heart rate coincides with a decrease in blood pressure and it may confound QT correction for heart rate translating into a small prolongation in QTcF in the first few minutes following dosing. 2). Concomitant use of opioids Concomitant use of remimazolam and opioids may result in profound sedation, respiratory depression, coma and death.

5). Concomitant use of alcohol / CNS depressants The concomitant use of remimazolam with alcohol or/and CNS depressants should be avoided. Alcohol intake should be avoided for 24 hours before remimazolam administration. Such concomitant use has the potential to increase the clinical effects of remimazolam, possibly including severe sedation or clinically relevant respiratory depression.

, for insomnia or anxiety disorders) may develop tolerance to the sedative effects of remimazolam. Hence, a larger cumulative dose of remimazolam may be required to achieve the desired level of sedation. 2 and titrate up based on the patient’s sedation-response, until the desired depth of sedation is achieved.

5) Monitoring 5 Remimazolam should be administered only by health care professionals experienced in sedation who are not involved in conducting the procedure, in a setting fully equipped for the monitoring and support of respiratory and cardiovascular function.

2). Patients should be monitored closely during and after the procedure for signs and symptoms of respiratory depression and sedation. 1), but that this may vary in individual patients. Patients should be closely monitored until they are judged by the healthcare professional to be sufficiently recovered.

1. Unstable myasthenia gravis.