of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.trimipramineMonitor Closely (1)remimazolam, trimipramine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.valbenazineMonitor Closely (1)remimazolam, valbenazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.venlafaxineMonitor Closely (1)remimazolam, venlafaxine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.vilazodoneMonitor Closely (1)remimazolam, vilazodone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.vortioxetineMonitor Closely (1)remimazolam, vortioxetine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.zaleplonMonitor Closely (1)remimazolam, zaleplon. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.ziprasidoneMonitor Closely (1)remimazolam, ziprasidone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.zolpidemMonitor Closely (1)remimazolam, zolpidem. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics. >10% Hypotension (33-58%) Hypertension (20-42%) Diastolic hypertension (10-25%) Systolic hypertension (6-22%) Hypoxia (22%) Respiratory acidosis (19%) Increased respiratory rate (14%) Diastolic hypotension (3-14%) Bradycardia (3-11%) 1-10% Nausea (4%) Pyrexia (4%) Headache (3%) Respiratory rate decreased (3%) Black Box Warnings Personnel and equipment for monitoring and resuscitation Administer only by personnel trained in procedural sedation who are not involved in conducting the diagnostic or therapeutic procedure Administering personnel must be trained in the detection and management of airway obstruction, hypoventilation, and apnea, including maintenance of airway patency, supportive ventilation, and cardiovascular resuscitation Hypoxia, bradycardia, and hypotension reported Continuously monitor vital signs during sedation and during recovery period Resuscitative drugs, and age- and size-appropriate equipment for bag/valve/mask assisted ventilation, must be immediately available during administration Risks from coadministration with opioids and other sedative hypnotics Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death Sedative effect of remimazolam can be accentuated by concomitantly administered CNS depressants, including other benzodiazepines and propofol Continuously monitor for respiratory depression and depth of sedation Contraindications Severe hypersensitivity reaction to dextran 40 Cautions Clinically notable hypoxia, bradycardia, and hypotension observed in clinical trials; continuously monitor vital signs during sedation and through the recovery period Contains dextran 40, which can cause hypersensitivity reactions, including rash, urticaria, pruritus, and anaphylaxis Benzodiazepine use in late-stage pregnancy can result in sedation in the neonate; observe newborns for signs or sedation and manage accordingly Pediatric neurotoxicity Published animal studies demonstrate that the administration of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity increase neuronal apoptosis in the developing brain and result in long-term cognitive deficits when used for longer than 3 hr Some published studies in children suggest that similar deficits may occur after repeated or prolonged exposures to anesthetic agents early in life and may result in adverse cognitive or behavioral effects Drug interaction overview Coadministration with opioid analgesics may result in profound sedation, respiratory depression, coma, and death Sedative effect of remimazolam can be accentuated by concomitantly administered CNS depressant medications, including other benzodiazepines and propofol Titrate dose when administered with opioid analgesics and sedative-hypnotics to desired clinical response Continuously monitor sedated patients for hypotension, airway obstruction, hypoventilation, apnea, and oxygen desaturation; these cardiorespiratory effects may be more likely to occur in patients with obstructive sleep apnea, geriatric patients, or ASA-PS III or IV patients Pregnancy Benzodiazepines cross the placenta; receiving benzodiazepines late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate Therapy may produce respiratory depression, hypotonia, and sedation in neonates; monitor neonates exposed to therapy during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems; monitor neonates exposed to this drug during pregnancy for signs of withdrawal; manage these neonates accordingly Published observational studies of pregnant women exposed to benzodiazepines have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes Clinical considerations Benzodiazepines cross the placenta and may produce respiratory depression and sedation in neonates Monitor neonates exposed to benzodiazepines during pregnancy and labor for signs of sedation and respiratory depression and manage accordingly Lactation There are reports of sedation, poor feeding, and poor weight gain in infants exposed to benzodiazepines through breast milk; there are no data on effects of this drug in human milk, effects on breastfed infant or on milk production Developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from this drug or from underlying maternal condition Remimazolam is present in animal milk; when a drug is present in animal milk, it is likely that it will be present in human milk Infants exposed to the drug through breast milk should be monitored for sedation, poor feeding, and poor weight gainPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Binds receptors at several sites within the CNS, including the limbic system and reticular formation; effects may be mediated through GABA receptor system; increase in neuronal membrane permeability to chloride ions enhances the inhibitory effects of GABA; the shift in chloride ions causes hyperpolarization (less excitability) and stabilization of the neuronal membrane Absorption Peak plasma time: 20-30 minutes Peak plasma concentration: 189-6960 ng/mL (0.01-9.5 mg/kg) AUC: 12.1-452 ng⋅h/mL (0.01-9.5 mg/kg) Distribution Half-life (distribution): 0.5-2 minutes Vd: 0.76-0.98 L/kg Protein bound: >91% (primarily to albumin) Metabolism Conversion to primary inactive metabolite CNS7054, which is then subject to hydroxylation and glucuronidation Conversion to CNS7054 is mediated by tissue carboxylesterases (primarily type 1A), with no meaningful contribution by cytochrome P450 enzyme Elimination Half-life (terminal): 37-53 minutes Clearance: 54-75 L/hr Excretion Healthy volunteers: Urine 80% (inactive metabolite) Colonoscopy: Urine 50-60% (inactive metabolite); 0.003% (unchanged) IV Compatibilities 0.9% NaCl D5W D20W D5W/0.45% NaCl Ringers solution IV Preparation Do not mix with other drugs or fluids before administration, except those known to be compatible Product does not contain preservative; use strict aseptic technique Once removed from packaging, protect vials from light. Reconstitution Add 8.2 mL sterile 0.9% NaCl to the vial, directing the stream of solution toward the wall of the vial Gently swirl vial (do not shake) until contents are fully dissolved Resulting solution is 2.5 mg/mL Inspect visually for particulate matter and discoloration before administration; solution should appear clear, colorless to pale yellow Discard if particulate matter or discoloration is observed IV Administration Induction: Administer over 1 minute Maintenance: Administer over 15 seconds; at least 2 minutes must elapse before administration of any supplemental dose See Warnings for monitoring and equipment requirements Storage Unopened vials: Store at controlled room temperature 20-25ºC (68-77ºF); excursions to 15-30ºC (59-86ºF) allowed Reconstituted vials: May store at controlled room temperature 20-25ºC (68-77ºF) for up to 8 hr Protect vials from light once removed from packaging No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. NC NOT COVERED – Drugs that are not covered by the plan. Code Definition PA Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription. 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