remimazolam (Rx)

Brand and Other Names:Byfavo
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

lyophilized powder for reconstitution

  • 20mg/vial

Procedural Sedation

Indicated for induction and maintenance of procedural sedation in adults undergoing procedures lasting ≤30 minutes

Individualize dosing and titration to desired clinical response

Note: In clinical studies, fentanyl 25-75 mcg was administered for analgesia before the first dose of remimazolam

Induction

  • 5 mg IV push over 1 minute
  • ASA-PS III/IV patients: 2.5-5 mg IV push over 1 minute based on patient’s general condition

Maintenance

  • 2.5 mg IV push over 15 seconds
  • ASA-PS III/IV patients: 1.25-2.5 mg IV push over 15 seconds; at least 2 minutes must elapse before administration of any supplemental dose

Dosage Modifications

Renal impairment

  • Mild to end-stage renal disease not requiring dialysis: Pharmacokinetics not altered

Hepatic impairment

  • Half-life is prolonged with increasing severity of hepatic impairment leading to a need for careful dose titration in patients with severe hepatic impairment
  • Carefully titrate dose to effect; depending on patient’s ASA-PS status, lower frequency of supplemental doses may be needed to achieve the level of sedation required for the procedure
  • Monitor all patients for sedation-related cardiorespiratory complications

Safety and efficacy not established

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Interactions

Interaction Checker

and remimazolam

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >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%)

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            Warnings

            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
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            Pregnancy & Lactation

            Pregnancy

            Infants born to mothers using benzodiazepines during the later stages of pregnancy have been reported to experience symptoms of sedation

            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

            Data are not available on effects in human milk, effects on breastfed infants, or on milk production

            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

            There are reports of sedation in infants exposed to benzodiazepines through breast milk

            Monitor infants exposed through breast milk for sedation, respiratory depression, and feeding problems

            Pregnancy 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.

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            Pharmacology

            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)
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            Administration

            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

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            Formulary

            FormularyPatient Discounts

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            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.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.