Drugs List

Therapeutic Indications

Uses

Sedation for procedures

Administration

To be administered by intravenous injection after reconstitution.

Contraindications

Children under 18 years
Breastfeeding
Pregnancy
Respiratory depression
Unstable myasthenia gravis

Precautions and Warnings

Debilitation
Patients over 65 years
Weight below 50kg
Cardiac impairment
History of alcohol abuse
History of drug misuse
Myasthenia gravis
Respiratory impairment
Severe hepatic impairment

Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive until they know how the medicine affects them
Ensure benzodiazepine reversal medicinal product (flumazenil) is available
Treatment to be prescribed under the supervision of a specialist
Observe patient closely during and immediately after administration
Resuscitation facilities must be immediately available
Monitor blood pressure
Monitor cardiac function
Monitor patient for signs and symptoms of respiratory depression
Monitor respiratory function
Tolerance and dependence may occur
Amnesia may occur
Reduce dose in debilitated patients
Reduce dose in elderly
Advise that effects are potentiated by CNS depressants (including alcohol)
Alcohol should not be ingested for at least 24 hours prior to treatment

Patients with severe hepatic impairment may be more susceptible to respiratory depression.

Administration of remimazolam can be associated with a transient increase in heart rate (10 to 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 30 minutes after the end of administration. A decrease in blood pressure coincides with the increase in heart rate and it may confound QT correction for heart rate translating into a small prolongation on QTcF in the first few minutes following administration.

Concomitant use of remimazolam and opioids may result in deep sedation and respiratory depression.

Patients receiving chronic benzodiazepine therapy for insomnia or anxiety disorders may develop tolerance to the sedative effects of remimazolam. In order to achieve the desired level of sedation, a larger cumulative dose of remimazolam may be required. In such cases, titrate up until the desired level of sedation is achieved.

Patients should be assessed for amnesia before leaving the hospital or clinic and given the necessary advice and support.

Contains 79.13mg of dextran 40 for injection in each vial. Dextrans can cause anaphylactic or anaphylactoid reactions in some patients.

Pregnancy and Lactation

Pregnancy

Remimazolam is contraindicated during pregnancy.

The manufacturer recommends that it is advisable to avoid the use of remimazolam during pregnancy. Animal studies do not indicate direct or indirect harmful effects with regards to reproductive toxicity. At the time of writing there are no or limited amount of data (less than 300 pregnancy outcomes) from the use of remimazolam in pregnant women. Risks are unknown.

Lactation

Remimazolam is contraindicated during breastfeeding.

The manufacturer advises that breastfeeding should be avoided. If remimazolam is administered then breastfeeding should be discontinued for 24 hours after administration of remimazolam. Animal data indicates excretion of remimazolam and its main metabolite in milk however presence in human milk is unknown. A risk to neonates cannot be excluded.

Side Effects

Bradycardia
Bradypnoea
Chills
Dizziness
Dyspnoea
Headache
Hiccups
Hypotension
Hypoxia
Nausea
Oxygen saturation decreased
Respiratory depression
Respiratory distress
Sensation of cold
Sinus bradycardia
Somnolence
Vomiting

Presentation

Parenteral formulation of remimazolam besilate.

Drugs List

Therapeutic Indications

Uses

Sedation for procedures

Dosage

Dosing should be individually titrated to an effective dose which provides the desired level of sedation and minimises adverse reactions. Administer additional doses as needed in order to induce or maintain the desired level of sedation.
Ensure at least 2 minutes have elapsed prior to administration in order to fully assess the sedative effect. If the desired level of sedation is not achieved after 5 doses of remimazolam within 15 minutes then an additional or another sedative should be considered.

Peak sedation occurred 3 to 3.5 minutes after the initial bolus and patients became fully alert 12 to 14 minutes for the last dose of remimazolam in clinical trials.

Adults

Elderly

Patients with Hepatic Impairment

Administration

To be administered by intravenous injection after reconstitution.

Contraindications

Children under 18 years
Breastfeeding
Pregnancy
Respiratory depression
Unstable myasthenia gravis

Precautions and Warnings

Debilitation
Patients over 65 years
Weight below 50kg
Cardiac impairment
History of alcohol abuse
History of drug misuse
Myasthenia gravis
Respiratory impairment
Severe hepatic impairment

Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive until they know how the medicine affects them
Ensure benzodiazepine reversal medicinal product (flumazenil) is available
Treatment to be prescribed under the supervision of a specialist
Observe patient closely during and immediately after administration
Resuscitation facilities must be immediately available
Monitor blood pressure
Monitor cardiac function
Monitor patient for signs and symptoms of respiratory depression
Monitor respiratory function
Tolerance and dependence may occur
Amnesia may occur
Reduce dose in debilitated patients
Reduce dose in elderly
Advise that effects are potentiated by CNS depressants (including alcohol)
Alcohol should not be ingested for at least 24 hours prior to treatment

Patients with severe hepatic impairment may be more susceptible to respiratory depression.

Administration of remimazolam can be associated with a transient increase in heart rate (10 to 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 30 minutes after the end of administration. A decrease in blood pressure coincides with the increase in heart rate and it may confound QT correction for heart rate translating into a small prolongation on QTcF in the first few minutes following administration.

Concomitant use of remimazolam and opioids may result in deep sedation and respiratory depression.

Patients receiving chronic benzodiazepine therapy for insomnia or anxiety disorders may develop tolerance to the sedative effects of remimazolam. In order to achieve the desired level of sedation, a larger cumulative dose of remimazolam may be required. In such cases, titrate up until the desired level of sedation is achieved.

Patients should be assessed for amnesia before leaving the hospital or clinic and given the necessary advice and support.

Contains 79.13mg of dextran 40 for injection in each vial. Dextrans can cause anaphylactic or anaphylactoid reactions in some patients.

Pregnancy and Lactation

Pregnancy

Remimazolam is contraindicated during pregnancy.

The manufacturer recommends that it is advisable to avoid the use of remimazolam during pregnancy. Animal studies do not indicate direct or indirect harmful effects with regards to reproductive toxicity. At the time of writing there are no or limited amount of data (less than 300 pregnancy outcomes) from the use of remimazolam in pregnant women. Risks are unknown.

Lactation

Remimazolam is contraindicated during breastfeeding.

The manufacturer advises that breastfeeding should be avoided. If remimazolam is administered then breastfeeding should be discontinued for 24 hours after administration of remimazolam. Animal data indicates excretion of remimazolam and its main metabolite in milk however presence in human milk is unknown. A risk to neonates cannot be excluded.

Side Effects

Bradycardia
Bradypnoea
Chills
Dizziness
Dyspnoea
Headache
Hiccups
Hypotension
Hypoxia
Nausea
Oxygen saturation decreased
Respiratory depression
Respiratory distress
Sensation of cold
Sinus bradycardia
Somnolence
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: January 2022

Reference Sources

Summary of Product Characteristics: Byfavo 20mg powder for solution for injection. Paion UK Ltd. Revised June 2021.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 07 January 2022