Drugs List

Therapeutic Indications

Uses

Status epilepticus

Unlicensed Uses

Febrile convulsions
Sedative cover for minor medical, dental, and surgical procedures

Contraindications

Acute respiratory impairment
Myasthenia gravis
Severe hepatic impairment
Severe respiratory impairment
Sleep apnoea

Precautions and Warnings

Adults aged 18 years and above
Children under 6 months
Chronic illness
Debilitation
Hypothermia
Breastfeeding
Cardiac impairment
Children with cardiovascular impairment
Chronic renal failure
Chronic respiratory impairment
Hepatic impairment
Hereditary fructose intolerance
History of alcohol abuse
History of drug misuse
Hypovolaemia
Peripheral vasoconstriction
Pregnancy
Renal impairment
Respiratory depression

Advise ability to drive/operate machinery may be affected by side effects
Advise patient not to drive or operate machinery until assessed
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Oral solution with maltitol unsuitable in hereditary fructose intolerance
Children aged up to 6 months to be treated in a hospital environment
Monitor patient for signs and symptoms of respiratory depression
Monitor patients with a history of alcoholism and drug abuse
Monitor patients with hepatic impairment for toxic effects
Tolerance and dependence may occur
Amnesia may occur
May cause paradoxical behaviour
Not licensed for all indications in all age groups
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise patient to avoid grapefruit products

Use with caution in children with cardiovascular impairment. There is a risk of airways obstruction and hypoventilation in children under 6 months - respiratory rate and oxygen saturation should be monitored.

Pregnancy and Lactation

Pregnancy

Use midazolam with caution in pregnancy.

Highly limited data are available on midazolam to assess its safety during pregnancy. Animal studies do not indicate a teratogenic effect, but foetotoxicity was observed as with other benzodiazepines. No data on exposed pregnancies are available for the first two trimesters of pregnancy. The administration of high doses of midazolam in the last trimester of pregnancy or during labour has been reported to produce maternal or foetal adverse reactions (risk of aspiration of fluids and stomach contents during labour in the mother, irregularities in the foetal heart rate, hypotonia, poor suckling, hypothermia and respiratory depression in the new-born infant). The manufacturer suggests midazolam may be used during pregnancy if clearly necessary
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use midazolam with caution in pregnancy.

Midazolam passes in low quantities (0.6%) into breast milk. As a result it may not be necessary to stop breast feeding following a single dose of midazolam.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Aggression
Agitation
Amnesia
Anaphylaxis
Anger
Anterograde amnesia
Apnoea
Ataxia
Blood disorders
Blood dyscrasias
Bradycardia
Cardiac arrest
Changes in libido
Confusion
Constipation
Dizziness
Drowsiness
Dry mouth
Dysarthria
Dyspnoea
Euphoria
Excitement (paradoxical)
Fatigue
Gastro-intestinal disturbances
Hallucinations
Headache
Hiccups
Hostility
Hypotension
Impaired consciousness
Incontinence
Increased appetite
Involuntary movement disorders
Jaundice
Laryngospasm
Muscle weakness
Nausea
Paradoxical reactions
Pruritus
Rash
Reduced alertness
Respiratory arrest
Respiratory depression
Salivation
Salivation changes
Sedation
Seizures
Skin reactions
Somnolence
Thrombosis
Urinary retention
Urticaria
Variation in heart rate
Vasodilatation
Vertigo
Visual disturbances
Vomiting

Presentation

Oromucosal solution containing midazolam in pre-filled oral syringe

Drugs List

Therapeutic Indications

Uses

Status epilepticus

Unlicensed Uses

Febrile convulsions
Sedative cover for minor medical, dental, and surgical procedures

Dosage

The full amount of solution should be inserted slowly into the space between the gum and the cheek. Laryngo-tracheal insertion should be avoided to prevent accidental aspiration of the solution. If necessary (for larger volumes and/or smaller patients), approximately half the dose should be given slowly into one side of the mouth, then the other half given slowly into the other side.

Carers should only administer a single dose of midazolam. If the seizure has not stopped within 10 minutes after administration of midazolam, seek emergency medical assistance and provide the empty syringe to the healthcare professional for information on the dose received by the patient.

A second or repeat dose when seizures re-occur after an initial response should not be given without prior medical advice.

Children

Additional Dosage Information

Contraindications

Acute respiratory impairment
Myasthenia gravis
Severe hepatic impairment
Severe respiratory impairment
Sleep apnoea

Precautions and Warnings

Adults aged 18 years and above
Children under 6 months
Chronic illness
Debilitation
Hypothermia
Breastfeeding
Cardiac impairment
Children with cardiovascular impairment
Chronic renal failure
Chronic respiratory impairment
Hepatic impairment
Hereditary fructose intolerance
History of alcohol abuse
History of drug misuse
Hypovolaemia
Peripheral vasoconstriction
Pregnancy
Renal impairment
Respiratory depression

Advise ability to drive/operate machinery may be affected by side effects
Advise patient not to drive or operate machinery until assessed
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Oral solution with maltitol unsuitable in hereditary fructose intolerance
Children aged up to 6 months to be treated in a hospital environment
Monitor patient for signs and symptoms of respiratory depression
Monitor patients with a history of alcoholism and drug abuse
Monitor patients with hepatic impairment for toxic effects
Tolerance and dependence may occur
Amnesia may occur
May cause paradoxical behaviour
Not licensed for all indications in all age groups
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise patient to avoid grapefruit products

Use with caution in children with cardiovascular impairment. There is a risk of airways obstruction and hypoventilation in children under 6 months - respiratory rate and oxygen saturation should be monitored.

Pregnancy and Lactation

Pregnancy

Use midazolam with caution in pregnancy.

Highly limited data are available on midazolam to assess its safety during pregnancy. Animal studies do not indicate a teratogenic effect, but foetotoxicity was observed as with other benzodiazepines. No data on exposed pregnancies are available for the first two trimesters of pregnancy. The administration of high doses of midazolam in the last trimester of pregnancy or during labour has been reported to produce maternal or foetal adverse reactions (risk of aspiration of fluids and stomach contents during labour in the mother, irregularities in the foetal heart rate, hypotonia, poor suckling, hypothermia and respiratory depression in the new-born infant). The manufacturer suggests midazolam may be used during pregnancy if clearly necessary
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use midazolam with caution in pregnancy.

Midazolam passes in low quantities (0.6%) into breast milk. As a result it may not be necessary to stop breast feeding following a single dose of midazolam.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them.

Counselling

Advise carers that if the seizure has not stopped within 10 minutes, emergency medical assistance must be sought, and the empty syringe given to the healthcare professional to provide information on the dose received by the patient.

Advise patients not to drive a vehicle or operate machinery until completely recovered.

Risk of inhalation/ingestion of tip cap of prefilled plastic syringes. Advise patients and carers to check the syringe before administering and remove the translucent tip cap if it is still on the syringe after the red cap has been removed.

Side Effects

Aggression
Agitation
Amnesia
Anaphylaxis
Anger
Anterograde amnesia
Apnoea
Ataxia
Blood disorders
Blood dyscrasias
Bradycardia
Cardiac arrest
Changes in libido
Confusion
Constipation
Dizziness
Drowsiness
Dry mouth
Dysarthria
Dyspnoea
Euphoria
Excitement (paradoxical)
Fatigue
Gastro-intestinal disturbances
Hallucinations
Headache
Hiccups
Hostility
Hypotension
Impaired consciousness
Incontinence
Increased appetite
Involuntary movement disorders
Jaundice
Laryngospasm
Muscle weakness
Nausea
Paradoxical reactions
Pruritus
Rash
Reduced alertness
Respiratory arrest
Respiratory depression
Salivation
Salivation changes
Sedation
Seizures
Skin reactions
Somnolence
Thrombosis
Urinary retention
Urticaria
Variation in heart rate
Vasodilatation
Vertigo
Visual disturbances
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: February 2015

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Summary of Product Characteristics: Buccolam oromucosal solution. Viropharma Ltd. Revised March 2014.

Summary of Product Characteristics: Epistatus 10mg Oromucosal Solution. Veriton Pharma Ltd. Revised February 2019.

MHRA Drug Safety Update Vol 5, Issue 3, October 2011
Buccal midazolam (Buccolam): new authorised medicine for paediatric use - care needed when transferring from unlicensed formulations
Available at: www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/index.htm
Last accessed: October 24, 2011

Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk Last accessed: 6 January 2015 New drug driving offence implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 6 January 2015

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 07 August 2017