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Cannabidiol oral

Updated 2 Feb 2023 | Other antiepileptics

Presentation

Oral formulations of cannabidiol.

Drugs List

  • cannabidiol 100mg/ml oral solution sugar-free
  • EPIDYOLEX 100mg/ml oral solution
  • Therapeutic Indications

    Uses

    Seizures associated with Dravet syndrome: adjunctive treatment
    Seizures associated with Lennox-Gastaut Syndrome: adjunctive treatment
    Seizures associated with tuberous sclerosis complex: adjunctive treatment

    Adjunctive therapy of seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in conjunction with clobazam, for patients 2 years of age and older.

    Adjunctive therapy of seizures associated with tuberous sclerosis complex (TSC) for patients 2 years of age and older.

    Dosage

    Adults

    Lennox-Gastaut and Dravet syndromes
    Initial dose: 2.5mg/kg twice daily for one week
    Increasing to a maintenance dose of: 5mg/kg twice daily.

    If clinically required and tolerated, the maintenance dose can be increased in weekly increments of 2.5mg/kg given twice daily, up to a maximum dose of 10mg/kg twice daily. Any dose increases above 10mg/kg/day should only be made once the risk and benefit of the patient has been considered.

    Tuberous sclerosis complex
    Initial dose: 2.5mg/kg taken twice daily for one week.
    Increasing to a maintenance dose of 5mg/kg twice daily.

    If clinically required and tolerated, the maintenance dose can be increased in weekly increments of 2.5mg/kg given twice daily, up to maximum dose of 12.5mg/kg twice daily. Any dose increases above 10mg/kg/day should only be made once the risk and benefit of the patient has been considered.

    Children

    Children aged 2 to 18 years
    Lennox-Gastaut and Dravet syndromes
    (See Dosage; Adults)

    Tuberous sclerosis complex
    (See Dosage; Adults)

    Patients with Hepatic Impairment

    Moderate hepatic impairment
    Initial dose: 1.25mg/kg twice daily.
    Maintenance dose: 2.5mg/kg twice daily.
    Maximum daily dose: 5mg/kg twice daily.

    Severe hepatic impairment
    Initial dose: 0.5mg/kg twice daily.
    Maintenance dose: 1mg/kg twice daily.
    Maximum daily dose: 2mg/kg twice daily.

    Higher doses of cannabidiol may be considered in patients with severe hepatic impairment where the potential benefits outweigh the risks.

    Additional Dosage Information

    Missed doses
    If less than 7 days have been missed, they should not be compensated. Treatment should resume at the usual schedule.
    If more than 7 days of doses are missed, the dose should be re-titrated to the therapeutic dose.

    Administration

    Oral administration recommended; however, when required, nasogastric and gastrostomy tubes may be acceptable for enteral administration.

    Contraindications

    Children under 2 years
    Breastfeeding
    Serum bilirubin above 2 times upper limit of normal
    Serum transaminases above 3 times upper limit of normal

    Precautions and Warnings

    Patients over 65 years
    Suicidal ideation
    End stage renal disease
    Moderate hepatic impairment
    Pregnancy

    Reduce dose in patients with moderate 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
    Advise patient this medicine may be subject to driving restrictions
    Treatment to be initiated and supervised by a specialist
    Oral solution contains alcohol
    Product contains sesame oil
    Take at the same time in respect to food as absorption may be affected
    Monitor serum transaminases before treatment
    May increase seizure frequency
    Monitor bilirubin levels before treatment
    Monitor for signs of suicide ideation or behaviour
    Monitor transaminases/bilirubin at 1 month, 3 months and at 6 months
    Consider discontinuing treatment if serum transaminase levels rise
    To discontinue, reduce dose gradually
    Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
    Advise patient not to take St John's wort concurrently
    Advise that effects are potentiated by CNS depressants (including alcohol)
    Advise patient/carers to report signs of suicide ideation or behaviour

    Cannabidiol can cause elevations of alanine aminotransferase and/or aspartate aminotransferase. The elevations typically occur in the first two months of treatment initiation; however, there were cases observed up to 18 months after initiation of treatment, particularly in patients taking concomitant valproate.

    Early identification of elevated transaminase may decrease the risk of a serious liver outcome. If required consider discontinuation or dose reduction of cannabidiol. Should elevations occur whilst being co-administered, dose adjustment of co-administered products known to affect the liver should be considered e.g. valproate and clobazam.

    Serum transaminases and total bilirubin levels should be obtained at 1 month, 3 months, and at 6 months after starting treatment with cannabidiol, and periodically thereafter or as clinically indicated. Patients with baseline elevations of ALT or AST and those who are taking valproate should have serum transaminases and total bilirubin levels obtained at 2 weeks, 1 month, 2 months, 3 months and 6 months after starting treatment, and periodically thereafter or as clinically required. With doses above 10mg/kg/day or changes in therapy (dose change or additions) that are known to impact the liver, this monitoring schedule should be restarted.

    Seizure frequency may be increased, consider dose adjustment or discontinuation of cannabidiol.

    Pregnancy and Lactation

    Pregnancy

    Use cannabidiol with caution during pregnancy.

    The manufacturer advises only using cannabidiol if the benefit to the mother outweighs the potential risk to the foetus. At the time of writing there is limited published data regarding the use of cannabidiol in pregnancy. Potential risks are unknown, however animal studies have shown reproductive toxicity.

    Lactation

    Cannabidiol is contraindicated during breastfeeding.

    The manufacturer recommends either discontinuing treatment or discontinuing breastfeeding. At the time of writing there is limited data available regarding the presence of cannabidiol in breast milk, however given that it is highly protein bound it will likely pass easily into the breast milk from plasma. Effects on exposed infants are unknown. Animal studies have shown toxicological changes in lactating animals treated with cannabidiol.

    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.

    Side Effects

    Aggression
    Agitation
    Altered liver function tests
    Behavioural disturbances
    Bronchitis
    Cough
    Decreased appetite
    Diarrhoea
    Drooling
    Fatigue
    Gamma glutamyl transferase (GGT) increased
    Increased appetite
    Increases in serum transaminases (transient)
    Insomnia
    Irritability
    Lethargy
    Nasopharyngitis
    Pneumonia
    Pyrexia
    Rash
    Sedation
    Somnolence
    Suicidal tendencies
    Tremor
    Urinary tract infections
    Vomiting
    Weight loss

    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 2021

    Reference Sources

    Summary of Product Characteristics: Epidyolex 100mg/ml oral solution. GW Pharma Ltd. Revised August 2022.

    NICE Evidence Services Available at: www.nice.org.uk Last accessed: 07 January 2021

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