Drug Detail:Cannabidiol (Cannabidiol [ kan-a-bi-dye-ol ])
Drug Class: Miscellaneous anticonvulsants
Usual Adult Dose for Lennox-Gastaut Syndrome
Initial dose: 2.5 mg/kg orally twice a day
- After 1 week, may increase dose to 5 mg/kg orally twice a day
- For patients tolerating therapy and requiring further seizure reduction, may increase in 2.5 mg/kg twice a day increments as tolerated but no more frequently than every other day
Maximum dose: 20 mg/kg/day
Comments:
- A dose of 20 mg/kg/day has demonstrated a greater reduction in seizure rates, but is associated with an increase in adverse reactions.
- Consistent dosing with respect to meals is recommended to reduce variability in cannabidiol plasma exposure.
Use: For the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome.
Usual Adult Dose for Dravet Syndrome
Initial dose: 2.5 mg/kg orally twice a day
- After 1 week, may increase dose to 5 mg/kg orally twice a day
- For patients tolerating therapy and requiring further seizure reduction, may increase in 2.5 mg/kg twice a day increments as tolerated but no more frequently than every other day
Maximum dose: 20 mg/kg/day
Comments:
- A dose of 20 mg/kg/day has demonstrated a greater reduction in seizure rates, but is associated with an increase in adverse reactions.
- Consistent dosing with respect to meals is recommended to reduce variability in cannabidiol plasma exposure.
Use: For the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome.
Usual Adult Dose for Tuberous Sclerosis Complex
Initial dose: 2.5 mg/kg orally twice a day
- Increase dose in weekly increments of 2.5 mg twice a day (5 mg/kg/day) as tolerated to 12.5 mg/kg twice a day
- For patients requiring a more rapid titration, the dose may be increased no more frequently than every other day
Maximum dose: 25 mg/kg/day
Comments:
- The effectiveness of doses lower than 25 mg/kg/day has not been studied.
- Consistent dosing with respect to meals is recommended to reduce variability in cannabidiol plasma exposure.
Use: For the treatment of seizures associated with tuberous sclerosis complex.
Usual Pediatric Dose for Lennox-Gastaut Syndrome
1 year or older:
Initial dose: 2.5 mg/kg orally twice a day
- After 1 week, may increase dose to 5 mg/kg orally twice a day
- For patients tolerating therapy and requiring further seizure reduction, may increase in 2.5 mg/kg twice a day increments as tolerated but no more frequently than every other day
Maximum dose: 20 mg/kg/day
Comments:
- A dose of 20 mg/kg/day has demonstrated a greater reduction in seizure rates, but is associated with an increase in adverse reactions.
- Consistent dosing with respect to meals is recommended to reduce variability in cannabidiol plasma exposure.
Use: For the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 1 year and older.
Usual Pediatric Dose for Dravet Syndrome
1 year or older:
Initial dose: 2.5 mg/kg orally twice a day
- After 1 week, may increase dose to 5 mg/kg orally twice a day
- For patients tolerating therapy and requiring further seizure reduction, may increase in 2.5 mg/kg twice a day increments as tolerated but no more frequently than every other day
Maximum dose: 20 mg/kg/day
Comments:
- A dose of 20 mg/kg/day has demonstrated a greater reduction in seizure rates, but is associated with an increase in adverse reactions.
- Consistent dosing with respect to meals is recommended to reduce variability in cannabidiol plasma exposure.
Use: For the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 1 year and older.
Usual Pediatric Dose for Tuberous Sclerosis Complex
1 year or older:
Initial dose: 2.5 mg/kg orally twice a day
- Increase dose in weekly increments of 2.5 mg twice a day (5 mg/kg/day) as tolerata to 12.5 mg/kg twice a day
- For patients requiring a more rapid titration, the dose may be increased no more frequently than every other day
Maximum dose: 25 mg/kg/day
Comments:
- The effectiveness of doses lower than 25 mg/kg/day has not been studied.
- Consistent dosing with respect to meals is recommended to reduce variability in cannabidiol plasma exposure.
Use: For the treatment of seizures associated with tuberous sclerosis complex in patients 1 year and older.
Renal Dose Adjustments
No adjustment recommended
Liver Dose Adjustments
Mild hepatic impairment: No adjustment recommended
Moderate hepatic impairment (Child-Pugh B):
- Initial dose: 1.25 mg/kg orally twice a day
- Maintenance dose (Lennox-Gastaut syndrome; Dravet syndrome): 2.5 to 5 mg/kg orally twice a day
- Maintenance dose (tuberous sclerosis complex): 6.25 mg/kg orally twice a day
Severe hepatic impairment (Child-Pugh C):
- Initial dose: 0.5 mg/kg orally twice a day
- Maintenance dose (Lennox-Gastaut syndrome; Dravet syndrome): 1 to 2 mg/kg orally twice a day
- Maintenance dose (tuberous sclerosis complex): 2.5 mg/kg orally twice a day
Comments:
- For patients with moderate to severe hepatic impairment, it may be necessary to have a slower dose titration.
- Discontinue therapy for transaminase elevations greater than 3 times upper limit of normal (3 x ULN) and bilirubin levels greater than 2 x ULN
- Discontinue therapy for sustained transaminase elevations greater than 5 x ULN
Dose Adjustments
Elderly: Dose selection should be cautious, usually starting at the low end of the dosing range
Discontinuation of therapy:
- Gradual dose reduction is recommended to reduce the risk of increased seizure frequency and status epilepticus.
Precautions
CONTRAINDICATIONS:
- Hypersensitivity to active substance or any product excipients
Safety and efficacy have not been established in patients younger than 1 year.
Consult WARNINGS section for additional precautions.
Dialysis
Data not available
Other Comments
Administration advice:
- For oral administration only
- Take consistently with or without food to reduce variability in plasma exposure
- A calibrated measuring device should be used to ensure accuracy in dosing
- Enteral feeding tube (nasogastric or gastrostomy) may be used if needed: do not use tubes made of polyvinyl chloride (PVC)
Storage requirements:
- Store upright at 20C to 25C (68F to 77F); excursions permitted 15C to 30C (59F to 86F)
- Do not refrigerate or freeze
- Keep cap tightly closed
- Use within 12 weeks of opening bottle; discard any remainder
Reconstitution/preparation techniques:
- Product will be dispensed with a bottle adapter and 5 mL oral syringe
- If dose is less than 100 mg (1 mL), the pharmacist should provide a 1 mL oral syringe
Monitoring:
- Obtain baseline serum transaminases (ALT and AST) and total bilirubin levels; repeat at 1, 3, and 6 months, then periodically or as clinically indicated.
- Additionally, serum transaminase and total bilirubin levels should also be obtained within 1 month a change in dose of this drug or changes in medications that are known to impact the liver
- Increased monitoring should be considered in those concomitantly taking valproate or who have elevated liver enzymes at baseline.
- Monitor for emergence or worsening of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts of self-harm
Patient Advice:
- Read the US FDA-approved patient labeling (Medication Guide and Instructions for Use).
- Patients should understand that this drug may be taken with or without food, however, once decided, it should always be taken the same way.
- Patients should be advised of the signs and symptoms of hepatic dysfunction and the need to contact their healthcare provider if these occur.
- Patients should be advised not to drive or operate hazardous equipment until they understand how this drug affects them.
- Patients should be instructed not to abruptly discontinue therapy without talking with their health care provider.
- Patients, families, and caregivers should understand that this drug may increase the risk of suicidal thoughts and behavior and they should be instructed to report any unusual change in mood or behavior, worsening of depression, or suicidal thoughts or behaviors to their healthcare provider immediately.
- Patients should understand that this drug may cause a positive cannabis drug screen.
- Women should speak with their healthcare provider if they are pregnant or planning on becoming pregnant
Frequently asked questions
- Does Epidiolex contain marijuana?
- What type of drug is Epidiolex?
