General Information

Epidiolex (cannabidiol) is a pharmaceutical formulation of highly-purified, plant-derived cannabidiol.

Epidiolex is specifically indicated for the treatment of seizures associated with Lennox Gastaut syndrome (LGS), Dravet syndrome (DS) or tuberous sclerosis complex in patients 1 year of age and older.

Epidiolex is supplied as an oral solution.

Dosing for seizures related to LGS and DS:

• The recommended starting dosage is 2.5 mg/kg twice daily (5 mg/kg/day). After one week, the dosage can be increased to a maintenance dosage of 5 mg/kg twice daily (10 mg/kg/day). Patients who are tolerating Epidiolex at 5 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 10 mg/kg twice daily (20 mg/kg/day), in weekly increments of 2.5 mg/kg twice daily (5 mg/kg/day), as tolerated. For patients in whom a more rapid titration from 10 mg/kg/day to 20 mg/kg/day is warranted, the dosage may be increased no more frequently than every other day. Administration of the 20 mg/kg/day dosage resulted in somewhat greater reductions in seizure rates than the recommended maintenance dosage of 10 mg/kg/day, but with an increase in adverse reactions. 

Dosing for Seizures Associated with TSC

• The starting dosage is 2.5 mg/kg by mouth twice daily (5 mg/kg/day). Increase the dose in weekly increments of 2.5 mg/kg twice daily (5 mg/kg/day), as tolerated, to a recommended maintenance dosage of 12.5 mg/kg twice daily (25 mg/kg/day). For patients in whom a more rapid titration to 25 mg/kg/day is warranted, the dosage may be increased no more frequently than every other day. The effectiveness of doses lower than 12.5 mg/kg twice daily has not been studied in patients with TSC.

Mechanism of Action

Epidiolex (cannabidiol) is a pharmaceutical formulation of highly-purified, plant-derived cannabidiol. The precise mechanisms by which Epidiolex exerts its anticonvulsant effect in humans are unknown. Cannabidiol does not appear to exert its anticonvulsant effects through interaction with cannabinoid receptors.

Side Effects

Adverse effects associated with the use of Epidiolex in patients with LGS or DS may include, but are not limited to, the following:

• somnolence
• decreased appetite
• diarrhea
• transaminase elevations
• fatigue
• malaise and asthenia
• rash
• insomnia
• sleep disorder and poor quality sleep
• infections

Adverse effects associated with the use of Epidiolex in patients with TSC may include, but are not limited to, the following:

• diarrhea
• transaminase elevations
• decreased appetite
• somnolence
• pyrexia
• vomiting

Clinical Trial Results

Lennox–Gastaut Syndrome: The FDA approval of Epidiolex for the treatment of seizures associated with LGS was established in two randomized, double-blind, placebo-controlled trials in patients aged 2 to 55 years. Study 1 (N=171) compared a dose of Epidiolex 20 mg/kg/day with placebo. Study 2 (N=225) compared a 10 mg/kg/day dose and a 20 mg/kg/day dose of Epidiolex with placebo. In both studies, patients had a diagnosis of LGS and were inadequately controlled on at least one AED, with or without vagal nerve stimulation and/or ketogenic diet. Both trials had a 4-week baseline period, during which patients were required to have a minimum of 8 drop seizures (≥2 drop seizures per week). The baseline period was followed by a 2-week titration period and a 12-week maintenance period. The primary efficacy measure in both studies was the percent change from baseline in the frequency (per 28 days) of drop seizures (atonic, tonic, or tonic clonic seizures) over the 14-week treatment period. The primary efficacy measure in both studies was the percent change from baseline in the frequency (per 28 days) of drop seizures (atonic, tonic, or tonic clonic seizures) over the 14-week treatment period. In Studies 1 and 2, the median percent change from baseline (reduction) in the frequency of drop seizures was significantly greater for both dosage groups of Epidiolex than for placebo. A reduction in drop seizures was observed within 4 weeks of initiating treatment with Epidiolex, and the effect remained generally consistent over the 14-week treatment period. 

Dravat Syndrome: The effectiveness of Epidiolex for the treatment of seizures associated with DS was demonstrated in a single randomized, double-blind, placebo-controlled trial in 120 patients aged 2 to 18 years. The study compared a dose of Epidiolex 20 mg/kg/day with placebo. Patients had a diagnosis of treatment-resistant DS and were inadequately controlled with at least one concomitant AED, with or without vagal nerve stimulation or ketogenic diet. During the 4-week baseline period, patients were required to have at least 4 convulsive seizures while on stable AED therapy. The baseline period was followed by a 2-week titration period and a 12-week maintenance period. The primary efficacy measure was the percent change from baseline in the frequency (per 28 days) of convulsive seizures (all countable atonic, tonic, clonic, and tonic-clonic seizures) over the 14-week treatment period. The median percent change from baseline (reduction) in the frequency of convulsive seizures was significantly greater for Epidiolex 20 mg/kg/day than for placebo. A reduction in convulsive seizures was observed within 4 weeks of initiating treatment with Epidiolex and the effect remained generally consistent over the 14-week treatment period.

TSC: FDA approval was based on a randomized, double-blind, placebo-controlled trial in 224 patients aged 1 to 65 years. The study met its primary endpoint, which was the reduction in seizure frequency compared to baseline of Epidiolex vs placebo, with seizure reduction of 48 percent in patients taking Epidiolex 25 mg/kg/day compared with 24 percent for placebo.