In June, the FDA approved cannabidiol oral solution (COS; Epidiolex, GWPharmaceuticals) for treatment of seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients 2 years and older.1 LGS and DS are rare forms of severe epilepsy that emerge in early childhood. Patients often experience treatment-resistant seizures despite taking multiple antiseizure medications.2,3 COS is the first approved medication that contains a purified drug derived from marijuana, and the first approved drug for DS.4
Approval of COS was based on data from three randomized double-blind placebo-controlled trials of 516 patients with either LGS or DS. Treatment with COS 20 mg/kg/day was tested in both LGS and DS patients (Studies 1, 2, and 3), and COS 10 mg/kg/day was tested in LGS patients (Study 2).1
In LGS patients, COS was associated with a significant (p<0.01) reduction in total seizure frequency. The median percent reduction (per 28 days) was 41% in patients treated with 20 mg/kg/day versus 14% in placebo patients in Study 1 and 36% in the 10 mg/kg/day group, 38% in the 20 mg/kg/day group versus 18% in the placebo group in Study 2. Additionally, a greater improvement on the subject/caregiver global impression of change was reported in patients treated with COS compared with placebo in Studies 1 and 2.1
In DS patients, COS was associated with a significant (p=0.01) reduction in total seizure frequency. The median percent reduction (per 28 days) was 39% in patients treated with COS 20 mg/kg/dayversus 13% in placebo patients in Study 3.
The most common adverse effects(>10%) were elevated transaminases (16%), decreased appetite (22%), diarrhea (20%), somnolence (25%), fatigue (12%), insomnia (11%), infection (41%), and rash (13%).1
COS caused dose-related elevations of liver transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase[AST]). The majority of ALT elevation occurred in patients also taking valproate, and to a lesser extent, clobazam.
Patients with baseline Transaminase elevation experienced higher rates of transaminase elevation while on COS. Obtain serum transaminases and total bilirubin levels prior to treatment initiation, and at 1, 3, and 6 months after initiation, as well as 1 month after dose change or addition/discontinuation of any drug that affects the liver. If a patient develops clinical signs or symptoms of hepatic dysfunction, interrupt or discontinue treatment.1 As with most antiepileptic drugs, COS increases the risk of suicidal thoughts or behavior. Monitor patients for the emergence or worsening of depression or any unusual changes in mood or behavior.1
COS should be withdrawn gradually to avoid increased seizure frequency and status epilepticus. No contraindications with COS are known other than hypersensitivity to any ingredient. Insufficient information exists on the risks of COS on a fetus or breastfeeding infant.1
The recommended starting dose of COSis 2.5 mg/kg twice daily (5 mg/ kg/day). After1week, the dose can be increased to a maintenance dose of 5 mg/kg twice daily(10 mg/kg/day). If further seizure control is warranted, the dose can be increased to the maximum recommended maintenance dosage of 10 mg/kg twice daily (20 mg/kg/day). Dose adjustment is recommended for patients with moderate or severe hepatic impairment.1 Epidiolex is supplied as a 100 mL bottle of 100 mg/mL solution.
Feature image: Manufacturing Epidiolex, courtesy of GWPharmaceuticals
- Epidiolex (cannabidiol) Package insert. Carlsbad, CA: Greenwich Biosciences, Inc.; June 2018.
- Lennox-Gastaut syndrome. Genetics Home Reference. http://bit.ly/2LXg2GX. Published July 17, 2018. Accessed July 23, 2018.
- Genetic epilepsy with febrile seizures plus. Genetics Home Reference. http://bit.ly/2oHZPfA. Published July 17, 2018. Accessed July 23, 2018.
- FDA. FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. http://bit.ly/2LZ9vLT Published June 25, 2018. Accessed July 23, 2018.
- GW Pharmaceuticals. GW Pharmaceuticals plc and its U.S. subsidiary Greenwich Biosciences announce FDA approval of EPIDIOLEX® (cannabidiol) oral solution – the first plant-derived cannabinoid prescription medicine. https://bit.ly/2K9Fop8. Published June 25, 2018. Accessed July 23, 2018.