How effective is CBD for pediatric epilepsy?

1.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 1, 2024.

Description Cannabidiol is an oral cannabinoid indicated for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. Cannabidiol is a marijuana derivative; however, it lacks the psychoactive properties that are commonly associated with delta-9-tetrahydrocannabinol (THC). Adjunctive cannabidiol treatment significantly reduced seizure frequency in patients with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex, with a reduction in seizures observed within 4 weeks of initiation. In patients with Dravet syndrome, the median percent reduction in monthly convulsive seizures from baseline was 39% for those receiving cannabidiol 20 mg/kg/day vs. 13% for those receiving placebo. During the maintenance period, 6.7% of cannabidiol-treated patients were seizure-free. In patients with Lennox-Gastaut syndrome, the median percent reduction in monthly drop seizure frequency from baseline was 37% for those receiving cannabidiol 10 mg/kg/day, 42% to 44% for those receiving 20 mg/kg/day, and 17% to 22% for those receiving placebo. In patients with tuberous sclerosis complex, the median percent reduction in monthly seizures was 43% for those receiving cannabidiol 25 mg/kg/day and 20% for those receiving placebo. Somnolence, decreased appetite, and diarrhea are among the most common adverse reactions of cannabidiol. Dose-related elevations in liver transaminases can occur, and routine monitoring of hepatic enzymes is necessary.

Description Epidiolex Solution is an oral cannabinoid indicated for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. Epidiolex Solution is a marijuana derivative; however, it lacks the psychoactive properties that are commonly associated with delta-9-tetrahydrocannabinol (THC). Adjunctive epidiolex solution treatment significantly reduced seizure frequency in patients with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex, with a reduction in seizures observed within 4 weeks of initiation. In patients with Dravet syndrome, the median percent reduction in monthly convulsive seizures from baseline was 39% for those receiving epidiolex solution 20 mg/kg/day vs. 13% for those receiving placebo. During the maintenance period, 6.7% of epidiolex solution-treated patients were seizure-free. In patients with Lennox-Gastaut syndrome, the median percent reduction in monthly drop seizure frequency from baseline was 37% for those receiving epidiolex solution 10 mg/kg/day, 42% to 44% for those receiving 20 mg/kg/day, and 17% to 22% for those receiving placebo. In patients with tuberous sclerosis complex, the median percent reduction in monthly seizures was 43% for those receiving epidiolex solution 25 mg/kg/day and 20% for those receiving placebo. Somnolence, decreased appetite, and diarrhea are among the most common adverse reactions of epidiolex solution. Dose-related elevations in liver transaminases can occur, and routine monitoring of hepatic enzymes is necessary.

2.

Food and Drug Administration (DailyMed).

Publish date: March 3, 2024.

Pediatric Use 8.4 Pediatric Use Safety and effectiveness of Epidiolex (cannabidiol) for the treatment of seizures associated with LGS, DS, or TSC have been established in patients 1 year of age and older. The use of Epidiolex (cannabidiol) in these indications is supported by adequate and well-controlled studies in patients 2 years of age and older with LGS and DS and in patients 1 year of age and older with TSC [see Clinical Studies ( 14.1, 14.2, 14.3 )]. Safety and effectiveness of Epidiolex (cannabidiol) in pediatric patients below 1 year of age have not been established. Juvenile Animal Data Administration of Epidiolex (cannabidiol) (subcutaneous doses of 0 or 15 mg/kg on Postnatal Days (PNDs) 4-6 followed by oral administration of 0, 100, 150, or 250 mg/kg on PNDs 7-77) to juvenile rats for 10 weeks resulted in increased body weight, delayed male sexual maturation, neurobehavioral effects (decreased locomotor activity and auditory startle habituation), increased bone mineral density, and liver hepatocyte vacuolation. A no-effect dose was not established. The lowest dose causing developmental toxicity in juvenile rats (15 sc/100 po mg/kg) was associated with Epidiolex (cannabidiol) exposures (AUC) approximately 15 and 8 times that in humans at the RHDs of 20 and 25 mg/kg/day, respectively.

Use In Specific Populations 8.4 Pediatric Use Safety and effectiveness of Epidiolex (cannabidiol) for the treatment of seizures associated with LGS, DS, or TSC have been established in patients 1 year of age and older. The use of Epidiolex (cannabidiol) in these indications is supported by adequate and well-controlled studies in patients 2 years of age and older with LGS and DS and in patients 1 year of age and older with TSC [see Clinical Studies ( 14.1, 14.2, 14.3 )]. Safety and effectiveness of Epidiolex (cannabidiol) in pediatric patients below 1 year of age have not been established. Juvenile Animal Data Administration of Epidiolex (cannabidiol) (subcutaneous doses of 0 or 15 mg/kg on Postnatal Days (PNDs) 4-6 followed by oral administration of 0, 100, 150, or 250 mg/kg on PNDs 7-77) to juvenile rats for 10 weeks resulted in increased body weight, delayed male sexual maturation, neurobehavioral effects (decreased locomotor activity and auditory startle habituation), increased bone mineral density, and liver hepatocyte vacuolation. A no-effect dose was not established. The lowest dose causing developmental toxicity in juvenile rats (15 sc/100 po mg/kg) was associated with Epidiolex (cannabidiol) exposures (AUC) approximately 15 and 8 times that in humans at the RHDs of 20 and 25 mg/kg/day, respectively. 8.5 Geriatric Use Clinical trials of Epidiolex (cannabidiol) in the treatment of LGS, DS, and TSC did not include a sufficient number of patients aged above 55 years to determine whether or not they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see Dosage and Administration ( 2.6 ), Warnings and Precautions ( 5.1 ), and Clinical Pharmacology ( 12.3 )].

Dosage And Administration • 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 (cannabidiol) 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. 2.3 Dosing for Seizures Associated with Tuberous Sclerosis Complex • 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. 2.4 Administration Instructions Food may affect Epidiolex (cannabidiol) levels [see Clinical Pharmacology ( 12.3 )]. Consistent dosing of Epidiolex (cannabidiol) with respect to meals is recommended to reduce variability in Epidiolex (cannabidiol) plasma exposure. Calibrated measuring devices (1 mL and 5 mL oral syringes) will be provided and are recommended to measure and deliver the prescribed dose accurately [see How Supplied/Storage and Handling ( 16.1 )].