EPIDIOLEX Oral solution Ref.[10063] Active ingredients: Cannabidiol

2.1 Assessments Prior to Initiating EPIDIOLEX

Because of the risk of hepatocellular injury, obtain serum transaminases (ALT and AST) and total bilirubin levels in all patients prior to starting treatment with EPIDIOLEX [see Warnings and Precautions (5.1)].

2.2 Dosing for Seizures Associated with Lennox-Gastaut Syndrome or Dravet Syndrome

• The starting dosage is 2.5 mg/kg by mouth 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.

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 levels [see Clinical Pharmacology (12.3)]. Consistent dosing of EPIDIOLEX with respect to meals is recommended to reduce variability in 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)]. A household teaspoon or tablespoon is not an adequate measuring device.

Oral administration is recommended. When necessary, EPIDIOLEX can be enterally administered via silicone feeding tubes, such as nasogastric or gastrostomy tubes. The recommended volume for flushing (with room temperature drinking water) after each dose is approximately 5 times the priming volume of the tube. The flushing volume may need to be modified in patients with fluid restrictions. Do not use with tubes made of polyvinyl chloride (PVC) or polyurethane and avoid use of silicone nasogastric tubes with short lengths and narrow diameters (e.g., less than 50 cm and less than 5 FR).

Discard any unused EPIDIOLEX remaining 12 weeks after first opening the bottle [see How Supplied/Storage and Handling (16.2)].

2.5 Discontinuation of EPIDIOLEX

When discontinuing EPIDIOLEX, the dose should be decreased gradually. As with most antiepileptic drugs, abrupt discontinuation should be avoided when possible, to minimize the risk of increased seizure frequency and status epilepticus [see Warnings and Precautions (5.5)].

2.6 Patients with Hepatic Impairment

Dose adjustment is recommended in patients with moderate (Child-Pugh B) hepatic impairment or severe (Child-Pugh C) hepatic impairment [see Warnings and Precautions (5.1), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)]. It may be necessary to have slower dose titration in patients with moderate or severe hepatic impairment than in patients without hepatic impairment (see Table 1).

EPIDIOLEX does not require dose adjustment in patients with mild (Child-Pugh A) hepatic impairment.

Table 1. Dose Adjustments in Patients with Hepatic Impairment:

Store EPIDIOLEX in an upright position at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Do not freeze. Keep the cap tightly closed. Use within 12 weeks of first opening the bottle, then discard any remainder.