Cannabidiol

PRODUCT: Epidyolex 100 mg/mL oral solution (UK SPC). Should be initiated and supervised by physicians with experience in the treatment of epilepsy. The dose is weight-based and is the same for adults and children. TITRATION: after the first week at 2.5 mg/kg twice daily and the second week at 5 mg/kg twice daily, each dose can be further increased based on individual clinical response and tolerability in weekly increments of 2.5 mg/kg administered twice daily (5 mg/kg/day), up to the maximum recommended dose. For TSC the clinical response and tolerability should be assessed after reaching 5 mg/kg twice daily. Any dose increases above 10 mg/kg/day (up to 20 mg/kg/day for LGS/DS or 25 mg/kg/day for TSC) should be made considering individual benefit and risk and with adherence to the full liver-function monitoring schedule. MEASURING: each carton supplies two 1 mL syringes graduated in 0.05 mL increments (each 0.05 mL = 5 mg cannabidiol) and two 5 mL syringes graduated in 0.1 mL increments (each 0.1 mL = 10 mg); use the 1 mL syringe if the calculated dose is 100 mg (1 mL) or less and the 5 mL syringe if more than 100 mg, rounding the calculated dose to the nearest graduated increment. DISCONTINUATION: the dose should be decreased gradually - in clinical trials discontinuation was achieved by reducing the dose by approximately 10% per day for 10 days; slower or faster down-titration may be required at the prescriber's discretion. MISSED DOSES: missed doses should not be compensated; resume the existing schedule. If more than 7 days' doses are missed, re-titration to the therapeutic dose should be made. HEPATIC IMPAIRMENT: no dose adjustment in mild impairment (Child-Pugh A); caution and a lower starting dose in moderate (Child-Pugh B) or severe (Child-Pugh C) impairment. MODERATE - starting dose 1.25 mg/kg twice daily (2.5 mg/kg/day); second step 2.5 mg/kg twice daily (5 mg/kg/day), which is the maintenance dose for LGS/DS and the second-week dose for TSC; maximum recommended 5 mg/kg twice daily (10 mg/kg/day) for LGS/DS and 6.25 mg/kg twice daily (12.5 mg/kg/day) for TSC. SEVERE - starting dose 0.5 mg/kg twice daily (1 mg/kg/day); second step 1 mg/kg twice daily (2 mg/kg/day); maximum recommended 2 mg/kg twice daily (4 mg/kg/day) for LGS/DS and 2.5 mg/kg twice daily (5 mg/kg/day) for TSC, with the SPC noting higher doses may be considered in severe hepatic impairment where the potential benefits outweigh the risks. ELDERLY: trials did not include sufficient patients above 55 years; in general dose selection should be cautious, usually starting at the low end of the dosing range. CONCOMITANT ANTIEPILEPTICS: a physician experienced in treating patients on concomitant antiepileptic drugs should evaluate the need for dose adjustments of cannabidiol or of the concomitant medicinal product(s) to manage potential drug interactions. INTERACTIONS CAVEAT: SPC section 4.5 was not included in this source bundle - the interaction entries below are taken from sections 4.2, 4.4 and 4.8 only, and section 4.5 should be reviewed in full.

The UK SPC dose is weight-based and identical for adults and children: 2.5 mg/kg twice daily (5 mg/kg/day) for one week, then 5 mg/kg twice daily (10 mg/kg/day), with further weekly increments of 2.5 mg/kg twice daily (5 mg/kg/day) as clinical response and tolerability allow. AGE LIMITS - LGS and DS: there is no relevant use in children aged below 6 months, and the safety and efficacy in children aged 6 months to 2 years have not yet been established (no data available). TSC: there is no relevant use in children aged below 1 month, and the safety and efficacy in children aged 1 month to 2 years have not been established - data in patients aged 1 to 2 years exist but no recommendation on a posology can be made. Dose increases above 10 mg/kg/day require adherence to the full liver-function monitoring schedule. Reduced doses apply in moderate and severe hepatic impairment (see adult notes). Verify against a children's formulary before use.