EPIDYOLEX Oral solution Ref.[27759] Active ingredients: Cannabidiol

Epidyolex should be initiated and supervised by physicians with experience in the treatment of epilepsy.

Posology

For LGS and DS

The recommended starting dose of cannabidiol is 2.5 mg/kg taken twice daily (5 mg/kg/day) for one week. After one week, the dose should be increased to a maintenance dose of 5 mg/kg twice daily (10 mg/kg/day). Based on individual clinical response and tolerability, each dose can be further increased in weekly increments of 2.5 mg/kg administered twice daily (5 mg/kg/day) up to a maximum recommended dose of 10 mg/kg twice daily (20 mg/kg/day).

Any dose increases above 10 mg/kg/day, up to the maximum recommended dose of 20 mg/kg/day, should be made considering individual benefit and risk and with adherence to the full monitoring schedule (see section 4.4).

For TSC

The recommended starting dose of cannabidiol is 2.5 mg/kg taken twice daily (5 mg/kg/day) for one week. After one week, the dose should be increased to a dose of 5 mg/kg twice daily (10 mg/kg/day) and the clinical response and tolerability should be assessed. Based on individual clinical response and tolerability, each dose can be further increased in weekly increments of 2.5 mg/kg administered twice daily (5 mg/kg/day) up to a maximum recommended dose of 12.5 mg/kg twice daily (25 mg/kg/day).

Any dose increases above 10 mg/kg/day, up to the maximum recommended dose of 25 mg/kg/day, should be made considering individual benefit and risk and with adherence to the full monitoring schedule (see section 4.4).

The dosage recommendations for LGS, DS and TSC are summarised in the following table:

Table 1. Dosage recommendations:

Each Epidyolex carton is supplied with:

• Two 1 ml syringes graduated in 0.05 ml increments (each 0.05 ml increment corresponds to 5 mg cannabidiol)
• Two 5 ml syringes graduated in 0.1 ml increments (each 0.1 ml increment corresponds to 10 mg cannabidiol)

If the calculated dose is 100 mg (1 ml) or less, the smaller 1 ml oral syringe should be used.

If the calculated dose is more than 100 mg (1 ml), the larger 5 ml oral syringe should be used.

The calculated dose should be rounded to the nearest graduated increment.

Discontinuation

If cannabidiol has to be discontinued, the dose should be decreased gradually. In clinical trials, cannabidiol discontinuation was achieved by reducing the dose by approximately 10% per day for 10 days. A slower or faster down titration may be required, as clinically indicated, at the discretion of the prescriber.

Missed doses

In the case of one or more missed doses, the missed doses should not be compensated. Dosing should be resumed at the existing treatment schedule. In the case of more than 7 days' missed doses, re-titration to the therapeutic dose should be made.

Special populations

Elderly

Clinical trials of 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 concurrent therapy (see sections 4.4 under hepatocellular injury and 5.2).

Renal impairment

Cannabidiol can be administered to patients with mild, moderate, or severe renal impairment without dose adjustment (see section 5.2). There is no experience in patients with end-stage renal disease. It is not known if cannabidiol is dialysable.

Hepatic impairment

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

Caution should be used in patients with moderate (Child-Pugh B) or severe hepatic impairment (Child-Pugh C). A lower starting dose is recommended in patients with moderate or severe hepatic impairment. The dose titration should be performed as detailed in the table below.

Table 2. Dose adjustments in patients with moderate or severe hepatic impairment:

^* Higher doses of cannabidiol may be considered in patients with severe hepatic impairment where the potential benefits outweigh the risks.

Paediatric population

With LGS and DS

There is no relevant use of cannabidiol in children aged below 6 months. The safety and efficacy of cannabidiol in children aged 6 months to 2 years have not yet been established. No data are available.

With TSC

There is no relevant use of cannabidiol in children aged below 1 month. The safety and efficacy of cannabidiol in children aged 1 month to 2 years have not yet been established. Currently available data in patients aged 1 to 2 years are described in section 5.1 but no recommendation on a posology can be made.

Dose adjustments of other medicinal products used in combination with cannabidiol

A physician experienced in treating patients who are on concomitant antiepileptic drugs (AEDs) should evaluate the need for dose adjustments of cannabidiol or of the concomitant medicinal product(s) to manage potential drug interactions (see sections 4.4 and 4.5).

Method of administration

Oral use.

Food may increase cannabidiol levels and therefore it should be taken consistently either with or without food, including the ketogenic diet. When taken with food, a similar composition of food should be considered, if possible (see section 5.2).

Symptoms

Experience with doses higher than the recommended therapeutic dose is limited. Mild to moderate diarrhoea and somnolence have been reported in healthy adult subjects taking a single dose of 6000 mg; this equates to a dose of over 85 mg/kg for a 70 kg adult. These adverse reactions resolved upon study completion.

Management of overdose

In the event of overdose the patient should be observed and appropriate symptomatic treatment given, including monitoring of vital signs.

2 years.

Use within 12 weeks after first opening the bottle.

This medicinal product does not require any special storage conditions.

Amber glass bottle (type III) with a child-resistant and tamper-evident screw cap (polypropylene). The bottle is packaged in a carton with two 5 ml and two 1 ml calibrated oral dosing syringes (plunger HDPE and barrel polypropylene) and two bottle adaptors (LDPE). The 5 ml syringes are graduated in 0.1 ml increments and the 1 ml syringes are graduated in 0.05 ml increments.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.