Epidyolex (Cannabidiol)

What Is Epidyolex and What Is It Used For?

Epidyolex is a prescription oral solution containing cannabidiol (CBD), used as an adjunctive treatment for seizures in patients with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex (TSC). It is approved for adults and children aged 2 years and older.

Epidyolex contains cannabidiol, a naturally occurring compound derived from the Cannabis sativa plant. Unlike tetrahydrocannabinol (THC), cannabidiol does not produce psychoactive effects or a sensation of being "high." Epidyolex is manufactured under strict pharmaceutical standards to ensure consistent purity and potency, distinguishing it clearly from unregulated CBD supplements available over the counter.

The medicine is indicated for three specific epilepsy-related conditions, all of which are characterised by seizures that are often difficult to control with conventional antiepileptic drugs:

• Dravet syndrome: A rare and severe form of epilepsy that begins in infancy, typically before the age of one year. Seizures are often triggered by fever and are notoriously resistant to standard treatments. Epidyolex is used in combination with clobazam for this condition.
• Lennox-Gastaut syndrome (LGS): A severe childhood-onset epilepsy characterised by multiple seizure types, cognitive impairment, and a distinctive pattern on electroencephalography (EEG). Epidyolex is used in combination with clobazam for LGS.
• Tuberous sclerosis complex (TSC): A genetic disorder that causes non-cancerous tumours to grow in the brain and other organs. Epilepsy affects up to 85% of individuals with TSC and often begins in early childhood. Epidyolex is used alongside other antiepileptic medicines for TSC-associated seizures.

The precise mechanism by which cannabidiol exerts its antiseizure effects is not fully understood. Research suggests multiple pathways may be involved, including modulation of intracellular calcium signalling through GPR55 receptors, enhancement of adenosine-mediated signalling, and desensitisation of TRPV1 ion channels. Importantly, cannabidiol does not appear to work through the endocannabinoid CB1 or CB2 receptors, which are the primary targets of THC.

In pivotal clinical trials, Epidyolex demonstrated statistically significant reductions in seizure frequency compared to placebo. In studies of Dravet syndrome, patients receiving Epidyolex experienced a median reduction in convulsive seizure frequency of approximately 39% compared to 13% with placebo. For Lennox-Gastaut syndrome, drop seizure frequency was reduced by approximately 42-44% with Epidyolex versus 17-22% with placebo.

What Should You Know Before Taking Epidyolex?

Before starting Epidyolex, your doctor will assess your liver function and review all other medications you are taking. The medicine should not be used if you are allergic to cannabidiol or have certain liver abnormalities.

Contraindications

Do not take Epidyolex if:

• You are allergic to cannabidiol or any of the other ingredients in the medicine (including refined sesame oil, ethanol, sucralose, strawberry flavouring, or benzyl alcohol)
• Your doctor has identified certain abnormal liver enzyme levels in blood tests

If you have a known allergy to sesame seeds or sesame-derived products, inform your doctor before starting treatment, as Epidyolex contains refined sesame oil which in rare cases can cause severe allergic reactions.

Warnings and Precautions

Speak to your doctor or pharmacist before taking Epidyolex, or during treatment, in the following situations:

• Liver problems: If you have or have had liver disease, your doctor may need to adjust your dose or decide that Epidyolex is not suitable for you. Liver function blood tests are required before starting treatment and will be performed periodically during therapy, as Epidyolex can cause elevated liver enzymes (transaminases). If the liver is not functioning properly, treatment may need to be interrupted or discontinued.
• Mood and behaviour changes: If you notice unusual changes in mood, behaviour, or if you experience thoughts of self-harm or suicide, contact your doctor or go to a hospital immediately. Antiepileptic medicines as a class have been associated with a small increased risk of suicidal thoughts and behaviour.
• Drowsiness: Epidyolex may make you drowsy. Do not drive, operate machinery, or engage in activities requiring alertness and good motor coordination (such as cycling) until you know how the medicine affects you.
• Abrupt discontinuation: Do not suddenly stop taking Epidyolex without consulting your doctor, as this may increase your seizure frequency. Your doctor will explain how to reduce the dose gradually.
• Increased seizure frequency: If your seizures become more frequent or severe while taking Epidyolex, contact your doctor or seek medical attention immediately.
• Weight loss: If you lose weight or are unable to gain weight during treatment, your doctor will monitor your weight and assess whether to continue therapy.

Pregnancy and Breastfeeding

If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using Epidyolex. You should only take Epidyolex during pregnancy if your doctor determines that the benefit of treatment outweighs the potential risk to the foetus.

You should not breastfeed while taking Epidyolex, as cannabidiol is likely to pass into breast milk. The effects of cannabidiol on a breastfed infant are not fully known, and as a precaution, breastfeeding is not recommended during treatment.

Use in Children

Epidyolex is approved for use in children aged 2 years and older. It is not recommended for children under 2 years of age, as the safety and efficacy in this age group have not been established. The medicine contains small amounts of benzyl alcohol and ethanol; use in very young children (under 3 years) for longer than one week should only occur on the recommendation of a healthcare professional.

Driving and Operating Machinery

Epidyolex may cause drowsiness and somnolence, which can impair your ability to drive or operate machinery safely. Discuss with your doctor whether you should drive, and whether children taking the medicine should engage in activities such as cycling or sports. Do not drive, operate machinery, or participate in activities requiring alertness until you are confident that your ability is not impaired.

Important Information About Ingredients

Epidyolex contains several excipients that require awareness:

• Refined sesame oil: May in rare cases cause severe allergic reactions in individuals sensitive to sesame.
• Ethanol (alcohol): Each ml contains 79 mg of ethanol (approximately 10% v/v). At the maximum single dose of 12.5 mg/kg, this equates to up to 691.3 mg of ethanol for a 70 kg adult, equivalent to approximately 17 ml of beer or 7 ml of wine per dose. The low amount of alcohol in this medicine is unlikely to produce noticeable effects.
• Benzyl alcohol: Present in very small quantities (0.0003 mg/ml). Benzyl alcohol may cause allergic reactions. Large amounts can accumulate in the body and cause metabolic acidosis, particularly in individuals with impaired liver or kidney function.

How Does Epidyolex Interact with Other Drugs?

Epidyolex can interact with many other medicines, including common antiepileptic drugs, immunosuppressants, and certain painkillers. Always inform your doctor about all medications you are taking, as dose adjustments may be necessary.

Cannabidiol is metabolised by the liver and can affect the way other medicines are broken down, potentially increasing or decreasing their levels in the blood. Conversely, some medicines can affect the levels of cannabidiol itself. It is essential to tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including herbal preparations. Do not start or stop any medicine without consulting your doctor first.

Major Interactions

The following medicines require particular attention when used with Epidyolex, and dose adjustments may be needed:

Other Interactions

The following medicines may also interact with Epidyolex and should be discussed with your doctor:

What Is the Correct Dosage of Epidyolex?

Epidyolex dosage is individualised based on body weight. Treatment typically starts at a low dose that is gradually increased. The maximum recommended dose varies by condition: up to 20 mg/kg/day for Dravet syndrome and LGS, and up to 25 mg/kg/day for TSC.

Always take Epidyolex exactly as your doctor has told you. The dose is calculated based on your body weight and is measured in milligrams per kilogram (mg/kg). Your doctor will start you on a low dose and increase it gradually to find the optimal balance between seizure control and tolerability. Epidyolex is taken twice daily (morning and evening).

Adults and Children (2 Years and Older)

Patients with Liver Impairment

If you have liver problems, your doctor may need to adjust your dose. Patients with moderate or severe hepatic impairment generally require lower starting doses, slower titration, and lower maximum doses. Your doctor will perform additional liver function monitoring in these cases.

How to Take Epidyolex

Epidyolex is an oral solution that comes with calibrated dosing syringes (1 ml and 5 ml sizes). Your doctor or pharmacist will tell you which syringe to use based on your prescribed dose. Key administration instructions include:

• Shake the bottle well and use the provided dosing syringe to measure the exact dose
• Place the syringe tip against the inside of the cheek and push the plunger gently — do not squirt the medicine to the back of the throat
• For doses exceeding 5 ml, you will need to measure and administer multiple syringe-fulls, keeping careful count
• If needed, Epidyolex can be administered via a nasogastric or gastrostomy tube — your doctor will provide instructions
• Clean the syringe after each use by drawing warm soapy water through it, then rinsing and allowing it to air dry completely

Missed Dose

If you miss a dose of Epidyolex, do not take a double dose to make up for it. Simply take the next dose at the usual scheduled time. If you miss multiple doses, speak with your doctor about which dose to take when resuming.

Overdose

If you may have taken more Epidyolex than prescribed, tell your doctor or pharmacist immediately, or go to the nearest emergency department. Bring the medicine with you. Signs of overdose may include diarrhoea and excessive drowsiness.

What Are the Side Effects of Epidyolex?

Like all medicines, Epidyolex can cause side effects. The most common include drowsiness, diarrhoea, decreased appetite, fever, vomiting, and fatigue. Liver enzyme elevations are a clinically significant side effect that requires monitoring.

Not everyone who takes Epidyolex will experience side effects, but it is important to be aware of them so you can report any concerns to your doctor promptly. Side effects are categorised below by how frequently they occur.

The risk of liver enzyme elevations appears to be higher in patients who are also taking valproate, in patients receiving higher doses of Epidyolex, and in patients with elevated liver enzymes at baseline. In clinical trials, most cases of liver enzyme elevation were reversible upon dose reduction or discontinuation of treatment.

Drowsiness and sedation are more likely to occur when Epidyolex is used together with clobazam, as cannabidiol increases the blood levels of the active metabolite of clobazam. In some cases, the clobazam dose may need to be reduced to manage this effect.

Weight loss and decreased appetite have been observed, particularly in younger patients. Regular weight monitoring is recommended, especially in children, to ensure adequate nutrition and growth are maintained during treatment.

How Should You Store Epidyolex?

Epidyolex does not require special storage conditions. Keep it out of reach of children and discard the opened bottle after 12 weeks.

Store Epidyolex in accordance with the following guidelines to ensure the medicine remains effective and safe to use:

• Temperature: No special temperature requirements — store at room temperature
• Keep out of reach: Always store the bottle with the child-resistant cap securely fastened, out of the sight and reach of children
• Expiry date: Do not use Epidyolex after the expiry date printed on the bottle (EXP). The expiry date refers to the last day of that month
• After opening: Once opened, any solution remaining in the bottle after 12 weeks should be discarded, even if the bottle is not empty
• Disposal: Do not dispose of Epidyolex via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use, in order to help protect the environment

If the solution in the bottle appears cloudy, this does not affect its effectiveness. Continue to use the medicine as normal. Ensure that the dosing syringe is completely dry before reinserting it into the bottle, as water ingress may cause the solution to appear cloudy.

What Does Epidyolex Contain?

The active substance is cannabidiol at a concentration of 100 mg per ml. Other ingredients include refined sesame oil, ethanol, sucralose, and strawberry flavouring.

Each millilitre of Epidyolex oral solution contains:

• Active ingredient: Cannabidiol 100 mg
• Excipients: Refined sesame oil, anhydrous ethanol, sucralose (sweetener), and strawberry flavouring (including benzyl alcohol)

Epidyolex is a clear, colourless to yellow oral solution. It is supplied in a glass bottle with a child-resistant cap. Each pack includes two dosing syringes of the same size (either 1 ml or 5 ml) and two bottle adapters. The 5 ml syringe is graduated in 0.1 ml increments, and the 1 ml syringe in 0.05 ml increments. A spare syringe of each size is included in case the first is lost or damaged.

The marketing authorisation holder for Epidyolex is Jazz Pharmaceuticals Ireland Ltd, Dublin, Ireland. The medicine is manufactured by Jazz Pharmaceuticals Netherlands B.V. in Amersfoort, the Netherlands. For additional information, patients can contact their local representative or the company via email at [email protected].