Prescribing Information: Information for the Patient

Epidyolex 100 mg/ml Oral Solution

cannabidiol

Read this entire prescribing information carefully before starting to take this medicine, as it contains important information for you or the patient.

• Keep this prescribing information, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prescribing information. See section 4.

Epidyolex contains cannabidiol, a medication that may be used to treat epilepsy, a disease that causes seizures or convulsions.

Epidyolex is used in combination with clobazam or with clobazam and other antiepileptic medications to treat seizures caused by two rare diseases, Dravet syndrome and Lennox-Gastaut syndrome. It may be used in adults, adolescents, and children aged 2 years and older.

Epidyolex is also used along with other antiepileptic medications to treat seizures associated with a genetic disorder called tuberous sclerosis complex (TSC). It may be used in adults, adolescents, and children aged 2 years and older.

Do not take Epidyolex

• if you are allergic to cannabidiol or any of the other components of this medication (listed in section 6).
• if your doctor determines that your blood liver tests show abnormalities.

Warnings and precautions

Consult your doctor or pharmacist before taking Epidyolex or during treatment if:

• you have or have had liver problems, as your doctor may need to change the dose of Epidyolex or decide that Epidyolex is not suitable for you.

Your doctor may perform blood tests to examine your liver before starting to take this medication or during treatment, as Epidyolex may cause liver problems. If your liver does not function properly, it may be necessary to interrupt treatment.

• you notice unusual changes in your mood or behavior, or if you have thoughts that move you to self-harm or suicide.Get in touch with your doctor orgo to the hospital immediately(see section 4).

• Epidyolex may cause drowsiness. Do not drive, use machines, and do not participate in activities that require you to be alert and have adequate control of your body, such as riding a bicycle, until you know how Epidyolex affects you.

• stop taking Epidyolex abruptly (see section 3).
• you experience more frequent seizures or a severe seizure while taking Epidyolex.Get in touch with your doctor or go to the hospital immediately.
• you experience weight loss or are unable to gain weight. Your doctor will perform a weight check and evaluate the continuation of treatment with Epidyolex.

Children and adolescents

Epidyolex is not recommended for children under 2 years old.

Other medications and Epidyolex

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. Taking Epidyolex with certain medications may cause adverse effects, may affect the functioning of other medications, or may affect the functioning of Epidyolex. Do not start or stop treatment with other medications without consulting your doctor or pharmacist.

Inform your doctor if you are taking any of the following medications, as your dose may need to be adjusted:

• other medications for epilepsy, such as carbamazepine, clobazam, lamotrigine, lorazepam, phenytoin, stiripentol, and valproate used to treat seizures;
• other medications for the treatment of CET, including everolimus and tacrolimus;
• medications used to treat gastroesophageal reflux (heartburn or acid regurgitation), such as omeprazole;
• mitotane (medication used to treat tumors located in the adrenal gland);
• morphine or diflunisal (medications used to treat pain);
• efavirenz (medication used to treat HIV/AIDS);
• theophylline (medication used to treat asthma);
• caffeine (medication for babies who need help breathing);
• propofol (anesthetic used for people undergoing surgery);
• simvastatin, fenofibrate, and gemfibrozil (medications used to reduce cholesterol/lipids);
• enzalutamide (medication used to treat prostate cancer);
• bupropion (medication used to quit smoking or treat obesity);
• St. John's Wort (Hypericum perforatum), a herbal medication used to treat mild anxiety;
• medications used to treat bacterial infections, such as rifampicin, clarithromycin, and erythromycin.

Use of Epidyolex with food

Take Epidyolex according to the instructions provided by your doctor and consistently with or without food, including ketogenic diets (such as ketogenic diets). If you take Epidyolex with food, you should maintain a similar diet, if possible. (See also section 3: How to take Epidyolex.)

Pregnancy, breastfeeding, and fertility

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication. Do not take Epidyolex during pregnancy unless your doctor decides that the benefits outweigh the potential risks. Do not breastfeed while taking Epidyolex, as it is possible that Epidyolex may be present in breast milk.

Driving and operating machines

Consult your doctor about driving, operating machines, or when children engage in activities such as riding a bicycle or other sports, as you or the patient may feel drowsiness after taking the medication.

Do not drive, do not use machinery, and do not participate in activities that require you to be alert and have adequate control of your body until it is determined that your ability to perform such activities is not affected.

Epidyolex contains sesame oil, ethanol, and flavor components that provide a strawberry flavor (including benzyl alcohol).

Epidyolex contains refined sesame oil, which rarely may cause severe allergic reactions.

Each ml of Epidyolex contains 79mg of ethanol, which is equivalent to a 10%v/v of anhydrous ethanol, i.e., up to 691.3ml of ethanol per single maximum dose of Epidyolex (12.5mg/kg) for an adult of 70kg of weight (9.9mg of ethanol/kg). For an adult of 70kg of weight, this is equivalent to 17ml of beer or 7ml of wine per dose.The small amount of alcohol contained in this medication does not produce any perceptible effect.

This medication contains 0.0003mg/ml of benzyl alcohol, which is equivalent to 0.0026mg per maximum dose of Epidyolex (Epidyolex 12.5mg/kg per dose for an adult of 70kg of weight). Benzyl alcohol may cause allergic reactions.

This product should not be used for more than a week in children (under 3 years of age), unless instructed by your doctor or pharmacist.

Consult your doctor or pharmacist if you are pregnant or breastfeeding. This is because large amounts of benzyl alcohol may accumulate in your body and cause adverse effects (designated "metabolic acidosis").

Consult your doctor or pharmacist if you have liver or kidney disease. This is because large amounts of benzyl alcohol may accumulate in your body and cause adverse effects (designated "metabolic acidosis").

Follow exactly the administration instructions of this medication indicated by your doctor.

In case of doubt, consult your doctor or pharmacist again.

Epidyolex is an oral solution (a liquid that must be ingested). Your doctor or pharmacist will indicate how much Epidyolex (number of ml) you should take per day, how many times a day you should take it, and what syringe you should use for your dose (1 ml or 5 ml).

Your doctor will calculate the dose according to your body weight. You may start treatment with a low dose that your doctor will gradually increase over time. Contact your doctor if you are unsure of your dose or if you think you may need it to be adjusted.

Taking Epidyolex with food may increase the amount of medication your body absorbs. You should try to take Epidyolex as consistently as possible with or without food, and according to your daily routine to achieve the same effect each time. If you take Epidyolex with food, you should ingest a similar type of food (e.g., with a similar fat content), if possible.

If necessary, Epidyolex can be administered through a nasogastric or gastrostomy tube. Your doctor will provide you with instructions on this. Consult your doctor or pharmacist if you are unsure how to do it.

Inform your doctor if you have liver problems, as your doctor may need to adjust the dose.

Do not reduce the dose or interrupt treatment with this medication unless your doctor tells you to.

Instructions for oral use of Epidyolex

The 1-bottle package contains the following items:

• Epidyolex oral solution bottle
• A plastic bag with two 1 ml oral syringes and an adapter for the bottle
• A plastic bag with two 5 ml oral syringes and an adapter for the bottle

The 3-bottle package contains the following items:

• Three Epidyolex oral solution bottles
• A plastic bag with two 1 ml oral syringes and an adapter for the bottle
• A plastic bag with two 5 ml oral syringes and two adapters for the bottle

The package includes a spare syringe of each size in case the first one is damaged or lost. For the 3-bottle package, three adapters from both syringe packages are needed.

The above image is for illustrative purposes only.

1. Open the bag containing the correct oral syringe to measure your dose.

• If your dose is 1 ml (100 mg) or less, you will use the smaller 1 ml syringe.
• If your dose is more than 1 ml (100 mg), you will use the larger 5 ml syringe.

• If your dose is more than 5 ml (500 mg), you will need to use the larger 5 ml syringe more than once. In this case, carefully track the number of times you fill the syringe (e.g., marking each 5 ml dose accordingly) to take the correct dose.

It is essential to use the correct oral syringe to measure your dose. Your doctor or pharmacist will indicate which syringe to use based on the prescribed dose.

According to the doctor's or pharmacist's instructions, the bag containing the other syringes should be discarded, unless your doctor or pharmacist tells you to conserve the two syringes until the final dose. If you are prescribed a 3-bottle package, the three adapters should be conserved.

If you or the patient take more Epidyolex than they should

In case you have taken more Epidyolex than you should, consult your doctor or pharmacist immediately, or contact the nearest hospital emergency department and bring the medication with you.

Among the signs indicating you have taken too much Epidyolex are diarrhea and drowsiness.

If you or the patient forgot to take Epidyolex

If you forgot to take a dose, do not take a double dose to compensate for the missed dose. Take the next dose when it is scheduled. If you forget several doses, consult your doctor about what dose you should take.

If you or the patient interrupted treatment with Epidyolex

Do not reduce the dose or interrupt treatment with Epidyolex without consulting your doctor first. Abruptly stopping this treatment may increase your seizures. Your doctor will explain how to gradually stop treatment with Epidyolex.

If you have any other questions about using this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

The following adverse effects may bevery serious:

Frequent Adverse Effects(may affect more than 1 in 100 people):

• In patients treated with Epidyolex, elevated levels of liver enzymes (increases in transaminases) have been reported in blood tests, which may be a sign of liver damage.

Adverse Effects of Unknown Frequency(cannot be estimated from available data):

• People taking this medicine may have thoughts that move them to self-harm or suicide. If you experience these thoughts at any time, contact your doctor.

You may experience the following adverse effects with this medicine. Inform your doctor if you notice any of the following:

Very Frequent Adverse Effects(may affect more than 1 in 10 people):

• drowsiness
• diarrhea
• loss of appetite

• fever
• vomiting
• fatigue

Frequent Adverse Effects(may affect more than 1 in 100 people):

• seizures
• presenting a bad temper (irritable, aggressive)
• skin rash
• lack of energy
• cough
• pneumonia
• weight loss
• feeling unwell
• urinary tract infection

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.By reporting adverse effects, you can contribute to providing more information about the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the bottle. The expiration date is the last day of the month indicated.

If there is solution left in the bottle more than 12 weeks after opening it for the first time, do not use it.

This medication does not require special storage conditions.

Medications should not be disposed of through drains or trash. Ask your pharmacist how to dispose of the medication that is no longer needed. This will help protect the environment.

Composition of Epidyolex

• The active ingredient is cannabidiol. Each milliliter of oral solution contains 100 mg of cannabidiol.
• The other components are refined sesame oil, anhydrous ethanol, sucralose, and strawberry flavor (including benzyl alcohol) (see section 2).

Appearance of Epidyolex and contents of the container

Epidyolex is a transparent and colorless to yellowish oral solution. It is supplied in an amber glass bottle with a child-resistant tamper-evident closure.

The following container sizes are available for Epidyolex:

100ml (1bottle of100ml) with2 oral syringes for use calibrated in 5ml,2 of1mland two bottle adapters.

300ml (3bottles of 100ml) with2 oral syringes for use calibrated in5ml, 2 of1ml and three bottle adapters.

The 5 ml syringes are graduated in increments of 0.1 ml and the 1 ml syringes have increments of 0.05 ml.

Only some container sizes may be commercially available.

Marketing Authorization Holder

Jazz Pharmaceuticals Ireland Ltd

5th Floor

Waterloo Exchange

Waterloo Road

Dublin 4

D04 E5W7

Ireland

Email:[email protected]

Manufacturer

Jazz Pharmaceuticals Netherlands B.V.,

Smallepad 32, 3811MG, Amersfoort,

Netherlands

Email:[email protected]

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Last update of this leaflet: 08/2024

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.There are also links to other websites on rare diseases and orphan medicines.