Epidiolex

What is the difference between cannabidiol (CBD) and Epidiolex?

Cannabidiol (CBD) is one of the active ingredients in cannabis. In the US, the brand Epidiolex is the first and only highly concentrated, pharmaceutical-grade CBD to be regulated and approved for the treatment of seizures associated with certain rare genetic conditions, including Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC).

CBD is available in the US at cannabis dispensaries, but it is not the same as Epidiolex, which is officially categorized as an antiepileptic drug. Epidiolex is regulated by the US Food and Drug Administration (FDA) and can only be obtained with a prescription for specific indications. It is approved to treat seizures in adults and children aged one and older with specified disease conditions.

Whether or not other CBD products are legal or regulated varies by US state. Also, unregulated CBD products may contain strictly cannabidiol, or they may contain both cannabidiol and tetrahydrocannabinol, more commonly known as THC. THC is the compound associated with the “high” people experience when using cannabis products.

Studies have shown improved seizure control, as well as improved sleep and behavior with the use of CBD-based medicines.¹

More research is needed to learn exactly how CBD reduces seizures. The exact mechanism of action is unknown, but the data so far suggest that Epidiolex does not stop seizures by interacting with the body’s cannabinoid receptors (endocannabinoid system). This counterintuitive finding underscores the importance of conducting further research.²

What is Epidiolex used to treat?

The FDA has approved the brand Epidiolex for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC), in patients one year of age and up.³

Everything You Need To Know About Epilepsy

The severe epilepsy related to these conditions is classified as treatment-resistant, meaning it is generally not as responsive to seizure medications as other forms of epilepsy. Epidiolex is not used as a monotherapy (standalone treatment), so it does not replace other prescribed seizure medications. Rather, it is taken as a therapeutic add-on for improved seizure control.⁴

Epidiolex dosage forms and strengths

Epidiolex is a clear, strawberry-flavored, oral solution.

It is available by prescription only in liquid form, at a strength of 100mg/mL.⁵

How do you take Epidiolex?

A doctor must determine the exact dosage of Epidiolex according to the type of seizures, their severity and responsiveness to therapy, and the patient’s individual health needs.

Unless your doctor instructs you differently, Epidiolex should be taken twice daily, at a consistent time of day, with a full meal.

To ensure you are getting the exact dose needed, it is best to use the oral syringe (dropper) or measuring tool provided with this medication. A kitchen spoon is not accurate for medication dosing.

Typical recommended dosing for Epidiolex

Lennox-Gastaut syndrome or Dravet syndrome

• The typical starting dose is 2.5mg/kg taken twice daily, orally.

• Depending on the response after one week, the dose may be increased by 5 mg/kg weekly to a maximum dose of 20 mg/kg/day.

Tuberous sclerosis complex

• The starting dose is 2.5 mg/kg twice daily, orally.

• With time, the doctor may increase the dose by 5 mg/kg/day weekly to a maximum of 12.5mg/kg/dose taken twice daily.

Your doctor may modify the dosage if you have problems with liver function.

Seeing results

Many individuals with the indicated conditions who have treatment-resistant seizures begin to experience improved seizure control within the first two weeks, sometimes sooner.⁶ ⁷ ⁸

Lennox-Gastaut syndrome

For those living with LGS, Epidiolex has been found to significantly reduce drop seizures (the type that can cause a fall and subsequent injuries), including atonic, tonic, and tonic-clonic seizures.⁹

Dravet syndrome

In those with convulsive seizures associated with DS, Epidiolex has been shown to significantly reduce the number of atonic, tonic, tonic-clonic, and clonic seizures.¹⁰

Tuberous sclerosis complex

Epidiolex significantly reduces clonic, atonic, tonic, tonic-clonic, and partial-onset seizures associated with TSC.¹¹

The pharmaceutical maker of Epidiolex, Jazz Pharmaceuticals, has indicated that patients in clinical trials with LGS, DS, and TSC saw a 37%–48% reduction in seizures after 14 weeks of treatment.¹²

As with any medication, results vary from person to person.

Who should not take Epidiolex?

Epidiolex is not suitable for everyone. Be sure to discuss your medical and family history with your doctor before taking Epidiolex.

Possible indications for not using this medication (or reasons you will need to be monitored closely) include but are not necessarily limited to the following:¹³

• Being pregnant, breastfeeding, or thinking about conceiving

• History of an allergic reaction to cannabidiol (CBD) products or Epidiolex

• Allergy to sesame seeds (the base oil in Epidiolex is made from sesame seed oil)

• History of alcohol or drug use, including dependency resulting in liver injury or reduced liver function

• Presence of liver disease

• History of depression, mood disorder, or suicidal thoughts

Before prescribing Epidiolex, your doctor will weigh the known risks against the potential benefits of taking the medication for seizures in your case.

Your prescribing doctor will typically order tests to evaluate your liver function before you start this medication and then continue to monitor you periodically.¹⁴

Potential side effects of Epidiolex

Epidiolex can cause several common side effects that range from mild to severe.¹⁵

These include any of the following:

Gastrointestinal

• Reduced appetite and weight loss

• Diarrhea

• Vomiting

• Elevated liver enzymes

Infection

• Fever

• Increased infections, such as fungal, viral, or bacterial (pneumonia, urinary tract infections)

Nervous system

• Drowsiness

• Malaise

• Fatigue

• Irritability, aggression

• Insomnia

• Poor sleep quality or disordered sleep

• Abnormal walking

Skin problems

• Rash

Other

• Low platelet count

• Anemia

Warnings

Suicidal thoughts or behavior

Taking any anti-epileptic drug, including Epidiolex, is associated with an increased risk for suicidal behavior and thoughts of suicide. Suicidal thoughts or actions associated with Epidiolex are rare, impacting an estimated 1 in 500 people.¹⁶ ¹⁷ ¹⁸

Your doctor will monitor you closely while you are taking the medication. If you experience changes in your mood or behavior, feel agitated or restless, or think about harming yourself or suicide, call 911 or get emergency medical help.

Liver injury

Contact your doctor immediately if you experience any of the following symptoms, which may suggest the presence of a liver problem or liver injury during Epidiolex treatment:¹⁹

• Darkened urine

• Feeling poorly or unusually tired

• Itchiness

• Fever

• Nausea, vomiting, or a loss of appetite

• Jaundice (skin and eye yellowing)

• Pain in the upper right area of your abdomen

Additional precautions

Sedation

Monitor yourself for drowsiness, especially when you first start taking Epidiolex. Do not drive or operate machinery until you know how your body responds to the medication.

Overdose

If you or someone else takes a larger dose of Epidiolex than prescribed by a doctor, accidentally or on purpose, it is likely to cause adverse effects.²⁰

In most cases, an overdose is more likely to lead to extreme

• Drowsiness

• Stomach upset 

• Nausea, vomiting 

• Diarrhea

• Disorientation, confusion

• Loss of consciousness

In the event that someone has taken Epidiolex and isn’t breathing or loses consciousness, call 911 immediately. In the US, you can also contact the National Poison Control Center helpline at 1-800-222-1222.

If you realize you have taken too much Epidiolex but don't have any adverse effects, contact your doctor anyway. They may adjust the next dose and advise you on further actions.

Allergy information

Some people have allergic reactions to cannabidiol or its ingredients, which include sesame oil. The drug has synthetic strawberry flavoring, so it can be taken safely by people with an allergy to strawberries.²¹

If you have a history of an allergic reaction to this drug or cannabis, inform your doctor. 

The mild symptoms of cannabidiol allergies include:

• Skin rash

• Itching, hives

• Redness on the skin

If you experience any of those symptoms, contact your doctor for advice.

Severe allergic reactions to Epidiolex may also involve:

• Swelling of the face, throat, tongue, lips, hands, or feet

• Vomiting

• Trouble breathing

• Loss of consciousness

If you are experiencing severe allergy symptoms, call 911 or proceed to the closest emergency department. 

Long-term use of Epidiolex

Long-term use of Epidiolex for the treatment of refractory seizures is possible.

Many studies are underway to determine the safety profile for patients taking Epidiolex alone or with other medications for many months or years.²²

The primary concerns are for increased risk of impaired liver function and depression or suicidality.²³

Doctors will usually draw blood to evaluate your liver function upon starting the medication and then again periodically every few months to monitor for changes.

They will also instruct you and the people close to you about how to identify changes in behaviors, thoughts, and moods that may precede suicidal thoughts or actions. 

Pregnancy category

Epidiolex has not been assigned a pregnancy category.

Epidiolex and pregnancy

There is currently no human data on the developmental risks associated with taking Epidiolex during pregnancy and while breastfeeding.

Animal studies demonstrated increased fetal mortality in rats as well as decreased fetal body weight in rabbits.

Other side effects included delayed sexual development and adverse effects on the reproductive system of the offspring.²⁴

If you are planning a pregnancy or find out you are pregnant while taking Epidiolex, your doctor will talk with you and review the drug’s benefits and potential risks in your situation.

Missed doses

If you miss a dose of Epidiolex, take one as soon as you remember. If you remember within two hours of your next dose, skip the missed dose and take your next dose of the medication as usual. Don't double the dose. 

Drug interactions

Epidiolex has a number of known interactions with other drugs. Some of the most common ones include:²⁵

• Central nervous system depressants, including alcohol

• Potassium channel blockers such as amifampridine (Firdapse) and dalfampridine (Ampyra)

• Cardiac myosin inhibitors, including mavacamten (Camzyos)

• Other antiseizure medications, including valproic acid (Depakote), phenobarbital (Luminal, Solfoton), and oxcarbazepine (Trileptal)

• Antidepressants such as bupropion (Wellbutrin), phenelzine (Nardil), tranylcypromine (Parnate), and isocarboxazid (Marplan)

• Gout preventatives such as colchicine (Colcrys)

• GI drugs such as metoclopramide (Reglan) and promethazine (Phenergan)

• Abrocitinib (Cibinqo)

• Sleep medications, including zolpidem (Ambien) and doxylamine (Unisom)

• Other sedatives or anxiety medications such as midazolam (Versed) and lorazepam (Xanax)

• Pain medications like hydrocodone, codeine, and meperidine

• Muscle relaxants such as tizanidine (Zanaflex)

• Pulmonary arterial hypertension drugs, including bosentan (Tracleer)

• Blood thinners such as clopidogrel (Plavix), dabigatran (Pradaxa), apixaban (Eliquis), and rivaroxaban (Xarelto)

• Antibiotics such as lefamulin (Xenleta)

• Antiretroviral drugs like lenacapavir (Sunlenca)

• Hormonal contraceptives (birth control) such as norgestimate

• Medications for enlarged prostate such as silodosin (Rapaflo)

• Cancer medicines like tepotinib (Tepmetko), neratinib (Nerlynx), and venetoclax (Venclexta)

The above is not an exhaustive list of all possible drug interactions. Please discuss all medications, vitamins, and herbal supplements you take (or plan to take) with your prescribing doctor before you begin taking Epidiolex.

Can I drink alcohol while taking Epidiolex?

Drinking alcohol while you are taking Epidiolex should be avoided as it increases the risk of drowsiness and sedation.²⁶

What to discuss with your doctor before starting Epidiolex

Before starting the medication, you can discuss the following with your doctor:

• Your medical history, including liver disease, hepatitis, and any other health conditions 

• Your allergy history, especially an allergy to sesame seeds or cannabis

• Any history of mental health conditions, such as depression and suicidal thoughts or behavior

• All medications you are taking, including over-the-counter drugs, herbs, and supplements, and the use of any cannabis-related products

• History of drug or alcohol use disorder and regular use

• Plans for pregnancy, breastfeeding, and contraception

• Medications to avoid while you are taking Epidiolex

• When to expect the first results

• Initial dosage and plans for dosage increases

• What to do if you want to stop taking Epidiolex

• The suitability of driving while taking Epidiolex (due to the risk of drowsiness, especially at the beginning of treatment)

• If your occupation requires drug testing (in which case, you can inform the person giving the test that you take Epidiolex, a prescribed and FDA-approved medication)

Stopping Epidiolex

Don't stop using Epidiolex without talking to your doctor first. If your doctor recommends that you stop taking this medication, they may gradually reduce your dose over a period of time. Otherwise, there may be a risk of withdrawal symptoms, increased seizure frequency, and status epilepticus.²⁷

Drug approval history

Epidiolex is the only US FDA-approved cannabidiol medication. It was first approved for treating refractory seizures in patients with LGS and DS in June of 2018.²⁸

Originally a schedule V controlled substance, it was scheduled in April 2020.²⁹

Then, in July 2020, Epidiolex was approved for the treatment of seizures associated with TSC.³⁰ 

As of this writing, there are no other FDA-approved drug products that contain CBD. 

Tips for taking Epidiolex

• Take the medication as prescribed, at the same time every day, with or without food

• Store the drug in the upright position at room temperature

• Use the medication within 12 weeks of opening the bottle

• Use a dry dropper (pipette) every time you measure a dose of the medication

• Don't exceed the prescribed dose, even if you don't feel the effects

• Don’t drive or operate machinery until you know whether or not Epidiolex makes you drowsy

• Avoid alcohol and other sedatives while you are taking Epidiolex

• Be aware that you may test positive for marijuana in drug tests while taking Epidiolex

• Don't discontinue the medication abruptly, but contact your prescribing doctor to discuss whether it is safe to gradually reduce your medication. 

• Stop taking the drug if you experience any severe side effects, such as compromised breathing, jaundice, or suicidal feelings. Seek emergency medical attention, and contact your prescribing doctor as soon as you are able.

• Be sure to attend all scheduled appointments with your prescribing doctor and any other specialists, such as mental health professionals.

Frequently asked questions

Will my insurer cover Epidiolex?

Possibly. Check with your individual provider and health plan regarding their policies pertaining to prescription CBD products. Ask your prescribing doctor to specify the brand “Epidiolex” on your prescription or refill note (as opposed to simply “cannabidiol”) to facilitate approval.

How do I travel with Epidiolex?

Since Epidiolex is a FDA-approved form of CBD, you can carry it legally while traveling within the US. However, it is a good practice to carry proof of your prescription and keep the medication within its original, labeled container (do not transfer it into another container). If you reside in the US and plan to leave the country with Epidiolex, check your destination’s laws about cannabis-derived products before you travel. The American consulate can also give you guidance if you contact them, and you can also contact your destination country’s consulate.