Cannabidiol

Cannabidiol is a prescription medicine used to treat seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in people 1 year of age and older.

• Cannabidiol is available under the following different brand names: Epidiolex

Adult and pediatric dosage

Solution, oral

• 100mg/mL

Seizures

Adult dosage

LGS or DS

• 2.5 mg/kg orally twice a day initially; after 1 week, may increase to a maintenance dose of 5 mg/kg twice a day  
• If 5 mg/kg twice a day is tolerated and further seizure reduction is required, the patient may benefit from a dosage increase up to a maximum recommended maintenance dosage of 10 mg/kg twice a day (ie, 20 mg/kg/day)
• Increasing to 10 mg/kg twice a day may be achieved by increased weekly increments of 2.5 mg/kg twice a day, as tolerated
• If a more rapid titration from 10 mg/kg/day to 20 mg/kg/day is warranted, the dosage may be increased no more frequently than every other day
• Administration of the 20-mg/kg/day dosage resulted in somewhat greater reductions in seizure rates than the recommended maintenance dosage of 10 mg/kg/day, but with an increase in adverse reactions

TSC

• Starting dose: 2.5 mg/kg orally twice a day
• Increase dose in weekly increments of 2.5 mg/kg twice a day as tolerated, to recommended maintenance dose of 12.5 mg/kg twice a day
• If a more rapid titration is warranted, the dosage may be increased no more frequently than every other day
• Effectiveness of doses less than 12.5 mg/kg twice a day has not been studied in patients with TSC

Pediatric dosage

• Children above 1 year of age
• LGS or DS
  • 2.5 mg/kg orally twice a day initially; after 1 week, may increase to a maintenance dose of 5 mg/kg twice a day  
  • If 5 mg/kg twice a day is tolerated and further seizure reduction is required, the patient may benefit from a dosage increase up to a maximum recommended maintenance dosage of 10 mg/kg twice a day (ie, 20 mg/kg/day)
  • Increasing to 10 mg/kg twice a day may be achieved by increased weekly increments of 2.5 mg/kg twice a day, as tolerated
  • If a more rapid titration from 10 mg/kg/day to 20 mg/kg/day is warranted, the dosage may be increased no more frequently than every other day
  • Administration of the 20-mg/kg/day dosage resulted in somewhat greater reductions in seizure rates than the recommended maintenance dosage of 10 mg/kg/day, but with an increase in adverse reactions
• TSC
  • Starting dose: 2.5 mg/kg orally twice a day
  • Increase dose in weekly increments of 2.5 mg/kg twice a day as tolerated, to recommended maintenance dose of 12.5 mg/kg twice a day 
  • If a more rapid titration is warranted, the dosage may be increased no more frequently than every other day
  • The effectiveness of doses less than 12.5 mg/kg twice a day has not been studied in patients with TSC

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Cannabidiol include:

• drowsiness,
• changes in appetite or weight,
• feeling weak or tired,
• infections (fever, flu symptoms, cough, swelling, redness, itching),
• diarrhea,
• sleep problems (insomnia),
• rash,
• vomiting, and
• abnormal liver function tests.

Serious side effects of Cannabidiol include:

• liver problems: nausea, vomiting, loss of appetite, tiredness, not feeling well, right-sided upper stomach pain, itching, dark urine, jaundice (yellowing of the skin or eyes), and 
• new or worsening symptoms: mood or behavior changes, anxiety, panic attacks, trouble sleeping, impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), depressed, or have thoughts about suicide or hurting yourself.

Rare side effects of Cannabidiol include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Cannabidiol has severe interactions with no other drugs.
• Cannabidiol has serious interactions with the following drug:
  • Tucatinib
• Cannabidiol has moderate interactions with at least 196 other drugs.
• Cannabidiol has minor interactions with no other drugs. 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity to cannabidiol or any of the product ingredients

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Cannabidiol?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Cannabidiol?”

Cautions

• Can cause somnolence and sedation that is dose-related; clobazam and other CNS depressants, including alcohol, may potentiate this adverse effect; monitor for somnolence and sedation and advise patients not to drive or operate machinery until they have gained sufficient experience with the drug to gauge whether it adversely affects their ability to safely drive or operate machinery
• Antiepileptic drugs (AEDs), including cannabidiol, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication; patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior
• May cause hypersensitivity reactions (eg, pruritus, erythema, angioedema)
• As with other AEDs, cannabidiol should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus; if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered
• Therapy can cause weight loss, which may be dose-related
• A decrease in hemoglobin and hematocrit reported with no effect on red blood indices
• Elevation of serum creatinine reported within 2 weeks of initiating therapy that was reversible in healthy adults; mechanism not determined
• Hepatocellular injury
  • Dose-related liver transaminases (ALT and/or AST) elevations were reported, typically within the first 2 months of treatment
  • The majority of ALT elevations occurred when coadministered with valproate and, to a lesser extent, with clobazam
  • In 25 mg/kg/day treated patients with TSC, the incidence of ALT elevations greater than 3 times the ULN was 20% in patients taking both concomitant valproate and clobazam, 25% in patients taking concomitant valproate (without clobazam), 0% in patients taking concomitant clobazam (without valproate), and 6% in patients taking neither drug; consider discontinuation or dose adjustment of valproate or clobazam if liver enzyme elevations occur
  • Obtain serum transaminases before initiating and regularly afterward; consider more frequent monitoring of serum transaminases and bilirubin if also taking valproate or in patients who have elevated liver enzymes at baseline (see Dosing Considerations)
  • Discontinue transaminase levels more than 3 times ULN and bilirubin levels more than 2 times ULN
  • Without bilirubin elevation
    • Evaluate prolonged serum transaminases elevations for other possible causes; consider a dosage adjustment of any coadministered medication that is known to affect the liver (eg, valproate and clobazam)
    • Discontinue treatment with sustained transaminase elevations of more than 5 times ULN
• Drug interaction overview
  • Coadministration with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence
  • Effect of other drugs on cannabidiol
    • Moderate or strong CYP3A4 or CYP2C19 inhibitors: Consider cannabidiol dose reduction
    • Strong CYP3A4 or CYP2C19 inducers: Consider a cannabidiol dose increase
• Effect of cannabidiol on other drugs
  • UGT1A9, UGT2B7, CYP2C8, CYP2C9, and CYP2C19 substrates: Consider dose reduction of substrates
  • Sensitive CYP2C19 substrates include diazepam and clobazam; coadministration of cannabidiol with clobazam produces a 3-fold increase in plasma concentrations of N-desmethylclobazam, the active metabolite of clobazam
  • Coadministration of cannabidiol and valproate increases the incidence of liver enzyme elevations; discontinuation or reduction of cannabidiol and/or concomitant valproate should be considered
  • CYP1A2 and CYP2B6 substrates may also require dose adjustment
  • No dedicated drug-drug interaction studies have been conducted with mTOR inhibitors (eg, everolimus) or calcineurin inhibitors (eg, tacrolimus); reports in the literature suggest cannabidiol administration resulted in increased serum levels of everolimus, sirolimus, or tacrolimus; consider a reduction in dosage of everolimus, sirolimus, or tacrolimus, if adverse reactions known to occur with those medications are experienced when co-administered with cannabidiol

Pregnancy and Lactation

• There are no available data regarding use in pregnant women
• Based on animal data, may cause fetal harm
• AED pregnancy registry
  • There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs during pregnancy
  • Encourage women who are taking cannabidiol during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll-free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/
• Lactation
  • There are no data on the presence of cannabidiol or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production