Safety profile of EPIDIOLEX®
(cannabidiol) Cannabidiol CV Symbol

Evaluated in an expansive clinical trial program in LGS and Dravet syndrome1

MOST COMMON AEsADVERSE EVENTS (AEs) (≥10% AND GREATER THAN PLACEBO) OBSERVED DURING THE 14-WEEK TREATMENT PERIOD OF PHASE 3 CONTROLLED TRIALS1

Epidiolex Safety - Most Common Adverse Events (AEs) During Phase 3 Trial Epidiolex Safety - Most Common Adverse Events (AEs) Observed with Placebo Epidiolex Safety - Most Common Adverse Events (AEs) Observed with Epidiolex 10 mg/kg/day Epidiolex Safety - Most Common Adverse Events (AEs) Observed with Epidiolex 20 mg/kg/day

AEs were consistent across both indications in both children and adults.1

  • Hematologic abnormalities, decreased weight, and increased creatinine levels were also observed1
  • In controlled studies, the rate of discontinuation for any adverse event was 1% for patients treated with placebo, 3% with EPIDIOLEX 10 mg/kg/day, and 12% with EPIDIOLEX 20 mg/kg/day1
  • The most frequent causes of discontinuation were transaminase elevation, somnolence, sedation, and lethargy1
DISCOVER EFFICACY DATA

At the time of approval, some patients had already been treated for over 2 years1

850
patients

with LGS and Dravet syndrome had been treated with EPIDIOLEX in controlled and uncontrolled trials (N=689), and an expanded access program and other compassionate use programs (N=161)

482
patients

had been treated for more than 1 year

50
patients

were treated for more than 2 years

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Contraindication: hypersensitivity1

  • EPIDIOLEX (cannabidiol) oral solution is contraindicated in patients with a history of hypersensitivity to cannabidiol or any ingredients in the product

Hepatocellular injury1

EPIDIOLEX can cause dose-related transaminase elevations

In controlled studies, the incidence of ALT elevations (>3x the ULN) was 13% in EPIDIOLEX-treated patients and 1% on placebo; less than 1% of EPIDIOLEX-treated patients had ALT or AST 20x the ULN

  • Concomitant use of valproate and elevated transaminase levels at baseline increase this risk

INCIDENCE OF ALT ELEVATIONS >3x THE UPPER LIMIT OF NORMAL (ULN)1

Incidence of Transaminase (ALT) Elevations in Epidiolex-treated patients Incidence of Transaminase (ALT) Elevations in Epidiolex-treated patients
  • Transaminase and bilirubin levels should be obtained prior to starting treatment, at one, three, and six months after initiation of treatment, and periodically thereafter, or as clinically indicated

OBTAIN SERUM TRANSAMINASES (ALT AND AST) AND TOTAL BILIRUBIN LEVELS1

Monitoring Frequency of Serum Transaminases and Bilirubin in Patients Monitoring Frequency of Serum Transaminases and Bilirubin in Patients

Consider more frequent monitoring of serum transaminases and bilirubin in patients who are taking valproate or who have elevated liver enzymes at baseline with and without valproate1

  • Monitor within 1 month following changes in EPIDIOLEX dosage and addition of or changes in medications that are known to impact the liver
  • Consider discontinuation or dose reduction of EPIDIOLEX or concomitant medications known to affect the liver (eg, valproate or clobazam) if liver enzyme elevations occur (transaminase levels >3x the ULN and bilirubin levels >2x the ULN, or sustained transaminase elevations >5x the ULN)

Somnolence and sedation1

COMBINED INCIDENCE OF SOMNOLENCE AND SEDATION (INCLUDING LETHARGY)

Incidence of Somnolence and Sedation (Including Lethargy) in Epidiolex-treated Patients Incidence of Somnolence and Sedation (Including Lethargy) in Epidiolex-treated Patients
  • In general, these effects were more common early in treatment and may diminish with continued treatment
  • Other CNS depressants, including alcohol, could potentiate the somnolence and sedation effect of EPIDIOLEX
  • Monitor for somnolence and sedation and advise patients not to drive or operate machinery until they have gained sufficient experience on EPIDIOLEX

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Suicidal behavior and ideation1

  • Antiepileptic drugs (AEDs), including EPIDIOLEX, increase the risk of suicidal thoughts or behavior
  • Inform patients, caregivers, and families of the risk and advise to monitor and report any signs of depression, suicidal thoughts or behavior, or unusual changes in mood or behavior
  • If these symptoms occur, consider if they are related to the AED or the underlying illness

Withdrawal of antiepileptic drugs1

  • As with most AEDs, EPIDIOLEX should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus

Considerations for patients on multiple therapies1

  • Concomitant use of EPIDIOLEX and valproate increases the incidence of liver enzyme elevations
  • EPIDIOLEX may affect exposure to CYP2C19 substrates (e.g., clobazam, diazepam) or others. Dosage adjustment of EPIDIOLEX or other concomitant medications may be necessary
FACTORS DOSE ADJUSTMENTS BASED ON TOLERABILITY
Strong or moderate CYP3A4 and CYP2C19 inhibitors Droplet Icon with Minus Consider dose reduction of EPIDIOLEX
Strong CYP3A4 and CYP2C19 inducers Droplet Icon with Plus Consider dose increase of EPIDIOLEX
Substrates of UGT1A9, UGT2B7, CYP2C8, CYP2C9, and CYP2C19 Droplet Icon with Minus Consider dose reduction of the substrate
Substrates of CYP1A2 and CYP2B6 Droplet Icon with Plus Minus Consider adjusting dosage of the substrate

In clinical trials, the most commonly used concomitant AEDs were clobazam and valproate1

CLOBAZAM1
Coadministration of EPIDIOLEX with clobazam produces a 3-fold increase in plasma concentrations of the active metabolite of clobazam, which may increase the risk of clobazam-related adverse reactions, including somnolence/sedation and liver enzyme elevations.

Pill Bottle Icon Consider a reduction of dosage of clobazam if known clobazam adverse reactions occur

VALPROATE1
Coadministration of EPIDIOLEX with valproate increases the incidence of liver enzyme elevation.

When EPIDIOLEX was coadministered with valproate in drug interaction studies, there was no effect on valproate exposure.

Dose adjustments should be made by clinicians based on individual patient response and tolerability and physician experience.

Rapid withdrawal of any AED can lead to increased seizure frequency and status epilepticus1

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Pregnancy1

  • EPIDIOLEX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Encourage women who are taking EPIDIOLEX during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry

 

Drug abuse1

  • EPIDIOLEX is a Schedule V controlled substance and has a low potential for abuse

 

Please refer to the EPIDIOLEX full Prescribing Information for additional important information.

The EPIDIOLEX dosing calculator can help when adjusting dosage based on your patient’s weight

CALCULATE DOSE

Reference: 1. EPIDIOLEX [package insert]. Carlsbad, CA: Greenwich Biosciences, Inc.; 2018.