If necessary, Cannabidiol can be administered with certain nasogastric tubes (NG-tube) or gastrostomy tubes (G-tube). However, please check any possibility of reaction of tube material with cannabidiol.

• In controlled and uncontrolled trials, an expanded access program, and other compassionate use programs, 1183 patients with LGS, Dravet syndrome, and TSC have been treated with cannabidiol
  • 683 patients treated for more than 1 year
  • 155 patients treated for more than 2 years
• Cannabidiol was also studied in open-label extension trials up to 3 years in LGS and Dravet syndrome, and 48 weeks in patients with TSC. The safety profile in these trials was generally similar to that observed in the four phase 3 trials for LGS, Dravet syndrome, and TSC1-3
  • In the open-label extension trials, titration to doses over the recommended maximum maintenance dose was permitted. At higher doses, an increase in adverse reactions is possible1-3
  • Eleven deaths were reported in patients with LGS; none were deemed to be treatment-related by the investigator1
  • Four deaths were reported in patients with Dravet syndrome, none of which were deemed related to treatment by the investigator2
  • There was 1 death reported during the TSC open-label extension, which was deemed unrelated to treatment by the investigator3

References: 1. Patel AD, Chin RF, Mitchell W, et al. Poster presented at: American Epilepsy Society Annual Meeting; December 6-10, 2019; Baltimore, MD. 2. Scheffer IE, Halford J, Nabbout R, et al. Poster presented at: American Epilepsy Society Annual Meeting; December 6-10, 2019; Baltimore, MD. 3. Thiele E, Bebin EM, Filloux F, et al. Presented at: 2020 American Academy of Neurology Annual Meeting; May 2020; Virtual Meeting.

Yes. It may be used, but there are recommended dose adjustments.

As with most AEDs, Cannabidiol should be gradually withdrawn to minimize the risk of increased seizure frequency and status epilepticus.

How should Clasepi (Cannabidiol) be dosed while using concomitant valproate and clobazam? What additional monitoring for liver transaminase and bilirubin levels is recommended?

• Nearly half (49%) of the patients in the LGS clinical trials and 65% of patients in the Dravet syndrome clinical trial were taking concomitant clobazam
• Valproate was the most commonly used concomitant AED in the TSC phase 3 trial, with 45% of patients receiving concomitant valproate, and 27% of patients receiving concomitant clobazam
• Concomitant use of valproate and elevated transaminase levels at baseline increase the risk of cannabidiol dose-related transaminase elevations
• Cannabidiol can cause somnolence and sedation that generally occur early in treatment and may diminish over time; these effects occur more commonly in patients using clobazam and may be potentiated by other CNS depressants. Monitor patients for somnolence and sedation and advise patients not to drive or operate machinery until they have gained sufficient experience on cannabidiol
• Dose adjustment of cannabidiol or concomitant medications may be required

Cannabidiol is made without sugar or carbohydrates, so it can be used with most epilepsy diets, such as the ketogenic diet. If you or your loved one are on a dietary therapy, talk to your doctor before taking cannabidiol

• Cannabidiol should be taken consistently with respect to meals to reduce variability in cannabidiol plasma exposure
• Caffeine: In vivo data showed Cannabidiol increases exposure to caffeine by 15% for Cmax and 95% for AUC compared to when caffeine was administered alone
• Alcohol: Coadministration of Cannabidiol with alcohol increased exposure to cannabidiol, with 93% increased Cmax and 63% greater AUC
  • Concomitant use of Cannabidiol with other CNS depressants (including alcohol) may increase the risk of sedation and somnolence

Cannabidiol should be avoided in patients with a known or suspected allergy.

CONTRAINDICATION: HYPERSENSITIVITY

Cannabidiol oral solution is contraindicated in patients with a history of hypersensitivity to cannabidiol or any ingredients in the product.

WARNINGS & PRECAUTIONS

Hepatocellular Injury:

Cannabidiol can cause dose-related transaminase elevations. Concomitant use of valproate and elevated transaminase levels at baseline increase this risk. 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. Resolution of transaminase elevations occurred with discontinuation of Cannabidiol, reduction of Cannabidiol and/or concomitant valproate, or without dose reduction. For patients with elevated transaminase levels, consider dose reduction or discontinuation of Cannabidiol or concomitant medications known to affect the liver (e.g., valproate or clobazam). Dose adjustment and slower dose titration is recommended in patients with moderate or severe hepatic impairment. Consider not initiating Cannabidiol in patients with evidence of significant liver injury.

Somnolence and Sedation:

Cannabidiol can cause somnolence and sedation that generally occurs early in treatment and may diminish over time; these effects occur more commonly in patients using clobazam and may be potentiated by other CNS depressants.

Suicidal Behavior and Ideation:

Antiepileptic drugs (AEDs), including Cannabidiol, 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 Drugs:

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

ADVERSE REACTIONS:

The most common adverse reactions in patients receiving Cannabidiol include transaminase elevations; somnolence; decreased appetite; diarrhea; pyrexia; vomiting; fatigue, malaise, and asthenia; rash; insomnia, sleep disorder and poor-quality sleep. Hematologic abnormalities were also observed.

PREGNANCY:

Cannabidiol may be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

DRUG INTERACTIONS:

Strong inducers of CYP3A4 and CYP2C19 may affect Cannabidiol exposure. Cannabidiol may affect exposure to CYP2C19 substrates (e.g., clobazam, diazepam, stiripentol), orally administered P-gp substrates, or other substrates. Consider dose reduction of orally administered everolimus, with appropriate therapeutic drug monitoring, when everolimus is combined with Cannabidiol. A lower starting dose of everolimus is recommended when added to Cannabidiol therapy. Concomitant use of Cannabidiol and valproate increases the incidence of liver enzyme elevations. Dosage adjustment of Cannabidiol or other concomitant medications may be necessary.