Epidiolex (cannabidiol (CBD))
Last reviewed · Source: First Databank (FDB) drug data
Overview
Cannabidiol, a naturally occurring cannabinoid derived from the Cannabis sativa L. plant, is an anticonvulsant.
Cannabidiol is a highly purified cannabinoid extracted from the naturally occurring Cannabis sativa L. plant. Cannabidiol is structurally distinct from other currently available anticonvulsant drugs. The exact mechanism of action by which cannabidiol exerts its anticonvulsant activity in humans has not been fully elucidated, but does not appear to be related to a direct effect on cannabinoid receptors.
Cannabidiol and tetrahydrocannabinol (THC) are the 2 major pharmacologically active cannabinoids. Unlike THC, cannabidiol has little to no affinity for cannabinoid receptors CB1 or CB2 and does not possess psychoactive properties resulting in a lower potential for abuse. (See Abuse Potential and Dependence under Cautions.) Cannabidiol has exhibited anticonvulsant activity in several animal seizure models, including maximal electroshock, audiogenic seizures, and chemically induced seizures (e.g., pentylenetetrazole, 3-mercaptopropionic acid). Cannabidiol also has been shown to modulate various receptors and ion channels; however, further study is needed to determine whether these effects are responsible for the anticonvulsant properties of the drug.
Systemic exposure to cannabidiol increases in a less than proportional manner over a dosage range of 5-20 mg/kg daily. At steady state, peak plasma cannabidiol concentrations occur 2.5-5 hours following administration of the oral solution. Oral bioavailability of cannabidiol is low due to first-pass metabolism.
Administration of cannabidiol with a high-fat, high-calorie meal increased AUC and peak plasma concentrations of the drug by fourfold and fivefold, respectively, and decreased total variability, compared with administration in the fasted state. Administration with a low-fat, low-calorie meal increased AUC and peak plasma concentrations by threefold and fourfold, respectively. (See Administration under Dosage and Administration.) Plasma protein binding of cannabidiol and its metabolites exceeds 94%. The drug is highly lipophilic and rapidly distributes into the CNS and adipose tissue.
Cannabidiol is extensively metabolized in the liver and gut, principally by the CYP enzyme system (CYP2C19 and CYP3A4) and uridine diphosphate-glucuronosyltransferase (UGT) enzymes (1A7, 1A9, and 2B7). The active metabolite, 7-hydroxy-cannabidiol (7-OH-CBD), is equipotent to cannabidiol in seizure models and has a systemic exposure that is approximately 38% lower than the parent drug. Systemic exposure to the inactive metabolite 7-carboxy-cannabidiol (7-COOH-CBD) is approximately 40-fold higher than that of the parent drug.
Cannabidiol is excreted primarily in feces, with minor renal clearance. Following administration of a radiolabeled dose of cannabidiol, approximately 84% of the radioactivity was recovered in feces and 8% in urine. The mean elimination half-life of cannabidiol following repeated dosing is 56-61 hours.
Cannabidiol oral solution (Epidiolex(R)) is used for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex (TSC) in patients 1 year of age or older. The drug is a highly purified, plant-derived formulation of cannabidiol that has been approved by the FDA for treatment of these seizure disorders. Cannabidiol oral solution is designated an orphan drug by FDA for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and TSC.
Generic name: cannabidiol (CBD)
Pronunciation: (KAN-a-bi-DYE-ol)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Epidiolex
Indications
The following indications are listed for Epidiolex:
- Dravet Syndrome
- Lennox-Gastaut Epilepsy
- Seizures Associated With Tuberous Sclerosis Complex
Also known as: Epilepsy Of Lennox Gastaut Syndrome, Seizures Associated With Tsc, Seizures Associated With Tuberous Sclerosis Syndrome, Severe Myoclonic Epilepsy In Infancy.
Dosing
No dosing information is available for this tab.
Cannabidiol is administered orally twice daily as the commercially available oral solution (Epidiolex(R)). If necessary, the oral solution may be administered enterally through a non-PVC feeding tube (e.g., nasogastric or gastrostomy tube). Because food may increase exposure to cannabidiol, consistent dosing with respect to meals is recommended to reduce variability in drug exposure. (See Description.)
A calibrated measuring device (i.e., oral dosing syringe) should be used to measure and administer the prescribed dose of cannabidiol oral solution; a household teaspoon or tablespoon is not an adequate measuring device. If the prescribed dose is less than 1 mL, the manufacturer states that a 1-mL oral syringe should be obtained (e.g., from the pharmacy). If the prescribed dose is greater than 5 mL, the total dose should be administered in portions using the 5-mL oral syringe supplied by the manufacturer. The dose should be administered directly into the patient's mouth against the inside of the cheek.
Any unused portions of cannabidiol oral solution should be discarded 12 weeks after the container is first opened.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Cannabidiol is metabolized by cytochrome P-450 (CYP) isoenzymes 3A4 and 2C19, and also by uridine 5'-diphospho-glucuronosyltransferase (UGT) isoenzymes 1A7, 1A9, and 2B7.
Cannabidiol has the potential to inhibit CYP isoenzymes 2C8, 2C9, and 2C19, and may induce or inhibit CYP1A2 and CYP2B6 at clinically relevant concentrations.
Cannabidiol also inhibits UGT1A9 and UGT2B7, but does not inhibit UGT1A1, 1A3, 1A4, 1A6, or 2B17.
Cannabidiol and its active metabolite (7-OH-CBD) are not expected to affect breast cancer resistance protein (BCRP) and bile salt export pump (BSEP), P-glycoprotein (P-pg), organic anion transporters (OAT) 1 and OAT3, organic cation transporters (OCT) 1 and OCT2, multidrug and toxin extrusion transporters (MATE) 1 and MATE2K, or organic anion transport proteins (OATP) 1B1 or OATP1B3. The inactive metabolite, 7-COOH-CBD, inhibits BCRP and BSEP transport at clinically relevant concentrations.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Known hypersensitivity to cannabidiol or any excipient in the formulation, including sesame seed oil. (See Sensitivity Reactions under Cautions.)
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in at least 10% of patients with Lennox-Gastaut syndrome or Dravet syndrome receiving cannabidiol and more frequently than placebo include somnolence, decreased appetite, transaminase elevations, fatigue, malaise, asthenia, rash, insomnia, sleep disorder, poor sleep quality, and infections.
Adverse effects reported in at least 10% of patients with TSC receiving cannabidiol and more frequently than placebo include diarrhea, transaminase elevations, decreased appetite, somnolence, pyrexia, and vomiting.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of cannabidiol have not been established in pediatric patients younger than 1 year of age.
There are no adequate data on the developmental risks associated with the use of cannabidiol in pregnant women. Cannabidiol produced developmental toxicity (e.g., embryofetal mortality, decreased fetal body weight, decreased growth, delayed sexual maturation, long-term neurobehavioral changes) when administered orally to pregnant animals at exposure levels similar to or higher than those associated with the recommended human dosage.
Women who are pregnant while receiving cannabidiol should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry at 888-233-2334 or https://www.aedpregnancyregistry.org/.
It is not known whether cannabidiol or its metabolites are distributed into milk, affects milk production, or affects the breast-fed infant. The benefits of breast-feeding should be considered along with the importance of cannabidiol to the woman and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.
In geriatric patients, dosage should be selected cautiously, usually starting at the lower end of the dosage range.
There is no experience with cannabidiol in patients 55 years of age and older to determine whether these patients respond differently than younger adults.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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