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Cannabidiol

Medically reviewed by Drugs.com. Last updated on Apr 20, 2020.

Pronunciation

(kan a bi DYE ol)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Oral:

Epidiolex: 100 mg/mL (100 mL) [contains alcohol, usp, sesame oil; strawberry flavor]

Brand Names: U.S.

  • Epidiolex

Pharmacologic Category

  • Anticonvulsant
  • Cannabinoid

Pharmacology

The exact antiepileptic mechanism of action of cannabidiol is unknown; however, it does not appear to involve its effects on cannabinoid receptors.

Absorption

High-fat/high-calorie meals increase extent of absorption

Distribution

Vd: 20,963 L to 42,849 L

Metabolism

Hepatic (primarily) and gut by CYP2C19, CYP3A4, UGT1A7, UGT1A9, and UGT2B7 to active metabolite 7-OH-CBD and then to inactive metabolite 7-COOH-CBD

Excretion

Feces; urine (minor)

Onset of Action

Within 4 weeks

Time to Peak

2.5 to 5 hours at steady state

Half-Life Elimination

56 to 61 hours

Protein Binding

>94%

Special Populations: Hepatic Function Impairment

Patients with moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment had a higher AUC

Use: Labeled Indications

Seizure disorders: Treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex in patients ≥1 year of age.

Contraindications

Hypersensitivity to cannabidiol or any component of the formulation.

Dosing: Adult

Note: Assess ALT, AST, and total bilirubin prior to initiating treatment, with dose changes or the addition of or changes in hepatotoxic medications.

Seizure associated with Lennox-Gastaut syndrome or Dravet syndrome:

Oral: Initial: 2.5 mg/kg twice daily; may increase after 1 week to a maintenance dose of 5 mg/kg twice daily; if needed and tolerated, may increase in weekly increments of 2.5 mg/kg twice daily to a maximum dosage of 10 mg/kg twice daily. In patients needing a more rapid titration from 5 mg/kg twice daily to 10 mg/kg twice daily, may increase dose as quickly as every other day in increments of 2.5 mg/kg twice daily.

Note: The 20 mg/kg/day dosage resulted in somewhat greater reductions in seizure rates, but with an increase in adverse reactions. When discontinuing, the dose should be decreased gradually; avoid abrupt discontinuation.

Seizure associated with tuberous sclerosis complex:

Oral: Initial: 2.5 mg/kg twice daily; may increase dose in weekly increments of 2.5 mg/kg twice daily to a maintenance dose of 12.5 mg/kg twice daily. In patients needing a more rapid titration from 2.5 mg/kg twice daily to 12.5 mg/kg twice daily, may increase dose as quickly as every other day in increments of 2.5 mg/kg twice daily.

Note: The effectiveness of doses <12.5 mg/kg twice daily has not been studied. When discontinuing, the dose should be decreased gradually; avoid abrupt discontinuation.

Dosing: Geriatric

Refer to adult dosing; use with caution.

Dosing: Pediatric

Note: Assess baseline serum transaminases (ALT and AST) and total bilirubin levels.

Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS): Children and Adolescents: Oral: Initial: 2.5 mg/kg/dose twice daily, may increase in 1 week to a maintenance dose of 5 mg/kg/dose twice daily. If additional seizure control is needed, may further increase at weekly intervals by 2.5 mg/kg/dose twice daily increments; maximum daily dose: 20 mg/kg/day. For rapid titration, may increase no more frequently than every other day.

Tuberous sclerosis complex (TSC): Children and Adolescents: Oral: Initial: 2.5 mg/kg/dose twice daily, increase at weekly intervals by 2.5 mg/kg/dose twice daily increments to the recommended maintenance dose of 12.5 mg/kg/dose twice daily. Maximum daily dose: 25 mg/kg/day. For rapid titration, may increase no more frequently than every other day. Note: Effectiveness of doses below 25 mg/kg/day have not been studied in patients with TSC.

Discontinuation of therapy: Children and Adolescents: Oral: Withdraw gradually by decreasing the total daily dosage; abrupt discontinuation should be avoided to minimize the risk of increased seizures.

Administration

Oral: High-fat/high-calorie meals significantly increase absorption; consistent administration in the fasted or fed state will minimize variability in drug levels. Administer using the provided calibrated measuring device (1 or 5 mL oral syringe). May be administered enterally via an NG or gastrostomy tube; avoid tubes made of PVC.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Do not freeze. Use within 12 weeks of first opening the bottle; discard any unused solution.

Drug Interactions

Brivaracetam: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Brivaracetam. Monitor therapy

Carisoprodol: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Carisoprodol. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Carisoprodol. Monitor therapy

Cilostazol: CYP2C19 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Cilostazol. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Reduce the cilostazol dose to 50 mg twice daily in patients who are also receiving moderate inhibitors of CYP2C19. Monitor clinical response to cilostazol closely. Consider therapy modification

Citalopram: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a moderate CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (eg, serotonin syndrome, QT prolongation). Consider therapy modification

CloBAZam: CYP2C19 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of CloBAZam. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of CloBAZam. Monitor therapy

Clopidogrel: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Monitor therapy

CNS Depressants: Cannabidiol may enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CYP2C19 Inducers (Strong): May decrease the serum concentration of Cannabidiol. Monitor therapy

CYP2C19 Inhibitors (Moderate): May increase the serum concentration of Cannabidiol. Monitor therapy

CYP2C19 Inhibitors (Strong): May increase the serum concentration of Cannabidiol. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Cannabidiol. Exceptions: Fosphenytoin; Phenytoin. Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Cannabidiol. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Cannabidiol. Monitor therapy

Dexlansoprazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Dexlansoprazole. Monitor therapy

DiazePAM: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of DiazePAM. Monitor therapy

Escitalopram: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Escitalopram. Monitor therapy

Etravirine: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Etravirine. Monitor therapy

Everolimus: Cannabidiol may increase the serum concentration of Everolimus. Monitor therapy

Flibanserin: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Monitor therapy

Fosphenytoin-Phenytoin: Cannabidiol may increase the serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease the serum concentration of Cannabidiol. Monitor therapy

Lansoprazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Lansoprazole. Monitor therapy

Methadone: Cannabidiol may enhance the CNS depressant effect of Methadone. Cannabidiol may increase the serum concentration of Methadone. Monitor therapy

Moclobemide: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Moclobemide. Monitor therapy

Omeprazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Omeprazole. Monitor therapy

Proguanil: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Proguanil. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Proguanil. Monitor therapy

Sirolimus: Cannabidiol may increase the serum concentration of Sirolimus. Monitor therapy

Stiripentol: May increase the serum concentration of Cannabidiol. Cannabidiol may increase the serum concentration of Stiripentol. Monitor therapy

Tacrolimus (Systemic): Cannabidiol may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

Valproate Products: May enhance the hepatotoxic effect of Cannabidiol. Monitor therapy

Voriconazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Voriconazole. Monitor therapy

Warfarin: Cannabinoid-Containing Products may increase the serum concentration of Warfarin. Monitor therapy

Test Interactions

May cause a false-positive cannabis screening.

Adverse Reactions

>10%:

Central nervous system: Drowsiness (≤32%), lethargy (≤32%), sedation (≤32%), fatigue (≤12%), malaise (≤12%), insomnia (≤11%), sleep disorder (≤11%), sleep disturbance (≤11%)

Dermatologic: Skin rash (7% to 13%)

Endocrine & metabolic: Weight loss (3% to 18%)

Gastrointestinal: Decreased appetite (16% to 22%), diarrhea (9% to 20%)

Hematologic & oncologic: Anemia (30%)

Hepatic: Increased serum alanine aminotransferase (>3x ULN: 13% to 17%), increased serum transaminases (8% to 16%)

Infection: Infection (25% to 41%), viral infection (7% to 11%)

Neuromuscular & skeletal: Asthenia (≤12%)

1% to 10%:

Central nervous system: Agitation (≤9%), irritability (≤9%), aggressive behavior (≤5%), outbursts of anger (≤5%), drooling (≤4%), abnormal gait (2% to 3%)

Gastrointestinal: Gastroenteritis (4%), sialorrhea (≤4%), abdominal distress (≤3%), abdominal pain (≤3%)

Infection: Fungal infection (1% to 3%)

Respiratory: Pneumonia (5% to 8%), hypoxia (≤3%), respiratory failure (≤3%)

Frequency not defined:

Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin

Hepatic: Increased serum aspartate aminotransferase, increased serum transaminases (>20x ULN)

Hypersensitivity: Hypersensitivity reaction

Renal: Increased serum creatinine

<1%, postmarketing, and/or case reports: Angioedema, erythema, pruritus

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). Sedation and somnolence are dose-related, most common early in treatment, have a higher incidence in combination with clobazam, and may resolve with continued use.

• Hepatic effects: Dose-related elevations of liver transaminases (ALT and/or AST) have been reported, some resulting in hospitalization. Elevations typically occur within the first 2 months of treatment, but have occurred as late as 18 months after treatment initiation. Risk factors include high cannabidiol dose, concomitant hepatotoxic drugs (especially clobazam and valproate), and elevated baseline transaminases. Identifying elevated transaminases early may decrease the risk of serious hepatocellular injury. Although in clinical trials, transaminase levels normalized after continuing cannabidiol in some patients, others required discontinuation or lowering the dose of cannabidiol and/or concomitant hepatotoxic drugs. Interrupt and/or discontinue treatment (as appropriate) and check liver transaminases and bilirubin if clinical signs or symptoms of hepatic dysfunction develop (eg, unexplained anorexia, dark urine, fatigue, jaundice, nausea, right upper quadrant pain, vomiting). Discontinue treatment if transaminase levels >3 x ULN, bilirubin levels >2 x ULN, or sustained transaminase elevations >5 x ULN. In patients with elevated transaminases and bilirubin at baseline or prolonged elevations during cannabidiol treatment, assess for other possible causes of hepatotoxicity.

• Hypersensitivity: Hypersensitivity reactions (including angioedema, erythema, and pruritus requiring antihistamines and corticosteroids) have been reported. Discontinue cannabidiol if hypersensitivity reactions occur.

• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify health care provider immediately if symptoms occur.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment required in moderate or severe hepatic impairment.

Other warnings/precautions:

• Withdrawal: Antiepileptics should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency and status epilepticus, unless safety concerns require a more rapid withdrawal.

Monitoring Parameters

ALT, AST, and total bilirubin (baseline and 1, 3, and 6 months after initiation, followed by periodic monitoring as clinically indicated [eg, within 1 month of dose change or initiation of concomitant hepatotoxic drug or clinical signs or symptoms of hepatic dysfunction]).

Pregnancy Considerations

Cannabidiol can be detected in the umbilical cord serum and meconium following maternal use of inhaled, non-medicinal cannabis during pregnancy (Kim 2018).

Patients exposed to cannabidiol during pregnancy are encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.

Patient Education

What is this drug used for?

• It is used to help control certain kinds of seizures.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Fatigue

• Lack of appetite

• Weight loss

• Diarrhea

• Loss of strength and energy

• Trouble sleeping

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin

• Infection

• Depression like thoughts of suicide, anxiety, emotional instability, or confusion

• Irritability

• Panic attacks

• Mood changes

• Behavior changes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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