Controlled Substance Schedule: V
Seizures associated with Lennox-Gastaut syndrome or Dravet syndrome.
Cannabidiol is a cannabinoid that naturally occurs in the Cannabis sativa plant. Mechanism of anticonvulsant effect unknown; does not work by interacting with cannabinoid receptors.
Reduction in frequency of atonic, tonic, clonic, and tonic-clonic seizures.
Absorption: Extent of absorption unknown. High fat/high calorie meals increase extent of absorption.
Distribution: Extensively distributed to tissues.
Protein Binding: >94%.
Metabolism and Excretion: Primarily metabolized in the liver by the CYP2C9 and CYP3A4 isoenzymes to an active metabolite (7-OH-CBD). Primarily excreted in feces.
Half-life: 56–61 hr.
TIME/ACTION PROFILE (plasma concentrations)
- Hypersensitivity to cannabidiol or sesame oil.
Use Cautiously in:
- Concurrent use of valproic acid or clobazam;
- Concurrent use of sedatives, hypnotics, or other psychoactive drugs (↑ risk of adverse effects);
- Elevated liver enzymes (at baseline);
- Moderate to severe hepatic impairment;
- OB: Use only if the potential benefit justifies the potential risk to the fetus;
- Lactation: Use only if the potential benefit justifies the potential risk to the infant;
- Geri: Choose dose carefully, considering concurrent disease states, drug therapy, and age-related ↓ in hepatic and renal function;
- Pedi: Children <2 yr (safety and effectiveness not established).
Adverse Reactions/Side Effects
CNS: SUICIDAL THOUGHTS/BEHAVIORS, drowsiness, fatigue, insomnia, aggressive behavior, agitation
EENT: dry mouth
GI: HEPATOTOXICITY, ↓ appetite, diarrhea, ↑ liver enzymes, abdominal pain, ↓ weight
GU: ↑ serum creatinine
Misc: hypersensitivity reactions (angioedema, pruritus), infection, physical dependence, psychological dependence (high doses or prolonged therapy)
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Concurrent use of valproic acid or clobazam ↑ risk of hepatotoxicity.
- Moderate or strong CYP2C9 or CYP3A4 inhibitors may ↑ levels and risk of toxicity; consider ↓ cannabidiol dose.
- Strong CYP2C9 or CYP3A4 inducers may ↓ levels and effectiveness; consider ↑ cannabidiol dose.
- May ↑ levels and risk of toxicity of CYP2C8, CYP2C9, or CYP2C19 substrates ; consider ↓ dose of CYP2C8, CYP2C9, or CYP2C19 substrate.
- May ↑ or ↓ levels of CYP1A2 or CYP2B6 substrates ; consider ↓ dose of CYP1A2 or CYP2B6 substrate.
- Additive CNS depression with alcohol, antihistamines, barbiturates, benzodiazepines, muscle relaxants, opioid analgesics, tricyclic antidepressants, and sedative/hypnotics.
PO (Adults and Children ≥2 yr): 2.5 mg/kg twice daily; can ↑ dose to 5 mg/kg twice daily in 1 wk. If further reduction in seizure frequency needed, may continue to ↑ dose on weekly basis (every other day if more rapid titration warranted) in increments of 2.5 mg/kg twice daily (max dose = 10 mg/kg twice daily).
PO (Adults and Children ≥2 yr): Moderate hepatic impairment (Child–Pugh B)– 1.25 mg/kg twice daily; can ↑ dose to 2.5 mg/kg twice daily in 1 wk. If further reduction in seizure frequency needed, may continue to ↑ dose on weekly basis (every other day if more rapid titration warranted) in increments of 1.25 mg/kg twice daily (max dose = 5 mg/kg twice daily); Severe hepatic impairment (Child–Pugh C)– 0.5 mg/kg twice daily; can ↑ dose to 1 mg/kg twice daily in 1 wk. If further reduction in seizure frequency needed, may continue to ↑ dose on weekly basis (every other day if more rapid titration warranted) in increments of 0.5 mg/kg twice daily (max dose = 2 mg/kg twice daily).
Oral solution (strawberry flavor): 100 mg/mL
- Assess location, duration, and characteristics of seizure activity. Institute seizure precautions.
- Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
- Monitor for signs and symptom of hepatotoxicity (unexplained nausea, vomiting, right upper quadrant abdominal pain, fatigue, anorexia, jaundice and/or dark urine). If signs and symptoms occur, promptly measure serum transaminases and total bilirubin and interrupt or discontinue treatment with cannabidiol.
- Monitor for signs and symptoms of hypersensitivity reactions (pruritus, erythema, and angioedema) during therapy. Discontinue cannabidiol if symptoms occur.
Lab Test Considerations:
Obtain serum transaminases (ALT, AST) and total bilirubin levels before starting therapy. Elevations usually respond to decreased dose or discontinuation of therapy. Monitor levels at 1, 3, and 6 mo after starting therapy, within 1 mo following dose changes, and as needed thereafter. Discontinue cannabidiol if transaminase levels >3 times upper limit of normal (ULN) and bilirubin levels >2 times ULN. Also discontinue therapy if transaminase persistently >5 times ULN.
- Risk for injury (Indications)
- PO Administer orally twice daily. Use calibrated measuring device included with cannabidiol to ensure accurate dosing. Solution is strawberry flavored clear, colorless to yellow. Store at room temperature; do not refrigerate or freeze. Discard 12 wk after bottle is first opened.
- Instruct patient to take cannabidiol as directed. Advise patient not to stop cannabidiol without consulting health care professional; must be gradually discontinued to prevent seizures. Advise patient to read the Medication Guide before starting therapy and with each Rx refill in case of changes.
- May cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known. Tell patient not to resume driving until health care professional gives clearance based on control of seizure disorder.
- Advise patient to notify health care professional promptly if signs and symptoms of hepatotoxicity occur.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
- Inform patients and families of risk of suicidal thoughts and behavior and advise that behavioral changes, emergency or worsening signs and symptoms of depression, unusual changes in mood, or emergence of suicidal thoughts, behavior, or thoughts of self-harm should be reported to health care professional immediately.
- Inform patients of potential for positive cannabis drug screens.
- Rep: Advise female patients to notify health care professional if pregnancy is planned or suspected or if breast feeding. Encourage patients who become pregnant to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or on the web at www.aedpregnancyregistry.org. Enrollment must be done by patients themselves.
Decreased frequency and intensity of seizure activity.
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