cannabidiol

Absorption: Extent of absorption unknown. High-fat/high-calorie meals increase extent of absorption.

Distribution: Extensively distributed to tissues.

Protein Binding: >94%.

Metabolism/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)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2.5–5 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to cannabidiol or sesame oil.

Use Cautiously in:

Elevated liver enzymes (at baseline);
Moderate to severe hepatic impairment;
OB: Use during pregnancy only if the potential maternal benefit justifies the potential fetal risk;
Lactation: Use while breastfeeding only if the potential maternal benefit justifies the potential risk to the infant;
Pedi: Children <2 yr (safety and effectiveness not established);
Geri: Choose dose carefully in older adults, considering concurrent disease states, drug therapy, and age-related ↓ in hepatic and renal function.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash

EENT: dry mouth

GI: ↓appetite, ↑liver enzymes, diarrhea, abdominal pain, HEPATOTOXICITY, weight loss

GU: ↑serum creatinine

Hemat: anemia

Neuro: fatigue, insomnia, sedation, aggressive behavior, agitation, ataxia, SUICIDAL THOUGHTS/BEHAVIORS

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA), infection, physical dependence, psychological dependence (high doses or prolonged therapy)

Interactions ⬆ ⬇

Drug-drug:

Strong CYP2C9 inducers or strong CYP3A4 inducers may ↓ levels and effectiveness; consider ↑ cannabidiol dose.
May ↑ levels and risk of toxicity of CYP1A2 substrates, including theophylline and tizanidine; consider ↓ dose of CYP1A2 substrate.
May ↑ levels and risk of toxicity of CYP2B6 substrates, including bupropion and efavirenz.
May ↑ levels and risk of toxicity of CYP2C8 substrates and CYP2C9 substrates; consider ↓ dose of CYP2C8 or CYP2C9 substrate.
May ↑ levels and risk of toxicity of UGT1A9 substrates, including propofol and fenofibrate; consider ↓ dose of UGT1A9 substrate.
May ↑ levels and risk of toxicity of UGT2B7 substrates, including gemfibrozil, lamotrigine, morphine, and lorazepam; consider ↓ dose of UGT2B7 substrate.
May ↑ levels and risk of toxicity of CYP2C19 substrates, including diazepam; consider ↓ dose of CYP2C19 substrate.
May ↑ risk of toxicity of clobazam.
May ↑ levels and risk of toxicity of P-glycoprotein substrates, including everolimus, sirolimus, tacrolimus, and digoxin.
May ↑ levels and risk of toxicity of stiripentol.
Additive CNS depression with alcohol, antihistamines, barbiturates, benzodiazepines, muscle relaxants, opioid analgesics, tricyclic antidepressants, and sedative/hypnotics.
Valproic acid may ↑ risk of hepatotoxicity; consider discontinuation of or adjustment of dose of cannabidiol and/or valproic acid if ↑ liver enzymes occur.

Route/Dosage ⬆ ⬇

Seizures Associated With Lennox-Gastaut Syndrome or Dravet Syndrome

PO (Adults and Children ≥1 yr): 2.5 mg/kg twice daily; can ↑ to 5 mg/kg twice daily in 1 wk. If further ↓ 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).

Hepatic Impairment

PO (Adults and Children ≥1 yr): Moderate hepatic impairment: 1.25 mg/kg twice daily; can ↑ to 2.5 mg/kg twice daily in 1 wk. If further ↓ 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: 0.5 mg/kg twice daily; can ↑ to 1 mg/kg twice daily in 1 wk. If further ↓ 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).

Seizures Associated with Tuberous Sclerosis Complex

PO (Adults and Children ≥1 yr): 2.5 mg/kg twice daily; can ↑ on weekly basis (every other day if more rapid titration warranted) in increments of 2.5 mg/kg twice daily to recommended maintenance dosage of 12.5 mg/kg twice daily.

Hepatic Impairment

PO (Adults and Children ≥1 yr): Moderate hepatic impairment: 1.25 mg/kg twice daily; can ↑ on weekly basis (every other day if more rapid titration warranted) in increments of 1.25 mg/kg twice daily to recommended maintenance dosage of 6.25 mg/kg twice daily; Severe hepatic impairment: 0.5 mg/kg twice daily; can ↑ on weekly basis (every other day if more rapid titration warranted) in increments of 0.5 mg/kg twice daily to recommended maintenance dosage of 2.5 mg/kg twice daily.

Availability ⬆ ⬇

Oral solution strawberry flavor: 100 mg/mL

Assessment ⬆ ⬇

Assess location, duration, and characteristics of seizure activity. Institute seizure precautions.
Monitor closely for suicidal behavior and ideation as soon as 1 wk following initiation of therapy. If suicidal behavior occurs, consider if symptoms may be related to the illness being treated.
Monitor for signs and symptoms of hepatotoxicity. If signs and symptoms occur, promptly measure serum transaminases and total bilirubin and interrupt or discontinue cannabidiol therapy.
Monitor for signs and symptoms of hypersensitivity reactions (pruritus, erythema, angioedema) during therapy. If hypersensitivity reaction occurs, discontinue cannabidiol.

Lab Test Considerations:

Obtain serum transaminases (ALT, AST) and total bilirubin levels before initiation; then at 1, 3, and 6 mo; within 1 mo following dose change; and as needed thereafter. If ALT or AST >3 times upper limit of normal (ULN) and bilirubin >2 times ULN, discontinue cannabidiol. If ALT or AST persistently >5 times ULN, discontinue cannabidiol.

Implementation ⬆ ⬇

PO: Administer with consistency in regard to food. Use included calibrated measuring device to ensure accurate dosing. Store solution at room temperature; do not refrigerate or freeze. Discard 12 wk after bottle is first opened.
- May be administered enterally via silicone nasogastric or gastrostomy tube. After each dose, flush the tube with approximately 5 times the priming volume of the tube with room-temperature drinking water. Volume may need to be modified for fluid restrictions. Do not use with tubes made of polyvinyl chloride or polyurethane and avoid use of silicone nasogastric tubes <50 cm in length and <5 FR in diameter.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient not to stop cannabidiol without consulting health care provider; must be gradually discontinued to prevent seizures or discontinued rapidly under direct health care provider supervision.
Caution patient to avoid driving or other activities requiring alertness and not to resume driving until health care provider gives clearance based on control of seizure disorder and response to medication is known.
Advise patient to notify health care provider if signs and symptoms of hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine) occur.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken; consult health care provider before taking any new medications; and avoid alcohol during therapy.
Inform patient and caregiver of risk of suicidal thoughts and behavior, and to notify health care provider immediately if behavioral or mood changes, worsening signs and symptoms of depression, or suicidal thoughts occur.
Inform patients of potential for positive cannabis drug screens.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Encourage patients who become pregnant to enroll in both of the following registries: North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334; www.aedpregnancyregistry.org); and Epidiolex Pregnancy Surveillance Program (1-855-272-7158; www.epidiolexpregnancystudy.com). Enrollment must be done by patient.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇