Version July 2025
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.
There are no dosage adjustments provided in the manufacturer's labeling.
Baseline hepatic impairment:
Children and Adolescents: Oral:
Mild impairment: No adjustment needed.
Moderate impairment:
Dravet syndrome, Lennox-Gastaut syndrome: Initial: 1.25 mg/kg/dose twice daily; maintenance dose: 2.5 to 5 mg/kg/dose twice daily; maximum daily dose: 10 mg/kg/day.
Tuberous sclerosis complex: Initial: 1.25 mg/kg/dose twice daily; maintenance dose: 6.25 mg/kg/dose twice daily; maximum daily dose: 12.5 mg/kg/day.
Severe impairment:
Dravet syndrome, Lennox-Gastaut syndrome: Initial: 0.5 mg/kg/dose twice daily; maintenance dose: 1 to 2 mg/kg/dose twice daily; maximum daily dose: 4 mg/kg/day.
Tuberous sclerosis complex: Initial: 0.5 mg/kg/dose twice daily; maintenance dose: 2.5 mg/kg/dose twice daily; maximum daily dose: 5 mg/kg/day.
Hepatotoxicity during therapy: Adjustment based on transaminases elevation:
Children and Adolescents:
Clinical symptoms of hepatic dysfunction, AST/ALT >3 times ULN, and bilirubin >2 times ULN: Discontinue therapy.
Prolonged elevation of AST/ALT >5 times ULN: Discontinue therapy.
(For additional information see "Cannabidiol (pharmaceutical): Drug information")
Note: Assess ALT, AST, and total bilirubin prior to initiating treatment, with dose changes, and with the addition of or changes to concomitant hepatotoxic medications.
Seizure associated with Lennox-Gastaut syndrome or Dravet syndrome:
Oral: Initial: 2.5 mg/kg/dose twice daily; may increase after 1 week to a maintenance dose of 5 mg/kg/dose twice daily. If needed based on response and tolerability, may increase weekly in increments of 2.5 mg/kg/dose twice daily to a maximum of 20 mg/kg/day. In patients needing a more rapid titration from 5 mg/kg/dose twice daily to 10 mg/kg/dose twice daily, may increase dose as quickly as every other day in increments of 2.5 mg/kg/dose twice daily.
Seizure associated with tuberous sclerosis complex :
Oral: Initial: 2.5 mg/kg/dose twice daily; may increase dose in weekly increments of 2.5 mg/kg/dose twice daily to the recommended maintenance dose of 12.5 mg/kg/dose twice daily. In patients needing a more rapid titration from 2.5 mg/kg/dose twice daily to 12.5 mg/kg/dose twice daily, may increase dose as quickly as every other day in increments of 2.5 mg/kg/dose twice daily. Note: The effectiveness of doses <12.5 mg/kg/dose twice daily has not been studied.
Discontinuation of therapy: Unless safety concerns require rapid withdrawal, withdraw therapy gradually to minimize the potential of increased seizure frequency and status epilepticus.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
Hepatic impairment prior to treatment initiation:
Lennox-Gastaut syndrome or Dravet syndrome:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Initial: 1.25 mg/kg/dose twice daily; may increase after 1 week to a maintenance dose of 2.5 mg/kg/dose twice daily; if needed and tolerated, may increase after 1 week to 5 mg/kg/dose twice daily. Slower dosage increases may be necessary.
Severe impairment (Child-Pugh class C): Initial: 0.5 mg/kg/dose twice daily; may increase after 1 week to a maintenance dose of 1 mg/kg/dose twice daily; if needed and tolerated, may increase after 1 week to 2 mg/kg/dose twice daily. Slower dosage increases may be necessary.
Tuberous sclerosis complex:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Initial: 1.25 mg/kg/dose twice daily; may increase dose in weekly increments of 1.25 mg/kg/dose twice daily to a maintenance dose of 6.25 mg/kg/dose twice daily. Slower dosage increases may be necessary.
Severe impairment (Child-Pugh class C): Initial: 0.5 mg/kg/dose twice daily; may increase dose in weekly increments of 0.5 mg/kg/dose twice daily to a maintenance dose of 2.5 mg/kg/dose twice daily. Slower dosage increases may be necessary.
Hepatotoxicity during treatment:
Hepatic dysfunction symptoms (eg, unexplained anorexia, dark urine, fatigue, jaundice, nausea, right upper quadrant pain, vomiting): Promptly evaluate AST, ALT, and bilirubin; interrupt and/or discontinue treatment as appropriate.
AST and/or ALT >3 times ULN and total bilirubin >2 times ULN: Discontinue treatment.
AST and/or ALT >5 times ULN, sustained: Discontinue treatment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Skin rash (7% to 13%)
Endocrine & metabolic: Weight loss (3% to 31%)
Gastrointestinal: Decreased appetite (16% to 22%), diarrhea (20% to 31%), vomiting (17%)
Hematologic & oncologic: Anemia (7% to 38%)
Hepatic: Increased serum alanine aminotransferase (>3 × ULN: 1% to 17%; >20 × ULN: <1%), increased serum transaminases (8% to 25%)
Infection: Infection (40% to 41%), viral infection (7% to 11%)
Nervous system: Asthenia (≤12%), drowsiness (≤32%), fatigue (≤12%), insomnia (≤11%), lethargy (≤32%), malaise (≤12%), sedated state (≤32%), sleep disturbance (≤11%)
Miscellaneous: Fever (19%)
1% to 10%:
Gastrointestinal: Abdominal distress (≤3%), abdominal pain (≤3%), gastroenteritis (4% to 8%), nausea (9%), sialorrhea (≤4%)
Genitourinary: Urinary tract infection (5%)
Hematologic & oncologic: Decreased platelet count (5%), eosinophilia (5%)
Infection: Fungal infection (1% to 3%)
Nervous system: Abnormal gait (2% to 9%), aggressive behavior (≤5%), agitation (≤9%), drooling (≤4%), irritability (≤9%), outbursts of anger (≤5%)
Otic: Otic infection (8%)
Renal: Increased serum creatinine (10%)
Respiratory: Hypoxia (≤3%), pneumonia (4% to 8%), respiratory failure (≤3%), rhinorrhea (4%)
<1%: Hepatic: Increased serum aspartate aminotransferase (>20 × ULN)
Frequency not defined:
Dermatologic: Erythema of skin, pruritus
Hypersensitivity: Angioedema
Postmarketing:
Hepatic: Hepatic injury (cholestatic or mixed)
Nervous system: Suicidal ideation, suicidal tendencies
Hypersensitivity to cannabidiol or any component of the formulation.
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; concomitant elevations in ammonia levels were also reported in some patients. 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. Cases of cholestatic or mixed patterns of liver injury have also been reported. 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 antiseizure medications (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: Antiseizure medications 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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral:
Epidiolex: 100 mg/mL (60 mL) [contains alcohol, usp, sesame oil]
Epidiolex: 100 mg/mL (100 mL) [contains alcohol, usp, sesame oil; strawberry flavor]
No
Solution (Epidiolex Oral)
100 mg/mL (per mL): $20.52
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral:
Epidiolex: 100 mg/mL (60 mL, 100 mL) [contains alcohol, usp, sesame oil]
Oral: Administer consistently with respect to food to reduce variability in cannabidiol exposure; the absorption of cannabidiol is increased by food or milk. Use a calibrated measuring device (oral syringe) to accurately measure and administer the prescribed dose of liquid; for doses ≤1 mL, use the provided 1 mL oral syringe, and for other doses, the provided 5 mL oral syringe should be used; do not use a household spoon (overdosage may occur). After use, clean the inside of oral syringe with warm, soapy water by drawing water in and out of syringe using plunger, then separate plunger and oral syringe, give a final rinse with water (shaking off any excess), and allow separate parts to air dry. The inside of the oral syringe should be dry prior to measuring dose.
Silicone feeding tubes (eg, NG or gastrostomy tube) of adequate length and diameter: Silicone tube to be used should be ≥50 cm in length and ≥5 French diameter. After administration of each dose, flush tube with ~5 times the priming volume of the tube with room temperature drinking water; may modify flushing volume for fluid-restricted patients. Do not administer through tubes made of PVC or polyurethane
Oral: Administration with food or milk significantly increases absorption; administer consistently in the fasted or fed state to avoid variability in drug levels. Administer using the provided calibrated oral syringe (for doses ≤1 mL, use the provided 1 mL oral syringe; for other doses, use the provided 5 mL oral syringe). Syringe should be dry prior to measuring dose. Do not use a household teaspoon or tablespoon (overdosage may occur).
Gastrostomy/NG tube: Administer enterally via a silicone gastrostomy or NG tube; avoid tubes made of PVC or polyurethane or silicone NG tubes <50 cm in length or <5 FR in diameter. Flush tube with ~5 times the priming volume of room temperature drinking water after each dose; may modify flushing volume for fluid-restricted patients.
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.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Epidiolex: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/210365s020lbl.pdf
Treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) (FDA approved in ages ≥1 year and adults).
Substrate of CYP2C19 (Minor), CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors), UGT1A7, UGT1A9, UGT2B7; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BSEP, CYP1A2 (Weak), CYP2C19 (Moderate), CYP2C9 (Weak), CYP3A4 (Weak), P-glycoprotein;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Abrocitinib: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Abrocitinib. Risk C: Monitor
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider Therapy Modification
Agents with Clinically Relevant Anticholinergic Effects: May increase tachycardic effects of Cannabinoid-Containing Products. Risk C: Monitor
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Aliskiren. Risk C: Monitor
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of ALPRAZolam. Risk C: Monitor
Belzutifan: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Belzutifan. Risk C: Monitor
Beta-Acetyldigoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Beta-Acetyldigoxin. Risk C: Monitor
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Bilastine. Risk X: Avoid
Brivaracetam: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Brivaracetam. Risk C: Monitor
CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase serum concentration of CarBAMazepine. Risk C: Monitor
Carisoprodol: CYP2C19 Inhibitors (Moderate) may decrease active metabolite exposure of Carisoprodol. CYP2C19 Inhibitors (Moderate) may increase serum concentration of Carisoprodol. Risk C: Monitor
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Celiprolol. Risk C: Monitor
Cilostazol: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Cilostazol. CYP2C19 Inhibitors (Moderate) may increase active metabolite exposure 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. Risk D: Consider Therapy Modification
Citalopram: CYP2C19 Inhibitors (Moderate) may increase 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). Risk D: Consider Therapy Modification
CloBAZam: May increase hepatotoxic effects of Cannabidiol. Cannabidiol may increase serum concentration of CloBAZam. Cannabidiol may increase active metabolite exposure of CloBAZam. Risk C: Monitor
Clopidogrel: CYP2C19 Inhibitors (Moderate) may decrease active metabolite exposure of Clopidogrel. Risk C: Monitor
CloZAPine: CYP1A2 Inhibitors (Weak) may increase serum concentration of CloZAPine. Risk C: Monitor
CNS Depressants: May increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider Therapy Modification
CycloSPORINE (Systemic): Cannabidiol may increase serum concentration of CycloSPORINE (Systemic). Cannabidiol may decrease serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP2C19 Inducers (Strong): May decrease serum concentration of Cannabidiol. CYP2C19 Inducers (Strong) may decrease active metabolite exposure of Cannabidiol. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Cannabidiol. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Cannabidiol. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Cannabidiol. Risk C: Monitor
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase active metabolite exposure of Dabigatran Etexilate. Risk C: Monitor
Dexlansoprazole: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Dexlansoprazole. Risk C: Monitor
DiazePAM: CYP2C19 Inhibitors (Moderate) may increase serum concentration of DiazePAM. Risk C: Monitor
Digitoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digitoxin. Risk C: Monitor
Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider Therapy Modification
Dofetilide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Dofetilide. Risk C: Monitor
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Edoxaban. Risk C: Monitor
Ensartinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ensartinib. Risk X: Avoid
Escitalopram: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Escitalopram. Risk C: Monitor
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide Phosphate. Risk C: Monitor
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide. Risk C: Monitor
Etravirine: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Etravirine. Risk C: Monitor
Everolimus: Cannabidiol may increase serum concentration of Everolimus. Risk C: Monitor
Fenfluramine: Cannabidiol may increase CNS depressant effects of Fenfluramine. Cannabidiol may increase serum concentration of Fenfluramine. Risk C: Monitor
Fezolinetant: CYP1A2 Inhibitors (Weak) may increase serum concentration of Fezolinetant. Risk X: Avoid
Finerenone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Finerenone. Risk C: Monitor
Flibanserin: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Flibanserin. Risk C: Monitor
Fosphenytoin-Phenytoin: Cannabidiol may increase serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease serum concentration of Cannabidiol. Risk C: Monitor
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ixabepilone. Risk C: Monitor
Lansoprazole: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Lansoprazole. Risk C: Monitor
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Lapatinib. Risk C: Monitor
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Larotrectinib. Risk C: Monitor
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Risk D: Consider Therapy Modification
Lemborexant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Levomethadone: Cannabidiol may increase CNS depressant effects of Levomethadone. Risk C: Monitor
Lomitapide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider Therapy Modification
Mavacamten: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Mavacamten. Management: For patients on stable therapy with a moderate CYP2C19 inhibitor initiate mavacamten at 2.5 mg daily. For patients initiating a moderate CYP2C19 inhibitor during mavacamten therapy, dose reductions are recommended. See full mono for details. Risk D: Consider Therapy Modification
Mavorixafor: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Mavorixafor. Risk C: Monitor
Methadone: Cannabidiol may increase CNS depressant effects of Methadone. Cannabidiol may increase serum concentration of Methadone. Risk C: Monitor
Methylphenidate: Cannabidiol may increase serum concentration of Methylphenidate. Risk C: Monitor
Midazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Midazolam. Risk C: Monitor
Moclobemide: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Moclobemide. Risk C: Monitor
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Morphine (Systemic). Risk C: Monitor
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Nadolol. Risk C: Monitor
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naldemedine. Risk C: Monitor
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naloxegol. Risk C: Monitor
NiMODipine: CYP3A4 Inhibitors (Weak) may increase serum concentration of NiMODipine. Risk C: Monitor
Omeprazole: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Omeprazole. Risk C: Monitor
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid
Phenobarbital-Primidone: May decrease serum concentration of Cannabidiol. Cannabidiol may increase serum concentration of Phenobarbital-Primidone. Risk C: Monitor
Pimozide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Pimozide. Risk X: Avoid
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
Proguanil: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Proguanil. CYP2C19 Inhibitors (Moderate) may decrease active metabolite exposure of Proguanil. Risk C: Monitor
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ranolazine. Risk C: Monitor
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider Therapy Modification
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider Therapy Modification
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Repotrectinib. Risk X: Avoid
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RifAXIMin. Risk C: Monitor
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider Therapy Modification
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RisperiDONE. Risk C: Monitor
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RomiDEPsin. Risk C: Monitor
Saquinavir: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Saquinavir. Risk C: Monitor
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Silodosin. Risk C: Monitor
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Simvastatin. CYP3A4 Inhibitors (Weak) may increase active metabolite exposure of Simvastatin. Risk C: Monitor
Sirolimus (Conventional): Cannabidiol may increase serum concentration of Sirolimus (Conventional). Management: A dose reduction of sirolimus should be considered when combined with cannabidiol. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
Stiripentol: May increase serum concentration of Cannabidiol. Cannabidiol may increase serum concentration of Stiripentol. Risk C: Monitor
Tacrolimus (Systemic): Cannabidiol may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Teniposide. Risk C: Monitor
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Tetrahydrocannabinol: Cannabidiol may increase adverse/toxic effects of Tetrahydrocannabinol. Specifically, the psychoactive and tachycardic effects of tetrahydrocannabinol may be increased. Cannabidiol may increase serum concentration of Tetrahydrocannabinol. Risk C: Monitor
Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase serum concentration of Theophylline Derivatives. Risk C: Monitor
Tilidine: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Tilidine. CYP2C19 Inhibitors (Moderate) may increase active metabolite exposure of Tilidine. Risk C: Monitor
TiZANidine: CYP1A2 Inhibitors (Weak) may increase serum concentration of TiZANidine. Management: Avoid the use of tizanidine with weak CYP1A2 inhibitors when possible. If combined, monitor closely for increased tizanidine toxicities (eg, hypotension, bradycardia, drowsiness). Tizanidine dose reduction or discontinuation may be necessary. Risk D: Consider Therapy Modification
TOLBUTamide: CYP2C9 Inhibitors (Weak) may increase serum concentration of TOLBUTamide. Risk C: Monitor
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Triazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Triazolam. Risk C: Monitor
Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Risk D: Consider Therapy Modification
Valproic Acid and Derivatives: May increase hepatotoxic effects of Cannabidiol. Risk C: Monitor
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider Therapy Modification
VinCRIStine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of VinCRIStine. Risk X: Avoid
Vitamin K Antagonists: CYP2C9 Inhibitors (Weak) may increase serum concentration of Vitamin K Antagonists. Risk C: Monitor
Voriconazole: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Voriconazole. Risk C: Monitor
Warfarin: Cannabinoid-Containing Products may increase serum concentration of Warfarin. Risk C: Monitor
Food and milk increase extent of absorption. Management: Administer with or without food or milk, but consistent administration with regard to meals is recommended.
Cannabidiol can be detected in the umbilical cord serum and meconium following maternal use of inhaled, non-medicinal cannabis during pregnancy (Kim 2018).
Data collection to monitor pregnancy and infant outcomes following exposure to cannabidiol is ongoing. Patients exposed to cannabidiol during pregnancy are encouraged to enroll in both the Epidiolex pregnancy surveillance program and the antiepileptic drug pregnancy exposure registry. To enroll in the EPIDIOLEX Pregnancy Surveillance Program, call 1-855-272-7158 or visit www.epidiolexpregnancystudy.com. To enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry, call 1-888-233-2334 or visit www.aedpregnancyregistry.org.
Monitor hepatic function closely; serum transaminases (AST, ALT) and bilirubin levels (baseline, at 1 month, 3 months, and 6 months after initiation, and within 1 month of any dose change or addition/change in medication(s) known to affect hepatic function, then periodically thereafter as clinically necessary). More frequent monitoring is recommended for patients with elevated baseline liver enzymes or who are also taking valproate.
Weight, hemoglobin and hematocrit, SCr, CNS effects (eg, sedation, somnolence), signs and symptoms of suicidality (eg, anxiety, depression, behavior changes).
The exact antiseizure mechanism of action of cannabidiol is unknown; however, it does not appear to involve its effects on cannabinoid receptors.
Onset: Within 4 weeks.
Absorption: Food and milk increase extent of absorption.
Distribution: Vd: 20,963 L to 42,849 L.
Protein binding: >94%.
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.
Half-life elimination: 56 to 61 hours.
Time to peak: 2.5 to 5 hours at steady state.
Excretion: Feces; urine (minor).
Hepatic function impairment: Patients with moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment had a higher AUC
