cannabidiol (Rx)

Brand and Other Names:Epidiolex

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

solution, oral

  • 100mg/mL

Seizures

Indicated for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC)

LGS or DS

  • 2.5 mg/kg PO BID initially; after 1 week, may increase to maintenance dose of 5 mg/kg BID  
  • If 5 mg/kg BID tolerated and further seizure reduction required, patient may benefit from a dosage increase up to a maximum recommended maintenance dosage of 10 mg/kg BID (ie, 20 mg/kg/day)
  • Increasing to 10 mg/kg BID may be achieved by increased weekly increments of 2.5 mg/kg BID, as tolerated
  • If a more rapid titration from 10 mg/kg/day to 20 mg/kg/day is warranted, the dosage may be increased no more frequently than every other day
  • Administration of the 20-mg/kg/day dosage resulted in somewhat greater reductions in seizure rates than the recommended maintenance dosage of 10 mg/kg/day, but with an increase in adverse reactions

TSC

  • Starting dose: 2.5 mg/kg PO BID
  • Increase dose in weekly increments of 2.5 mg/kg BID as tolerated, to recommended maintenance dose of 12.5 mg/kg BID
  • If a more rapid titration is warranted, the dosage may be increased no more frequently than every other day
  • Effectiveness of doses <12.5 mg/kg BID has not been studied in patients with TSC

Dosage Modifications

Hepatic impairment

  • Mild (Child-Pugh A): No dose adjustment required
  • Moderate-to-severe (Child-Pugh B or C): Dosage adjustment recommended, including slower titration
  • Moderate (LGS or DS)
    • Starting dose: 1.25 mg/kg BID
    • Maintenance dose range: 2.5-5 mg/kg BID
  • Severe (LGS or DS)
    • Starting dose: 0.5 mg/kg BID
    • Maintenance dose range: 1 mg/kg BID
  • Moderate (TSC)
    • Starting dose: 1.25 mg/kg BID
    • Maintenance dose: 6.25 mg/kg BID
  • Severe (TSC)
    • Starting dose: 0.5 mg/kg BID
    • Maintenance dose: 2.5 mg/kg BID

Dosing Considerations

Because of the risk of hepatocellular injury, obtain serum transaminases (ALT and AST) and total bilirubin levels in all patients before initiating and at 1 month, 3 months, and 6 months, and periodically thereafter or as clinically indicated

Existing transaminase elevations >3 x ULN in presence of elevated bilirubin without alternative explanation are important predictors of severe liver injury and should be evaluated before initiating cannabidiol

Hepatitis (Orphan)

Orphan designation for treatment of autoimmune hepatitis

Orphan sponsor

  • Revive Therapeutics Ltd; 5 Director Court, Suite 105; Vaughan, Ontario; Canada

Huntington Disease (Orphan)

Orphan designation for delta-9-THC and cannabidiol for treatment of Huntington disease

Sponsor

  • MMJ International Holdings; 1895 Preston White Drive, Suite 101; Reston, Virginia 20191

Dosage Forms & Strengths

solution, oral

  • 100mg/mL

Seizures

Indicated for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in patients aged ≥1 yr

Age ≥1 year

  • LGS or DS
    • 2.5 mg/kg PO BID initially; after 1 week, may increase to maintenance dose of 5 mg/kg BID  
    • If 5 mg/kg BID tolerated and further seizure reduction required, patient may benefit from a dosage increase up to a maximum recommended maintenance dosage of 10 mg/kg BID (ie, 20 mg/kg/day)
    • Increasing to 10 mg/kg BID may be achieved by increased weekly increments of 2.5 mg/kg BID, as tolerated
    • If a more rapid titration from 10 mg/kg/day to 20 mg/kg/day is warranted, the dosage may be increased no more frequently than every other day
    • Administration of the 20-mg/kg/day dosage resulted in somewhat greater reductions in seizure rates than the recommended maintenance dosage of 10 mg/kg/day, but with an increase in adverse reactions
  • TSC
    • Starting dose: 2.5 mg/kg PO BID
    • Increase dose in weekly increments of 2.5 mg/kg BID as tolerated, to recommended maintenance dose of 12.5 mg/kg BID
    • If a more rapid titration is warranted, the dosage may be increased no more frequently than every other day
    • Effectiveness of doses <12.5 mg/kg BID has not been studied in patients with TSC

Dosage Modifications

Hepatic impairment

  • Mild (Child-Pugh A): No dose adjustment required
  • Moderate-to-severe (Child-Pugh B or C): Dosage adjustment recommended including, slower titration
  • Moderate (LGS or DS)
    • Starting dose: 1.25 mg/kg BID
    • Maintenance dose range: 2.5-5 mg/kg BID
  • Severe (LGS or DS)
    • Starting dose: 0.5 mg/kg BID
    • Maintenance dose range: 1-2 mg/kg BID
  • Moderate (TSC)
    • Starting dose: 1.25 mg/kg BID
    • Maintenance dose: 6.25 mg/kg BID
  • Severe (TSC)
    • Starting dose: 0.5 mg/kg BID
    • Maintenance dose: 2.5 mg/kg BID

Dosing Considerations

Because of the risk of hepatocellular injury, obtain serum transaminases (ALT and AST) and total bilirubin levels in all patients before initiating and at 1 month, 3 months, and 6 months, and periodically thereafter or as clinically indicated

Existing transaminase elevations >3 x ULN in presence of elevated bilirubin without alternative explanation are important predictors of severe liver injury and should be evaluated before initiating cannabidiol

Absence Epilepsy (Orphan)

Orphan designation for treatment of childhood absence epilepsy

Orphan sponsor

  • Insys Development Company, Inc; 1333 South Spectrum Blvd, Suite 100; Chandler, Arizona 85286

Clinical trials did not include any patients aged >55 yr to determine whether or not they respond differently from younger patients

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy

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Interactions

Interaction Checker

and cannabidiol

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            Contraindicated (2)

            • fezolinetant

              cannabidiol will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • mavacamten

              cannabidiol will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            Serious - Use Alternative (1)

            • tucatinib

              cannabidiol will increase the level or effect of tucatinib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of tucatinib (a CYP2C8 substrate) with a strong or moderate CYP2C8 inhibitors increases tucatinib plasma concentrations and risk of toxicities.

            Monitor Closely (200)

            • abiraterone

              abiraterone will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

            • ambrisentan

              cannabidiol will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • amiodarone

              amiodarone will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

              cannabidiol will increase the level or effect of amiodarone by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

              cannabidiol will increase the level or effect of amiodarone by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • amobarbital

              amobarbital will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

            • apalutamide

              cannabidiol will increase the level or effect of apalutamide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • aprepitant

              aprepitant will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • armodafinil

              armodafinil will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

            • atazanavir

              atazanavir will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • bicalutamide

              bicalutamide will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • bortezomib

              bortezomib will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of bortezomib by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • bosentan

              cannabidiol will increase the level or effect of bosentan by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • bupropion

              cannabidiol, bupropion. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP2B6 induction and inhibition with the coadministration of CYP2B6 substrates and cannabidiol, consider reducing dosage adjustment of CYP2B6 substrates as clinically appropriate.

            • butabarbital

              butabarbital will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

            • butalbital

              butalbital will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

            • carbamazepine

              carbamazepine will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

            • carisoprodol

              cannabidiol will increase the level or effect of carisoprodol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • carvedilol

              cannabidiol will increase the level or effect of carvedilol by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • celecoxib

              cannabidiol will increase the level or effect of celecoxib by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • ceritinib

              ceritinib will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • chloramphenicol

              chloramphenicol will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

              chloramphenicol will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP2C19 inhibitor.

            • chlorpropamide

              cannabidiol will increase the level or effect of chlorpropamide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • citalopram

              cannabidiol will increase the level or effect of citalopram by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • clarithromycin

              clarithromycin will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • clobazam

              cannabidiol will increase the level or effect of clobazam by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • clomipramine

              cannabidiol will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • clotrimazole

              clotrimazole will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • cobicistat

              cobicistat will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • conivaptan

              conivaptan will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • conjugated estrogens

              cannabidiol, conjugated estrogens. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • conjugated estrogens, vaginal

              cannabidiol, conjugated estrogens, vaginal. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • crizotinib

              crizotinib will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • cyclobenzaprine

              cannabidiol, cyclobenzaprine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • cyclophosphamide

              cannabidiol, cyclophosphamide. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP2B6 induction and inhibition with the coadministration of CYP2B6 substrates and cannabidiol, consider reducing dosage adjustment of CYP2B6 substrates as clinically appropriate.

            • cyclosporine

              cyclosporine will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • dabrafenib

              dabrafenib will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

              cannabidiol will increase the level or effect of dabrafenib by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • dacarbazine

              cannabidiol, dacarbazine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • daprodustat

              cannabidiol will increase the level or effect of daprodustat by Other (see comment). Modify Therapy/Monitor Closely. Moderate CYP2C8 inhibitors increase daprodustat exposure. If coadministered with moderate CYP2C8 inhibitors, reduce daprodustat starting dose by half (except if starting dose is already 1 mg). Monitor hemoglobin and adjust daprodustat dose when initiating or stopping therapy with moderate CYP2C8 inhibitors during treatment

            • dapsone

              cannabidiol will increase the level or effect of dapsone by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • darunavir

              darunavir will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • dasabuvir

              cannabidiol will increase the level or effect of dasabuvir by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • dexlansoprazole

              dexlansoprazole will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of dexlansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • diazepam

              cannabidiol will increase the level or effect of diazepam by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • diazepam intranasal

              cannabidiol will increase the level or effect of diazepam intranasal by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Strong or moderate CYP2C19 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

            • diclofenac

              cannabidiol will increase the level or effect of diclofenac by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • digoxin

              cannabidiol will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Therapeutic drug monitoring and dose reduction of P-gp substrates should be considered when given orally and concurrently with cannabidiol

            • diltiazem

              diltiazem will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor increased cannabidol effects and toxicities if coadministered with moderate CYP3A4 inhibitors. Reduce cannabidiol dose if necessary.

            • divalproex sodium

              cannabidiol increases toxicity of divalproex sodium by unspecified interaction mechanism. Use Caution/Monitor. associated with increased risk of ALT and/or AST elevation; manageable by dose reduction or, in more severe cases, by discontinuation of one or both drugs; monitor liver function, including serum transaminase and total bilirubin levels, during concomitant treatment.

            • doxepin cream

              cannabidiol, doxepin cream. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • doxycycline

              doxycycline will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • dronabinol

              cannabidiol will increase the level or effect of dronabinol by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • dronedarone

              dronedarone will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • duloxetine

              cannabidiol, duloxetine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • efavirenz

              efavirenz will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

              efavirenz will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

              cannabidiol, efavirenz. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP2B6 induction and inhibition with the coadministration of CYP2B6 substrates and cannabidiol, consider reducing dosage adjustment of CYP2B6 substrates as clinically appropriate.

            • enzalutamide

              enzalutamide will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

              enzalutamide will decrease the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP2C19 inducer.

              cannabidiol will increase the level or effect of enzalutamide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • erythromycin base

              erythromycin base will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • escitalopram

              cannabidiol will increase the level or effect of escitalopram by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • esketamine intranasal

              esketamine intranasal, cannabidiol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

            • eslicarbazepine acetate

              eslicarbazepine acetate will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

            • esomeprazole

              esomeprazole will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • estradiol

              cannabidiol, estradiol. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • estrogens conjugated synthetic

              cannabidiol, estrogens conjugated synthetic. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • etravirine

              etravirine will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

              etravirine will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

              cannabidiol will increase the level or effect of etravirine by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

              cannabidiol will increase the level or effect of etravirine by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • everolimus

              cannabidiol will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Therapeutic drug monitoring and dose reduction of P-gp substrates should be considered when given orally and concurrently with cannabidiol

            • fenofibrate

              cannabidiol will increase the level or effect of fenofibrate by Other (see comment). Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit UGT1A9 activity. Consider reducing the dose when concomitantly using UGT1A9 substrates.

            • flibanserin

              cannabidiol will increase the level or effect of flibanserin by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • fluconazole

              fluconazole will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

              fluconazole will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP2C19 inhibitor.

            • fluoxetine

              fluoxetine will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of fluoxetine by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • flutamide

              cannabidiol, flutamide. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • fluvastatin

              cannabidiol will increase the level or effect of fluvastatin by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • fluvoxamine

              fluvoxamine will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor

            • fosamprenavir

              fosamprenavir will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • fosaprepitant

              fosaprepitant will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

              cannabidiol will increase the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

              cannabidiol will increase the level or effect of fosphenytoin by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • fostamatinib

              fostamatinib will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • gemfibrozil

              gemfibrozil will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of gemfibrozil by Other (see comment). Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit UGT2B7 activity. Consider reducing the dose when concomitantly using UGT2B7 substrates.

            • glimepiride

              cannabidiol will increase the level or effect of glimepiride by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • glipizide

              cannabidiol will increase the level or effect of glipizide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • glyburide

              cannabidiol will increase the level or effect of glyburide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • grapefruit

              grapefruit will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • haloperidol

              haloperidol will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • idelalisib

              idelalisib will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • ifosfamide

              cannabidiol will increase the level or effect of ifosfamide by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • iloperidone

              iloperidone will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • imatinib

              imatinib will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

              cannabidiol will increase the level or effect of imatinib by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • imipramine

              cannabidiol will increase the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • indinavir

              indinavir will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • irinotecan

              cannabidiol, irinotecan. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP2B6 induction and inhibition with the coadministration of CYP2B6 substrates and cannabidiol, consider reducing dosage adjustment of CYP2B6 substrates as clinically appropriate.

            • isoniazid

              isoniazid will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

              isoniazid will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP2C19 inhibitor.

            • isotretinoin

              cannabidiol will increase the level or effect of isotretinoin by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • itraconazole

              itraconazole will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • ketamine

              cannabidiol will increase the level or effect of ketamine by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • ketoconazole

              ketoconazole will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

            • lacosamide

              cannabidiol will increase the level or effect of lacosamide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • lamotrigine

              cannabidiol will increase the level or effect of lamotrigine by Other (see comment). Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit UGT2B7 activity. Consider reducing the dose when concomitantly using UGT2B7 substrates.

            • lansoprazole

              lansoprazole will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of lansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • lapatinib

              lapatinib will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • lenacapavir

              lenacapavir will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

            • lesinurad

              cannabidiol will increase the level or effect of lesinurad by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • letermovir

              letermovir will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • levoketoconazole

              levoketoconazole will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

            • lidocaine

              cannabidiol, lidocaine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • lopinavir

              lopinavir will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • loratadine

              loratadine will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

            • lorazepam

              cannabidiol will increase the level or effect of lorazepam by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit UGT2B7 activity. Consider reducing the dose when concomitantly using UGT2B7 substrates.

            • losartan

              cannabidiol will increase the level or effect of losartan by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

            • mestranol

              cannabidiol will decrease the level or effect of mestranol by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • metaxalone

              cannabidiol, metaxalone. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • methadone

              cannabidiol will increase the level or effect of methadone by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • methsuximide

              cannabidiol will increase the level or effect of methsuximide by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • methylphenidate transdermal

              methylphenidate transdermal will increase the level or effect of cannabidiol by anti-hypertensive channel blocking. Modify Therapy/Monitor Closely. Consider decreasing the dose of these drugs when given coadministered with methylphenidate. Monitor for drug toxiticities when initiating or discontinuing methylphenidate.

            • metronidazole

              metronidazole will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • mexiletine

              cannabidiol, mexiletine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • miconazole oral

              miconazole oral will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of miconazole oral by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • mifepristone

              mifepristone will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • mirtazapine

              cannabidiol, mirtazapine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • mitotane

              mitotane will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

            • modafinil

              modafinil will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of modafinil by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • montelukast

              cannabidiol will increase the level or effect of montelukast by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • morphine

              cannabidiol will increase the level or effect of morphine by Other (see comment). Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit UGT2B7 activity. Consider reducing the dose when concomitantly using UGT2B7 substrates.

            • nafcillin

              nafcillin will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

            • nateglinide

              cannabidiol will increase the level or effect of nateglinide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • nefazodone

              nefazodone will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • nelfinavir

              nelfinavir will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

              cannabidiol will increase the level or effect of nelfinavir by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • netupitant/palonosetron

              netupitant/palonosetron will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • nevirapine

              nevirapine will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

            • nicardipine

              nicardipine will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

            • olanzapine

              cannabidiol, olanzapine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

              cannabidiol will increase the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • omeprazole

              omeprazole will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of omeprazole by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • ospemifene

              cannabidiol will increase the level or effect of ospemifene by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

              cannabidiol will increase the level or effect of ospemifene by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

            • paclitaxel

              cannabidiol will increase the level or effect of paclitaxel by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • paclitaxel protein bound

              cannabidiol will increase the level or effect of paclitaxel protein bound by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • pantoprazole

              pantoprazole will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of pantoprazole by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • pentamidine

              cannabidiol will increase the level or effect of pentamidine by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • pentobarbital

              pentobarbital will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

            • phenobarbital

              phenobarbital will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

              cannabidiol will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • phenytoin

              phenytoin will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

              cannabidiol will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

              cannabidiol will increase the level or effect of phenytoin by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • pimozide

              cannabidiol, pimozide. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • pioglitazone

              cannabidiol will increase the level or effect of pioglitazone by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • pirfenidone

              cannabidiol, pirfenidone. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • pomalidomide

              cannabidiol, pomalidomide. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • posaconazole

              posaconazole will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • progesterone intravaginal gel

              cannabidiol will increase the level or effect of progesterone intravaginal gel by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • progesterone micronized

              cannabidiol will increase the level or effect of progesterone micronized by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • propofol

              propofol will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of propofol by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

              cannabidiol will increase the level or effect of propofol by Other (see comment). Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit UGT1A9 activity. Consider reducing the dose when concomitantly using UGT1A9 substrates.

            • propranolol

              cannabidiol, propranolol. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • rabeprazole

              rabeprazole will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of rabeprazole by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • ramelteon

              cannabidiol, ramelteon. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • rasagiline

              cannabidiol, rasagiline. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • repaglinide

              cannabidiol will increase the level or effect of repaglinide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • ribociclib

              ribociclib will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • rifampin

              rifampin will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

              cannabidiol, rifampin. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP2B6 induction and inhibition with the coadministration of CYP2B6 substrates and cannabidiol, consider reducing dosage adjustment of CYP2B6 substrates as clinically appropriate.

            • rifapentine

              rifapentine will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

            • riluzole

              cannabidiol, riluzole. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • riociguat

              cannabidiol will increase the level or effect of riociguat by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • ritonavir

              ritonavir will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • ropinirole

              cannabidiol, ropinirole. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • ropivacaine

              cannabidiol, ropivacaine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • rosiglitazone

              cannabidiol will increase the level or effect of rosiglitazone by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • saquinavir

              saquinavir will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • schisandra

              schisandra will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • secobarbital

              secobarbital will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

            • selegiline

              cannabidiol, selegiline. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP2B6 induction and inhibition with the coadministration of CYP2B6 substrates and cannabidiol, consider reducing dosage adjustment of CYP2B6 substrates as clinically appropriate.

            • selexipag

              cannabidiol will increase the level or effect of selexipag by decreasing metabolism. Modify Therapy/Monitor Closely. Reduce selexipag dose to once daily if coadministered with moderate CYP2C8 inhibitors.

            • sertraline

              sertraline will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

              cannabidiol will increase the level or effect of sertraline by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • sirolimus

              cannabidiol will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Therapeutic drug monitoring and dose reduction of P-gp substrates should be considered when given orally and concurrently with cannabidiol

            • sparsentan

              sparsentan will decrease the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates.

            • St John's Wort

              St John's Wort will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

            • stiripentol

              cannabidiol will increase the level or effect of stiripentol by unknown mechanism. Use Caution/Monitor. Monitor for stiripentol adverse drug effects

            • sulfadiazine

              cannabidiol will increase the level or effect of sulfadiazine by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • sulfisoxazole

              cannabidiol will increase the level or effect of sulfisoxazole by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • tacrolimus

              cannabidiol will increase the level or effect of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Therapeutic drug monitoring and dose reduction of P-gp substrates should be considered when given orally and concurrently with cannabidiol

            • tamoxifen

              cannabidiol will increase the level or effect of tamoxifen by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • tasimelteon

              cannabidiol, tasimelteon. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • tetracycline

              tetracycline will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • theophylline

              cannabidiol, theophylline. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • thiothixene

              cannabidiol, thiothixene. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • ticlopidine

              ticlopidine will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP2C19 inhibitor.

            • tipranavir

              tipranavir will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

            • tizanidine

              cannabidiol, tizanidine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • tofacitinib

              cannabidiol will increase the level or effect of tofacitinib by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • tolbutamide

              cannabidiol will increase the level or effect of tolbutamide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • torsemide

              cannabidiol will increase the level or effect of torsemide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • tranylcypromine

              tranylcypromine will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

            • treprostinil

              cannabidiol will increase the level or effect of treprostinil by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • tretinoin

              cannabidiol will increase the level or effect of tretinoin by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • trifluoperazine

              cannabidiol, trifluoperazine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • trimethoprim

              cannabidiol will increase the level or effect of trimethoprim by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • trimipramine

              cannabidiol will increase the level or effect of trimipramine by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • velpatasvir

              cannabidiol, velpatasvir. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP2B6 induction and inhibition with the coadministration of CYP2B6 substrates and cannabidiol, consider reducing dosage adjustment of CYP2B6 substrates as clinically appropriate.

              cannabidiol will increase the level or effect of velpatasvir by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • verapamil

              verapamil will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • voriconazole

              voriconazole will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

              voriconazole will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of voriconazole by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

              cannabidiol will increase the level or effect of voriconazole by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • voxilaprevir

              cannabidiol, voxilaprevir. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

              cannabidiol will increase the level or effect of voxilaprevir by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • zafirlukast

              cannabidiol will increase the level or effect of zafirlukast by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            Minor (0)

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              Adverse Effects

              >10% (LGS or DS)

              Infections, all (40-41%)

              Somnolence (23-25%)

              Infection, other (21-25%)

              Decreased appetite (16-22%)

              Diarrhea (9-20%)

              Transaminases elevated (8-16%)

              Rash (7-13%)

              Fatigue, malaise, asthenia (11-12%)

              Infection, viral (7-11%)

              Insomnia (5-11%)

              >10% (TSC)

              Diarrhea (31%)

              Elevated transaminases (25%)

              Decreased appetite (20%)

              Pyrexia (19%)

              Vomiting (17%)

              Somnolence (13%)

              1-10% (LGS or DS)

              Irritability, agitation (5-9%)

              Pneumonia (5-8%)

              Sedation (3-6%)

              Anger, aggression (3-5%)

              Decreased weight (3-5%)

              Gastroenteritis (4%)

              Hypoxia, respiratory failure (3%)

              Infection, fungal (1-3%)

              1-10% (TSC)

              Gait disturbance (9%)

              Nausea (9%)

              Gastroenteritis (8%)

              Ear infection (8%)

              Rash (8%)

              Decreased weight (7%)

              Anemia (7%)

              Decreased platelet count (5%)

              Increased eosinophil count (5%)

              Fatigue, malaise, asthenia (5%)

              Urinary tract infection (5%)

              Pneumonia (4%)

              Rhinorrhea (4%)

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              Warnings

              Contraindications

              Hypersensitivity to cannabidiol or any of the product ingredients

              Cautions

              Can cause somnolence and sedation that is dose-related; clobazam and other CNS depressants, including alcohol, may potentiate this adverse effect; monitor for somnolence and sedation and advise patients not to drive or operate machinery until they have gained sufficient experience on drug to gauge whether it adversely affects their ability to safely drive or operate machinery

              Antiepileptic drugs (AEDs), including cannabidiol, increase risk of suicidal thoughts or behavior in patients taking these drugs for any indication; patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior

              May cause hypersensitivity reactions (eg, pruritus, erythema, angioedema)

              As with other AEDs, cannabidiol should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus; if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered

              Therapy can cause weight loss, which may be dose-related

              A decrease in hemoglobin and hematocrit reported with no effect on red blood indices

              Elevation of serum creatinine reported within 2 weeks of initiating therapy that was reversible in healthy adults; mechanism not determined

              Hepatocellular injury

              • Dose-related liver transaminases (ALT and/or AST) elevations reported, typically within the first 2 months of treatment
              • Majority of ALT elevations occurred when coadministered with valproate and, to a lesser extent, with clobazam
              • In 25 mg/kg/day treated patients with TSC, the incidence of ALT elevations greater than 3 times the ULN was 20% in patients taking both concomitant valproate and clobazam, 25% in patients taking concomitant valproate (without clobazam), 0% in patients taking concomitant clobazam (without valproate), and 6% in patients taking neither drug; consider discontinuation or dose adjustment of valproate or clobazam if liver enzyme elevations occur
              • Obtain serum transaminases before initiating and regularly afterward; consider more frequent monitoring of serum transaminases and bilirubin if also taking valproate or in patients who have elevated liver enzymes at baseline (see Dosing Considerations)
              • Discontinue with transaminase levels >3 x ULN and bilirubin levels >2 x ULN
              • Without bilirubin elevation
                • Evaluate prolonged serum transaminases elevations for other possible causes; consider dosage adjustment of any coadministered medication that is known to affect liver (eg, valproate and clobazam)
                • Discontinue treatment with sustained transaminase elevations of >5 x ULN

              Drug interaction overview

              • Coadministration with other CNS depressants, including alcohol, may increase risk of sedation and somnolence
              • Effect of other drugs on cannabidiol
                • Moderate or strong CYP3A4 or CYP2C19 inhibitors: Consider cannabidiol dose reduction
                • Strong CYP3A4 or CYP2C19 inducers: Consider cannabidiol dose increase
              • Effect of cannabidiol on other drugs
                • UGT1A9, UGT2B7, CYP2C8, CYP2C9, and CYP2C19 substrates: Consider dose reduction of substrates
                • Sensitive CYP2C19 substrates include diazepam and clobazam; coadministration of cannabidiol with clobazam produces a 3-fold increase in plasma concentrations of N-desmethylclobazam, the active metabolite of clobazam
                • Coadministration of cannabidiol and valproate increases the incidence of liver enzyme elevations; discontinuation or reduction of cannabidiol and/or concomitant valproate should be considered
                • CYP1A2 and CYP2B6 substrates may also require dose adjustment
                • No dedicated drug-drug interaction studies have been conducted with mTOR inhibitors (eg, everolimus) or calcineurin inhibitors (eg, tacrolimus); reports in literature suggest cannabidiol administration resulted in increased serum levels of everolimus, sirolimus, or tacrolimus; consider a reduction in dosage of everolimus, sirolimus, or tacrolimus, if adverse reactions known to occur with those medications are experienced when co-administered with cannabidiol
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              Pregnancy

              Pregnancy

              There are no available data regarding use in pregnant women

              Based on animal data, may cause fetal harm

              Animal data

              • Administration of cannabidiol to pregnant animals produced evidence of developmental toxicity (increased embryofetal mortality in rats and decreased fetal body weights in rabbits decreased growth, delayed sexual maturation, long-term neurobehavioral changes, and adverse effects on the reproductive system in rat offspring) at maternal plasma exposures similar to (rabbit) or greater than (rat) that in humans at therapeutic doses

              AED pregnancy registry

              • There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs during pregnancy
              • Encourage women who are taking cannabidiol during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll-free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/

              Lactation

              There are no data on the presence of cannabidiol or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Purified cannabidiol (CBD); the exact mechanism by which CBD produces its anticonvulsant effects is unknown

              Cannabidiol is a structurally novel anticonvulsant; it does not appear to exert its anticonvulsant effects through CB1 receptors, nor through voltage-gated sodium channels

              CBD may exert a cumulative anticonvulsant effect, modulating a number of endogenous systems including, but not limited to, neuronal inhibition (synaptic and extrasynaptic GABA channels), modulation of intracellular calcium (TRPV, VDAC, GPR55), and possible anti-inflammatory effects (adenosine)

              Absorption

              Demonstrated an increase in exposure that was less than dose-proportional over the range of 5-20 mg/kg/day

              Peak plasma time, steady-state: 2.5-5 hr

              Food: High-fat/high-calorie meal increased peak plasma concentration by 5-fold, AUC by 4-fold, and reduced the total variability compared with healthy volunteers

              Distribution

              Protein bound, including metabolites: >94%

              Vd: 20,963-42,849 L

              Metabolism

              Metabolized in the liver and the gut (primarily in the liver) by CYP2C19 and CYP3A4 enzymes, and UGT1A7, UGT1A9, and UGT2B7 isoforms

              After repeat dosing, 7-OH-CBD (active metabolite), has a 38% lower AUC than the parent drug

              The 7-OH-CBD metabolite is converted to 7-COO-CBD, which has ~40-fold higher AUC than the parent drug

              Based on preclinical models of seizure, the 7-OH-CBD metabolite is active; however, the 7-COOH-CBD metabolite is not active

              Elimination

              Half-life: 56-61 hr

              Clearance: 1111 L/hr (single 1500-mg dose)

              Excretion: Mainly feces; minor renal clearance

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              Administration

              Oral Administration

              Food may affect cannabidiol plasma concentration levels; consistent dosing with respect to meals is recommended to reduce variability in cannabidiol plasma exposure

              Measuring dose

              • Administer orally by calibrated oral dosing syringes in order to accurately measure and deliver the prescribed dose
              • Packaged in carton with two 5-mL calibrated oral dosing syringes and a bottle adapter
              • Pharmacy provides 1-mL calibrated oral dosing syringe when doses <1 mL are required
              • Do not use household teaspoon or tablespoon; it is not an adequate measuring device

              Discontinuing

              • Dose should be decreased gradually
              • As with all antiepileptic drugs, avoid abrupt discontinuation when possible, to minimize the risk of increased seizure frequency and status epilepticus

              Storage

              Store solution in its original bottle in an upright position at room temperature 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)

              Do not refrigerate or freeze

              Keep the cap tightly closed

              Use within 12 weeks of first opening the bottle, then discard any remainder

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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              • View the formulary and any restrictions for each plan.
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              • Compare formulary status to other drugs in the same class.
              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.