Cannabidiol is an oral cannabinoid indicated for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. Cannabidiol is a marijuana derivative; however, it lacks the psychoactive properties that are commonly associated with delta-9-tetrahydrocannabinol (THC). Adjunctive cannabidiol treatment significantly reduced seizure frequency in patients with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex, with a reduction in seizures observed within 4 weeks of initiation. In patients with Dravet syndrome, the median percent reduction in monthly convulsive seizures from baseline was 39% for those receiving cannabidiol 20 mg/kg/day vs. 13% for those receiving placebo. During the maintenance period, 6.7% of cannabidiol-treated patients were seizure-free. In patients with Lennox-Gastaut syndrome, the median percent reduction in monthly drop seizure frequency from baseline was 37% for those receiving cannabidiol 10 mg/kg/day, 42% to 44% for those receiving 20 mg/kg/day, and 17% to 22% for those receiving placebo. In patients with tuberous sclerosis complex, the median percent reduction in monthly seizures was 43% for those receiving cannabidiol 25 mg/kg/day and 20% for those receiving placebo. Somnolence, decreased appetite, and diarrhea are among the most common adverse reactions of cannabidiol. Dose-related elevations in liver transaminases can occur, and routine monitoring of hepatic enzymes is necessary.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer consistently either with or without food.
Oral Liquid Formulations
-Measure each dose using the bottle adapter and calibrated oral dosing syringes provided. Two 1 mL and two 5 mL dosing syringes are provided in each carton. Instruct patients on which syringe to use (1 or 5 mL).
-Oral administration is recommended; when necessary, enteral administration via silicone feeding tubes (e.g., nasogastric or gastrostomy tubes) is acceptable. Do not use with tubes made of polyvinyl chloride (PVC) or polyurethane. Avoid use of silicone nasogastric tubes with short lengths and narrow diameters (e.g., less than 50 cm and less than 5 FR).
-If administered via feeding tube, flush the feeding tube with room temperature drinking water after each dose. The recommended volume for flushing is approximately 5-times the priming volume of the tube; however, this may be modified in patients with fluid restrictions.
-Storage: Discard unused solution remaining 12 weeks after first opening the bottle.
Serum creatinine elevations of approximately 10% were observed within 2 weeks of starting cannabidiol in controlled studies. The mechanism has not been determined. The increase was reversible in healthy adults; reversibility was not assessed in patients with epilepsy.
Insomnia/sleep disorder/poor sleep quality (5% to 11%), irritability/agitation (5% to 9%), and aggression/anger (3% to 5%) were reported in cannabidiol-treated patients during clinical trials. Antiepileptic drugs (AEDs) such as cannabidiol increase the risk of suicidal ideation and behavior. Monitor all patients beginning treatment with AEDs or currently receiving such treatment closely for emerging or worsening suicidal thoughts/behavior or depression. Patients and caregivers should be informed of the increased risk of suicidal thoughts and behaviors and should be advised to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with an increased risk of suicidal thoughts and behavior. If suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any patient may be related to the illness being treated. A pooled analysis of 199 placebo-controlled trials including 11 different AEDs showed that patients (5 years of age and older) receiving AEDs had approximately twice the risk of suicidal behavior or ideation (0.43%) as patients receiving placebo (0.24%), with an adjusted relative risk of 1.8 (95% CI 1.2 to 2.7). Four completed suicides occurred in patients treated with AEDs compared to none among controls. The relative risk for suicidality was higher in patients with epilepsy compared to those with other conditions. Age was not a determining factor and risk was generally consistent among all AEDs examined. Suicidal ideation or behavior have occurred as early as 1 week after AED initiation and may occur at any time during treatment.
Cannabidiol causes elevated hepatic enzymes (8% to 25%). Promptly measure serum transaminases and total bilirubin and interrupt or discontinue cannabidiol treatment, as appropriate, if a person develops clinical signs or symptoms suggestive of liver injury (e.g., unexplained nausea, vomiting, right upper quadrant abdominal pain, fatigue, anorexia, jaundice, and/or dark urine). Discontinue cannabidiol in persons with elevated transaminase concentrations more than 3 times the upper limit of normal (ULN) and bilirubin concentrations more than 2 times the ULN or sustained transaminase elevations more than 5 times the ULN. Evaluate persons with prolonged elevations of serum transaminases for other possible causes. Consider dosage adjustment of any concomitant medication that is known to affect the liver. ALT elevations more than 3 times the ULN occurred in 12% to 13% of cannabidiol-treated subjects compared with 1% of subjects given placebo. Elevations more than 20 times the ULN occurred in less than 1% of subjects. Transaminase elevations are dose-related; ALT elevations more than 3 times the ULN occurred in 17% and 12% of subjects taking cannabidiol 20 or 25 mg/kg/day, respectively, compared with 1% of subjects taking 10 mg/kg/day. The risk of ALT elevations was higher (25%) in subjects with tuberous sclerosis complex receiving doses above 25 mg/kg/day during clinical trials. Persons with baseline transaminase elevations and those who are also receiving valproate and/or clobazam are at increased risk for hepatic injury. ALT elevations more than 3 times the ULN occurred in 20% to 30% of subjects taking concomitant valproate and clobazam, 21% to 25% of subjects taking concomitant valproate, 0% to 4% of subjects taking concomitant clobazam, and 3% to 6% of subjects taking cannabidiol alone. When ALT was above ULN at baseline, treatment-emergent elevations more than 3 times the ULN occurred in 11% to 30% of subjects compared to 12% when the ALT was within normal range at baseline in those receiving 20 to 25 mg/kg/day of cannabidiol. No subjects receiving cannabidiol 10 mg/kg/day experienced ALT elevations more than 3 times the ULN when ALT was above the ULN at baseline, compared with 2% of subjects who had ALT within normal range at baseline. Cases of hospitalization related to elevated transaminases have occurred. During clinical trials, serum transaminase elevations typically occurred in the first 2 months of treatment; however, cases were observed up to 18 months after initiation, particularly in subjects taking concomitant valproate. Resolution of laboratory abnormalities occurred with cannabidiol discontinuation or cannabidiol and/or concomitant valproate dosage reduction in approximately two-thirds of cases. In about one-third of cases, resolution occurred during continued cannabidiol treatment without dosage reduction. Cholestatic or mixed patterns of hepatic injury (i.e, based on calculated ratio of [ALT/ULN]/[ALP/ULN] less than 2 and between 2 and 5, respectively) were reported with cannabidiol in postmarketing setting experience. Cases of elevated ammonia concentrations were reported in some cannabidiol-treated persons who also had elevated transaminase concentrations, most often with concomitant use of valproate, clobazam, or both. Consider discontinuation or dose adjustment of valproate or clobazam if hyperammonemia occurs.
Anorexia (16% to 22%), diarrhea (9% to 31%), vomiting (17%), nausea (9%), weight loss (3% to 7%), gastroenteritis (0% to 8%), and abdominal pain/discomfort (3%) were reported in cannabidiol-treated patients during clinical trials. Weight loss of 5% or more from baseline weight occurred in 16% of active-treatment patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS), 31% of active-treatment patients with tuberous sclerosis complex, and 8% of patients receiving placebo. Most gastrointestinal effects appear to be dose-related. Weight loss of 5% or more occurred in 31% of patients treated with cannabidiol 25 mg/kg/day, 18% of patients treated with 20 mg/kg/day, and 9% of patients treated with 10 mg/kg/day.
Drowsiness/somnolence (13% to 25%), lethargy (4% to 8%), sedation (3% to 6%), gait disturbance (2% to 9%), and drooling or hypersalivation (1% to 4%) were reported in cannabidiol-treated patients during clinical trials. Collectively, somnolence, sedation, and lethargy occurred in 32% of cannabidiol-treated patients with Lennox-Gastaut syndrome and Dravet syndrome compared to 11% of patients given placebo. These effects were dose-related (27% with 10 mg/kg/day vs. 34% with 20 mg/kg/day). Patients taking concomitant clobazam experienced more somnolence and sedation (46% of cannabidiol-treated patients taking clobazam vs. 16% of patients not taking clobazam). In patients with tuberous sclerosis complex, the collective incidence of somnolence, sedation, and lethargy was 19% in cannabidiol-treated patients compared to 17% of patients given placebo. The rate was higher in patients on concomitant clobazam (33% of cannabidiol-treated patients taking clobazam vs. 14% of patients not taking clobazam). In general, these effects were more common in early treatment and diminished with continued treatment.
Fatigue, malaise, or asthenia were reported in 5% to 12% of cannabidiol-treated patients during clinical trials.
Hypersensitivity reactions including rash (7% to 13%), pruritus, erythema, and angioedema were reported during clinical trials. Discontinue cannabidiol if a patient develops a hypersensitivity reaction after treatment.
Overall, infection occurred in 40% to 41% of patients with Lennox-Gastaut syndrome and Dravet syndrome who received cannabidiol during clinical trials. Viral infection (7% to 11%), pneumonia (5% to 8%), fungal infection (1% to 3%), and other unspecified infection (21% to 25%) were reported in this population. Pyrexia/fever (19%), pneumonia (4%), ear infection (8%), and urinary tract infection (5%) were reported in cannabidiol-treated patients with tuberous sclerosis complex.
Hypoxia/respiratory failure (3%) and rhinorrhea (4%) were reported in patients who received cannabidiol during clinical trials.
Cannabidiol can cause decreases in hemoglobin and hematocrit. Anemia (7%), decreased platelet count/thrombocytopenia (5%), and increased eosinophil count/eosinophilia (5%) were reported in cannabidiol-treated patients during tuberous sclerosis complex (TSC) trials. New laboratory-defined anemia (defined as normal hemoglobin at baseline with a reported value less than the lower limit of normal at a subsequent time point) developed in 30% (Lennox-Gaustaut syndrome [LGS] or Dravet syndrome [DS]) and 38% (TSC) of cannabidiol-treated patients compared to 13% (LGS or DS) and 15% (TSC) of patients given placebo in controlled trials. The mean decrease in hemoglobin from baseline to end of treatment was -0.42 g/dL (LGS or DS) and -0.37 g/dL (TSC) in cannabidiol-treated patients and -0.03 g/dL (LGS or DS) and -0.07 g/dL (TSC) in patients given placebo. A corresponding decrease in hematocrit, with a mean change of -1.5% (LGS or DS) and -1.2% (TSC) in cannabidiol-treated patients and -0.4% (LGS and DS) and -0.2% (TSC) in patients given placebo was also observed. No effect on red blood cell indices was observed.
Cannabidiol is contraindicated in patients with a history of cannabidiol hypersensitivity, sesame oil hypersensitivity, or hypersensitivity to any of the ingredients in the product. Cannabidiol can cause hypersensitivity reactions. If a patient develops hypersensitivity reactions after treatment with cannabidiol, discontinue the drug.
Monitor all patients beginning treatment with antiepileptic drugs (AEDs) or currently receiving cannabidiol closely for emerging or worsening depression or suicidal ideation. Advise patients and caregivers of the increased risk of suicidal thoughts and behaviors and to immediately report the emergence of new or worsening of depression, suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. AEDs should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with an increased risk of suicidal thoughts and behavior. If suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any patient may be related to the illness being treated. There is an increased risk of suicidal ideation and behavior in patients receiving AEDs to treat epilepsy, psychiatric disorders, or other conditions (e.g., migraine, neuropathic pain). The primary analysis consisted of 199 placebo-controlled clinical studies with a total of 27,863 patients in drug treatment groups and 16,029 patients in placebo groups (5 years of age and older). There were 4 completed suicides among patients in drug treatment groups versus none in the placebo groups. Patients receiving AEDs had approximately twice the risk of suicidal behavior or ideation as patients receiving placebo (0.43% vs. 0.24%, respectively; RR 1.8, 95% CI: 1.2 to 2.7). The relative risk for suicidality was higher in patients with epilepsy compared to those with other conditions; however, the absolute risk differences were similar in trials for epilepsy and psychiatric indications. Age was not a determining factor. The increased risk of suicidal ideation and behavior was observed between 1 and 24 weeks after therapy initiation. However, a longer duration of therapy should not preclude the possibility of an association to the drug since most studies included in the analysis did not continue beyond 24 weeks.
Cannabidiol dosage adjustment is recommended in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic disease. Risk factors for cannabidiol-related serum transaminase elevations include concomitant valproate or clobazam use or baseline transaminase concentrations more than the upper limit of normal (ULN). Obtain serum transaminase (ALT and AST) and total bilirubin concentrations prior to starting cannabidiol treatment, at 1 month, 3 months, and 6 months after initiation, and periodically thereafter or as clinically indicated. Measure serum transaminases and total bilirubin concentrations within 1 month after cannabidiol dose changes or the addition of or changes in medications that are known to impact the liver. Consider more frequent monitoring of serum transaminases and bilirubin in patients who are taking valproate or who have elevated baseline hepatic enzymes. Evaluate patients with elevated baseline transaminase concentrations more than 3 times the ULN accompanied by elevations in bilirubin more than 2 times the ULN prior to cannabidiol treatment. Transaminase elevations of more than 3 times the ULN in the presence of elevated bilirubin without an alternative explanation are an important predictor of severe hepatic injury. If a patient develops clinical signs or symptoms suggestive of liver injury (e.g., unexplained nausea, vomiting, right upper quadrant abdominal pain, fatigue, jaundice, or dark urine), measure serum transaminases and total bilirubin promptly, and interrupt or discontinue cannabidiol treatment, as appropriate. Discontinue cannabidiol in patients with elevated transaminase concentrations more than 3 times the ULN and bilirubin concentrations more than 2 times the ULN or sustained transaminase elevations more than 5 times the ULN. Evaluate patients with prolonged elevations of serum transaminases for other possible causes. Consider dosage adjustment of any concomitant medication that is known to affect the liver. Cannabidiol causes dose-related serum transaminase elevations. Cases of hospitalization related to elevated transaminases in patients taking cannabidiol have occurred. During clinical trials, serum transaminase elevations typically occurred in the first 2 months of cannabidiol treatment; however, cases were observed up to 18 months after initiation, particularly in patients taking concomitant valproate. Cannabidiol discontinuation or cannabidiol and/or concomitant valproate dose reduction resulted in resolution of transaminase elevations in approximately two-thirds of cases. Resolution of transaminase elevations occurred without cannabidiol dose reduction in about one-third of cases.
Cannabidiol can cause sedation and drowsiness. Advise patients to avoid driving or operating machinery or performing other tasks that require mental alertness until they are reasonably certain that cannabidiol does not adversely affect them (e.g., impair judgement, thinking, or motor skills). Other CNS depressants, including alcohol, could potentiate the somnolence and sedation effect of cannabidiol.
Withdraw cannabidiol gradually, in general. As with all antiepileptic drugs, avoid abrupt discontinuation of cannabidiol to minimize the risk of increased seizure frequency and status epilepticus. In the case of a serious adverse event, rapid discontinuation of cannabidiol can be considered.
There are no adequate data on the developmental risks associated with cannabidiol use during human pregnancy. In animal studies, oral administration of cannabidiol to rats throughout organogenesis resulted in embryofetal mortality at a dose of 250 mg/kg/day. The highest no-effect dose for embryofetal toxicity was associated with maternal plasma cannabidiol exposures approximately 16 times those in humans at the recommended human dose (RHD) of 20 mg/kg/day. Decreased growth, delayed sexual maturation, long-term neurobehavioral changes (decreased activity), and adverse effects on the male reproductive system (small testes in adult offspring) and fertility were observed in rats given cannabidiol at doses of 150 to 250 mg/kg/day throughout pregnancy and lactation. The no-effect dose for pre- and postnatal developmental toxicity in rats was associated with maternal plasma cannabidiol exposures approximately 9 times that in humans at the RHD. Administration of cannabidiol (0, 50, 80, or 125 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in decreased fetal body weights and increased fetal structural variations at the highest dose. Maternal plasma cannabidiol exposures at the no-effect level for embryofetal developmental toxicity in rabbits were less than that in humans at the RHD. There are 2 pregnancy exposure registries that monitor outcomes in pregnant persons exposed to cannabidiol. Information about the Epidiolex Pregnancy Surveillance Program can be obtained at www.epidiolexpregnancystudy.com or by calling 1-855-272-7158, and information about the North American Antiepileptic Drug (NAAED) Pregnancy Registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.
There are no data on the presence of cannabidiol or its metabolites in human milk, the effects on the breast-fed infant, or the effects on milk production. Cannabidiol is highly lipophilic, and it is expected to be secreted in human milk. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for cannabidiol and any potential adverse effects on the breast-fed infant from cannabidiol or the underlying maternal condition.
General dosing information:
-Prior to treatment initiation, obtain serum transaminases (ALT and AST) and total bilirubin concentrations in all patients.
-When discontinuing cannabidiol, decrease the dose gradually. Avoid abrupt discontinuation to minimize the risk of increased seizure frequency and status epilepticus.
For the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome:
Oral dosage:
Adults: 2.5 mg/kg/dose PO twice daily; increase in weekly increments of 2.5 mg/kg/dose twice daily as tolerated to the recommended maintenance dosage of 5 mg/kg/dose PO twice daily. Max: 10 mg/kg/dose PO twice daily. If more rapid titration is necessary, increase the dosage no more frequently than every other day.
Children and Adolescents 1 to 17 years: 2.5 mg/kg/dose PO twice daily; increase in weekly increments of 2.5 mg/kg/dose twice daily as tolerated to the recommended maintenance dosage of 5 mg/kg/dose PO twice daily. Max: 10 mg/kg/dose PO twice daily. If more rapid titration is necessary, increase the dosage no more frequently than every other day.
For the treatment of seizures associated with tuberous sclerosis complex (TSC):
Oral dosage:
Adults: 2.5 mg/kg/dose PO twice daily; increase in weekly increments of 2.5 mg/kg/dose twice daily as tolerated to the recommended maintenance dosage of 12.5 mg/kg/dose PO twice daily. If more rapid titration is necessary, increase the dosage no more frequently than every other day. The effectiveness of dosages lower than 12.5 mg/kg/dose twice daily has not been studied in patients with TSC.
Children and Adolescents 1 to 17 years: 2.5 mg/kg/dose PO twice daily; increase in weekly increments of 2.5 mg/kg/dose twice daily as tolerated to the recommended maintenance dosage of 12.5 mg/kg/dose PO twice daily. If more rapid titration is necessary, increase the dosage no more frequently than every other day. The effectiveness of dosages lower than 12.5 mg/kg/dose twice daily has not been studied in patients with TSC.
Maximum Dosage Limits:
-Adults
25 mg/kg/day PO.
-Geriatric
25 mg/kg/day PO.
-Adolescents
25 mg/kg/day PO.
-Children
25 mg/kg/day PO.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Lennox-Gastaut syndrome or Dravet syndrome:
Mild hepatic impairment (Child-Pugh A): No dosage adjustment necessary.
Moderate hepatic impairment (Child-Pugh B): 1.25 mg/kg/dose PO twice daily; titrate to a maintenance dosage of 2.5 to 5 mg/kg/dose PO twice daily. Slower dose titration may be necessary.
Severe hepatic impairment (Child-Pugh C): 0.5 mg/kg/dose PO twice daily; titrate to a maintenance dosage of 1 to 2 mg/kg/dose PO twice daily. Slower dose titration may be necessary.
Tuberous sclerosis complex:
Mild hepatic impairment (Child-Pugh A): No dosage adjustment necessary.
Moderate hepatic impairment (Child-Pugh B): 1.25 mg/kg/dose PO twice daily; titrate to a maintenance dosage of 6.25 mg/kg/dose PO twice daily. Slower dose titration may be necessary.
Severe hepatic impairment (Child-Pugh C): 0.5 mg/kg/dose PO twice daily; titrate to a maintenance dosage of 2.5 mg/kg/dose PO twice daily. Slower dose titration may be necessary.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with cannabidiol. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Consider a dose reduction of caffeine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased caffeine exposure is possible. Caffeine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Acetaminophen; Caffeine: (Moderate) Consider a dose reduction of caffeine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased caffeine exposure is possible. Caffeine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Consider a dose reduction of caffeine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased caffeine exposure is possible. Caffeine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Consider a dose reduction of caffeine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased caffeine exposure is possible. Caffeine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Acetaminophen; Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Acetaminophen; Codeine: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Acetaminophen; Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Ibuprofen: (Moderate) Consider a dose reduction of ibuprofen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased ibuprofen exposure is possible. Ibuprofen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Acetaminophen; Oxycodone: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Acrivastine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Afatinib: (Moderate) If the concomitant use of cannabidiol and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of cannabidiol. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-gp substrate and cannabidiol is a P-gp inhibitor. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
Alfentanil: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Alogliptin; Pioglitazone: (Moderate) Consider a dose reduction of pioglitazone as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased pioglitazone exposure is possible. Pioglitazone is a CYP2C8 substrate. In vitro data predicts inhibition of CYP2C8 by cannabidiol potentially resulting in clinically significant interactions.
Alprazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and alprazolam. CNS depressants can potentiate the effects of cannabidiol.
Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and amitriptyline. Concurrent use may result in additive CNS depression.
Amlodipine; Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with cannabidiol is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Amlodipine; Celecoxib: (Moderate) Consider a dose reduction of celecoxib as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased celecoxib exposure is possible. Celecoxib is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Amobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and amobarbital. CNS depressants can potentiate the effects of cannabidiol.
Amoxapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and amoxapine. CNS depressants can potentiate the effects of cannabidiol.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Consider a dose reduction of omeprazole when coadministered with cannabidiol due to the risk of omeprazole-associated adverse reactions. In vivo data shows cannabidiol is a CYP219 inhibitor; omeprazole is a sensitive 2C19 substrate.
Anagrelide: (Moderate) Monitor for cardiovascular events and titrate the anagrelide dose accordingly when coadministered with cannabidiol. Consider a dose reduction of anagrelide as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased anagrelide exposure is possible. Anagrelide is a CYP1A2 substrate. In vitro data predicts weak inhibition of CYP1A2 by cannabidiol potentially resulting in clinically significant interactions.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Monitor for excessive sedation and somnolence during coadministration. CNS depressants can potentiate the effects of cannabidiol.
Apalutamide: (Moderate) Consider a dose increase of cannabidiol if coadministered with apalutamide. Consider a dose reduction of apalutamide if apalutamide adverse reactions occur. Coadministration may decrease cannabidiol plasma concentrations resulting in a decrease in efficacy and increase apalutamide exposure increasing the risk of adverse effects. Cannabidiol is metabolized by CYP3A4 and CYP2C19; in vitro data predicts cannabidiol inhibits CYP2C8. Apalutamide is a strong inducer of CYP3A4 and CYP2C19 and a substrate of CYP2C8.
Apomorphine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and apomorphine. CNS depressants can potentiate the effects of cannabidiol.
Aripiprazole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and aripiprazole. Concurrent use may result in additive CNS depression.
Asenapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and asenapine. Concurrent use may result in additive CNS depression.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Consider a dose reduction of caffeine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased caffeine exposure is possible. Caffeine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and butalbital. CNS depressants can potentiate the effects of cannabidiol.
Aspirin, ASA; Caffeine: (Moderate) Consider a dose reduction of caffeine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased caffeine exposure is possible. Caffeine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Consider a dose reduction of caffeine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased caffeine exposure is possible. Caffeine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and orphenadrine. CNS depressants can potentiate the effects of cannabidiol.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and carisoprodol. CNS depressants can potentiate the effects of cannabidiol.
Aspirin, ASA; Omeprazole: (Moderate) Consider a dose reduction of omeprazole when coadministered with cannabidiol due to the risk of omeprazole-associated adverse reactions. In vivo data shows cannabidiol is a CYP219 inhibitor; omeprazole is a sensitive 2C19 substrate.
Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with cannabidiol is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Atropine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and atropine. CNS depressants can potentiate the effects of cannabidiol.
Atropine; Difenoxin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and atropine. CNS depressants can potentiate the effects of cannabidiol.
Azelastine: (Major) Avoid concomitant use of cannabidiol with azelastine nasal solution. Concomitant use may cause somnolence, reductions in mental alertness, or additional CNS impairment. Educate patients about the signs and symptoms of CNS depression.
Azelastine; Fluticasone: (Major) Avoid concomitant use of cannabidiol with azelastine nasal solution. Concomitant use may cause somnolence, reductions in mental alertness, or additional CNS impairment. Educate patients about the signs and symptoms of CNS depression.
Baclofen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and baclofen. CNS depressants can potentiate the effects of cannabidiol.
Belladonna; Opium: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and belladonna. CNS depressants can potentiate the effects of cannabidiol.
Bendamustine: (Major) Consider the use of an alternative therapy if cannabidiol treatment is needed in patients receiving bendamustine. Cannabidiol may increase bendamustine exposure, which may increase the risk of adverse reactions (e.g., myelosuppression, infection, hepatotoxicity). Bendamustine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor.
Benzhydrocodone; Acetaminophen: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving cannabidiol. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving cannabidiol. Concurrent use may increase betrixaban exposure resulting in an increased bleeding risk; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a P-gp substrate; cannabidiol is a P-gp inhibitor. Coadministration of other P-gp inhibitors increased betrixaban exposure by 2 to 3-fold.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with cannabidiol may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Bosentan: (Moderate) Consider a dose reduction of bosentan as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased bosentan exposure is possible. Bosentan is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Brexpiprazole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and brexpiprazole. Concurrent use may result in additive CNS depression.
Brompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Brompheniramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Brompheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Bupivacaine; Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with cannabidiol is necessary as concurrent use may increase lidocaine exposure. Consider a dose reduction of lidocaine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Lidocaine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Bupivacaine; Meloxicam: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with cannabidiol is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and cannabidiol is a weak CYP2C9 inhibitor.
Buprenorphine: (Moderate) Concomitant use of mixed opioid agonists/antagonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of mixed opioid agonists/antagonists with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opioid agonist/antagonist is initiated in a patient taking cannabidiol, reduce initial dosage and titrate to clinical response. If cannabidiol is initiated in a patient taking a mixed opioid agonist/antagonist, use a lower initial dose of cannabidiol and titrate to clinical response. Educate patients about the risks and symptoms of excessive CNS depression.
Buprenorphine; Naloxone: (Moderate) Concomitant use of mixed opioid agonists/antagonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of mixed opioid agonists/antagonists with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opioid agonist/antagonist is initiated in a patient taking cannabidiol, reduce initial dosage and titrate to clinical response. If cannabidiol is initiated in a patient taking a mixed opioid agonist/antagonist, use a lower initial dose of cannabidiol and titrate to clinical response. Educate patients about the risks and symptoms of excessive CNS depression.
Bupropion: (Moderate) Consider a dose adjustment of bupropion when coadministered with cannabidiol. Coadministration may alter plasma concentrations of bupropion resulting in an increased risk of adverse reactions and/or decreased efficacy. Bupropion is a substrate of CYP2B6; cannabidiol may inhibit and/or induce CYP2B6 at clinically relevant concentrations.
Bupropion; Naltrexone: (Moderate) Consider a dose adjustment of bupropion when coadministered with cannabidiol. Coadministration may alter plasma concentrations of bupropion resulting in an increased risk of adverse reactions and/or decreased efficacy. Bupropion is a substrate of CYP2B6; cannabidiol may inhibit and/or induce CYP2B6 at clinically relevant concentrations.
Butalbital; Acetaminophen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and butalbital. CNS depressants can potentiate the effects of cannabidiol.
Butalbital; Acetaminophen; Caffeine: (Moderate) Consider a dose reduction of caffeine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased caffeine exposure is possible. Caffeine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and butalbital. CNS depressants can potentiate the effects of cannabidiol.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Consider a dose reduction of caffeine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased caffeine exposure is possible. Caffeine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and butalbital. CNS depressants can potentiate the effects of cannabidiol.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Consider a dose reduction of caffeine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased caffeine exposure is possible. Caffeine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and butalbital. CNS depressants can potentiate the effects of cannabidiol.
Butorphanol: (Moderate) Concomitant use of mixed opioid agonists/antagonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of mixed opioid agonists/antagonists with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opioid agonist/antagonist is initiated in a patient taking cannabidiol, reduce initial dosage and titrate to clinical response. If cannabidiol is initiated in a patient taking a mixed opioid agonist/antagonist, use a lower initial dose of cannabidiol and titrate to clinical response. Educate patients about the risks and symptoms of excessive CNS depression.
Caffeine: (Moderate) Coadministration of cannabidiol and caffeine-containing foods/beverages may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a substrate of CYP1A2; cannabidiol may inhibit and/or induce CYP1A2 at clinically relevant concentrations. (Moderate) Consider a dose reduction of caffeine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased caffeine exposure is possible. Caffeine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor.
Caffeine; Sodium Benzoate: (Moderate) Consider a dose reduction of caffeine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased caffeine exposure is possible. Caffeine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sodium oxybate. CNS depressants can potentiate the effects of cannabidiol.
Capsaicin; Metaxalone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and metaxalone. CNS depressants can potentiate the effects of cannabidiol.
Carbidopa; Levodopa; Entacapone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and entacapone. CNS depressants can potentiate the effects of cannabidiol.
Carbinoxamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Cariprazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and cariprazine. Concurrent use may result in additive CNS depression.
Carisoprodol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and carisoprodol. CNS depressants can potentiate the effects of cannabidiol.
Carvedilol: (Moderate) Consider a dose reduction of carvedilol with increased monitoring for signs of bradycardia or heart block, as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased carvedilol exposure is possible. Carvedilol is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Celecoxib: (Moderate) Consider a dose reduction of celecoxib as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased celecoxib exposure is possible. Celecoxib is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Celecoxib; Tramadol: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Consider a dose reduction of celecoxib as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased celecoxib exposure is possible. Celecoxib is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Central-acting adrenergic agents: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and central-acting adrenergic agents. CNS depressants can potentiate the effects of cannabidiol.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with cannabidiol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with cannabidiol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Chlophedianol; Dexbrompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Chlorcyclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Chlordiazepoxide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and chlordiazepoxide. CNS depressants can potentiate the effects of cannabidiol.
Chlordiazepoxide; Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and amitriptyline. Concurrent use may result in additive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and chlordiazepoxide. CNS depressants can potentiate the effects of cannabidiol.
Chlordiazepoxide; Clidinium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and chlordiazepoxide. CNS depressants can potentiate the effects of cannabidiol.
Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Consider a dose reduction of ibuprofen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased ibuprofen exposure is possible. Ibuprofen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Chlorpheniramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Chlorpheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Chlorpromazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
Chlorzoxazone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and chlorzoxazone. CNS depressants can potentiate the effects of cannabidiol.
Clemastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Clobazam: (Moderate) Consider a dosage reduction of clobazam if adverse reactions known to occur with clobazam are experienced when coadministered with cannabidiol and consider discontinuation or dosage adjustment of clobazam if hepatic enzyme elevations occur. Concomitant use of cannabidiol and clobazam increased the incidence of elevated hepatic enzymes. Pneumonia has been observed more frequently in patients receiving cannabidiol and concomitant clobazam. Additive sedation and somnolence may also occur. Coadministration produces a 3-fold increase in plasma concentrations of N-desmethylclobazam, the active metabolite of clobazam. Clobazam is a CYP2C19 substrate and cannabidiol is a CYP2C19 inhibitor.
Clomipramine: (Moderate) Monitor clomipramine plasma concentrations and consider a dose reduction of clomipramine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased clomipramine exposure is possible. Clomipramine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. Also monitor for excessive sedation and somnolence during coadministration of cannabidiol and clomipramine; additive CNS depression may occur.
Clonazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and clonazepam. CNS depressants can potentiate the effects of cannabidiol.
Clonidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and central-acting adrenergic agents. CNS depressants can potentiate the effects of cannabidiol.
Clorazepate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and clorazepate. CNS depressants can potentiate the effects of cannabidiol.
Clozapine: (Moderate) Consider a clozapine dose reduction if coadministered with cannabidiol and monitor for adverse reactions. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use. Clozapine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. Also monitor for excessive sedation and somnolence during coadministration of cannabidiol and clozapine; additive CNS depression may occur.
Cobimetinib: (Moderate) Monitor for an increase in cobimetinib-related adverse reactions if coadministration with cannabidiol is necessary. Concomitant use may increase cobimetinib exposure. In vitro, cobimetinib is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Codeine: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Guaifenesin: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
Codeine; Promethazine: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
Colchicine: (Major) Avoid concomitant use of colchicine and cannabidiol due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Cyclobenzaprine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and cyclobenzaprine. CNS depressants can potentiate the effects of cannabidiol.
Cyclosporine: (Moderate) Closely monitor cyclosporine whole blood trough concentrations as appropriate and watch for cyclosporine-related adverse reactions if coadministration with cannabidiol is necessary. The dose of cyclosporine may need to be adjusted. Concurrent use may increase cyclosporine exposure causing an increased risk for cyclosporine-related adverse events. Cyclosporine is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Cyproheptadine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Dabigatran: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with cannabidiol is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute and non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Dabrafenib: (Moderate) Consider a dose reduction of dabrafenib as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased dabrafenib exposure is possible. Dabrafenib is a CYP2C8 substrate. In vitro data predicts inhibition of CYP2C8 by cannabidiol potentially resulting in clinically significant interactions.
Dantrolene: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and dantrolene. CNS depressants can potentiate the effects of cannabidiol.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with cannabidiol may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Desflurane: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and halogenated anesthetics. CNS depressants can potentiate the effects of cannabidiol.
Desipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and desipramine. Concurrent use may result in additive CNS depression.
Deutetrabenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and deutetrabenazine. CNS depressants can potentiate the effects of cannabidiol.
Dexbrompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Dexchlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Dexmedetomidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and dexmedetomidine. CNS depressants can potentiate the effects of cannabidiol.
Dextromethorphan; Bupropion: (Moderate) Consider a dose adjustment of bupropion when coadministered with cannabidiol. Coadministration may alter plasma concentrations of bupropion resulting in an increased risk of adverse reactions and/or decreased efficacy. Bupropion is a substrate of CYP2B6; cannabidiol may inhibit and/or induce CYP2B6 at clinically relevant concentrations.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Diazepam: (Moderate) Consider a dose reduction of diazepam as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Additive sedation and somnolence may occur. Increased diazepam exposure is possible. Diazepam is a CYP2C19 substrate. In vitro data predicts inhibition of CYP2C19 by cannabidiol potentially resulting in clinically significant interactions.
Diclofenac: (Moderate) Consider a dose reduction of diclofenac as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased diclofenac exposure is possible. Diclofenac is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Diclofenac; Misoprostol: (Moderate) Consider a dose reduction of diclofenac as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased diclofenac exposure is possible. Diclofenac is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Diflunisal: (Moderate) Consider a dose reduction of diflunisal as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased diflunisal exposure is possible. Diflunisal is a UGT1A9 substrate. In vitro data predicts inhibition of UGT1A9 by cannabidiol potentially resulting in clinically significant interactions.
Digoxin: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing cannabidiol. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and cannabidiol is a P-gp inhibitor.
Dimenhydrinate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Diphenhydramine; Ibuprofen: (Moderate) Consider a dose reduction of ibuprofen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased ibuprofen exposure is possible. Ibuprofen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Diphenhydramine; Naproxen: (Moderate) Consider a dose reduction of naproxen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased naproxen exposure is possible. Naproxen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Diphenhydramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Diphenoxylate; Atropine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and atropine. CNS depressants can potentiate the effects of cannabidiol.
Dolutegravir: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with cannabidiol. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with cannabidiol. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Dolutegravir; Rilpivirine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with cannabidiol. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with cannabidiol may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Doxepin: (Moderate) Consider a dose reduction of doxepin as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased doxepin exposure is possible. Doxepin is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. Also monitor for excessive sedation and somnolence during coadministration of cannabidiol and doxepin; additive CNS depression may occur.
Doxorubicin Liposomal: (Major) Avoid coadministration of cannabidiol with doxorubicin due to the risk for increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a P-gp substrate and cannabidiol is a P-gp inhibitor. Concurrent use of P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of cannabidiol with doxorubicin due to the risk for increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a P-gp substrate and cannabidiol is a P-gp inhibitor. Concurrent use of P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxylamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Doxylamine; Pyridoxine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Dronabinol: (Moderate) Concomitant use of dronabinol and cannabidiol may increase dronabinol exposure and/or result in additive CNS depression and increased seizure risk. Monitor for excessive sedation and somnolence, and consider a dronabinol dose reduction. Monitor patients with a history of seizures for worsened seizure control. Dronabinol is a CYP2C9 substrate; cannabidiol is a CYP2C9 inhibitor.
Droperidol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and droperidol. CNS depressants can potentiate the effects of cannabidiol.
Edoxaban: (Major) Consider an edoxaban dosage reduction for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism (PE) if concomitant use of cannabidiol is necessary. Concomitant use may increase edoxaban exposure; edoxaban is a P-gp substrate and cannabidiol is a P-gp inhibitor. An edoxaban dose reduction to 30 mg PO once daily is recommended by the manufacturer for use with certain P-gp inhibitors; however, because use of concomitant P-gp inhibitors was limited to only certain drugs that inhibit P-gp in DVT/PE clinical trials, clinicians should use professional judgment and guide edoxaban dose adjustments based on patient response if coadministered with cannabidiol. Based on clinical experience in patients with non-valvular atrial fibrillation no dose reduction is recommended for concomitant use of cannabidiol. Increased concentrations of edoxaban may occur during concomitant use of cannabidiol; monitor for increased adverse effects of edoxaban.
Efavirenz: (Moderate) Consider a dose adjustment of efavirenz when coadministered with cannabidiol due to an increased risk of adverse reactions and/or decreased efficacy. Efavirenz is a CYP2B6 substrate; cannabidiol may induce or inhibit CYP2B6.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with cannabidiol may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and cannabidiol is a P-gp inhibitor. (Moderate) Consider a dose adjustment of efavirenz when coadministered with cannabidiol due to an increased risk of adverse reactions and/or decreased efficacy. Efavirenz is a CYP2B6 substrate; cannabidiol may induce or inhibit CYP2B6.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with cannabidiol may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and cannabidiol is a P-gp inhibitor. (Moderate) Consider a dose adjustment of efavirenz when coadministered with cannabidiol due to an increased risk of adverse reactions and/or decreased efficacy. Efavirenz is a CYP2B6 substrate; cannabidiol may induce or inhibit CYP2B6.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with cannabidiol may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with cannabidiol may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with cannabidiol may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with cannabidiol may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with cannabidiol may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with cannabidiol may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Encorafenib: (Moderate) Consider a dose increase of cannabidiol if coadministered with encorafenib. Coadministration may decrease cannabidiol plasma concentrations resulting in a decrease in efficacy. Cannabidiol is metabolized by CYP3A; encorafenib is a strong inducer of CYP3A.
Entacapone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and entacapone. CNS depressants can potentiate the effects of cannabidiol.
Enzalutamide: (Moderate) Consider a dose increase of cannabidiol if coadministered with enzalutamide. Coadministration may decrease cannabidiol plasma concentrations resulting in a decrease in efficacy. Cannabidiol is metabolized by CYP3A4; enzalutamide is a strong inducer of CYP3A4.
Ergotamine; Caffeine: (Moderate) Consider a dose reduction of caffeine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased caffeine exposure is possible. Caffeine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor.
Esketamine: (Moderate) Closely monitor patients receiving esketamine and cannabidiol for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Estazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and estazolam. CNS depressants can potentiate the effects of cannabidiol.
Eszopiclone: (Moderate) Monitor for excessive sedation and somnolence during coadministration. CNS depressants can potentiate the effects of cannabidiol.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression. Alcohol has also been observed to increase cannabidiol exposure with a 93% increase in Cmax and a 63% greater AUC.
Etomidate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and etomidate. CNS depressants can potentiate the effects of cannabidiol.
Etravirine: (Moderate) Consider a dose reduction of etravirine as clinically appropriate, if etravirine-related adverse reactions occur when administered with cannabidiol. Etravirine a substrate of CYP2C9 and CYP2C19; cannabidiol has the potential to inhibit these isoenzymes.
Everolimus: (Moderate) Monitor everolimus whole blood concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with cannabidiol is necessary. The dose of everolimus may need to be reduced. If everolimus is initiated in a patient receiving a stable dose of cannabidiol, consider a lower starting dose of everolimus especially in patients at increased risk for adverse effects. Coadministration of cannabidiol and everolimus results in an approximately 2.5-fold increase in everolimus exposure.
Ezetimibe; Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with cannabidiol is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and cannabidiol. Concurrent use may result in additive CNS depression.
Fenofibrate: (Moderate) Consider a dose reduction of fenofibrate as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased fenofibrate exposure is possible. Fenofibrate is a UGT1A9 substrate. In vitro data predicts inhibition of UGT1A9 by cannabidiol potentially resulting in clinically significant interactions.
Fentanyl: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Fezolinetant: (Contraindicated) Concomitant use of fezolinetant and cannabidiol is contraindicated due to the risk of increased fezolinetant exposure which may increase the risk of fezolinetant-related adverse effects. Fezolinetant is a CYP1A2 substrate; cannabidiol is a weak CYP1A2 inhibitor. Concomitant use with another weak CYP1A2 inhibitor increased fezolinetant overall exposure by 100%.
Flibanserin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and flibanserin. CNS depressants can potentiate the effects of cannabidiol.
Fluphenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
Flurazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and flurazepam. CNS depressants can potentiate the effects of cannabidiol.
Flurbiprofen: (Moderate) Consider a dose reduction of flurbiprofen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased flurbiprofen exposure is possible. Flurbiprofen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosphenytoin: (Moderate) Consider a dose increase of cannabidiol and monitor serum phenytoin concentrations if coadministered. Consider a dose reduction of fosphenytoin if fosphenytoin adverse reactions occur. Coadministration may decrease cannabidiol plasma concentrations resulting in a decrease in efficacy and increase phenytoin exposure resulting in increased adverse effects. Cannabidiol is metabolized by CYP3A4; in vitro data predicts inhibition of CYP2C9 by cannabidiol. Phenytoin is a strong inducer of CYP3A4 and is a CYP2C9 substrate.
Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and gabapentin. Concurrent use may result in additive CNS depression.
Gemfibrozil: (Moderate) Consider a dose reduction of gemfibrozil as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased gemfibrozil exposure is possible. Gemfibrozil is a UGT2B7 substrate. In vitro data predicts inhibition of UGT2B7 by cannabidiol potentially resulting in clinically significant interactions.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with coadministration of glecaprevir and cannabidiol as increased plasma concentrations of glecaprevir may occur resulting in increased risk of glecaprevir-related adverse events. Glecaprevir is a substrate of P-gp and cannabidiol is a P-gp inhibitor. (Moderate) Monitor for an increase in pibrentasvir-related adverse effects if concomitant use of cannabidiol is necessary. Concomitant use may increase pibrentasvir exposure. Pibrentasvir is a substrate of P-gp and cannabidiol is a P-gp inhibitor.
Glimepiride: (Moderate) Consider a dose reduction of glimepride as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased glimepride exposure is possible. Glimepiride is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Glipizide: (Moderate) Consider a dose reduction of glipizide as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased glipizide exposure is possible. Glipizide is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Glipizide; Metformin: (Moderate) Consider a dose reduction of glipizide as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased glipizide exposure is possible. Glipizide is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Glyburide: (Moderate) Consider a dose reduction of glyburide as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased glyburide exposure is possible. Glyburide is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Glyburide; Metformin: (Moderate) Consider a dose reduction of glyburide as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased glyburide exposure is possible. Glyburide is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Guanfacine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and central-acting adrenergic agents. CNS depressants can potentiate the effects of cannabidiol.
Halogenated Anesthetics: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and halogenated anesthetics. CNS depressants can potentiate the effects of cannabidiol.
Haloperidol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and haloperidol. CNS depressants can potentiate the effects of cannabidiol.
Homatropine; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydrocodone: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Consider a dose reduction of ibuprofen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased ibuprofen exposure is possible. Ibuprofen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking cannabidiol. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydromorphone: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydroxyzine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Ibuprofen: (Moderate) Consider a dose reduction of ibuprofen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased ibuprofen exposure is possible. Ibuprofen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Ibuprofen; Famotidine: (Moderate) Consider a dose reduction of ibuprofen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased ibuprofen exposure is possible. Ibuprofen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Ibuprofen; Oxycodone: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Consider a dose reduction of ibuprofen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased ibuprofen exposure is possible. Ibuprofen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Ibuprofen; Pseudoephedrine: (Moderate) Consider a dose reduction of ibuprofen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased ibuprofen exposure is possible. Ibuprofen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Iloperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and iloperidone. Concurrent use may result in additive CNS depression.
Imipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and imipramine. Concurrent use may result in additive CNS depression.
Indomethacin: (Moderate) Consider a dose reduction of indomethacin as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased indomethacin exposure is possible. Indomethacin is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Isoflurane: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and halogenated anesthetics. CNS depressants can potentiate the effects of cannabidiol.
Ketamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and ketamine. CNS depressants can potentiate the effects of cannabidiol.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with cannabidiol may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Lamotrigine: (Moderate) Consider a dose reduction of lamotrigine, as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased lamotrigine exposure is possible. Lamotrigine is a UGT2B7 substrate. In vitro data predicts inhibition of UGT2B7 by cannabidiol potentially resulting in clinically significant interactions.
Lapatinib: (Moderate) Monitor for an increase in lapatinib-related adverse reactions if coadministration with cannabidiol is necessary. Lapatinib is a P-gp substrate and cannabidiol is a P-gp inhibitor. Increased plasma concentrations of lapatinib are likely.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and cannabidiol. Concurrent use may result in additive CNS depression.
Lefamulin: (Major) Avoid coadministration of cannabidiol with oral lefamulin unless the benefits outweigh the risks as concurrent use may increase lefamulin exposure and adverse effects; cannabidiol may be administered with intravenous lefamulin. Lefamulin is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and cannabidiol. Dosage adjustments of lemborexant and cannabidiol may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with cannabidiol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Levorphanol: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with cannabidiol is necessary as concurrent use may increase lidocaine exposure. Consider a dose reduction of lidocaine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Lidocaine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Lidocaine; Epinephrine: (Moderate) Monitor for lidocaine toxicity if coadministration with cannabidiol is necessary as concurrent use may increase lidocaine exposure. Consider a dose reduction of lidocaine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Lidocaine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Lidocaine; Prilocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with cannabidiol is necessary as concurrent use may increase lidocaine exposure. Consider a dose reduction of lidocaine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Lidocaine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Lofexidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration. Cannabidiol may potentiate the sedative effects of lofexidine.
Lonafarnib: (Major) Avoid coadministration of lonafarnib and cannabidiol; concurrent use may increase the exposure of lonafarnib and the risk of adverse effects. If coadministration is unavoidable, closely monitor patients for lonafarnib-related adverse reactions. Lonafarnib is a CYP2C9 substrate and cannabidiol is a CYP2C9 inhibitor.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest) if coadministered with cannabidiol. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and cannabidiol is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest) if coadministered with cannabidiol. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and cannabidiol is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lorazepam: (Moderate) Monitor for an increase in lorazepam-related adverse reactions and consider reducing the dose of lorazepam if concomitant use of lorazepam and cannabidiol is necessary. Avoid lorazepam extended-release capsules and utilize lorazepam immediate-release dosage forms that can be easily titrated. Lorazepam is a UGT2B7 substrate. In vitro data predicts inhibition of UGT2B7 by cannabidiol, potentially resulting in clinically significant interactions.
Lovastatin: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with cannabidiol is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Loxapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and loxapine. CNS depressants can potentiate the effects of cannabidiol.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and lumateperone. Concurrent use may result in additive CNS depression.
Lurasidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and lurasidone. Concurrent use may result in additive CNS depression.
Maprotiline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and maprotiline. CNS depressants can potentiate the effects of cannabidiol.
Maraviroc: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with cannabidiol is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Meclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Mefloquine: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of cannabidiol is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Melatonin: (Moderate) Consider a dose reduction of melatonin as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased melatonin exposure is possible. Melatonin is a sensitive CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. Also monitor for excessive sedation and somnolence during coadministration of cannabidiol and melatonin; additive CNS depression may occur.
Meloxicam: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with cannabidiol is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and cannabidiol is a weak CYP2C9 inhibitor.
Meperidine: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Meprobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration. CNS depressants can potentiate the effects of cannabidiol.
Metaxalone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and metaxalone. CNS depressants can potentiate the effects of cannabidiol.
Metformin; Repaglinide: (Moderate) Consider a dose reduction of repaglinide as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased repaglinide exposure is possible. Repaglinide is a CYP2C8 substrate. In vitro data predicts inhibition of CYP2C8 by cannabidiol potentially resulting in clinically significant interactions.
Methadone: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Additionally, increased methadone exposure is possible. Methadone is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Methocarbamol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and methocarbamol. CNS depressants can potentiate the effects of cannabidiol.
Methohexital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and methohexital. CNS depressants can potentiate the effects of cannabidiol.
Methyldopa: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and central-acting adrenergic agents. CNS depressants can potentiate the effects of cannabidiol.
Metoclopramide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and metoclopramide. CNS depressants can potentiate the effects of cannabidiol.
Mexiletine: (Moderate) Consider a dose reduction of mexiletine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased mexiletine exposure is possible. Mexiletine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. The clearance of mexiletine was decreased by 38% after the administration of another CYP1A2 inhibitor.
Midazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and midazolam. CNS depressants can potentiate the effects of cannabidiol.
Mirtazapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and mirtazapine. CNS depressants can potentiate the effects of cannabidiol.
Molindone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and molindone. CNS depressants can potentiate the effects of cannabidiol.
Morphine: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Monitor for adverse reactions, including hypotension, sedation, and respiratory depression and decrease the dose of morphine as necessary. In addition, morphine is a P-gp and UGT2B7 substrate and cannabidiol is a P-gp and UGT2B7 inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold.
Morphine; Naltrexone: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Monitor for adverse reactions, including hypotension, sedation, and respiratory depression and decrease the dose of morphine as necessary. In addition, morphine is a P-gp and UGT2B7 substrate and cannabidiol is a P-gp and UGT2B7 inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold.
Nabilone: (Major) Monitor for excessive sedation and somnolence during coadministration of nabilone and cannabidiol. The use of nabilone with other cannabinoids is to be avoided and is not recommended. Consider an alternative agent to nabilone. Concurrent use may result in additive CNS depression.
Nalbuphine: (Moderate) Concomitant use of mixed opioid agonists/antagonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of mixed opioid agonists/antagonists with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opioid agonist/antagonist is initiated in a patient taking cannabidiol, reduce initial dosage and titrate to clinical response. If cannabidiol is initiated in a patient taking a mixed opioid agonist/antagonist, use a lower initial dose of cannabidiol and titrate to clinical response. Educate patients about the risks and symptoms of excessive CNS depression.
Naldemedine: (Moderate) Monitor for naldemedine-related adverse reactions if coadministered with cannabidiol. Naldemedine plasma concentrations may increase during concomitant use. Naldemedine is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with cannabidiol is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and cannabidiol is a weak CYP2C8 inhibitor.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and cannabidiol. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Naproxen: (Moderate) Consider a dose reduction of naproxen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased naproxen exposure is possible. Naproxen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Naproxen; Esomeprazole: (Moderate) Consider a dose reduction of naproxen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased naproxen exposure is possible. Naproxen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Naproxen; Pseudoephedrine: (Moderate) Consider a dose reduction of naproxen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased naproxen exposure is possible. Naproxen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Nateglinide: (Moderate) Monitor for an increase in nateglinide-related adverse effects, such as hypoglycemia, if concomitant use with cannabidiol is necessary; a nateglinide dosage reduction may be required. Concomitant use may increase nateglinide exposure. Nateglinide is a CYP2C9 substrate and cannabidiol is a CYP2C9 inhibitor.
Nortriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and nortriptyline. Concurrent use may result in additive CNS depression.
Olanzapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and olanzapine. Concurrent use may result in additive CNS depression.
Olanzapine; Fluoxetine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and olanzapine. Concurrent use may result in additive CNS depression.
Olanzapine; Samidorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and olanzapine. Concurrent use may result in additive CNS depression.
Oliceridine: (Moderate) Concomitant use of oliceridine with cannabidiol may cause excessive sedation and somnolence. Limit the use of oliceridine with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Omeprazole: (Moderate) Consider a dose reduction of omeprazole when coadministered with cannabidiol due to the risk of omeprazole-associated adverse reactions. In vivo data shows cannabidiol is a CYP219 inhibitor; omeprazole is a sensitive 2C19 substrate.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Consider a dose reduction of omeprazole when coadministered with cannabidiol due to the risk of omeprazole-associated adverse reactions. In vivo data shows cannabidiol is a CYP219 inhibitor; omeprazole is a sensitive 2C19 substrate.
Omeprazole; Sodium Bicarbonate: (Moderate) Consider a dose reduction of omeprazole when coadministered with cannabidiol due to the risk of omeprazole-associated adverse reactions. In vivo data shows cannabidiol is a CYP219 inhibitor; omeprazole is a sensitive 2C19 substrate.
Opiate Agonists-Antagonists: (Moderate) Concomitant use of mixed opioid agonists/antagonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of mixed opioid agonists/antagonists with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opioid agonist/antagonist is initiated in a patient taking cannabidiol, reduce initial dosage and titrate to clinical response. If cannabidiol is initiated in a patient taking a mixed opioid agonist/antagonist, use a lower initial dose of cannabidiol and titrate to clinical response. Educate patients about the risks and symptoms of excessive CNS depression.
Opicapone: (Moderate) Opicapone should be given cautiously with other agents that cause CNS depression, including cannabidiol, due to the possibility of additive sedation. COMT inhibitors, such as cannabidiol, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Orphenadrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and orphenadrine. CNS depressants can potentiate the effects of cannabidiol.
Oxazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and oxazepam. CNS depressants can potentiate the effects of cannabidiol.
Oxycodone: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Oxymorphone: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Paliperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and paliperidone. Concurrent use may result in additive CNS depression.
Pazopanib: (Major) Avoid coadministration of pazopanib and cannabidiol due to the potential for increased pazopanib exposure. Pazopanib is a P-gp substrate; cannabidiol is a P-gp inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp.
Pentazocine: (Moderate) Concomitant use of mixed opioid agonists/antagonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of mixed opioid agonists/antagonists with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opioid agonist/antagonist is initiated in a patient taking cannabidiol, reduce initial dosage and titrate to clinical response. If cannabidiol is initiated in a patient taking a mixed opioid agonist/antagonist, use a lower initial dose of cannabidiol and titrate to clinical response. Educate patients about the risks and symptoms of excessive CNS depression.
Pentazocine; Naloxone: (Moderate) Concomitant use of mixed opioid agonists/antagonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of mixed opioid agonists/antagonists with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opioid agonist/antagonist is initiated in a patient taking cannabidiol, reduce initial dosage and titrate to clinical response. If cannabidiol is initiated in a patient taking a mixed opioid agonist/antagonist, use a lower initial dose of cannabidiol and titrate to clinical response. Educate patients about the risks and symptoms of excessive CNS depression.
Pentobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and pentobarbital. CNS depressants can potentiate the effects of cannabidiol.
Perampanel: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and perampanel. CNS depressants can potentiate the effects of cannabidiol.
Perphenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
Perphenazine; Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and amitriptyline. Concurrent use may result in additive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and cannabidiol due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If cannabidiol is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of cannabidiol. Pexidartinib is a UGT substrate; cannabidiol is a UGT inhibitor. Coadministration of another UGT inhibitor increased pexidartinib exposure by 60%.
Phenobarbital: (Moderate) Consider a dose increase of cannabidiol if coadministered with phenobarbital. Consider a dosage reduction of phenobarbital as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Additive sedation and somnolence may occur. Coadministration may decrease cannabidiol plasma concentrations resulting in a decrease in efficacy and increase phenobarbital exposure resulting in adverse effects. Cannabidiol is metabolized by CYP3A4; in vitro data predicts inhibition of CYP2C9 by cannabidiol. Phenobarbital is a strong inducer of CYP3A4 and is metabolized by CYP2C9.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Consider a dose increase of cannabidiol if coadministered with phenobarbital. Consider a dosage reduction of phenobarbital as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Additive sedation and somnolence may occur. Coadministration may decrease cannabidiol plasma concentrations resulting in a decrease in efficacy and increase phenobarbital exposure resulting in adverse effects. Cannabidiol is metabolized by CYP3A4; in vitro data predicts inhibition of CYP2C9 by cannabidiol. Phenobarbital is a strong inducer of CYP3A4 and is metabolized by CYP2C9. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and atropine. CNS depressants can potentiate the effects of cannabidiol. (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and scopolamine. CNS depressants can potentiate the effects of cannabidiol.
Phenothiazines: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
Phenytoin: (Moderate) Consider a dose increase of cannabidiol and monitor serum phenytoin concentrations if coadministered. Consider a dose reduction of phenytoin if phenytoin adverse reactions occur. Coadministration may decrease cannabidiol plasma concentrations resulting in a decrease in efficacy and increase phenytoin exposure resulting in increased adverse effects. Cannabidiol is metabolized by CYP3A4; in vitro data predicts inhibition of CYP2C9 by cannabidiol. Phenytoin is a strong inducer of CYP3A4 and is a CYP2C9 substrate.
Pimavanserin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and pimavanserin. CNS depressants can potentiate the effects of cannabidiol.
Pimozide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and pimozide. CNS depressants can potentiate the effects of cannabidiol.
Pioglitazone: (Moderate) Consider a dose reduction of pioglitazone as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased pioglitazone exposure is possible. Pioglitazone is a CYP2C8 substrate. In vitro data predicts inhibition of CYP2C8 by cannabidiol potentially resulting in clinically significant interactions.
Pioglitazone; Glimepiride: (Moderate) Consider a dose reduction of glimepride as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased glimepride exposure is possible. Glimepiride is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions. (Moderate) Consider a dose reduction of pioglitazone as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased pioglitazone exposure is possible. Pioglitazone is a CYP2C8 substrate. In vitro data predicts inhibition of CYP2C8 by cannabidiol potentially resulting in clinically significant interactions.
Pioglitazone; Metformin: (Moderate) Consider a dose reduction of pioglitazone as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased pioglitazone exposure is possible. Pioglitazone is a CYP2C8 substrate. In vitro data predicts inhibition of CYP2C8 by cannabidiol potentially resulting in clinically significant interactions.
Piroxicam: (Moderate) Consider a dose reduction of piroxicam as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased piroxicam exposure is possible. Piroxicam is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Pitavastatin: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with cannabidiol is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Posaconazole: (Moderate) Monitor for an increase in posaconazole-related adverse reactions if coadministration with cannabidiol is necessary. Concomitant use may increase posaconazole exposure. Posaconazole is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Pralsetinib: (Major) Avoid concomitant use of cannabidiol with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and cannabidiol is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Pramipexole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and pramipexole. CNS depressants can potentiate the effects of cannabidiol.
Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and pregabalin. Concurrent use may result in additive CNS depression.
Primidone: (Moderate) Consider a dose increase of cannabidiol if coadministered with primidone. Consider a dosage reduction of primidone as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Additive sedation and somnolence may occur. Coadministration may decrease cannabidiol plasma concentrations resulting in a decrease in efficacy and increase primidone exposure resulting in adverse effects. Cannabidiol is metabolized by CYP3A4; in vitro data predicts inhibition of CYP2C9 by cannabidiol. Primidone is a strong inducer of CYP3A4 and is metabolized by CYP2C9.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and cannabidiol due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Prochlorperazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
Promethazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
Promethazine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
Promethazine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
Propafenone: (Moderate) Coadministration of cannabidiol may increase propafenone concentrations, which may lead to cardiac arrhythmias. Consider a dose reduction of propafenone as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Propafenone is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor.
Propofol: (Moderate) Consider a dose reduction of propofol as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased propofol exposure is possible. Additive somnolence and sedation may occur. Propofol is a UGT1A9 substrate. In vitro data predicts inhibition of UGT1A9 by cannabidiol potentially resulting in clinically significant interactions.
Propranolol: (Moderate) Use caution when propranolol is administered with cannabidiol due to possible increased propranolol concentrations. Consider a dose reduction of propranolol as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Propranolol is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor.
Protriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and protriptyline. Concurrent use may result in additive CNS depression.
Pseudoephedrine; Triprolidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Quazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and quazepam. CNS depressants can potentiate the effects of cannabidiol.
Quetiapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and quetiapine. Concurrent use may result in additive CNS depression.
Ramelteon: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and ramelteon. CNS depressants can potentiate the effects of cannabidiol.
Ranolazine: (Moderate) Monitor for an increase in ranolazine-related adverse reactions if coadministration with cannabidiol is necessary and consider a ranolazine dosage adjustment. Concomitant use may increase ranolazine exposure. Ranolazine is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Rasagiline: (Moderate) Monitor for dopaminergic adverse effects during concurrent use of rasagiline and cannabidiol. Coadministration may result in increased rasagiline concentrations. A dose reduction of rasagiline may be necessary. Rasagiline is primarily metabolized by CYP1A2. In vitro data predicts weak inhibition of CYP1A2 by cannabidiol potentially resulting in clinically significant interactions. When administered with a strong CYP1A2 inhibitor, the AUC of rasagiline was increased by 83%.
Relugolix: (Major) Avoid concomitant use of relugolix and oral cannabidiol. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer cannabidiol at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of cannabidiol is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral cannabidiol. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer cannabidiol at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of cannabidiol is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Remifentanil: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Repaglinide: (Moderate) Consider a dose reduction of repaglinide as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased repaglinide exposure is possible. Repaglinide is a CYP2C8 substrate. In vitro data predicts inhibition of CYP2C8 by cannabidiol potentially resulting in clinically significant interactions.
Repotrectinib: (Major) Avoid coadministration of repotrectinib with cannabidiol due to increased repotrectinib exposure which may increase the risk for repotrectinib-related adverse effects. Repotrectinib is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with cannabidiol is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and cannabidiol is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with cannabidiol; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Risperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and risperidone. Concurrent use may result in additive CNS depression.
Ropinirole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and ropinirole. CNS depressants can potentiate the effects of cannabidiol.
Rosiglitazone: (Moderate) Consider a dose reduction of rosiglitazone as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased rosiglitazone exposure is possible. Rosiglitazone is a CYP2C8 substrate. In vitro data predicts inhibition of CYP2C8 by cannabidiol potentially resulting in clinically significant interactions.
Rotigotine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and rotigotine. CNS depressants can potentiate the effects of cannabidiol.
Rufinamide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and rufinamide. CNS depressants can potentiate the effects of cannabidiol.
Saquinavir: (Moderate) Monitor for an increase in saquinavir-related adverse reactions if coadministration with cannabidiol is necessary. Concomitant use may increase saquinavir exposure. Saquinavir is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Scopolamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and scopolamine. CNS depressants can potentiate the effects of cannabidiol.
Secobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and secobarbital. CNS depressants can potentiate the effects of cannabidiol.
Sedating H1-blockers: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Selexipag: (Moderate) Consider a dose reduction of selexipag as clinically appropriate if adverse reactions occur when administered with cannabidiol. Increased exposure to the active metabolite of selexipag is possible. Selexipag is a CYP2C8 substrate. In vitro data predicts inhibition of CYP2C8 by cannabidiol potentially resulting in clinically significant interactions.
Sevoflurane: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and halogenated anesthetics. CNS depressants can potentiate the effects of cannabidiol.
Silodosin: (Major) Avoid coadministration of silodosin and cannabidiol due to the potential for increased silodosin exposure. In vitro data indicate that silodosin is a P-glycoprotein substrate; cannabidiol is a P-gp inhibitor.
Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with cannabidiol is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of cannabidiol. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Sodium Oxybate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sodium oxybate. CNS depressants can potentiate the effects of cannabidiol.
Stiripentol: (Moderate) Monitor for stiripentol-related adverse reactions during coadministration with cannabidiol. Concomitant use causes an increase in stiripentol exposure. Coadministration increased stiripentol Cmax and AUC by 28% and 55%, respectively, in healthy volunteers and 17% and 30%, respectively, in patients with epilepsy. Also monitor for excessive sedation and somnolence during coadministration of cannabidiol and stiripentol; additive CNS depression may occur.
Sufentanil: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Sumatriptan; Naproxen: (Moderate) Consider a dose reduction of naproxen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased naproxen exposure is possible. Naproxen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Suvorexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and suvorexant. CNS depressants can potentiate the effects of cannabidiol.
Tacrolimus: (Moderate) Monitor tacrolimus serum concentrations as appropriate and watch for tacrolimus-related adverse reactions if coadministration with cannabidiol is necessary. The dose of tacrolimus may need to be reduced. Concomitant use is expected to increase tacrolimus overall exposure.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with cannabidiol is necessary. Talazoparib is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Tapentadol: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Tasimelteon: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and tasimelteon. CNS depressants can potentiate the effects of cannabidiol.
Temazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and temazepam. CNS depressants can potentiate the effects of cannabidiol.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with cannabidiol is necessary due to the risk of increased temsirolimus exposure. Temsirolimus is a P-gp substrate and cannabidiol is a P-gp inhibitor. Coadministration is likely to increase plasma concentrations of temsirolimus.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with cannabidiol may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with cannabidiol may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with cannabidiol may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Tetrabenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and tetrabenazine. CNS depressants can potentiate the effects of cannabidiol.
Thalidomide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and thalidomide. CNS depressants can potentiate the effects of cannabidiol.
Theophylline, Aminophylline: (Moderate) Monitor theophylline concentrations during coadministration with cannabidiol. Consider a dose reduction of theophylline as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased theophylline exposure is possible. Theophylline is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor.
Thioridazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
Thiothixene: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and thiothixene. CNS depressants can potentiate the effects of cannabidiol.
Ticagrelor: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with cannabidiol as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Tipranavir: (Moderate) Monitor for an increase in tipranavir-related adverse reactions if coadministration with cannabidiol is necessary. Concomitant use may increase tipranavir exposure. Tipranavir is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Tizanidine: (Major) Avoid concomitant use of tizanidine and cannabidiol as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor.
Tolcapone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and tolcapone. CNS depressants can potentiate the effects of cannabidiol.
Topotecan: (Major) Avoid coadministration of cannabidiol with oral topotecan due to increased topotecan exposure; cannabidiol may be administered with intravenous topotecan. Oral topotecan is a substrate of the P-gp and cannabidiol is a P-gp inhibitor. Coadministration increases the risk of topotecan-related adverse reactions. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Torsemide: (Moderate) Consider a dose reduction of torsemide as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased torsemide exposure is possible. Torsemide is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Tramadol: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Tramadol; Acetaminophen: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Trazodone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and trazodone. CNS depressants can potentiate the effects of cannabidiol.
Treprostinil: (Moderate) Consider a dose reduction of treprostinil as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased treprostinil exposure is possible. Treprostinil is a CYP2C8 substrate. In vitro data predicts inhibition of CYP2C8 by cannabidiol potentially resulting in clinically significant interactions.
Triazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and triazolam. CNS depressants can potentiate the effects of cannabidiol.
Trifluoperazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
Trimipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and trimipramine. Concurrent use may result in additive CNS depression.
Triprolidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with cannabidiol. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the P-gp drug transporter; cannabidiol is a P-gp inhibitor.
Valerian, Valeriana officinalis: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and valerian. CNS depressants can potentiate the effects of cannabidiol.
Valproic Acid, Divalproex Sodium: (Moderate) Consider more frequent monitoring of hepatic enzymes and bilirubin in patients who are taking cannabidiol and valproic acid concomitantly due to increased incidence of elevated hepatic enzymes. Consider discontinuation or dosage reduction of cannabidiol and/or concomitant valproic acid if hepatic enzyme elevations occur. Additive sedation and somnolence may also occur.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with cannabidiol due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of cannabidiol. Venetoclax is a P-gp substrate; cannabidiol is a P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Vigabatrin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and vigabatrin. CNS depressants can potentiate the effects of cannabidiol.
Vincristine Liposomal: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of cannabidiol is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Vincristine: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of cannabidiol is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Voriconazole: (Moderate) Consider a dose reduction of voriconazole as clinically appropriate, if voriconazole-related adverse reactions occur when administered with cannabidiol. Cannabidiol has the potential to inhibit CYP2C9; voriconazole is a CYP2C9 substrate.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with cannabidiol is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Cannabidiol is a CYP2C9 and weak CYP1A2 inhibitor. The R-enantiomer of warfarin is a CYP1A2 substrate and generally has a slower clearance than the S-enantiomer. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer and is metabolized by CYP2C9.
Zafirlukast: (Moderate) Consider a dose reduction of zafirlukast as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased zafirlukast exposure is possible. Zafirlukast is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Zaleplon: (Moderate) Monitor for excessive sedation and somnolence during coadministration. CNS depressants can potentiate the effects of cannabidiol.
Ziprasidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and ziprasidone. Concurrent use may result in additive CNS depression.
Zolpidem: (Moderate) Monitor for excessive sedation and somnolence during coadministration. CNS depressants can potentiate the effects of cannabidiol.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
The precise mechanisms of action by which cannabidiol exerts its anticonvulsant effect are not known. Cannabidiol does not appear to bind to cannabinoid receptors. It may be effective in epilepsy by modulation of the endocannabinoid system. Cannabidiol prevents the degradation of anandamide, an endocannabinoid which may have a role in seizure inhibition. Cannabidiol may be involved with the regulation of T-type calcium channels and nuclear peroxisome proliferator-activated receptor-gamma, both of which may be involved in seizure activity.
Cannabidiol is administered orally. Protein binding of cannabidiol and its metabolites is more than 94%. Apparent Vd is 20,963 to 42,849 L. Cannabidiol is metabolized by the liver (primarily) and the gut via CYP2C19, CYP3A4, UGT1A7, UGT1A9, and UGT2B7. The active metabolite, 7-OH-CBD, is further converted to an inactive metabolite, 7-COOH-CBD. The half-life of cannabidiol ranges from 56 to 61 hours after twice-daily dosing for 7 days in healthy volunteers. Plasma clearance after a single 1,500 mg dose (1.1 times the maximum recommended daily dose) is 1,111 L/hour. Excretion occurs in the feces with minor renal clearance.
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, P-gp, UGT1A7, UGT1A9, UGT2B7
Cannabidiol is a substrate for CYP2C19, CYP3A4, UGT1A7, UGT1A9, and UGT2B7. It has the potential to inhibit CYP1A2, CYP2C8, CYP2C9, CYP2C19, UGT1A9, and UGT2B7. Cannabidiol is a weak inhibitor of CYP1A2. It may induce or inhibit CYP2B6. In vivo data show that cannabidiol can affect P-glycoprotein (P-gp) efflux activity in the intestine.
-Route-Specific Pharmacokinetics
Oral Route
Time to maximum concentration at steady state is 2.5 to 5 hours. Cannabidiol demonstrates a less than dose-proportional increase in exposure over the dosage range of 5 to 25 mg/kg/day. Coadministration of a high-fat, high-calorie meal increases Cmax by 5-fold and AUC by 4-fold compared to the fasted state. Coadministration of cannabidiol with a low-fat, low-calorie meal increased Cmax and AUC 4- and 3-fold, respectively. When administered with bovine milk, exposure increased by approximately 3- and 2.5-fold for Cmax and AUC, respectively.
-Special Populations
Hepatic Impairment
Patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment have an approximately 2.5- to 5.2-fold higher AUC compared to those with normal hepatic function. There is no effect on the exposure of cannabidiol or its metabolites in those with mild (Child-Pugh A) hepatic impairment.