Marinol

Cannabinoid Antiemetics
Cannabinoids

Oral Administration

For use in appetite stimulation, administer orally 1 hour before meals (lunch and dinner). If necessary, a single dose may be given 1 hour before dinner or at bedtime to minimize side effects.
For chemotherapy-induced nausea/vomiting (CINV), administer 1 to 3 hours before administration of chemotherapy, and then 2 to 4 hours afterwards for a total of 4 to 6 doses per day.
Because of the potential for adverse CNS effects, patients should remain under the supervision of a responsible adult during the initial use of dronabinol and following dosage adjustments.

Oral Liquid Formulations

Always use the calibrated oral dosing syringe provided by the manufacturer to ensure accuracy in measuring.
If the prescribed dose is greater than 5 mg, the total dose will need to be divided and drawn up in 2 or more portions using the oral syringe.
Take each dose with 6 to 8 ounces of water.
The first dose should be taken on an empty stomach, at least 30 minutes prior to food; subsequent doses can be taken without regard to meals. Keep the timing of dronabinol administration consistent with regard to meals for each cycle of chemotherapy.
Feeding tube administration (silicone only, greater than or equal to 14 French): Dronabinol can be administered via enteral feeding tubes that are manufactured using silicone, size greater than or equal to 14 French, such as Naso-Gastric (NG), Gastrostomy Tube (G-tube), Percutaneous Endoscopic Gastrostomy tube (PEG-tube) and Gastro-Jejunostomy tube (GJ-tube). Do not use tubes manufactured of polyurethane.
Draw up the prescribed dose with the calibrated dosing syringe provided by the manufacturer.
If the prescribed dose is greater than 5 mg, the total dose will need to be divided and drawn up in 2 or more portions using the oral syringe.
Using the calibrated dosing syringe, administer the dose via the feeding tube.
Using a catheter-tip syringe, flush the feeding tube with 30 mL of water

Severe

bradycardia / Rapid / Incidence not known
seizures / Delayed / Incidence not known

Moderate

impaired cognition / Early / 3.0-10.0
dysphoria / Early / 3.0-10.0
euphoria / Early / 3.0-10.0
depression / Delayed / 0-1.0
hypotension / Rapid / 0-1.0
conjunctivitis / Delayed / 0.3-1.0
hallucinations / Early / 1.0
confusion / Early / 1.0
amnesia / Delayed / 1.0
ataxia / Delayed / 1.0
delirium / Early / Incidence not known
tolerance / Delayed / Incidence not known
dehydration / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
hypertension / Early / Incidence not known
peripheral vasodilation / Rapid / Incidence not known
palpitations / Early / Incidence not known
orthostatic hypotension / Delayed / Incidence not known

Mild

emotional lability / Early / 8.0-24.0
drowsiness / Early / 3.0-10.0
paranoia / Early / 3.0-10.0
dizziness / Early / 3.0-10.0
abdominal pain / Early / 3.0-10.0
nausea / Early / 3.0-10.0
vomiting / Early / 3.0-10.0
tinnitus / Delayed / 0-1.0
nightmares / Early / 0-1.0
diarrhea / Early / 0.3-1.0
myalgia / Early / 0-1.0
sinusitis / Delayed / 0-1.0
hyperhidrosis / Delayed / 0-1.0
chills / Rapid / 0-1.0
cough / Delayed / 0-1.0
rhinitis / Early / 0-1.0
anxiety / Delayed / 1.0
asthenia / Delayed / 1.0
malaise / Early / Incidence not known
insomnia / Early / Incidence not known
fatigue / Early / Incidence not known
syncope / Early / Incidence not known
rash / Early / Incidence not known

Marinol, SYNDROS

Rx, schedule III, schedule II

Oral synthetic cannabinoid that provides standardized THC concentrations
Used for refractory chemotherapy-induced nausea/vomiting (CINV) and the treatment of anorexia with weight loss
Capsules are contraindicated in patients with hypersensitivity to sesame seed oil; oral solution is contraindicated in patients with hypersensitivity to alcohol, or with recent (past 14 days) use of disulfiram- or metronidazole-containing products

For the treatment of chemotherapy-induced nausea/vomiting (CINV) refractory to conventional antiemetic agents. Oral dosage, liquid-filled capsules Adults

5 mg/m2/dose PO 1 to 3 hours before chemotherapy then every 2 to 4 hours for a total of 4 to 6 doses per day. Consider reducing the dose to 2.5 mg/m2/dose PO once daily to reduce the risk of CNS symptoms, particularly in the elderly. Titrate dosage in increments of 2.5 mg/m2 to clinical response. Max: 15 mg/m2/dose for 4 to 6 doses per day. Administer the first dose on an empty stomach at least 30 minutes before eating; subsequent doses can be taken without regard to meals. Keep administration times in regard to meals consistent for each chemotherapy cycle once the dosage has been determined from the titration process.

Children and Adolescents 5 to 17 years†

2.5 to 5 mg/m2/dose (Max: 15 mg/m2/dose) PO 1 to 3 hours prior to chemotherapy and then every 2 to 6 hours for a total of 4 to 6 doses per day. Limited data is available for optimal pediatric dosing. Dronabinol administration resulted in a good response (0 to 1 bouts of emesis) in 60% of pediatric patients in a retrospective study (n = 47; age range: 6 to 18 years). Most received 2.5 mg/m2/dose PO every 6 hours as needed. A higher dronabinol dosage of 10 mg/m2/dose 2 hours before chemotherapy, then at 4, 8, 16, and 24 hours after the first dose, was used in double-blind studies of patients with CINV refractory to metoclopramide or prochlorperazine (n = 33; age range: 5 to 19 years). Fifty percent of patients experienced complete response after dronabinol initiation. A recent review of prescribing data from the Pediatric Health Information System reported a median dose of 2.5 mg/m2.

Oral dosage, solution Adults

4.2 mg/m2/dose (rounded to the nearest 0.1 mg increment, or the nearest 0.1 mL increment on the calibrated dosing syringe) PO 1 to 3 hours prior to chemotherapy then every 2 to 4 hours for a total of 4 to 6 doses per day. Consider reducing the dose to 2.1 mg/m2/dose PO once daily to reduce the risk of CNS symptoms, particularly in the elderly. Titrate dosage in increments of 2.1 mg/m2 to clinical response. Max: 12.6 mg/m2/dose for 4 to 6 doses per day. Administer the first dose on an empty stomach at least 30 minutes before eating; subsequent doses can be taken without regard to meals. Keep administration times in regard to meals consistent for each chemotherapy cycle once the dosage has been determined from the titration process.[60951]

For use as an appetite stimulant in the treatment of anorexia associated with weight loss. For use as an appetite stimulant in the treatment of anorexia associated with weight loss in patients with cancer†. Oral dosage, liquid-filled capsules Adults

2.5 mg by mouth twice daily, 1 hour before lunch and dinner. Data are not available in cancer patients for increasing the dose above 2.5 mg 3 times daily; however, in patients with AIDS-related anorexia, doses up to 8.4 mg twice daily have improved appetite. In a phase 2 clinical trial of cancer patients with anorexia, dronabinol capsules administered at a dose of 2.5 mg 3 times daily improved appetite in 13 of 19 patients (68.4%); however, significant side effects were noted in approximately 20% of patients. In a double-blind, randomized, placebo-controlled clinical trial, dronabinol 2.5 mg twice daily did not improve appetite (49% vs. 75%; p = 0.0001) or weight gain (3% vs. 11%; p = 0.02) compared with megestrol 800 mg daily. In another multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, dronabinol 2.5 mg twice daily (58%) did not improve appetite compared with cannabis extract (73%) or placebo (69%).

For the treatment of anorexia associated with weight loss in patients with AIDS. Oral dosage, liquid-filled capsules Adults

2.5 mg PO twice daily, 1 hour before lunch and 1 hour before dinner. Consider reducing the dose to 2.5 mg PO once daily 1 hour before dinner or at bedtime to reduce the risk of CNS symptoms, particularly in the elderly. May titrate dosage gradually, first to 2.5 mg PO 1 hour before lunch and 5 mg PO 1 hour before dinner, then to 5 mg PO twice daily. Max: 10 mg PO twice daily. Monitor patients for adverse reactions and reduce the dosage as needed. CNS adverse reactions (e.g., feeling high, dizziness, confusion, somnolence) usually resolve in 1 to 3 days and do not require dosage reduction. For severe or persistent adverse reactions, reduce the dose to 2.5 mg in the evening or at bedtime. Dosing later in the day may reduce the frequency of CNS symptoms.

Oral dosage, solution Adults

2.1 mg PO twice daily, 1 hour before lunch and 1 hour before dinner. Consider reducing the dose to 2.1 mg PO once daily 1 hour before dinner or at bedtime to reduce the risk of CNS symptoms, particularly in the elderly. May titrate dosage gradually, first to 2.1 mg PO 1 hour before lunch and 4.2 mg PO 1 hour before dinner, then to 4.2 mg PO twice daily. Max: 8.4 mg PO twice daily. Monitor patients for adverse reactions and reduce the dosage as needed. CNS adverse reactions (e.g., feeling high, dizziness, confusion, somnolence) usually resolve in 1 to 3 days and do not require dosage reduction. For severe or persistent adverse reactions, reduce the dose to 2.1 mg in the evening or at bedtime. Dosing later in the day may reduce the frequency of CNS symptoms.

For the treatment of intractable pruritus† secondary to cholestatic liver disease. Oral dosage, liquid-filled capsules Adults

In a case report, 3 patients were treated with dronabinol 5 mg PO at bedtime. All 3 patients reported a decrease in pruritus, marked improvement in sleep, and eventually were able to return to work. The duration of antipruritic effect was approximately 4 to 6 hours in all 3 patients, suggesting the need for more frequent dosing.

†Indicates off-label use

Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available. Because dronabinol is extensively metabolized, patients with hepatic impairment may not tolerate high doses and could be at increased risk for adverse reactions.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. It is unknown if dronabinol is removed by dialysis.

Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Acetaminophen; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Acetaminophen; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Acrivastine; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Adagrasib: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with adagrasib. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A and CYP2C9 substrate; adagrasib is a strong CYP3A and moderate CYP2C9 inhibitor.
Aldesleukin, IL-2: (Moderate) Use caution if coadministration of dronabinol with aldesleukin, IL-2 is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; aldesleukin is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Amiodarone: (Major) Use caution if coadministration of dronabinol with amiodarone is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; amiodarone is a moderate inhibitor of CYP2C9 and 3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Amitriptyline: (Moderate) Use caution if coadministration of dronabinol with tricyclic antidepressants (e.g., amitriptyline, desipramine) is necessary. Concurrent use of dronabinol, THC with tricyclic antidepressants may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Amlodipine: (Moderate) Use caution if coadministration of dronabinol with amlodipine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; amlodipine is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Amlodipine; Atorvastatin: (Moderate) Use caution if coadministration of dronabinol with amlodipine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; amlodipine is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Amlodipine; Benazepril: (Moderate) Use caution if coadministration of dronabinol with amlodipine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; amlodipine is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Amlodipine; Celecoxib: (Moderate) Use caution if coadministration of dronabinol with amlodipine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; amlodipine is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Amlodipine; Olmesartan: (Moderate) Use caution if coadministration of dronabinol with amlodipine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; amlodipine is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Amlodipine; Valsartan: (Moderate) Use caution if coadministration of dronabinol with amlodipine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; amlodipine is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Use caution if coadministration of dronabinol with amlodipine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; amlodipine is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Amoxapine: (Moderate) Use caution if coadministration of dronabinol with amoxapine is necessary. Concurrent use of dronabinol, THC with amoxapine may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Use caution if coadministration of dronabinol with clarithromycin is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; clarithromycin is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Amphetamine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Amphetamine; Dextroamphetamine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Amphotericin B lipid complex (ABLC): (Major) Use caution if coadministration of dronabinol with amphotericin B is necessary, and monitor for an increase in amphotericin-related adverse reactions. Dronabinol is also highly bound to plasma proteins and may displace and increase the free fraction of other concomitantly administered protein-bound drugs such as amphotericin B.
Amphotericin B liposomal (LAmB): (Major) Use caution if coadministration of dronabinol with amphotericin B is necessary, and monitor for an increase in amphotericin-related adverse reactions. Dronabinol is also highly bound to plasma proteins and may displace and increase the free fraction of other concomitantly administered protein-bound drugs such as amphotericin B.
Amphotericin B: (Major) Use caution if coadministration of dronabinol with amphotericin B is necessary, and monitor for an increase in amphotericin-related adverse reactions. Dronabinol is also highly bound to plasma proteins and may displace and increase the free fraction of other concomitantly administered protein-bound drugs such as amphotericin B.
Anticholinergics: (Moderate) Use caution if coadministration of dronabinol with anticholinergics is necessary. Concurrent use of dronabinol, THC with anticholinergics may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Apalutamide: (Moderate) Monitor for a decrease in dronabinol efficacy if coadministration with apalutamide is necessary. Dronabinol is a CYP2C9 and CYP3A4 substrate. Apalutamide is a strong CYP3A4 inducer and a weak inducer of CYP2C9.
Apomorphine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants, such as dronabinol, could result in additive depressant effects. Careful monitoring is recommended during combined use of a CNS depressant and apomorphine. A dose reduction of one or both drugs may be warranted.
Aprepitant, Fosaprepitant: (Moderate) Use caution if dronabinol and aprepitant, fosaprepitant are used concurrently and monitor for an increase in dronabinol-related adverse effects (e.g., feeling high, dizziness, confusion, somnolence) for several days after administration of a multi-day aprepitant regimen. Dronabinol is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of dronabinol. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. Additionally, dronabinol is a CYP2C9 substrate and aprepitant is a CYP2C9 inducer. Administration of another CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant.
Armodafinil: (Moderate) Use caution if coadministration of dronabinol with armodafinil is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; armodafinil is a weak inducer of CYP3A4 in vitro. Concomitant use may result in decreased plasma concentrations of dronabinol.
Articaine; Epinephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Asciminib: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with asciminib 200 mg twice daily. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP2C9 substrate; asciminib 200 mg twice daily is a moderate CYP2C9 inhibitor. An interaction is not expected with asciminib doses less than 200 mg twice daily.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Aspirin, ASA; Carisoprodol: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Atazanavir: (Major) Use caution if coadministration of dronabinol with atazanavir is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Atazanavir; Cobicistat: (Major) Use caution if coadministration of dronabinol with atazanavir is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. (Moderate) Use caution if coadministration of dronabinol with cobicistat is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Concomitant use may result in elevated plasma concentrations of dronabinol. Cobicistat is a strong inhibitor of CYP3A4; dronabinol is a CYP2C9 and 3A4 substrate.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with dronabinol can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
atypical antipsychotic: (Moderate) Drugs that can cause CNS depression such as dronabinol, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
Baclofen: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Barbiturates: (Moderate) Use caution if coadministration of dronabinol with barbiturates is necessary, and monitor for an increase in barbiturate-related adverse reactions and a decrease in the efficacy of dronabinol. Additive dizziness, confusion, somnolence, and other CNS effects may also occur. Dronabinol is a CYP2C9 and 3A4 substrate; barbiturates are moderate or strong (phenobarbital) inducers of CYP3A4; additionally phenobarbital is a moderate CYP2C9 inducer. Concomitant use may result in decreased plasma concentrations of dronabinol. Decreased clearance of barbiturates has also been reported with dronabinol use, possibly by competitive inhibition of metabolism. Published data show an increase in the elimination half-life of pentobarbital by 4 hours when concomitantly dosed with dronabinol.
Benzodiazepines: (Moderate) Use caution if the use of benzodiazepines are necessary with dronabinol, and monitor for additive dizziness, confusion, somnolence, and other CNS effects.
Benzphetamine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Berotralstat: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with berotralstat. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A4 substrate; berotralstat is a moderate CYP3A inhibitor.
Bexarotene: (Moderate) Use caution if coadministration of dronabinol with bexarotene is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; bexarotene is a moderate inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) The use of metronidazole within 14 days of beginning therapy with dronabinol oral solution is contraindicated, due to the risk of a disulfiram-like reaction. Do not administer metronidazole within 7 days of completing therapy with the oral solution. Dronabinol oral solution contains 50% (w/w) dehydrated alcohol and 5% (w/w) propylene glycol, which can produce disulfiram-like reactions (e.g., abdominal cramps, nausea/vomiting, headaches, and flushing) with drugs such as metronidazole. Ethanol competitively inhibits the metabolism of propylene glycol; however, the contribution of propylene glycol to these reactions is unknown. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations (e.g., dronabinol oral capsules).
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) The use of metronidazole within 14 days of beginning therapy with dronabinol oral solution is contraindicated, due to the risk of a disulfiram-like reaction. Do not administer metronidazole within 7 days of completing therapy with the oral solution. Dronabinol oral solution contains 50% (w/w) dehydrated alcohol and 5% (w/w) propylene glycol, which can produce disulfiram-like reactions (e.g., abdominal cramps, nausea/vomiting, headaches, and flushing) with drugs such as metronidazole. Ethanol competitively inhibits the metabolism of propylene glycol; however, the contribution of propylene glycol to these reactions is unknown. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations (e.g., dronabinol oral capsules).
Bosentan: (Moderate) Use caution if coadministration of dronabinol with bosentan is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; bosentan is a moderate inducer of CYP2C9 and 3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Brompheniramine; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Brompheniramine; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Bupivacaine; Epinephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Buprenorphine: (Moderate) Concomitant use of buprenorphine with other CNS depressants can lead to additive CNS depressive effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur; examples of other CNS depressants can include dronabinol. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A dose reduction of one or both drugs may be warranted. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Buprenorphine; Naloxone: (Moderate) Concomitant use of buprenorphine with other CNS depressants can lead to additive CNS depressive effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur; examples of other CNS depressants can include dronabinol. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A dose reduction of one or both drugs may be warranted. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Bupropion; Naltrexone: (Moderate) Concomitant administration of naltrexone and oral THC like dronabinol enhances the positive subjective effects of oral THC. Data from separate investigations demonstrate that pretreatment with an opioid receptor blocker such as naltrexone significantly increases many of the euphoric effects of oral THC in heavy marijuana smokers.
Buspirone: (Moderate) Use caution if coadministration of dronabinol with buspirone is necessary, and monitor for additive dizziness, confusion, somnolence, and other CNS effects.
Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as dronabinol, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Moderate) Concomitant use of dronabinol with other CNS depressants like sodium oxybate can potentiate the effects of dronabinol on respiratory depression.
Cannabidiol: (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.
Capsaicin; Metaxalone: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Carbamazepine: (Major) Use caution if coadministration of dronabinol with carbamazepine is necessary, and monitor for a decrease in the efficacy of dronabinol; also monitor for an increase in carbamazepine-related adverse effects. Dronabinol is a CYP2C9 and 3A4 substrate; carbamazepine is a strong inducer of CYP2C9 and 3A4. Concomitant use may result in decreased plasma concentrations of dronabinol. Additionally, dronabinol is highly bound to plasma proteins, and may displace and increase the free fraction of other concomitantly administered protein-bound drugs; caution is recommended with other drugs with a narrow therapeutic index.
Carbidopa; Levodopa; Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including dronabinol, due to the possibility of additive sedation. COMT inhibitors 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.
Carisoprodol: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and dronabinol. Concurrent use may result in additive CNS depression. Additionally, monitor for decreased efficacy of dronabinol if coadministration with cenobamate is necessary. Dronabinol is a CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer. Formal drug interaction studies have not been conducted; however, inducers of CYP3A4 may decrease dronabinol exposure.
Ceritinib: (Moderate) Monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, feeling high, dizziness, somnolence) if coadministration with ceritinib is necessary. Concomitant use may result in elevated plasma concentrations of dronabinol. Ceritinib is a strong CYP3A4 inhibitor and a weak inhibitor of CYP2C9. Dronabinol is a CYP2C9 and 3A4 substrate.
Cetirizine: (Moderate) Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, including dronabinol.
Cetirizine; Pseudoephedrine: (Moderate) Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, including dronabinol. (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Chloramphenicol: (Major) Use caution if coadministration of dronabinol with chloramphenicol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; chloramphenicol is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Chlordiazepoxide; Amitriptyline: (Moderate) Use caution if coadministration of dronabinol with tricyclic antidepressants (e.g., amitriptyline, desipramine) is necessary. Concurrent use of dronabinol, THC with tricyclic antidepressants may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Chlorpheniramine; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Chlorpheniramine; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Chlorzoxazone: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Cimetidine: (Moderate) Use caution if coadministration of dronabinol with cimetidine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; cimetidine is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Ciprofloxacin: (Moderate) Use caution if coadministration of dronabinol with ciprofloxacin is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP3A4 substrate; ciprofloxacin is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Clarithromycin: (Major) Use caution if coadministration of dronabinol with clarithromycin is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; clarithromycin is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Clobazam: (Moderate) Use caution if coadministration of dronabinol with clobazam is necessary due to the potential for additive dizziness, confusion, somnolence, and other CNS effects.
Clomipramine: (Moderate) Use caution if coadministration of dronabinol with tricyclic antidepressants (e.g., amitriptyline, desipramine) is necessary. Concurrent use of dronabinol, THC with tricyclic antidepressants may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Cobicistat: (Moderate) Use caution if coadministration of dronabinol with cobicistat is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Concomitant use may result in elevated plasma concentrations of dronabinol. Cobicistat is a strong inhibitor of CYP3A4; dronabinol is a CYP2C9 and 3A4 substrate.
Cocaine: (Major) Use caution with coadministration of dronabinol and cocaine, and monitor for additive hypertension, tachycardia, and possible cardiotoxicity, as well as an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol can be associated with hemodynamic instability (e.g., occasional hypotension, hypertension, syncope, and tachycardia) which may be enhanced when coadministered with drugs that have similar cardiac effects. In a study of 7 adult males, combinations of cocaine (IV) and smoked marijuana (1 g marijuana cigarette, <= 2.7% delta-9-THC) increased the heart rate above levels seen with either agent alone, with increases reaching a plateau at 50 bpm. Additionally, dronabinol is a CYP2C9 and 3A4 substrate; cocaine is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Codeine; Phenylephrine; Promethazine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
COMT inhibitors: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including dronabinol, due to the possibility of additive sedation. COMT inhibitors 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.
Conivaptan: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with conivaptan. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A substrate; conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Moderate) Monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence) if coadministration with crizotinib is necessary. Crizotinib is a moderate CYP3A inhibitor and dronabinol is a CYP3A substrate.
Cyclobenzaprine: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Cyclosporine: (Major) Use caution if coadministration of dronabinol with cyclosporine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence) as well as increased cyclosporine levels. Dronabinol is a CYP2C9 and 3A4 substrate; cyclosporine is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. Dronabinol is also highly bound to plasma proteins and may displace and increase the free fraction of other concomitantly administered protein-bound drugs such as cyclosporine.
Dabrafenib: (Moderate) Use caution if coadministration of dronabinol with dabrafenib is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; dabrafenib is a moderate inducer of CYP3A4 and a weak CYP2C9 inducer. Concomitant use may result in decreased plasma concentrations of dronabinol.
Danazol: (Major) Use caution if coadministration of dronabinol with danazol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; danazol is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Dantrolene: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Darunavir: (Major) Use caution if coadministration of dronabinol with darunavir is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Darunavir is a strong inhibitor of CYP3A4, and is contraindicated with sensitive drugs that are highly dependent on CYP3A4/5 for clearance. Dronabinol is a CYP2C9 and 3A4 substrate; concomitant use may result in elevated plasma concentrations of dronabinol.
Darunavir; Cobicistat: (Major) Use caution if coadministration of dronabinol with darunavir is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Darunavir is a strong inhibitor of CYP3A4, and is contraindicated with sensitive drugs that are highly dependent on CYP3A4/5 for clearance. Dronabinol is a CYP2C9 and 3A4 substrate; concomitant use may result in elevated plasma concentrations of dronabinol. (Moderate) Use caution if coadministration of dronabinol with cobicistat is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Concomitant use may result in elevated plasma concentrations of dronabinol. Cobicistat is a strong inhibitor of CYP3A4; dronabinol is a CYP2C9 and 3A4 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Use caution if coadministration of dronabinol with darunavir is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Darunavir is a strong inhibitor of CYP3A4, and is contraindicated with sensitive drugs that are highly dependent on CYP3A4/5 for clearance. Dronabinol is a CYP2C9 and 3A4 substrate; concomitant use may result in elevated plasma concentrations of dronabinol. (Moderate) Use caution if coadministration of dronabinol with cobicistat is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Concomitant use may result in elevated plasma concentrations of dronabinol. Cobicistat is a strong inhibitor of CYP3A4; dronabinol is a CYP2C9 and 3A4 substrate.
Deferasirox: (Moderate) Use caution if coadministration of dronabinol with deferasirox is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; deferasirox is a moderate inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Delavirdine: (Major) Use caution if coadministration of dronabinol with delavirdine is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Delavirdine is a strong inhibitor of CYP3A4 and a moderate CYP2C9 inhibitor in vitro; it is contraindicated with sensitive drugs that are highly dependent on CYP3A4/5 for clearance. Dronabinol is a CYP2C9 and 3A4 substrate; concomitant use may result in elevated plasma concentrations of dronabinol.
Desipramine: (Moderate) Use caution if coadministration of dronabinol with tricyclic antidepressants (e.g., amitriptyline, desipramine) is necessary. Concurrent use of dronabinol, THC with tricyclic antidepressants may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Desloratadine; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Desogestrel; Ethinyl Estradiol: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Dexmethylphenidate: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Dextroamphetamine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Diethylpropion: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
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.
Digoxin: (Major) Use caution if coadministration of dronabinol with digoxin is necessary, and monitor for an increase in digoxin levels and digoxin-related adverse effects. Dronabinol is highly bound to plasma proteins, and may displace and increase the free fraction of other concomitantly administered protein-bound drugs; caution is recommended with other drugs with a narrow therapeutic index.
Diltiazem: (Major) Use caution if coadministration of dronabinol with diltiazem is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; diltiazem is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with dronabinol can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Disulfiram: (Major) Dronabinol oral solution is contraindicated for use within 14 days of disulfiram. Discontinue disulfiram at least 14 days before starting dronabinol oral solution and do not administer disulfiram within 7 days of completing treatment with dronabinol oral solution. Concomitant use may cause a disulfiram-reaction. Dronabinol oral solution contains 50% (w/w) dehydrated alcohol.
Dobutamine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Dopamine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Doxapram: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Doxepin: (Moderate) Use caution if coadministration of dronabinol with tricyclic antidepressants (e.g., amitriptyline, desipramine) is necessary. Concurrent use of dronabinol, THC with tricyclic antidepressants may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Dronedarone: (Major) Use caution if coadministration of dronabinol with dronedarone is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; dronedarone is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Droperidol: (Moderate) Concomitant use of dronabinol with other CNS depressants, such as droperidol, can potentiate the effects of dronabinol on respiratory depression.
Drospirenone; Ethinyl Estradiol: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Duvelisib: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with duvelisib. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Efavirenz: (Moderate) Use caution if coadministration of dronabinol with efavirenz is necessary, and monitor for changes in the efficacy or adverse effect profile of dronabinol (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate. Efavirenz is a moderate inhibitor of CYP2C9 in vitro, and a CYP3A4 inducer. Concomitant use may result in altered plasma concentrations of dronabinol.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Use caution if coadministration of dronabinol with efavirenz is necessary, and monitor for changes in the efficacy or adverse effect profile of dronabinol (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate. Efavirenz is a moderate inhibitor of CYP2C9 in vitro, and a CYP3A4 inducer. Concomitant use may result in altered plasma concentrations of dronabinol.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Use caution if coadministration of dronabinol with efavirenz is necessary, and monitor for changes in the efficacy or adverse effect profile of dronabinol (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate. Efavirenz is a moderate inhibitor of CYP2C9 in vitro, and a CYP3A4 inducer. Concomitant use may result

in altered plasma concentrations of dronabinol.
Elbasvir; Grazoprevir: (Moderate) Use caution if coadministration of dronabinol with elbasvir; grazoprevir is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; grazoprevir is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Elexacaftor; tezacaftor; ivacaftor: (Minor) Use caution if coadministration of dronabinol with ivacaftor is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ivacaftor is a weak inhibitor of CYP3A4 and a weak CYP2C9 inhibitor in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Use caution if coadministration of dronabinol with cobicistat is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Concomitant use may result in elevated plasma concentrations of dronabinol. Cobicistat is a strong inhibitor of CYP3A4; dronabinol is a CYP2C9 and 3A4 substrate. (Moderate) Use caution if coadministration of dronabinol with elvitegravir is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; elvitegravir is a moderate inducer of CYP2C9. Concomitant use may result in decreased plasma concentrations of dronabinol.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Use caution if coadministration of dronabinol with cobicistat is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Concomitant use may result in elevated plasma concentrations of dronabinol. Cobicistat is a strong inhibitor of CYP3A4; dronabinol is a CYP2C9 and 3A4 substrate. (Moderate) Use caution if coadministration of dronabinol with elvitegravir is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; elvitegravir is a moderate inducer of CYP2C9. Concomitant use may result in decreased plasma concentrations of dronabinol.
Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including dronabinol, due to the possibility of additive sedation. COMT inhibitors 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.
Enzalutamide: (Moderate) Monitor for a decrease in dronabinol efficacy if coadministration with enzalutamide is necessary. Dronabinol is a CYP2C9 and CYP3A4 substrate. Enzalutamide is a strong CYP3A4 inducer and a moderate inducer of CYP2C9.
Ephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Ephedrine; Guaifenesin: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Epinephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Erythromycin: (Major) Use caution if coadministration of dronabinol with erythromycin is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; erythromycin is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Eslicarbazepine: (Moderate) Use caution if coadministration of dronabinol with eslicarbazepine is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; eslicarbazepine is a moderate inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Eszopiclone: (Moderate) Using eszopiclone with other CNS depressants, such as dronabinol, may have cumulative effects and can increase the risk for sedation. A reduction in the dose of both or either drug should be considered to minimize additive sedative effects. The risk of next-day psychomotor impairment is increased during co-administration, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Ethinyl Estradiol; Norelgestromin: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Ethinyl Estradiol; Norgestrel: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Ethosuximide: (Major) Use caution if coadministration of dronabinol with ethosuximide is necessary, and monitor for an increase in ethosuximide-related adverse effects. Dronabinol is highly bound to plasma proteins, and may displace and increase the free fraction of other concomitantly administered protein-bound drugs; caution is recommended with other drugs with a narrow therapeutic index.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Etonogestrel; Ethinyl Estradiol: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Etravirine: (Moderate) Monitor for a decrease in dronabinol efficacy if coadministration with etravirine is necessary. Coadministration may decrease the exposure of dronabinol. Dronabinol is a CYP3A substrate; etravirine is a moderate CYP3A inducer.
Fedratinib: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with fedratinib. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A substrate; fedratinib is a moderate CYP3A inhibitor.
Felbamate: (Moderate) Use caution if coadministration of dronabinol with felbamate is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; felbamate is a weak inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and dronabinol. Concurrent use may result in additive CNS depression.
Fenofibric Acid: (Moderate) Use caution if coadministration of dronabinol with fenofibric acid is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; fenofibric acid is a weak-to-moderate inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol.
Fexofenadine; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Flibanserin: (Moderate) The concomitant use of flibanserin with CNS depressants, such as dronabinol, THC, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Fluconazole: (Moderate) Use caution if coadministration of dronabinol with fluconazole is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Concomitant use may result in elevated plasma concentrations of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; fluconazole is a moderate inhibitor of both enzymes.
Fluorouracil, 5-FU: (Major) Use caution if coadministration of dronabinol with fluorouracil, 5-FU is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; 5-FU is a moderate inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol.
Fluoxetine: (Moderate) Use caution if coadministration of dronabinol with fluoxetine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; fluoxetine is a weak inhibitor of CYP2C9 and 3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. A hypomanic episode was reported in a 21 year old female with depression and bulimia receiving fluoxetine 20 mg per day for 4 weeks after smoking marijuana. Her symptoms resolved in 4 days. Because dronabinol, THC is a synthetic analog of a naturally occurring substance found in marijuana, interactions with fluoxetine may also occur with dronabinol.
Flutamide: (Moderate) Use caution if coadministration of dronabinol with flutamide is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; flutamide is a moderate inducer of CYP3A4 in vitro. Concomitant use may result in decreased plasma concentrations of dronabinol.
Fluvastatin: (Moderate) Use caution if coadministration of dronabinol with fluvastatin is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; fluvastatin is a weak inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol.
Fluvoxamine: (Major) Use caution if coadministration of dronabinol with fluvoxamine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; fluvoxamine is a moderate inhibitor of CYP3A4 and a weak CYP2C9 inhibitor. Concomitant use may result in elevated plasma concentrations of dronabinol.
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.
Fosamprenavir: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with fosamprenavir. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor.
Fosphenytoin: (Major) Use caution if coadministration of dronabinol with fosphenytoin is necessary, and monitor for an increase in phenytoin levels and fosphenytoin-related adverse effects, as well as a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; fosphenytoin is a strong inducer of CYP3A4 and a moderate CYP2C9 inducer. Concomitant use may result in decreased plasma concentrations of dronabinol. Additionally, dronabinol is highly bound to plasma proteins, and may displace and increase the free fraction of other concomitantly administered protein-bound drugs; caution is recommended with other drugs with a narrow therapeutic index.
Gemfibrozil: (Moderate) Use caution if coadministration of dronabinol with gemfibrozil is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; gemfibrozil is a weak inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol.
General anesthetics: (Moderate) Concomitant use of dronabinol with other CNS depressants like general anesthetics can potentiate the effects of dronabinol on respiratory depression.
Grapefruit juice: (Major) Use caution if coadministration of dronabinol with grapefruit juice is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; grapefruit juice is a moderate inhibitor of CYP2C9 in vitro, and a strong 3A4 inhibitor. Concomitant use may result in elevated plasma concentrations of dronabinol.
Griseofulvin: (Major) Oral solutions of dronabinol contain ethanol. Administration of dronabinol oral solution to patients receiving or who have recently received griseofulvin may result in disulfiram-like reactions (e.g., abdominal cramps, nausea/vomiting, headaches, and flushing). A disulfiram reaction would not be expected to occur with non-ethanol containing formulations of dronabinol (e.g., capsules).
Guaifenesin; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Guaifenesin; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Haloperidol: (Moderate) Use caution if the use of haloperidol is necessary with dronabinol, and monitor for additive dizziness, confusion, somnolence, and other CNS effects.
Hydrocodone; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Ibuprofen; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Idelalisib: (Major) Avoid the coadministration of dronabinol with idelalisib, due to the risk of serious dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; idelalisib is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. In healthy subjects, the geometric mean Cmax of midazolam increased by 2.4-fold and the geometric mean AUC of midazolam by 5.4-fold when administered after idelalisib (150 mg by mouth for 15 doses).
Imatinib: (Major) Use caution if coadministration of dronabinol with imatinib is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Concomitant use may result in elevated plasma concentrations of dronabinol. Dronabinol is a 3A4 substrate; imatinib is a moderate inhibitor of 3A4.
Imipramine: (Moderate) Use caution if coadministration of dronabinol with tricyclic antidepressants (e.g., amitriptyline, desipramine) is necessary. Concurrent use of dronabinol, THC with tricyclic antidepressants may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Indinavir: (Major) Use caution if coadministration of dronabinol with indinavir is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Indinavir is a strong inhibitor of CYP3A4, and is contraindicated with sensitive drugs that are highly dependent on CYP3A4/5 for clearance. Dronabinol is a CYP2C9 and 3A4 substrate; concomitant use may result in elevated plasma concentrations of dronabinol. The effect of marijuana and dronabinol, THC on the pharmacokinetics of indinavir has also been evaluated in a randomized trial. Although a statistically significant decrease in the Cmax of indinavir was noted in the marijuana arm, the magnitude of changes in indinavir pharmacokinetics were not thought to be clinically significant. In the authors' opinion, the use of marijuana or dronabinol is unlikely to affect the antiretroviral efficacy of indinavir.
Ipecac: (Major) Ipecac has been shown to be effective in producing emesis in patients who have ingested antiemetics, provided ipecac is given promptly (usually within 1 hour of antiemetic consumption). If ipecac is administered after antiemetic therapy has begun to exert therapeutic effects, ipecac may be less effective. It is suggested the irritating GI effects of ipecac lead to emesis following antiemetic consumption.
Isavuconazonium: (Major) Use caution if coadministration of dronabinol with isavuconazonium is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; isavuconazonium is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Isoniazid, INH: (Moderate) Use caution if coadministration of dronabinol with isoniazid, INH is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a 3A4 substrate; isoniazid is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Use caution if coadministration of dronabinol with isoniazid, INH is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a 3A4 substrate; isoniazid is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. (Moderate) Use caution if coadministration of dronabinol with rifampin is necessary, and monitor for a decrease in the efficacy of dronabinol. Concomitant use may result in decreased plasma concentrations of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; rifampin is a strong inducer of CYP3A4 and a moderate CYP2C9 inducer.
Isoniazid, INH; Rifampin: (Moderate) Use caution if coadministration of dronabinol with isoniazid, INH is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a 3A4 substrate; isoniazid is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. (Moderate) Use caution if coadministration of dronabinol with rifampin is necessary, and monitor for a decrease in the efficacy of dronabinol. Concomitant use may result in decreased plasma concentrations of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; rifampin is a strong inducer of CYP3A4 and a moderate CYP2C9 inducer.
Isoproterenol: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Itraconazole: (Major) Use caution if coadministration of dronabinol with itraconazole is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; itraconazole is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Ivacaftor: (Minor) Use caution if coadministration of dronabinol with ivacaftor is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ivacaftor is a weak inhibitor of CYP3A4 and a weak CYP2C9 inhibitor in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Ketoconazole: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with ketoconazole. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A4 substrate and ketoconazole is a strong CYP3A inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Use caution if coadministration of dronabinol with clarithromycin is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; clarithromycin is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Lapatinib: (Moderate) Monitor for an increase in dronabinol-related adverse reactions if coadministration with lapatinib is necessary. Dronabinol is a CYP3A4 substrate and lapatinib is a weak CYP3A4 inhibitor.
Lefamulin: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with oral lefamulin. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A substrate; oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin.
Leflunomide: (Major) Use caution if coadministration of dronabinol with leflunomide is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; leflunomide is a moderate inhibitor of CYP2C9 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and dronabinol. Dosage adjustments of lemborexant and dronabinol 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.
Lenacapavir: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with lenacapavir. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A substrate; lenacapavir is a moderate CYP3A inhibitor.
Lesinurad: (Moderate) Use caution if coadministration of dronabinol with lesinurad is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; lesinurad is a weak inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Lesinurad; Allopurinol: (Moderate) Use caution if coadministration of dronabinol with lesinurad is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; lesinurad is a weak inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Letermovir: (Moderate) Plasma concentrations of dronabinol could be increased when administered concurrently with letermovir. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. If these drugs are given together, monitor for dronabinol-related adverse events. Dronabinol is a substrate of CYP3A4. Letermovir is a moderate inhibitor of CYP3A4. When given with cyclosporine, the combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Levamlodipine: (Moderate) Use caution if coadministration of dronabinol with amlodipine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; amlodipine is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Levocetirizine: (Moderate) Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, including dronabinol.
Levoketoconazole: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with ketoconazole. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A4 substrate and ketoconazole is a strong CYP3A inhibitor.
Levonorgestrel; Ethinyl Estradiol: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Lidocaine; Epinephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Lisdexamfetamine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Lithium: (Major) Use caution if coadministration of dronabinol with lithium is necessary, and monitor for an increase in lithium plasma concentrations and lithium-related adverse effects. Additive dizziness, confusion, somnolence, and other CNS effects may also occur. Dronabinol is highly bound to plasma proteins, and may displace and increase the free fraction of other concomitantly administered protein-bound drugs; caution is recommended with other drugs with a narrow therapeutic index.
Lonafarnib: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with lonafarnib. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A4 substrate; lonafarnib is a strong CYP3A inhibitor.
Lopinavir; Ritonavir: (Major) Use caution if coadministration of dronabinol with ritonavir is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Ritonavir is a strong inhibitor of CYP3A4 and a moderate CYP2C9 inducer; it is contraindicated with sensitive drugs that are highly dependent on CYP3A4/5 for clearance. Dronabinol is a CYP2C9 and 3A4 substrate; concomitant use may result in elevated plasma concentrations of dronabinol.
Loratadine; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Lorlatinib: (Moderate) Monitor for decreased efficacy of dronabinol if coadministration with lorlatinib is necessary. Dronabinol is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer. Formal drug interaction studies have not been conducted; however, inducers of CYP3A4 may decrease dronabinol exposure.
Lumacaftor; Ivacaftor: (Minor) Use caution if coadministration of dronabinol with ivacaftor is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ivacaftor is a weak inhibitor of CYP3A4 and a weak CYP2C9 inhibitor in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Lumacaftor; Ivacaftor: (Moderate) Use caution if coadministration of dronabinol with lumacaftor; ivacaftor is necessary, and monitor for changes in the efficacy or adverse effect profile of dronabinol (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate. Ivacaftor is a weak inhibitor of CYP3A4 and a weak CYP2C9 inhibitor in vitro, while lumacaftor is a strong CYP3A4 inducer. Concomitant use may result in altered plasma concentrations of dronabinol.
Maprotiline: (Moderate) Use caution if the use of maprotioline is necessary with dronabinol, and monitor for additive dizziness, confusion, somnolence, and other CNS effects.
Mavacamten: (Moderate) Monitor for a decrease in dronabinol efficacy if coadministration with mavacamten is necessary. Coadministration may decrease the exposure of dronabinol. Dronabinol is a CYP2C9 and CYP3A4 substrate; mavacamten is a moderate CYP2C9 and CYP3A inducer.
Meprobamate: (Moderate) The CNS-depressant effects of meprobamate can be potentiated with concomitant administration of other drugs known to cause CNS depression including dronabinol.
Metaxalone: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Methamphetamine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Methocarbamol: (Moderate) Concomitant use of dronabinol with other CNS depressants, such as methocarbamol, can potentiate the effects of dronabinol on respiratory depression.
Methylphenidate: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Metronidazole: (Major) The use of metronidazole within 14 days of beginning therapy with dronabinol oral solution is contraindicated, due to the risk of a disulfiram-like reaction. Do not administer metronidazole within 7 days of completing therapy with the oral solution. Dronabinol oral solution contains 50% (w/w) dehydrated alcohol and 5% (w/w) propylene glycol, which can produce disulfiram-like reactions (e.g., abdominal cramps, nausea/vomiting, headaches, and flushing) with drugs such as metronidazole. Ethanol competitively inhibits the metabolism of propylene glycol; however, the contribution of propylene glycol to these reactions is unknown. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations (e.g., dronabinol oral capsules).
Metyrapone: (Moderate) Metyrapone may cause drowsiness or dizziness. Use caution if coadministration of dronabinol with metyrapone is necessary, and monitor for additive CNS effects, such as drowsiness or dizziness.
Midodrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Mifepristone: (Moderate) Use caution if coadministration of dronabinol with mifepristone is necessary; monitor for an increase in dronabinol-related CNS adverse reactions (e.g., cognitive impairment, euphoria, dizziness, confusion, somnolence, or changes in moods or behaviors) if mifepristone is used chronically for hormonal conditions such as Cushing's syndrome. A dose reduction of dronabinol may be needed in some patients to reduce the risk of central nervous system (CNS) symptoms. Dronabinol is a CYP2C9 and 3A4 substrate; mifepristone is an inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Mirtazapine: (Moderate) Consistent with the pharmacology of mirtazapine and the drug's side effect profile, additive effects may occur with other CNS-active agents, such as dronabinol.
Mitotane: (Moderate) Use caution if coadministration of dronabinol with mitotane is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; mitotane is a strong inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Modafinil: (Moderate) Use caution if coadministration of dronabinol with modafinil is necessary, and monitor for changes in the efficacy or adverse effect profile of dronabinol (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate. Modafinil is a weak inhibitor of CYP2C9 and moderate CYP3A4 inducer. Concomitant use may result in altered plasma concentrations of dronabinol.
Molindone: (Moderate) Molindone may cause central nervous system (CNS) depression thereby having additive effects with other drugs that can cause CNS depression such as dronabinol, THC. Caution is advisable during concurrent use.
Monoamine oxidase inhibitors: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including dronabinol.
Nabilone: (Contraindicated) Avoid use together. While a patient is taking dronabinol or is taking nabilone, the patient should not be treated with other oral or inhaled cannabinoids. Combining 2 cannabinoids will lead to an increase in psychotoxic effects, and would not represent any therapeutic benefit to the patient.
Nafcillin: (Moderate) Use caution if coadministration of dronabinol with nafcillin is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; nafcillin is a moderate inducer of CYP3A4 in vitro. Concomitant use may result in decreased plasma concentrations of dronabinol.
Nalbuphine: (Moderate) Concomitant use of nalbuphine with other CNS depressants, such as dronabinol, can potentiate the effects of nalbuphine on respiratory depression, CNS depression, and sedation.
Naltrexone: (Moderate) Concomitant administration of naltrexone and oral THC like dronabinol enhances the positive subjective effects of oral THC. Data from separate investigations demonstrate that pretreatment with an opioid receptor blocker such as naltrexone significantly increases many of the euphoric effects of oral THC in heavy marijuana smokers.
Naproxen; Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Nefazodone: (Major) Use caution if coadministration of dronabinol with nefazodone is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; nefazodone is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Nelfinavir: (Major) Use caution if coadministration of dronabinol with nelfinavir is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Nelfinavir is a strong inhibitor of CYP3A4, and is contraindicated with sensitive drugs that are highly dependent on CYP3A4/5 for clearance. Dronabinol is a CYP2C9 and 3A4 substrate; concomitant use may result in elevated plasma concentrations of dronabinol. The effect of marijuana and dronabinol, THC on the pharmacokinetics of nelfinavir has also been evaluated in a randomized trial. Although a statistically significant decrease in the Cmax of nelfinavir was noted in the marijuana arm, the magnitude of changes in nelfinavir pharmacokinetics were not thought to be clinically significant. In the authors' opinion, the use of marijuana or dronabinol is unlikely to affect the antiretroviral efficacy of nelfinavir.
Netupitant, Fosnetupitant; Palonosetron: (Major) Use caution if coadministration of dronabinol with netupitant; palonosetron is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; netupitant is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Nilotinib: (Moderate) Use caution if coadministration of dronabinol with nilotinib is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; nilotinib is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Nirmatrelvir; Ritonavir: (Major) Use caution if coadministration of dronabinol with ritonavir is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Ritonavir is a strong inhibitor of CYP3A4 and a moderate CYP2C9 inducer; it is contraindicated with sensitive drugs that are highly dependent on CYP3A4/5 for clearance. Dronabinol is a CYP2C9 and 3A4 substrate; concomitant use may result in elevated plasma concentrations of dronabinol.
Norepinephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Norethindrone; Ethinyl Estradiol: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Norgestimate; Ethinyl Estradiol: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Nortriptyline: (Moderate) Use caution if coadministration of dronabinol with tricyclic antidepressants (e.g., amitriptyline, desipramine) is necessary. Concurrent use of dronabinol, THC with tricyclic antidepressants may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Olanzapine; Fluoxetine: (Moderate) Use caution if coadministration of dronabinol with fluoxetine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; fluoxetine is a weak inhibitor of CYP2C9 and 3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. A hypomanic episode was reported in a 21 year old female with depression and bulimia receiving fluoxetine 20 mg per day for 4 weeks after smoking marijuana. Her symptoms resolved in 4 days. Because dronabinol, THC is a synthetic analog of a naturally occurring substance found in marijuana, interactions with fluoxetine may also occur with dronabinol.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Use caution if coadministration of dronabinol with amlodipine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; amlodipine is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Use caution if coadministration of dronabinol with rifabutin is necessary, and monitor for a decrease in the efficacy of dronabinol. Concomitant use may result in decreased plasma concentrations of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; rifabutin is a moderate inducer of CYP3A4.
Opiate Agonists: (Moderate) Concomitant use of opioid agonists with dronabinol may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dronabinol 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.
Opicapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including dronabinol, due to the possibility of additive sedation. COMT inhibitors 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.
Oritavancin: (Moderate) Use caution if coadministration of dronabinol with oritavancin is necessary, and monitor for changes in the efficacy or adverse effect profile of dronabinol (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate. Oritavancin is a weak inhibitor of CYP2C9 as well as a weak CYP3A4 inducer. Concomitant use may result in altered plasma concentrations of dronabinol.
Orphenadrine: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Palbociclib: (Moderate) Monitor for an increase in dronabinol-related adverse reactions if coadministration with palbociclib is necessary. Dronabinol is a CYP3A4 substrate and palbociclib is a weak time-dependent CYP3A4 inhibitor.
Pazopanib: (Moderate) Use caution if coadministration of dronabinol with pazopanib is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; pazopanib is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Pentazocine: (Moderate) Concomitant use of dronabinol with other CNS depressants, such as pentazocine, can potentiate the effects of dronabinol on respiratory depression.
Pentazocine; Naloxone: (Moderate) Concomitant use of dronabinol with other CNS depressants, such as pentazocine, can potentiate the effects of dronabinol on respiratory depression.
Perampanel: (Moderate) Use caution if coadministration of dronabinol with perampanel is necessary, and monitor for a decrease in the efficacy of dronabinol. Additive dizziness, confusion, somnolence, and other CNS effects may also occur. Dronabinol is a CYP2C9 and 3A4 substrate; perampanel is a weak in vitro inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Perindopril; Amlodipine: (Moderate) Use caution if coadministration of dronabinol with amlodipine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; amlodipine is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Perphenazine; Amitriptyline: (Moderate) Use caution if coadministration of dronabinol with tricyclic antidepressants (e.g., amitriptyline, desipramine) is necessary. Concurrent use of dronabinol, THC with tricyclic antidepressants may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Pexidartinib: (Moderate) Monitor for a decrease in dronabinol efficacy if coadministration with pexidartinib is necessary. Coadministration may decrease the exposure of dronabinol. Dronabinol is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer.
Phendimetrazine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Phenothiazines: (Moderate) Use caution if coadministration of phenothiazines with dronabinol is necessary. Administration of dronabinol with phenothiazines (e.g., prochlorperazine) has resulted in improved antiemetic efficacy as compared to either drug alone, without additional toxicity. However, it is also possible that coadministration may result in additive dizziness, confusion, somnolence, and other CNS effects.
Phentermine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Phentermine; Topiramate: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm. (Moderate) Use caution if coadministration of dronabinol with topiramate is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; topiramate is a weak inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Phenytoin: (Major) Use caution if coadministration of dronabinol with phenytoin is necessary, and monitor for an increase in phenytoin levels and phenytoin-related adverse effects, as well as a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; phenytoin is a strong inducer of CYP3A4 and a moderate CYP2C9 inducer. Concomitant use may result in decreased plasma concentrations of dronabinol. Additionally, dronabinol is highly bound to plasma proteins, and may displace and increase the free fraction of other concomitantly administered protein-bound drugs; caution is recommended with other drugs with a narrow therapeutic index.
Pimozide: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including dronabinol.
Pirfenidone: (Moderate) Use caution if coadministration of dronabinol with pirfenidone is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; pirfenidone is a weak inhibitor of CYP2C9 and 3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Posaconazole: (Major) Use caution if coadministration of dronabinol with posaconazole is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; posaconazole is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Pramipexole: (Moderate) Concomitant use of dronabinol with other CNS depressants, such as pramipexole, can potentiate the effects of dronabinol on respiratory depression.
Pregabalin: (Moderate) Concomitant use of dronabinol with other CNS depressants can potentiate the effects of dronabinol on respiratory depression. Pregabalin can cause considerable somnolence and the combined use of ethanol or other CNS depressants with pregabalin may lead to an additive drowsy effect.
Prilocaine; Epinephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Procainamide: (Major) Use caution if coadministration of dronabinol with procainamide is necessary, and monitor for an increase in procainamide-related adverse effects. Dronabinol is highly bound to plasma proteins, and may displace and increase the free fraction of other concomitantly administered protein-bound drugs; caution is recommended with other drugs with a narrow therapeutic index.
Promethazine; Phenylephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Protriptyline: (Moderate) Use caution if coadministration of dronabinol with tricyclic antidepressants (e.g., amitriptyline, desipramine) is necessary. Concurrent use of dronabinol, THC with tricyclic antidepressants may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Pseudoephedrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Pseudoephedrine; Triprolidine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Quinine: (Moderate) Use caution if coadministration of dronabinol with quinine is necessary, and monitor for changes in the efficacy or adverse effect profile of dronabinol (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate. Quinine is a moderate inhibitor and inducer (in vitro) of CYP3A4. Concomitant use may result in altered plasma concentrations of dronabinol.
Racepinephrine: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in addit ive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Ranolazine: (Moderate) Use caution if coadministration of dronabinol with ranolazine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ranolazine is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Rasagiline: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including dronabinol, THC. Use dronabinol cautiously with MAOIs; warn patients to not drive or perform other hazardous activities until they know how a particular drug combination affects them. In some cases, the dosages of the CNS depressants may need to be reduced.
Ribociclib: (Moderate) Monitor for an increase in dronabinol-related adverse reactions if coadministration with ribociclib is necessary. Dronabinol is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Ribociclib; Letrozole: (Moderate) Monitor for an increase in dronabinol-related adverse reactions if coadministration with ribociclib is necessary. Dronabinol is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Rifabutin: (Moderate) Use caution if coadministration of dronabinol with rifabutin is necessary, and monitor for a decrease in the efficacy of dronabinol. Concomitant use may result in decreased plasma concentrations of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; rifabutin is a moderate inducer of CYP3A4.
Rifampin: (Moderate) Use caution if coadministration of dronabinol with rifampin is necessary, and monitor for a decrease in the efficacy of dronabinol. Concomitant use may result in decreased plasma concentrations of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; rifampin is a strong inducer of CYP3A4 and a moderate CYP2C9 inducer.
Rifapentine: (Moderate) Monitor for a decrease in dronabinol efficacy if coadministration with rifapentine is necessary. Coadministration may decrease the exposure of dronabinol. Dronabinol is a CYP3A4 and CYP2C9 substrate; rifapentine is a strong CYP3A4 inducer and moderate CYP2C9 inducer.
Ritlecitinib: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with ritlecitinib. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A substrate; ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Major) Use caution if coadministration of dronabinol with ritonavir is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Ritonavir is a strong inhibitor of CYP3A4 and a moderate CYP2C9 inducer; it is contraindicated with sensitive drugs that are highly dependent on CYP3A4/5 for clearance. Dronabinol is a CYP2C9 and 3A4 substrate; concomitant use may result in elevated plasma concentrations of dronabinol.
Rotigotine: (Moderate) Concomitant use of rotigotine with other CNS depressants, such as dronabinol, THC, can potentiate the sedation effects of rotigotine.
Saquinavir: (Major) Avoid the use of dronabinol with saquinavir due to the risk of increased dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; saquinavir is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Sedating H1-blockers: (Moderate) Use caution if coadministration of dronabinol with antihistamines is necessary. Concurrent use of dronabinol, THC with antihistamines may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) Use caution if coadministration of dronabinol with ethinyl estradiol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ethinyl estradiol is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Selegiline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dronabinol. Concurrent use may result in additive CNS depression.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Skeletal Muscle Relaxants: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Sodium Oxybate: (Moderate) Concomitant use of dronabinol with other CNS depressants like sodium oxybate can potentiate the effects of dronabinol on respiratory depression.
Solifenacin: (Moderate) Use caution if coadministration of dronabinol with an anticholinergic drug like solifenacin is necessary. Concurrent use of dronabinol, THC with anticholinergics may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Sotorasib: (Moderate) Monitor for a decrease in dronabinol efficacy if coadministration with sotorasib is necessary. Coadministration may decrease the exposure of dronabinol. Dronabinol is a CYP3A4 substrate; sotorasib is a moderate CYP3A4 inducer.
St. John's Wort, Hypericum perforatum: (Moderate) Use caution if coadministration of dronabinol with St. John's Wort, Hypericum perforatum is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate. St. John's Wort is a strong inducer of CYP3A4 and a moderate CYP2C9 inducer; however, the amount of individual constituents in various products may alter the inhibiting or inducing effects, making drug interactions unpredictable. Concomitant use may result in decreased plasma concentrations of dronabinol.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) Use caution if coadministration of dronabinol with sulfamethoxazole is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; sulfamethoxazole is a moderate inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol.
Suvorexant: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
Sympathomimetics: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Tacrolimus: (Major) Use caution if coadministration of dronabinol with tacrolimus is necessary, and monitor for an increase in tacrolimus concentrations as well as tacrolimus-related adverse effects. Dronabinol is highly bound to plasma proteins, and may displace and increase the free fraction of other concomitantly administered protein-bound drugs; caution is recommended with other drugs with a narrow therapeutic index.
Telmisartan; Amlodipine: (Moderate) Use caution if coadministration of dronabinol with amlodipine is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; amlodipine is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Teniposide: (Moderate) Acute central nervous system (CNS) depression, hypotension, and metabolic acidosis have been observed in patients receiving investigational infusions of high-dose teniposide who were pretreated with antiemetics with CNS-depressant activities (e.g., phenothiazine and related antiemetics). The depressant effects of the antiemetic agents and the alcohol content of the teniposide formulation may place patients receiving higher than recommended doses of teniposide at risk for central nervous system depression.
Tetrabenazine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as dronabinol, THC, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
Tezacaftor; Ivacaftor: (Minor) Use caution if coadministration of dronabinol with ivacaftor is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ivacaftor is a weak inhibitor of CYP3A4 and a weak CYP2C9 inhibitor in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Theophylline, Aminophylline: (Major) Use caution if coadministration of dronabinol with theophylline, aminophylline is necessary, and monitor for increased theophylline levels and theophylline-related adverse effects. Dronabinol is highly bound to plasma proteins, and may displace and increase the free fraction of other concomitantly administered protein-bound drugs; caution is recommended with other drugs with a narrow therapeutic index. Additionally, however, increased theophylline metabolism has been reported with smoking of marijuana; the interaction is similar in effect to that of smoking tobacco, which may substantially decrease theophylline serum concentrations. Because dronabinol, THC is a synthetic analog of a naturally occurring substance found in marijuana, this interaction may also theoretically occur with dronabinol. However, it is also probable that compounds produced via the smoking process (i.e., hydrocarbons) may be responsible for the reduced theophylline levels seen with marijuana smoking, as occurs with tobacco smoking; the smoke contains hydrocarbons that induce hepatic CYP450 microsomal enzymes.
Thiothixene: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as dronabinol. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Ticagrelor: (Moderate) Use caution if coadministration of dronabinol with ticagrelor is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ticagrelor is a weak inhibitor of CYP2C9 and 3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Tinidazole: (Major) The use of tinidazole within 14 days of beginning therapy with dronabinol oral solution is contraindicated, due to the risk of a disulfiram-like reaction. Do not administer tinidazole within 7 days of completing therapy with the oral solution. Dronabinol oral solution contains 50% (w/w) dehydrated alcohol and 5% (w/w) propylene glycol, which can produce disulfiram-like reactions (e.g., abdominal cramps, nausea/vomiting, headaches, and flushing) with drugs such as tinidazole. Ethanol competitively inhibits the metabolism of propylene glycol; however, the contribution of propylene glycol to these reactions is unknown. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations (e.g., capsules).
Tipranavir: (Major) Use caution if coadministration of dronabinol with tipranavir is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Tipranavir is a strong inhibitor of CYP3A4, and is contraindicated with sensitive drugs that are highly dependent on CYP3A4/5 for clearance. Dronabinol is a CYP2C9 and 3A4 substrate; concomitant use may result in elevated plasma concentrations of dronabinol.
Tizanidine: (Moderate) Concomitant use of dronabinol with other CNS depressants, like tizanidine, can potentiate the effects of dronabinol on respiratory depression.
Tolcapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including dronabinol, due to the possibility of additive sedation. COMT inhibitors 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.
Topiramate: (Moderate) Use caution if coadministration of dronabinol with topiramate is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; topiramate is a weak inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Toremifene: (Moderate) Use caution if coadministration of dronabinol with toremifene is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; toremifene is a weak inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol.
Trandolapril; Verapamil: (Moderate) Use caution if coadministration of dronabinol with verapamil is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; verapamil is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Trazodone: (Moderate) CNS depressants, such as dronabinol, should be used cautiously in patients receiving trazodone because of additive CNS-depressant effects, including possible respiratory depression or hypotension. A dose reduction of one or both drugs may be warranted.
Tricyclic antidepressants: (Moderate) Use caution if coadministration of dronabinol with tricyclic antidepressants (e.g., amitriptyline, desipramine) is necessary. Concurrent use of dronabinol, THC with tricyclic antidepressants may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Trimethobenzamide: (Moderate) The concurrent use of trimethobenzamide with other medications that cause CNS depression, such as dronabinol, may potentiate the effects of either trimethobenzamide or dronabinol.
Trimipramine: (Moderate) Use caution if coadministration of dronabinol with tricyclic antidepressants (e.g., amitriptyline, desipramine) is necessary. Concurrent use of dronabinol, THC with tricyclic antidepressants may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Trospium: (Moderate) Use caution if coadministration of dronabinol with an anticholinergic drug like trospium is necessary. Concurrent use of dronabinol, THC with anticholinergics may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Tucatinib: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with tucatinib. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A4 substrate; tucatinib is a strong CYP3A inhibitor.
Valproic Acid, Divalproex Sodium: (Moderate) Use caution if coadministration of dronabinol with valproic acid, divalproex sodium is necessary, and monitor for changes in the efficacy or adverse effect profile of dronabinol (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate. Valproic acid is a moderate inhibitor of CYP2C9 as well as a weak inhibitor and inducer (in vitro) of CYP3A4. Concomitant use may result in altered plasma concentrations of dronabinol.
Vemurafenib: (Moderate) Vemurafenib is an inhibitor of CYP2C9 and may increase concentrations of dronabinol, THC, a CYP2C9 substrate. Use caution if these drugs are coadministered, as severe dronabinol, THC related adverse reactions may occur. A decreased dose of dronabinol may be needed if these drugs are coadministered.
Verapamil: (Moderate) Use caution if coadministration of dronabinol with verapamil is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; verapamil is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Vigabatrin: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with dronabinol, THC.
Vilazodone: (Moderate) Due to the CNS effects of vilazodone, caution should be used when vilazodone is given in combination with other centrally acting medications such as dronabinol, THC.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Use caution if coadministration of dronabinol with clarithromycin is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; clarithromycin is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Voriconazole: (Moderate) Use caution if coadministration of dronabinol with voriconazole is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate. Voriconazole is a strong CYP3A4 inhibitor and a moderate inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol.
Voxelotor: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with voxelotor. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A substrate; voxelotor is a moderate CYP3A inhibitor.
Warfarin: (Major) Use caution if coadministration of dronabinol with warfarin is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence) as well as increased bleeding or an increased PT/INR. Dronabinol is a CYP2C9 and 3A4 substrate; warfarin is a weak inhibitor of CYP2C9 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol. Dronabinol is also highly bound to plasma proteins and may displace and increase the free fraction of other concomitantly administered protein-bound drugs such as warfarin.
Zafirlukast: (Major) Use caution if coadministration of dronabinol with zafirlukast is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; zafirlukast is a moderate inhibitor of CYP2C9 and a weak 3A4 inhibitor in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
Zaleplon: (Moderate) Concomitant use of dronabinol with other CNS depressants, such as zaleplon, can potentiate the effects of dronabinol on respiratory depression.
Zolpidem: (Moderate) Concomitant use of dronabinol with other CNS depressants can potentiate the effects of dronabinol on respiratory depression. If used together, a reduction in the dose of one or both drugs may be needed. For Intermezzo brand of sublingual zolpidem tablets, reduce the dose to 1.75 mg/night.

Dronabinol/Marinol Oral Cap: 2.5mg, 5mg, 10mg
SYNDROS Oral Sol: 1mL, 5mg

Adults

Oral capsule, antiemetic: 15 mg/m2/dose for 4 to 6 doses/day.
Oral solution, antiemetic: 12.6 mg/m2/dose for 4 to 6 doses/day.
Oral capsule, appetite stimulant: 10 mg twice daily.
Oral solution, appetite stimulant: 16.8 mg/day.

Geriatric

Oral capsule, antiemetic: 15 mg/m2/dose for 4 to 6 doses/day.
Oral solution, antiemetic: 12.6 mg/m2/dose for 4 to 6 doses/day.
Oral capsule, appetite stimulant: 10 mg twice daily.
Oral solution, appetite stimulant: 16.8 mg/day.

Adolescents

Safety and efficacy have not been established; however, doses up to 15 mg/m2/dose have been used off-label for CINV.

Children

5 to 12 years: Safety and efficacy have not been established; however, doses up to 15 mg/m2/dose have been used off-label for CINV.
1 to 4 years: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Dronabinol (delta-9-tetrahydrocannabinol, delta-9-THC) is an orally active cannabinoid, having complex effects on the CNS, including central sympathomimetic activity. At least two endogenous cannabinoid receptors, CB1 and CB2, have been identified, and an endogenous cannabinoid ligand (e.g., anandamide) has also been isolated. Cannabinoid receptors exert signal transduction effects through G-protein-coupled receptors, resulting in decreased excitability of neurons; however, some reports have suggested that cannabinoids can stimulate adenylyl cyclase. The CB2 receptor is generally only found peripherally and has been shown to affect the immune system. The CB1 receptor is highly distributed throughout the brain and can also be found in several peripheral tissues. Cannabinoids exert a wide range of CNS effects including short-term memory deficits, sense of time dilation, enhanced sensation, and higher-order cognitive impairment. Cannabinoids also produce both euphoria and dysphoria, depending upon the prior experience of the individual and the dose administered. The brain distribution of CB1 receptors and receptor-activated G-proteins correlates with the behavioral effects of these compounds.
 
Cannabinoids also exhibit CNS-mediated effects on thermoregulation, feeding behavior, nausea, and reward mechanisms. They were thought to produce antiemetic effects by affecting sites in the upper cortex, which then influence the vomiting center in the medulla; however, it is now hypothesized that the antiemetic effects are mediated by cannabinoid receptors in the vomiting center of the medulla, the area subpostrema of the nucleus tractus solitarii (ASNTS). Cannabinoids may act in the vomiting center to oppose the effects of serotonin (5-HT3) to block the release of neurotransmitters from vagal afferent terminals, which help to produce emesis.
 
The appetite stimulating effects are mediated by cannabinoid receptors in the lateral hypothalamus. There is also evidence that appetite stimulation and antiemetic effects are both mediated at the ASNTS, since this region is directly connected to the hypothalamus. Cannabinoids exert their effects on body temperature directly at brain regulatory centers, possibly inhibiting noradrenergic activity in the hypothalamus.
 
Tachyphylaxis and tolerance develop to some of the cardiovascular and CNS effects of dronabinol and other cannabinoids with chronic use, suggesting an indirect effect on sympathetic neurons. In a study of the pharmacodynamics of chronic dronabinol exposure, healthy male volunteers (n = 12) treated with dronabinol (approximately 200 mg per day, divided, for 16 days) initially experienced tachycardia, replaced successively by normal sinus rhythm, and then bradycardia. An initial decrease in supine blood pressure, made worse by standing, was also observed. Tolerance developed to the cardiovascular and subjective CNS effects of dronabinol within 12 days of treatment initiation; however, tachyphylaxis and tolerance do not appear to develop to the appetite stimulant effect of dronabinol. In studies involving patients with acquired immune deficiency syndrome (AIDS), the appetite stimulant effect of dronabinol has been sustained for up to five months in clinical trials, at dosages ranging from 2.5 mg/day to 20 mg/day.

Dronabinol is administered orally. Plasma protein binding of dronabinol and its metabolites is approximately 97%. Due to lipid solubility, the apparent volume of distribution (Vd) is 10 L/kg. The elimination of dronabinol is biphasic; there is a rapid distribution phase (initial half-life about 4 to 5 hours), believed to be due to the highly lipophilic nature of the drug and redistribution into lipid-rich tissues, and a terminal half-life of around 25 to 36 hours; the average clearance is about 0.2 L/kg*h, but is highly variable due to the complexity of cannabinoid distribution. Dronabinol and its biotransformation products are excreted in both feces and urine; excretion is mainly fecal by way of the bile, with about 50% of a dose being recovered in feces within 72 hours in contrast to 10% to 15% recovered from urine. Less than 5% of an oral dose is recovered unchanged in the feces. Because of its large volume of distribution, dronabinol and its metabolites may be excreted at low levels for prolonged periods of time. Following single dose administration, low levels of dronabinol metabolites have been detected for more than 5 weeks in the urine and feces.
 
Affected cytochrome P450 isoenzymes: CYP2C9, CYP3A4
Dronabinol undergoes extensive first-pass metabolism, primarily by microsomal hydroxylation, yielding both active and inactive metabolites. Based on in vitro data, CYP2C9 appears to be responsible for the formation of the primary active metabolite, while CYP3A4 is also responsible for dronabinol metabolism. Patients with diminished CYP2C9 function have a 2- to 3-fold higher exposure to dronabinol; these patients should be monitored for increased adverse events. Dronabinol and its principal active metabolite, 11-OH-delta-9-THC, are present in approximately equal concentrations in plasma; the enzyme inhibition and induction potential of both are not completely understood.

Oral Route

Dronabinol is almost completely absorbed (90% to 95%) after single oral doses; however, due to first pass metabolism and high lipid solubility, only 10% to 20% of the administered dose reaches the systemic circulation. Under fasting conditions, relative bioavailability data suggests that dronabinol oral solution at a dose of 4.2 mg provides similar exposure (Cmax and AUC) to dronabinol capsules at a dose of 5 mg. Concentrations of both parent drug and the active metabolite (11-hydroxy-delta-9-THC) peak at approximately 0.5 to 4 hours after oral dosing, and decline over several days for both the oral solution and capsule.
 
The mean Cmax was 1.9 ng/mL (+/- 1.3 ng/mL) after administration of dronabinol oral solution (4.2 mg) to healthy, fasting patients, and was 1.32 ng/mL (+/- 0.62 ng/mL), 2.96 ng/mL (+/- 1.81 ng/mL), and 7.88 ng/mL (+/- 4.54 ng/mL) after administration of dronabinol capsules (2.5 mg, 5 mg, and 10 mg, respectively); a slight increase in dose proportionality for dronabinol capsules was observed with increasing dose. The mean AUC was 3.8 ng*h/mL (+/- 1.8 ng*h/mL) after administration of the solution and 2.88 ng*h/mL (+/- 1.57 ng*h/mL), 6.16 ng*h/mL (+/- 1.85 ng*h/mL), and 15.2 ng*h/mL (+/- 5.52 ng*h/mL) after administration of 2.5 mg, 5 mg, and 10 mg capsules, respectively. Dronabinol capsules have an onset of action of approximately 0.5 to 1 hours, and peak effect at 2 to 4 hours after administration; the duration of action for psychoactive effects is 4 to 6 hours, but the appetite stimulant effect may continue for 24 hours or longer. Following administration of the oral solution, the mean inter- and intra-subject variability in Cmax was approximately 66% and 47%, respectively, and was 67% and 14%, respectively, in AUC.
 
A high-fat, high calorie meal (950 calories; 59 grams of fat, approximately 50% of total caloric content of the meal) resulted in approximately a 2.5-fold increase in total exposure (AUC) and approximately a 5 hour delay in median Tmax with concomitant administration of dronabinol oral solution; the Cmax also decreased by approximately 20%.

Pregnancy

Due to the potential for fetal harm, pregnancy should be avoided during treatment with dronabinol, THC, a synthetic cannabinoid. Delta-9-THC has been measured in the cord blood of some infants whose mothers reported use of cannabis, suggesting that dronabinol may cross the placenta to the fetus during pregnancy. Although data on the use of synthetic cannabinoids during pregnancy are limited, published studies suggest that the use of cannabis (including THC) during pregnancy may increase the risk of adverse fetal/neonatal outcomes including fetal growth restriction, low birth weight, preterm birth, small-for-gestational age, admission to the NICU, and stillbirth. Toxicity studies in pregnant rats and newborn pups have not revealed evidence of teratogenicity; however, maternal administration of dronabinol to rats from pregnancy (implantation) through weaning was associated with maternal toxicity, including mortality of pups, and adverse developmental and neurodevelopmental effects on the pups at 2 to 6 times the maximum recommended human doses (MRHD) for patients with AIDS and 0.33 to 1 times the MRHD for patients with cancer. At the same doses, reduced pup bodyweight, increased stillbirths, and mortality of offspring were observed; no neurodevelopmental adverse effects were observed. Dronabinol oral solution additionally contains alcohol, which is associated with fetal harm including CNS abnormalities, behavioral disorders, and impaired intellectual development.

Breast-feeding infants should have their weight monitored during use of dronabinol for the treatment of nausea/vomiting from chemotherapy in a lactating patient. Advise HIV-infected lactating patients receiving dronabinol not to breastfeed due to the potential for HIV transmission. There are limited data on the presence of dronabinol in human milk, the effects on the breastfed infant, or the effects on milk production. The reported effects of inhaled cannabis transferred to the breastfed infant have been inconsistent and insufficient to establish causality. In rat offspring exposed to dronabinol during pregnancy and lactation, reduced bodyweight was observed during the lactation stage with maternal administration of dronabinol at 2 times and less than the maximum recommended human dose (MRHD) for patients with AIDS and cancer, respectively. Consider the developmental and health benefits of breast-feeding along with the clinical need for dronabinol and any potential adverse effects on the breastfed infant from dronabinol or from the underlying maternal condition.