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  • CLASSES

    Cannabinoid Antiemetics
    Cannabinoids

    DEA CLASS

    Rx, schedule III

    DESCRIPTION

    Oral synthetic cannabinoid that provides standardized THC concentrations
    Approved use for refractory chemotherapy-induced nausea / vomiting (CINV) and for the treatment of anorexia with weight loss in patients with AIDS
    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

    COMMON BRAND NAMES

    Marinol

    HOW SUPPLIED

    Dronabinol/Marinol Oral Cap: 2.5mg, 5mg, 10mg

    DOSAGE & INDICATIONS

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

    5 mg/m2 by mouth, given 1 to 3 hours before administration of chemotherapy, and then every 2 to 4 hours afterwards for a total of 4 to 6 doses per day; the pediatric dose is the same as the adult dose. The dose may be gradually increased as tolerated (in increments of 2.5 mg/m2) to achieve a therapeutic effect to a maximum of 15 mg/m2 per dose. Dronabinol capsules were evaluated for the treatment of CINV in 454 patients with various malignancies; the efficacy was greatest in patients receiving MOPP treatment for Hodgkin and non-Hodgkin lymphomas. In these patients, escalating the dosage above 7 mg/m2 increased the frequency of adverse reactions without additional antiemetic benefit. Administration with phenothiazines, such as prochlorperazine, has resulted in improved efficacy compared to either drug alone, without additional toxicity.

    Oral dosage, solution
    Adults

    4.2 mg/m2 by mouth (rounded to the nearest 0.1 mg), given 1 to 3 hours prior to chemotherapy and then every 2 to 4 hours after chemotherapy, for a total of 4 to 6 doses per day. To correspond with the calibrated dosing syringe, the dose may need to be rounded to the nearest 0.1 mL. If central nervous system (CNS) adverse events are severe or persistent, reduce the dose to 2.1 mg by mouth once daily, 1 to 3 hours before chemotherapy; in elderly patients, consider starting at a reduced dose of 2.1 mg/m2 prior to chemotherapy. The dose may be gradually increased as tolerated (in increments of 2.1 mg/m2) to achieve a therapeutic effect to a maximum of 12.6 mg/m2 per dose for 4 to 6 doses per day. Dronabinol capsules were evaluated for the treatment of CINV in 454 patients with various malignancies; the efficacy was greatest in patients receiving MOPP treatment for Hodgkin's and non-Hodgkin's lymphomas. In these patients, escalating the dosage above 7 mg/m2 increased the frequency of adverse reactions without additional antiemetic benefit.

    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, one hour before lunch and dinner. Data are not available in cancer patients for increasing the dose above 2.5 mg three 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 three 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.
    NOTE: Dronabinol is not recommended for AIDS-related anorexia in children because it has not been studied for that purpose in a pediatric population.
    Oral dosage, liquid-filled capsules
    Adults

    2.5 mg by mouth twice daily, before lunch and before dinner. The dose may gradually be increased as necessary to a maximum dose of 20 mg per day in divided doses; monitor for adverse events. If the starting dose is not tolerated, a single dose of 2.5 mg may be given by mouth before dinner; if CNS symptoms continue to be a problem, administer in the evening or at bedtime. In a randomized, double-blind, placebo controlled clinical trial of patients with AIDS (n = 139), treatment with dronabinol capsules significantly improved appetite as measured by a visual analog scale at weeks 4 and 6. Trends toward improved body weight and mood, and decreases in nausea, were also seen. 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 per day to 20 mg per day.

    Oral dosage, solution
    Adults

    2.1 mg by mouth twice daily, one hour before lunch and one hour before dinner. If CNS adverse effects are severe or persistent, decrease the dose to 2.1 mg once daily, one hour before dinner or in the evening at bedtime; in elderly patients, consider starting at this dose. If initial doses are ineffective and there are no significant side effects, then the dose may be gradually increased, up to a maximum dose of 8.4 mg twice daily. In a randomized, double-blind, placebo controlled clinical trial of patients with AIDS (n = 139), treatment with dronabinol capsules significantly improved appetite as measured by a visual analog scale at weeks 4 and 6. Trends toward improved body weight and mood, and decreases in nausea, were also seen. Tachyphylaxis and tolerance do not appear to develop to the appetite stimulant effect of dronabinol.

    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

    MAXIMUM DOSAGE

    Adults

    Oral capsule, antiemetic: 15 mg/m2 per dose, for 4 to 6 doses per day.
    Oral solution, antiemetic: 12.6 mg/m2 per dose, for 4 to 6 doses per day.
    Oral capsule, appetite stimulant: 20 mg per day in divided doses.
    Oral solution, appetite stimulant: 16.8 mg per day in divided doses.

    Geriatric

    Oral capsule, antiemetic: 15 mg/m2 per dose, for 4 to 6 doses per day.
    Oral solution, antiemetic: 12.6 mg/m2 per dose, for 4 to 6 doses per day.
    Oral capsule, appetite stimulant: 20 mg per day in divided doses.
    Oral solution, appetite stimulant: 16.8 mg per day in divided doses.

    Adolescents

    Oral capsule, antiemetic: 15 mg/m2 per dose, for 4 to 6 doses per day.
    Oral capsule, anorexia: not recommended, safety and efficacy not established.
    Oral solution, antiemetic and anorexia: safety and efficacy not established.

    Children

    Oral capsule, antiemetic: 15 mg/m2 per dose, for 4 to 6 doses per day.
    Oral capsule, anorexia: not recommended, safety and efficacy not established.
    Oral solution, antiemetic and anorexia: safety and efficacy not established.

    DOSING CONSIDERATIONS

    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.

    ADMINISTRATION

    Oral Administration

    For use in appetite stimulation, administer orally before meals (lunch and dinner). If necessary, a single dose may be given in the evening or at bedtime to minimize side effects.
    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 two 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.

    STORAGE

    Marinol:
    - Protect from freezing
    - Store refrigerated (36 to 46 degrees F) or in a cool place (between 46 and 59 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Sesame oil hypersensitivity

    Dronabinol oral capsules are contraindicated in patients with sesame oil hypersensitivity. Dronabinol oral solution is contraindicated in patients with a history of hypersensitivity to alcohol, and in patients who are receiving or who have received disulfiram- or metronidazole-containing products within 14 days. Dronabinol oral solution contains 50% (w/w) dehydrated alcohol and 5.5% (w/w) propylene glycol. Concomitant use with disulfiram or metronidazole may cause a disulfiram-like reaction, characterized by abdominal cramps, nausea, vomiting, headaches, and flushing. Discontinue products containing disulfiram or metronidazole at least 14 days before starting therapy with dronabinol oral solution, and do not administer these products within 7 days of completing treatment with dronabinol oral solution.

    CNS depression, driving or operating machinery

    Patients receiving dronabinol should be warned against driving or operating machinery or performing any hazardous activity until it has been established they are able to tolerate the drug and perform such tasks safely. Patients should also be warned of possible changes in mood and other adverse behavioral effects of the drug. Dronabinol may impair mental and/or physical abilities; concomitant use of other drugs that cause dizziness, confusion, sedation, or somnolence (e.g., barbiturates, benzodiazepines, lithium, opioids, buspirone, antihistamines, and muscle relaxants) may increase this effect. Patients should remain under the supervision of a responsible adult during the initial use of dronabinol and following dosage adjustments. If signs or symptoms of CNS depression or cognitive impairment develop, reduce the dose of dronabinol or discontinue therapy.

    Angina, cardiac arrhythmias, cardiac disease, coronary artery disease, hypertension, hypotension, orthostatic hypotension, syncope

    The risks versus benefits of dronabinol therapy should be carefully considered in patients with cardiac disease, such as angina, coronary artery disease, cardiac arrhythmias, or hypertension. Monitor patients for changes in blood pressure and heart rate after starting therapy or increasing the dose of dronabinol. Dronabinol increases sympathomimetic activity,which may result in tachycardia. Paradoxically, a orthostatic hypotension or syncope upon abrupt standing can occur with dronabinol. Patients with preexisting hypertension or hypotension can experience worsening of their condition if given dronabinol before their blood pressure is corrected.

    Alcoholism, substance abuse

    Patients who are known to have a history of substance abuse, including alcoholism, should be given dronabinol with caution because they may be more prone to abuse dronabinol. Physical dependence develops as a result of physiological adaptation in response to repeated drug use, and may manifest as withdrawal symptoms after abrupt discontinuation or significant dose reduction. A withdrawal syndrome manifested by hot flashes, sweating, rhinorrhea, loose stools, hiccups, and anorexia was reported within 12 hours after abrupt discontinuation of dronabinol capsules in subjects receiving doses of 210 mg per day for 12 to 16 consecutive days; EEG changes were consistent with the effects of drug withdrawal. These symptoms gradually dissipated over the next 48 hours. Addiction is uncommon and only seen after prolonged high-dose administration. Dronabinol (THC) is the main psychoactive component in marijuana. Ingestion of high doses increases the risk of psychiatric adverse reactions, including psychosis, hallucinations, depersonalization, mood alteration, and paranoia if abused or misused. In a randomized, single-dose, double-blind, placebo- and active-controlled crossover study of experienced marijuana smokers (n = 43), more "drug liking" scores were reported in patients receiving dronabinol 30 mg capsules and oral solution, compared with 10 mg capsules and oral solution and placebo. "Drug liking" scores were consistently greater for dronabinol oral solution compared to capsules, although these scores did not reach statistical significance. In an open-label study of patients with AIDS who received dronabinol capsules for up to 5 months, no abuse, diversion, or systematic change in personality or social functioning were observed, despite the inclusion of a substantial number of patients with a past history of drug abuse. Because the onset of action is slow and gradual, it is only weakly reinforcing, and many reports of users indicate dronabinol's effects are dysphoric and unappealing. In 1999, the US FDA and DEA changed the designation of dronabinol from a potentially highly abusive agent (schedule II controlled substance) to schedule III controlled substance as the abuse potential was determined to be low.

    Bipolar disorder, depression, mania, psychosis, schizophrenia

    Avoid the use of dronabinol in patients with a psychiatric history, including depression, schizophrenia, mania, psychosis, and bipolar disorder, as dronabinol can produce psychotoxic effects and may exacerbate psychiatric disorders. Additionally, avoid concomitant use with drugs associated with similar psychiatric effects. If avoidance is not possible, monitor patients for new or worsening psychiatric symptoms.

    Seizure disorder, seizures

    Dronabinol should be used with caution in patients with a history of seizure disorder or seizures, including patients receiving anti-epileptic medication or with other factors that can lower the seizure threshold. Monitor these patients for worsened seizure control, as dronabinol may lower the seizure threshold. Seizure and seizure-like activity have been reported in patients receiving dronabinol both during clinical trials and in post-marketing reports, although a causal relationship has not been established. Immediately discontinue dronabinol in patients who develop seizures during use.

    Dementia, geriatric

    Geriatric patients are more sensitive to the neurological, psychoactive, and postural hypotensive effects of dronabinol. It is recommended to initiate therapy at the lower end of the dosage range in this patient population if possible. Dronabinol should be used cautiously in geriatric patients with dementia, due to the possibility of falls resulting from the CNS effects of the drug on the underlying disease process. The manufacturer recommends placement of the patient on fall precautions prior to initiation of dronabinol.

    Children

    Dronabinol should be used with caution in children, as they may be more sensitive to the neurological and psychoactive effects of dronabinol. Dronabinol is not recommended for AIDS-related anorexia in children because it has not been studied for that purpose in a pediatric population.

    Infants, neonates

    Avoid the use of dronabinol oral solution in preterm neonates in the immediate postnatal period. Dronabinol oral solution contains dehydrated alcohol (50%, w/w) and propylene glycol (5.5%, w/w). Elevated concentrations of propylene glycol may occur due to competitive inhibition of its metabolism by ethanol. Preterm neonates or infants have a diminished ability to metabolize propylene glycol and may be at increased risk of propylene glycol-associated adverse reactions, such as hyperosmolarity (with or without lactic acidosis), nephrotoxicity, CNS depression (including stupor, coma, and apnea), seizures, hypotonia, cardiac arrhythmias, and hemolysis. Dronabinol should be used with caution in pediatric patients, as they may be more sensitive to the neurological and psychoactive effects of dronabinol. Dronabinol is not recommended for AIDS-related anorexia in this population because it has not been studied.

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during treatment with cannabis (including dronabinol, THC). Dronabinol, THC capsules are classified as FDA pregnancy risk category C. Delta-9-THC has been measured in the cord blood of some infants whose mothers reported prenatal use of cannabis, suggesting that dronabinol may cross the placenta to the fetus during pregnancy; the effects of delta-9-THC on the fetus are not known. There are no adequately controlled studies in pregnant women; however, animal studies have revealed no evidence of teratogenicity due to dronabinol. Published studies do suggest that during pregnancy, the use of cannabis (including THC) 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. Nonclinical toxicity studies in pregnant rats and newborn pups have shown that prenatal exposure to THC resulted in impairment of motor function, alteration in synaptic activity, and interference in cortical projection of neuron development in the offspring; overall, prenatal exposure to THC has resulted in significant and long-term changes in brain development, cognition, and behavior in rat offspring. Dronabinol oral solution additionally contains alcohol, which is associated with fetal harm including CNS abnormalities, behavioral disorders, and impaired intellectual development.

    Infertility, reproductive risk

    Counsel patients about the reproductive risk during dronabinol treatment. Females should avoid pregnancy during treatment with dronabinol. Women who become pregnant while receiving dronabinol should be apprised of the potential hazard to the fetus. During pregnancy, the use of cannabis (including dronabinol, THC) may increase the risk of adverse fetal/neonatal outcomes including growth restriction, low birth weight, preterm birth, small-for-gestational age, admission to the NICU,and stillbirth. In animal studies, prenatal exposure to THC has resulted in significant and long-term changes in brain development, cognition, and behavior in animal studies. Dronabinol oral solution additionally contains alcohol, which is associated with fetal harm including CNS abnormalities, behavioral disorders, and impaired intellectual development. In addition, dronabinol caused reduced ventral prostate, seminal vesicle and epididymal weights, and caused a decrease in seminal fluid volume in male rats; decreases in spermatogenesis, number of developing germ cells, and number of Leydig cells in the testis were also observed. However, sperm count, mating success, and testosterone levels were not affected. The significance of these findings in human fertility (infertility) is not known.

    Breast-feeding

    Due to the potential for serious adverse reactions in nursing infants from dronabinol, advise women to discontinue breast-feeding during treatment and for 9 days after the last dose. Dronabinol is secreted in and concentrated in human breast milk, and is absorbed by the nursing baby, although the data are limited. Data on the effects on a breast-fed infant, or the effects of dronabinol on milk production are also limited. The reported effects of inhaled cannabis transferred to the breast-feeding infant have been inconsistent and insufficient to establish causality.

    ADVERSE REACTIONS

    Severe

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

    Moderate

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

    Mild

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

    DRUG INTERACTIONS

    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: 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: 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; Phenyltoloxamine: 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: 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: 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: 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: 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: 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; Pentazocine: Concomitant use of dronabinol with other CNS depressants, such as pentazocine, can potentiate the effects of dronabinol on respiratory depression.
    Acetaminophen; Pseudoephedrine: 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; Tramadol: Dronabinol, THC can cause CNS depression. Tramadol use increases the risk of CNS depression and respiratory depression when used with other agents that are CNS depressants. Extreme caution is needed in using tramadol at the same time as other CNS depressants. A reduced dose of tramadol is recommended when used with another CNS depressant.
    Acrivastine; Pseudoephedrine: 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.
    Aldesleukin, IL-2: 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.
    Aliskiren; Amlodipine: 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.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: 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.
    Alogliptin; Pioglitazone: Use caution if coadministration of dronabinol with pioglitazone is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; pioglitazone is a weak inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
    Amiodarone: 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: 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.
    Amitriptyline; Chlordiazepoxide: 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: 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: 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: 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; Hydrochlorothiazide, HCTZ; Olmesartan: 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; Hydrochlorothiazide, HCTZ; Valsartan: 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: 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; Telmisartan: 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: 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: 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; Lansoprazole: 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. Use caution if coadministration of dronabinol with lansoprazole 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; lansoprazole is a moderate inhibitor of CYP2C9 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Amoxicillin; Clarithromycin; Omeprazole: 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. Use caution if coadministration of dronabinol with omeprazole 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; omeprazole is a moderate inhibitor of CYP2C9 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Amphetamine: 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: 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 cholesteryl sulfate complex (ABCD): 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 lipid complex (ABLC): 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): 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: 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: 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.
    Apomorphine: 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: 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: 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: 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.
    Aspirin, ASA; Carisoprodol: 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: 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; Omeprazole: Use caution if coadministration of dronabinol with omeprazole 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; omeprazole is a moderate inhibitor of CYP2C9 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Atazanavir: 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: 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. 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). Cobicistat 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.
    Atropine; Difenoxin: Concurrent administration of diphenoxylate/difenoxin with dronabinol can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Atropine; Diphenoxylate: Concurrent administration of diphenoxylate/difenoxin with dronabinol can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    atypical antipsychotic: 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: 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: 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.
    Basiliximab: Use caution if coadministration of dronabinol with basiliximab 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; basiliximab is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Benzodiazepines: Use caution if the use of benzodiazepines are necessary with dronabinol, and monitor for additive dizziness, confusion, somnolence, and other CNS effects.
    Benzphetamine: 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.
    Bexarotene: 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: 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: 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: 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.
    Bromocriptine: Use caution if coadministration of dronabinol with bromocriptine 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; bromicriptine is a moderate inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Brompheniramine; Carbetapentane; Phenylephrine: 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. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants.
    Brompheniramine; Hydrocodone; Pseudoephedrine: 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: 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: 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: 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: 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: Use caution if coadministration of dronabinol with buspirone is necessary, and monitor for additive dizziness, confusion, somnolence, and other CNS effects.
    Butorphanol: Concomitant use of butorphanol with other CNS depressants, such as dronabinol, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
    Cabozantinib: Use caution if coadministration of dronabinol with cabozantinib 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; cabozantinib is a weak inhibitor of CYP2C9 and 3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Capecitabine: Use caution if coadministration of capecitabine with dronabinol, THC is necessary, and 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). Dronabinol is a CYP2C9 and 3A4 substrate; capecitabine and/or its metabolites are thought to be inhibitors of CYP2C9. In a drug interaction study, the mean AUC of another CYP2C9 substrate, S-warfarin (single dose), significantly increased after coadministration with capecitabine; the maximum observed INR value also increased by 91%.
    Capsaicin; Metaxalone: 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: 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.
    Carbetapentane; Chlorpheniramine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants.
    Carbetapentane; Chlorpheniramine; Phenylephrine: 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. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants.
    Carbetapentane; Diphenhydramine; Phenylephrine: 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. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants.
    Carbetapentane; Guaifenesin: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants.
    Carbetapentane; Guaifenesin; Phenylephrine: 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. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants.
    Carbetapentane; Phenylephrine: 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. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants.
    Carbetapentane; Phenylephrine; Pyrilamine: 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. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants.
    Carbetapentane; Pseudoephedrine: 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. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants.
    Carbetapentane; Pyrilamine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants.
    Carbidopa; Levodopa; Entacapone: COMT inhibitors should be given cautiously with other agents that cause CNS depression, including dronabinol, due to the possibility of additive sedation.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: 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.
    Carbinoxamine; Hydrocodone; Phenylephrine: 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.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: 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.
    Carbinoxamine; Phenylephrine: 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.
    Carbinoxamine; Pseudoephedrine: 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.
    Carisoprodol: 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.
    Cetirizine: Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, including dronabinol.
    Cetirizine; Pseudoephedrine: Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, including dronabinol. 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: 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; Guaifenesin; Phenylephrine: 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.
    Chloral Hydrate: The central nervous system depressant effects of chloral hydrate can be potentiated by CNS depressants including dronabinol. If concurrent use is necessary, a dose reduction of one or both medications may be required.
    Chloramphenicol: 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.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: 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: 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; Pseudoephedrine: 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; Guaifenesin; Hydrocodone; Pseudoephedrine: 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; Hydrocodone; Phenylephrine: 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; Hydrocodone; Pseudoephedrine: 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: 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: 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: 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: 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: Use caution if coadministration of dronabinol with ciprofloxacin is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP3A4 substrate; ciprofloxacin is a weak inhibitor of CYP3A4 in vitro. In vivo data is conflicting (no interaction with cyclosporine, potential interaction with sildenafil); one study postulated that the in vivo concentrations reached with routine dosing may be below the inhibitory constant for CYP3A4 activity. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Clarithromycin: 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: Use caution if coadministration of dronabinol with clobazam 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; clobazam is a weak inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
    Clomipramine: 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.
    Clopidogrel: Use caution if coadministration of dronabinol with clopidogrel 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; clopidogrel is a weak inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Cobicistat: 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). Cobicistat 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.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: 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). Cobicistat 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. 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.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: 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). Cobicistat 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. 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.
    Codeine; Phenylephrine; Promethazine: Concomitant use of dronabinol with promethazine can potentiate the effects of dronabinol on respiratory depression. In addition, additive tachycardia and drowsiness may occur, which may be pronounced. 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; Promethazine: Concomitant use of dronabinol with promethazine can potentiate the effects of dronabinol on respiratory depression. In addition, additive tachycardia and drowsiness may occur, which may be pronounced.
    COMT inhibitors: COMT inhibitors should be given cautiously with other agents that cause CNS depression, including dronabinol, due to the possibility of additive sedation.
    Conivaptan: Avoid the coadministration of dronabinol with conivaptan, due to the increased risk of serious dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Subsequent treatment with dronabinol should be initiated no sooner than 1 week after the infusion of conivaptan is completed. Dronabinol is a CYP2C9 and 3A4 substrate; conivaptan is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. Coadministration of intravenous conivaptan (40 mg per day) increased the mean AUC values of another CYP3A4 substrate, midazolam, by approximately 2-fold and 3-fold.
    Crizotinib: Use caution if coadministration of dronabinol with crizotinib 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; crizotinib is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Cyclobenzaprine: 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: 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: 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.
    Dalfopristin; Quinupristin: Use caution if coadministration of dronabinol with dalfopristin; quinupristin 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; quinupristin is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Danazol: 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: 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: 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: 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). Cobicistat 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. 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.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: 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.
    Dasatinib: Use caution if coadministration of dronabinol with dasatinib 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; dasatinib is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Deferasirox: 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: 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: 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: 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.
    Dexamethasone: Use caution if coadministration of dronabinol with dexamethasone is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; dexamethasone is a moderate inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: 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: 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: 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: 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: 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: 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; Promethazine: Concomitant use of dronabinol with promethazine can potentiate the effects of dronabinol on respiratory depression. In addition, additive tachycardia and drowsiness may occur, which may be pronounced.
    Diethylpropion: 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.
    Digoxin: 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.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: 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.
    Diltiazem: 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; Hydrocodone; Phenylephrine: 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.
    Diphenhydramine; Phenylephrine: 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.
    Disulfiram: The use of disulfiram-containing products within 14 days of beginning therapy with dronabinol oral solution is contraindicated; use caution if coadministration with dronabinol capsules is necessary. Do not administer disulfiram-containing products 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 disulfiram or other drugs that produce this reaction. Ethanol competitively inhibits the metabolism of propylene gycol; 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). Additionally, a reversible hypomanic reaction was reported in a 28 year old male who smoked marijuana while taking disulfiram. This reaction was confirmed by dechallenge and rechallenge. Because dronabinol, THC is a synthetic analog of a naturally occurring substance found in marijuana, this interaction may also occur with dronabinol (oral solution and capsules).
    Dobutamine: 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: 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: 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: 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: Concomitant use of dronabinol with other CNS depressants, such as droperidol, can potentiate the effects of dronabinol on respiratory depression.
    Drospirenone; Ethinyl Estradiol: 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: 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.
    Efavirenz: 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: 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: 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.
    Eluxadoline: Use caution if coadministration of dronabinol with eluxadoline 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; eluxadoline is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Elvitegravir: 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: COMT inhibitors should be given cautiously with other agents that cause CNS depression, including dronabinol, due to the possibility of additive sedation.
    Enzalutamide: Use caution if coadministration of dronabinol with enzalutamide 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. Enzalutamide is a moderate inducer and weak inhibitor (in vitro) of CYP2C9, as well as a weak inhibitor (in vitro) and strong inducer of CYP3A4. Concomitant use may result in altered plasma concentrations of dronabinol.
    Ephedrine: 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: 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: 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.
    Erythromycin; Sulfisoxazole: 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: 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: 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: Alcohol is associated with CNS depression. The combined use of alcohol and CNS depressants can lead to additive CNS depression, which could be dangerous in tasks requiring mental alertness and fatal in overdose. Alcohol taken with other CNS depressants can lead to additive respiratory depression, hypotension, profound sedation, or coma. Consider the patient's use of alcohol or illicit drugs when prescribing CNS depressant medications. In many cases, the patient should receive a lower dose of the CNS depressant initially if the patient is not likely to be compliant with avoiding alcohol. Patients receiving dronabinol, THC should avoid alcohol due to the increased incidence of CNS effects. In a study of healthy volunteers, subjects who consumed alcohol experienced marijuana-like side effects more quickly, reported more episodes of euphoria, and had higher plasma THC levels as compared to the use of a placebo with marijuana. The data suggest that alcohol may increase the absorption of THC.
    Ethinyl Estradiol: 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; Desogestrel: 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; Ethynodiol Diacetate: 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; Etonogestrel: 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; Levonorgestrel: 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; Levonorgestrel; Folic Acid; Levomefolate: 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; Norelgestromin: 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: 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; Ferrous fumarate: 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: 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; Ferrous fumarate: 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; Norgestimate: 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: 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: 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.
    Etravirine: Use caution if coadministration of dronabinol with etravirine 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. Etravirine is a moderate inhibitor of CYP2C9 as well as a moderate CYP3A4 inducer. Concomitant use may result in altered plasma concentrations of dronabinol.
    Ezogabine: Due to the CNS effects of ezogabine, an enhanced CNS depressant effect may occur during concurrent use of other centrally-acting medications such as dronabinol, THC. Patients should be monitored for excessive somnolence during concurrent therapy with this agent.
    Felbamate: 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.
    Fenofibrate: Use caution if coadministration of dronabinol with fenofibrate 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; fenofibrate is a moderate inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Fenofibric Acid: 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: 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: 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: 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). Dronabinol is a CYP2C9 and 3A4 substrate; fluconazole is a strong inhibitor of CYP2C9 and a moderate CYP3A4 inhibitor. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Fluorouracil, 5-FU: 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: 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.
    Fluoxetine; Olanzapine: 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: 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: 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: 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-to-strong inhibitor of CYP3A4 and a weak CYP2C9 inhibitor. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Fosamprenavir: Use caution if coadministration of dronabinol with fosamprenavir 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). Fosamprenavir 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.
    Fosphenytoin: 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: 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: Concomitant use of dronabinol with other CNS depressants like general anesthetics can potentiate the effects of dronabinol on respiratory depression.
    Glimepiride; Pioglitazone: Use caution if coadministration of dronabinol with pioglitazone is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; pioglitazone is a weak inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
    Grapefruit juice: 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: Use caution if coadministration of dronabinol with griseofulvin is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; griseofulvin is a moderate inducer of CYP3A4 in vitro. Concomitant use may result in decreased plasma concentrations of dronabinol.
    Guaifenesin; Hydrocodone; Pseudoephedrine: 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; Phenylephrine: 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: 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: Use caution if the use of haloperidol is necessary with dronabinol, and monitor for additive dizziness, confusion, somnolence, and other CNS effects.
    Hydrocodone; Phenylephrine: 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.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: 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.
    Hydrocodone; Pseudoephedrine: 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: 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: 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, STI-571: Use caution if coadministration of dronabinol with imatinib, STI-571 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; imatinib is a moderate inhibitor of CYP2C9 and 3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Imipramine: 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: 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: 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: 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: 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 CYP2C9 and 3A4 substrate; isoniazid is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: 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 CYP2C9 and 3A4 substrate; isoniazid is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. 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: 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 CYP2C9 and 3A4 substrate; isoniazid is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. 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: 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: 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: 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: Use caution if coadministration of dronabinol with ketoconazole 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; ketoconazole is a strong inhibitor of CYP3A4 and a weak CYP2C9 inhibitor in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Lanreotide: Use caution if coadministration of dronabinol with lanreotide 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; lanreotide is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Lansoprazole: Use caution if coadministration of dronabinol with lansoprazole 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; lansoprazole is a moderate inhibitor of CYP2C9 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Lansoprazole; Naproxen: Use caution if coadministration of dronabinol with lansoprazole 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; lansoprazole is a moderate inhibitor of CYP2C9 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Lapatinib: Use caution if coadministration of dronabinol with lapatinib 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; lapatinib is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Leflunomide: 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.
    Lesinurad: 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.
    Levocetirizine: Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, including dronabinol.
    Levothyroxine: Use caution if coadministration of dronabinol with levothyroxine is necessary, and monitor for changes in thyroid function tests (TFTs) and an increase in levothyroxine-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.
    Liotrix: Use caution if coadministration of dronabinol with levothyroxine is necessary, and monitor for changes in thyroid function tests (TFTs) and an increase in levothyroxine-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.
    Lisdexamfetamine: 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: 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.
    Lopinavir; Ritonavir: Use caution if coadministration of dronabinol with lopinavir; 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. Lopinavir is also a strong CYP3A4 inhibitor, and dronabinol is a CYP2C9 and 3A4 substrate. Concomitant use may result in elevated plasma concentrations of dronabinol. 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: 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.
    Luliconazole: Use caution if coadministration of dronabinol with luliconazole 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. Although lulicaonazole is a topical medication, it may have systemic plasma concentrations and is a weak inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Lumacaftor; Ivacaftor: 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: 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: Use caution if the use of maprotioline is necessary with dronabinol, and monitor for additive dizziness, confusion, somnolence, and other CNS effects.
    Meperidine; Promethazine: Concomitant use of dronabinol with promethazine can potentiate the effects of dronabinol on respiratory depression. In addition, additive tachycardia and drowsiness may occur, which may be pronounced.
    Mepivacaine; Levonordefrin: 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.
    Meprobamate: The CNS-depressant effects of meprobamate can be potentiated with concomitant administration of other drugs known to cause CNS depression including dronabinol.
    Metaxalone: 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.
    Metformin; Pioglitazone: Use caution if coadministration of dronabinol with pioglitazone is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; pioglitazone is a weak inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
    Methamphetamine: 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: Concomitant use of dronabinol with other CNS depressants, such as methocarbamol, can potentiate the effects of dronabinol on respiratory depression.
    Methylphenidate: 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: 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: Use caution if coadministration of dronabinol with metyrapone is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; metyrapone is a moderate inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
    Midodrine: 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, RU-486: Use caution if coadministration of dronabinol with mifepristone, RU-486 is necessary, especially if mifepristone is used chronically as for Cushing's syndrome; monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; mifepristone is a moderate inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Mirabegron: Use caution if coadministration of dronabinol with mirabegron 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; mirabegron is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Mirtazapine: 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: 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: 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: 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: The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including dronabinol.
    Nabilone: While taking dronabinol, patients should not be treated with other oral or inhaled cannabinoids, including nabilone. Combining two cannabinoids will lead to an increase in psychotoxic effects, and would not represent any therapeutic benefit to the patient.
    Nafcillin: 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: 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: 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: 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: 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: 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; Palonosetron: 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.
    Nevirapine: Use caution if coadministration of dronabinol with nevirapine is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; nevirapine is a moderate inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
    Nicardipine: Use caution if coadministration of dronabinol with nicardipine 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; nicardipine is a moderate inhibitor of CYP3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Nilotinib: Use caution if coadministration of dronabinol with nilotinib 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. Nilotinib is a moderate inhibitor and inducer of CYP2C9 as well as a moderate CYP3A4 inhibitor. Concomitant use may result in altered plasma concentrations of dronabinol.
    Norepinephrine: 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.
    Nortriptyline: 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.
    Octreotide: Use caution if coadministration of dronabinol with octreotide 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; octreotide is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Ombitasvir; Paritaprevir; Ritonavir: 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.
    Omeprazole: Use caution if coadministration of dronabinol with omeprazole 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; omeprazole is a moderate inhibitor of CYP2C9 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Omeprazole; Sodium Bicarbonate: Use caution if coadministration of dronabinol with omeprazole 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; omeprazole is a moderate inhibitor of CYP2C9 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Opiate Agonists: Concomitant use of opiate agonists and other CNS depressants such as dronabinol, THC may result in respiratory depression, CNS depression, and/or hypotension. Prior to concurrent use of opiate agonists 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. When concomitant treatment is necessary, reduce the dose of 1 or both drugs. When levorphanol is used with dronabinol, reduce the initial levorphanol dose by approximately 50% or more.
    Oritavancin: 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: 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.
    Ospemifene: Use caution if coadministration of dronabinol with ospemifene 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; ospemifene is a weak inhibitor of CYP2C9 and 3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Oxcarbazepine: Use caution if coadministration of dronabinol with oxcarbazepine 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; oxcarbazepine is a moderate inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
    Palbociclib: Use caution if coadministration of dronabinol with palbociclib 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; palbociclib is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Pantoprazole: Use caution if coadministration of dronabinol with pantoprazole 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; pantoprazole is a moderate inhibitor of CYP2C9 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Pazopanib: 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.
    Pemoline: 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.
    Pentazocine: Concomitant use of dronabinol with other CNS depressants, such as pentazocine, can potentiate the effects of dronabinol on respiratory depression.
    Pentazocine; Naloxone: Concomitant use of dronabinol with other CNS depressants, such as pentazocine, can potentiate the effects of dronabinol on respiratory depression.
    Perampanel: 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: 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: 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.
    Phendimetrazine: 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: 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: 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: 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. 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: 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.
    Phenylephrine; Promethazine: Concomitant use of dronabinol with promethazine can potentiate the effects of dronabinol on respiratory depression. In addition, additive tachycardia and drowsiness may occur, which may be pronounced. 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: 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: Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including dronabinol.
    Pioglitazone: Use caution if coadministration of dronabinol with pioglitazone is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; pioglitazone is a weak inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
    Pirfenidone: 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: 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: Concomitant use of dronabinol with other CNS depressants, such as pramipexole, can potentiate the effects of dronabinol on respiratory depression.
    Pregabalin: 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: 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: 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: Concomitant use of dronabinol with promethazine can potentiate the effects of dronabinol on respiratory depression. In addition, additive tachycardia and drowsiness may occur, which may be pronounced.
    Protriptyline: 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: 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: 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: 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.
    Ranolazine: 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: 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.
    Regorafenib: Use caution if coadministration of dronabinol with regorafenib 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; regorafenib is a weak inhibitor of CYP2C9 and 3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Rifabutin: 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: 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: Use caution if coadministration of dronabinol with rifapentine 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; rifapentine is a moderate inducer of CYP2C9 and 3A4.
    Rifaximin: Use caution if coadministration of dronabinol with rifaximin is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate. Rifaximin is a moderate inducer of CYP3A4 in vitro; however, in patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations. Concomitant use may result in decreased plasma concentrations of dronabinol.
    Ritodrine: 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.
    Ritonavir: 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: Concomitant use of rotigotine with other CNS depressants, such as dronabinol, THC, can potentiate the sedation effects of rotigotine.
    Saquinavir: 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: 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.
    Skeletal Muscle Relaxants: 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: Concomitant use of dronabinol with other CNS depressants like sodium oxybate can potentiate the effects of dronabinol on respiratory depression.
    Solifenacin: 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.
    Sorafenib: Use caution if coadministration of dronabinol with sorafenib 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; sorafenib is a weak inhibitor of CYP2C9 and 3A4 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    St. John's Wort, Hypericum perforatum: 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.
    Streptogramins: Use caution if coadministration of dronabinol with dalfopristin; quinupristin 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; quinupristin is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: 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.
    Sulfinpyrazone: Use caution if coadministration of dronabinol with sulfinpyrazone 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; sulfinpyrazone is a moderate inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Suvorexant: 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: 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: 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.
    Tamoxifen: Use caution if coadministration of dronabinol with tamoxifen 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; tamoxifen is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Tapentadol: Additive CNS depressive effects are expected if tapentadol is used in conjunction with other CNS depressants including dronabinol, THC. Severe hypotension, profound sedation, coma, or respiratory depression may occur. Prior to concurrent use of tapentadol 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. If a CNS depressant is used concurrently with tapentadol, a reduced dosage of tapentadol and/or the CNS depressant is recommended. Monitor patients for sedation and respiratory depression.
    Telithromycin: Use caution if coadministration of dronabinol with telithromycin 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; telithromycin is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. Concomitant administration of telithromycin with another CYP3A4 substrate, midazolam, resulted in 2-fold (IV) and 6-fold (PO) increases in the AUC of midazolam.
    Teniposide: 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: 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.
    Theophylline, Aminophylline: 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: 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: 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.
    Tipranavir: 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: Concomitant use of dronabinol with other CNS depressants, like tizanidine, can potentiate the effects of dronabinol on respiratory depression.
    Tolcapone: COMT inhibitors should be given cautiously with other agents that cause CNS depression, including dronabinol, due to the possibility of additive sedation.
    Topiramate: 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: 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.
    Tramadol: Dronabinol, THC can cause CNS depression. Tramadol use increases the risk of CNS depression and respiratory depression when used with other agents that are CNS depressants. Extreme caution is needed in using tramadol at the same time as other CNS depressants. A reduced dose of tramadol is recommended when used with another CNS depressant.
    Trandolapril; Verapamil: 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: 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: 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: 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: 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: 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.
    Valproic Acid, Divalproex Sodium: 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: 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: 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: 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: 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.
    Voriconazole: 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 and its major metabolite, voriconazole N-oxide, are moderate CYP3A4 inhibitors; however, the inhibitory potential is less with voriconazole than with ketoconazole and itraconazole. Voriconazole is also a moderate inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol. In healthy male volunteers, voriconazole reduced the clearance of another CYP3A4 substrate, midazolam (IV), by 72% and prolonged the elimination half-life to about 8 hours in a randomized, crossover study. Voriconazole also increased the Cmax and AUC of oral midazolam by 3.8-fold and 10.3-fold, respectively. There was an increase in the bioavailability of oral midazolam from 31% to 84%.
    Warfarin: 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: 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: Concomitant use of dronabinol with other CNS depressants, such as zaleplon, can potentiate the effects of dronabinol on respiratory depression.
    Zolpidem: 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.

    PREGNANCY AND LACTATION

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during treatment with cannabis (including dronabinol, THC). Dronabinol, THC capsules are classified as FDA pregnancy risk category C. Delta-9-THC has been measured in the cord blood of some infants whose mothers reported prenatal use of cannabis, suggesting that dronabinol may cross the placenta to the fetus during pregnancy; the effects of delta-9-THC on the fetus are not known. There are no adequately controlled studies in pregnant women; however, animal studies have revealed no evidence of teratogenicity due to dronabinol. Published studies do suggest that during pregnancy, the use of cannabis (including THC) 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. Nonclinical toxicity studies in pregnant rats and newborn pups have shown that prenatal exposure to THC resulted in impairment of motor function, alteration in synaptic activity, and interference in cortical projection of neuron development in the offspring; overall, prenatal exposure to THC has resulted in significant and long-term changes in brain development, cognition, and behavior in rat offspring. Dronabinol oral solution additionally contains alcohol, which is associated with fetal harm including CNS abnormalities, behavioral disorders, and impaired intellectual development.

    Due to the potential for serious adverse reactions in nursing infants from dronabinol, advise women to discontinue breast-feeding during treatment and for 9 days after the last dose. Dronabinol is secreted in and concentrated in human breast milk, and is absorbed by the nursing baby, although the data are limited. Data on the effects on a breast-fed infant, or the effects of dronabinol on milk production are also limited. The reported effects of inhaled cannabis transferred to the breast-feeding infant have been inconsistent and insufficient to establish causality.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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%.