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Marinol

Generic Name: Dronabinol
Class: Antiemetics, Miscellaneous
VA Class: GA605
Chemical Name: (6aR-trans)-6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b, d]pyran-1-ol
Molecular Formula: C21H30O2
CAS Number: 1972-08-3

Medically reviewed by Drugs.com. Last updated on Nov 5, 2018.

Introduction

Antiemetic and appetite stimulant; a synthetic cannabinoid.1 2 3 4 5 6 7 8 10 11 12 13 14 17 26

Uses for Marinol

Anorexia Associated with Weight Loss in Patients with AIDS

Treatment of anorexia associated with weight loss in patients with acquired immunodeficiency syndrome (AIDS)1 2 3 4 5 7 8 26 (has been designated an orphan drug by FDA for this use).19

Cancer Chemotherapy-induced Nausea and Vomiting

Treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic therapy.1 10 11 12 13 14 26

ASCO does not consider cannabinoids (e.g., dronabinol, nabilone) appropriate first-line antiemetics for patients receiving chemotherapy of low, moderate, or high emetic risk.31 For patients in whom a cannabinoid is chosen for rescue or refractory antiemetic use, ASCO recommends dronabinol or nabilone over medical marijuana and states that dosage regimens for these synthetic cannabinoids are well established; however, such information is not available for the various preparations of medical marijuana.31

Marinol Dosage and Administration

Administration

Oral Administration

Administer orally as capsules (e.g., Marinol) or oral solution (Syndros).1 4 5 26

For the management of anorexia in adults with AIDS, initially administer dronabinol capsules or oral solution twice daily, one hour before lunch and dinner.1 26 (See Food under Pharmacokinetics.) In geriatric patients or patients unable to tolerate the recommended twice-daily dosage, may give dronabinol capsules or oral solution once daily, one hour before dinner or at bedtime.1 26 Administering dronabinol later in the day may help reduce the frequency of adverse CNS effects.1 26

For the management of cancer chemotherapy-induced nausea and vomiting, administer dronabinol capsules or oral solution 1–3 hours prior to chemotherapy and then every 2–4 hours after chemotherapy.1 26 Administer first dose of dronabinol capsules or oral solution on an empty stomach, at least 30 minutes before eating.1 26 May administer subsequent doses without regard to meals, but administer in a consistent manner relative to meals for each chemotherapy cycle.1 26 (See Food under Pharmacokinetics.)

Administer dronabinol oral solution using the calibrated dosing syringe supplied by manufacturer.26 The oral syringe measures a maximum dose of 5 mg (i.e., 1 mL of the oral solution); if the prescribed dose is >5 mg, divide the dose into 2 or more portions and administer the total dose using the oral syringe.26 Firmly insert bottle adapter into neck of bottle before first use and keep in place for duration of use (≤28 days).26 To dispense dose, firmly insert oral dosing syringe into adapter, then carefully invert bottle and withdraw appropriate dose into syringe.26 Administer dose slowly into the back of mouth on top of the tongue.26 Drink a full glass of water (180–240 mL) following administration.26 Replace cap over bottle adapter after each use.26

Dosage

A 4.2-mg dose of dronabinol oral solution appears to provide comparable systemic exposure to a 5-mg oral dose given as dronabinol capsules.26 (See Bioavailability under Pharmacokinetics.)

Adults

Anorexia Associated with Weight Loss in Patients with AIDS

Adverse CNS effects (e.g., feeling “high,” dizziness, confusion, somnolence) are dose related; monitor patients and reduce dosage, if necessary.1 CNS effects generally resolve within 1–3 days with continued therapy at the same dosage.1 26

Oral (Capsules)

Initially, 2.5 mg twice daily, given one hour before lunch and dinner.1 4 5

If unable to tolerate this dosage, consider initiating therapy at a dosage of 2.5 mg once daily, given one hour before dinner or at bedtime.1 (See Geriatric Patients under Dosage.)

If adverse CNS effects are severe or persistent, reduce dosage to 2.5 mg once daily given in the evening or at bedtime.1 If tolerated and additional therapeutic effect is desired, gradually increase dosage (e.g., 2.5 mg one hour before lunch and 5 mg one hour before dinner or 5 mg one hour before lunch and 5 mg one hour before dinner) up to a maximum of 20 mg daily, administered as 10 mg twice daily.1 4 5

In appetite stimulation studies, dosages ranged from 2.5–20 mg daily; most patients respond to 2.5 mg twice daily.1 4 5

Oral (Solution)

Initially, 2.1 mg twice daily, given one hour before lunch and dinner.26

If unable to tolerate this dosage, consider initiating therapy at a dosage of 2.1 mg once daily, given one hour before dinner or at bedtime.26 (See Geriatric Patients under Dosage.)

If adverse CNS effects are severe or persistent, reduce dosage to 2.1 mg once daily, given one hour before dinner or at bedtime.26 If tolerated and additional therapeutic effect is desired, gradually increase dosage (e.g., 2.1 mg one hour before lunch and 4.2 mg one hour before dinner or 4.2 mg one hour before lunch and 4.2 mg one hour before dinner) up to a maximum of 16.8 mg daily, administered as 8.4 mg twice daily.26

In appetite stimulation studies, dosages ranged from 2.5–20 mg daily (given as oral capsules); most patients respond to 2.1 mg twice daily (given as oral solution).1 4 5 26 30

Cancer Chemotherapy-induced Nausea and Vomiting

Adverse effects are dose related and incidence of adverse psychiatric effects increases substantially at the maximum dosage; monitor patients for adverse effects during dosage escalation.1 26

Oral (Capsules)

Initially, 5 mg/m2 given 1–3 hours before chemotherapy; repeat every 2–4 hours after chemotherapy up to a total of 4–6 doses daily.1 23

Based on clinical response and tolerability, may increase dosage in 2.5 mg/m2 increments during a chemotherapy cycle or at subsequent cycles up to a maximum of 15 mg/m2 for each dose for a total of 4–6 doses each day.1 23

To reduce the risk of adverse CNS effects, consider reducing dosage to 2.5 mg once daily given 1–3 hours before chemotherapy.1

Oral (Solution)

Initially, 4.2 mg/m2 given 1–3 hours before chemotherapy; repeat every 2–4 hours after chemotherapy up to a total of 4–6 doses daily.26 Round calculated doses to the nearest 0.1-mg increment to correspond with the calibrated oral dosing syringe; may need to round the dose to the nearest 0.1-mL increment.26

Based on clinical response and tolerability, may increase dosage in 2.1 mg/m2 increments during a chemotherapy cycle or at subsequent cycles up to a maximum of 12.6 mg/m2 for each dose for a total of 4–6 doses each day.26

To reduce the risk of adverse CNS effects, consider reducing dosage to 2.1 mg once daily given 1–3 hours before chemotherapy.26

Prescribing Limits

Adults

Anorexia Associated with Weight Loss in Patients with AIDS
Oral

Capsules: Maximum 20 mg daily (10 mg twice daily).1 4 5

Solution: Maximum 16.8 mg daily (8.4 mg twice daily).26

Cancer Chemotherapy-induced Nausea and Vomiting
Oral

Capsules: Maximum 15 mg/m2 for each dose for a total of 4–6 doses each day.1 23

Solution: Maximum 12.6 mg/m2 for each dose for a total of 4–6 doses each day.26

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.1 23 26

Renal Impairment

No specific dosage recommendations at this time.1 23 26

Geriatric Patients

Select dosage with caution, usually starting at low end of recommended dosage range because these patients have a greater frequency of falls; decreased hepatic, renal, or cardiac function; increased sensitivity to psychoactive effects; and of concomitant illnesses and medication.1 26 (See Geriatric Use under Cautions.)

Anorexia Associated with Weight Loss in Patients with AIDS

Oral (Capsules): Initially, 2.5 mg once daily given one hour before dinner or at bedtime.1

Oral (Solution): Initially, 2.1 mg once daily given one hour before dinner or at bedtime.26

Cancer Chemotherapy-induced Nausea and Vomiting

Oral (Capsules): Initially, 2.5 mg/m2 once daily, given 1–3 hours before chemotherapy.1

Oral (Solution): Initially, 2.1 mg/m2 once daily, given 1–3 hours before chemotherapy.26

Cautions for Marinol

Contraindications

  • History of hypersensitivity to dronabinol or any ingredient in the formulation.1 26 Hypersensitivity reactions reported with dronabinol include lip swelling, hives, disseminated rash, oral lesions, skin burning, flushing, and throat tightness.1 26

  • Capsules (e.g., Marinol): Hypersensitivity to sesame oil.1

  • Oral solution (Syndros): Hypersensitivity to alcohol; current or recent (i.e., within 14 days) therapy with disulfiram- or metronidazole-containing products.26 (See Specific Drugs and Foods under Interactions.)

Warnings/Precautions

Neuropsychiatric Adverse Effects

May cause adverse psychiatric effects, including exacerbation of mania, depression, or schizophrenia, 1 26 Prior to initiating dronabinol therapy, screen patients for a history of these psychiatric conditions.1 26 Avoid dronabinol therapy in patients with a history of psychiatric disorders; if therapy cannot be avoided, monitor for new or worsening psychiatric symptoms during therapy.1 26 Avoid concomitant use of other drugs associated with similar psychiatric adverse effects.1 26

May cause cognitive impairment and altered mental state.1 26 Geriatric1 26 and pediatric patients26 may be more sensitive to the neurologic and psychoactive effects.1 26 May impair cognitive and/or physical abilities required to perform hazardous tasks (e.g., operating a motor vehicle or other dangerous machinery).1 26 If signs or symptoms of cognitive impairment develop during therapy, reduce the dosage or discontinue dronabinol.1 26

Concomitant use of other drugs that cause dizziness, confusion, sedation, or somnolence increases the risk of such effects.1 26 (See Specific Drugs and Foods under Interactions.)

Hemodynamic Instability

Occasional hypotension, hypertension, syncope, or tachycardia may occur.1 26 Patients with cardiac disorders may be at increased risk.1 26 Monitor for changes in BP, heart rate, and syncope following initiation of therapy or increases in dosage.1 26

Avoid concomitant use of dronabinol and other drugs associated with similar cardiac effects.1 26 (See Specific Drugs and Foods under Interactions.)

Interaction with Disulfiram and Metronidazole

Dronabinol oral solution (Syndros) contains 50% dehydrated alcohol and 5.5% propylene glycol; therefore, disulfiram-like reactions (e.g., abdominal cramps, nausea, vomiting, headaches, flushing) can occur in patients concurrently receiving disulfiram, metronidazole, or other drugs associated with such reactions.26

Concomitant use of dronabinol oral solution and disulfiram- or metronidazole-containing preparations is contraindicated.26 Allow at least 14 days to elapse between discontinuance of disulfiram- or metronidazole-containing preparations and initiation of dronabinol oral solution and at least 7 days between discontinuance of dronabinol oral solution and initiation of such preparations.26 (See Specific Drugs and Foods under Interactions.)

Alcohol competitively inhibits the metabolism of propylene glycol, which may result in elevated concentrations of propylene glycol.26 However, the contribution of propylene glycol, if any, to the interaction between disulfiram and dronabinol oral solution is not known.26

Seizures

Seizures and seizure-like activity reported.1 26 Weigh potential risk of seizures against potential benefits of dronabinol before initiating therapy in patients with a history of seizures, including those receiving anticonvulsants or with other factors that can lower the seizure threshold.1 26

Monitor patients with a history of seizure disorders for worsening seizure control.1 26 If seizures occur, discontinue the drug.1 26 (See Advice to Patients.)

Abuse Potential

Patients with a history of substance abuse or dependence, including marijuana or alcohol, may be more likely to abuse dronabinol as well.1 26 Commercially available dronabinol formulations (e.g., Marinol, Syndros) contain the main psychoactive component in marijuana.1 26 Ingestion of high doses of dronabinol increases the risk of adverse psychiatric effects (e.g., psychosis, hallucinations, depersonalization, mood alteration, paranoia) if the drug is abused or misused, and continued administration can lead to addiction.1 26

Before prescribing dronabinol therapy, assess each patient's risk for abuse or misuse.1 26 Monitor patients with a history of substance abuse for the development of behaviors or conditions associated with substance abuse.1 26 (See Advice to Patients.)

Depending on the formulation, dronabinol is subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (oral solution) or schedule III drug (capsules).1 26 29

Paradoxical Nausea, Vomiting, or Abdominal Pain

May cause nausea, vomiting, or abdominal pain; can be severe (e.g., leading to dehydration or electrolyte abnormalities) and require dosage reduction or drug discontinuance.1 26 These symptoms are similar to cannabinoid hyperemesis syndrome, which has been described as cyclical events of abdominal pain, nausea, and vomiting in chronic users of products containing delta-9-tetrahydrocannabinol (delta-9-THC).1 26

Because patients may not recognize these symptoms as abnormal, clinicians should ask patients or their caregivers about development of worsening nausea, vomiting, or abdominal pain during dronabinol therapy.1 26 Consider dosage reduction or drug discontinuance if a patient develops such symptoms during therapy.1 26

Precautions Associated with Alcohol and Propylene Glycol in the Oral Solution

Dronabinol oral solution contains 50% dehydrated alcohol and 5.5% propylene glycol.26 Alcohol competitively inhibits metabolism of propylene glycol, which may lead to elevated propylene glycol concentrations.26

Preterm neonates have a decreased ability to metabolize propylene glycol and may be at increased risk of accumulation and propylene glycol-associated toxicities (e.g., hyperosmolarity, with or without lactic acidosis; renal toxicity; CNS depression, including stupor, coma, and apnea; seizures; hypotonia; cardiac arrhythmias; ECG changes; hemolysis).26

Safety and efficacy of dronabinol oral solution not established in pediatric patients.26 Avoid use in preterm neonates during the immediate postnatal period.26 (See Pediatric Use under Cautions.)

Specific Populations

Pregnancy

May cause fetal harm.1 26 Limited data regarding use of synthetic cannabinoids during pregnancy.1 26 Avoid use of dronabinol in pregnant women.1 26 (See Distribution under Pharmacokinetics.)

Cannabis use during pregnancy has been associated with adverse fetal/neonatal outcomes (e.g., fetal growth restriction, low birth weight, preterm birth, small-for-gestational age, admission to neonatal intensive care, stillbirth).1 26

Dronabinol oral solution (Syndros) contains alcohol, which is associated with fetal harm.26

In animal reproduction studies, dronabinol was not teratogenic.1 26 However, decreased maternal weight gain and number of viable pups and increased fetal mortality and early resorptions were observed.1 26 Prenatal exposure to delta-9-THC in animals has resulted in neurotoxicity with adverse effects on brain development, including abnormal neuronal connectivity and impairments in cognitive and motor function.1 26

Lactation

Manufacturers state that there are limited data available on presence of dronabinol in human milk, effects of the drug on the breastfed infant, and its effects on milk production.1 26 The reported effects of inhaled cannabis on breastfed infants have been inconsistent and insufficient to establish causality.1 26 (See Distribution under Pharmacokinetics.)

Because of the risk of serious adverse effects in the infant and the risk of HIV transmission, HIV-infected women should not breast-feed infants.1 26 32

Because of possible adverse effects on the breastfed infant, women with nausea and vomiting associated with cancer chemotherapy who are receiving dronabinol should not breastfeed during therapy and for 9 days after discontinuance of the drug.1 26

Pediatric Use

Safety and efficacy not established in pediatric patients.1 26 Pediatric patients may be more sensitive to neurologic and psychoactive effects.1 26

Because of potential propylene glycol-associated toxicity, avoid use of dronabinol oral solution (Syndros) in preterm neonates during the immediate postnatal period.26 (See Precautions Associated with Alcohol and Propylene Glycol in the Oral Solution under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.1 26 In antiemetic studies, no difference in efficacy observed in patients >55 years of age.1 26 Geriatric patients may be more sensitive to neuropsychiatric and postural hypotensive effects.1 26 (See Geriatric Patients under Dosage and Administration.)

Use with caution in geriatric patients with dementia; risk of falls as a result of their underlying disease may be exacerbated by dronabinol's adverse CNS effects (e.g., somnolence, dizziness).1 26 Initiate precautions to prevent falls before starting the drug and closely monitor such patients during therapy.1 26

Pharmacogenomics and Effect of CYP2C9 Polymorphism

Reduced dronabinol clearance and increased exposure (twofold to threefold higher exposure) reported in individuals carrying genetic variants associated with diminished CYP2C9 function (i.e., poor CYP2C9 metabolizers).1 26

Monitor such patients for possibly increased adverse effects.1 26

Common Adverse Effects

Adverse effects may be similar to those of marijuana (cannabis) and other cannabinoids (e.g., nabilone); adverse effects most commonly affect CNS.1 4 5 6 8 10 11 12 17 26

A cannabinoid, dose-related “high” (e.g., easy laughing, elation, heightened awareness), asthenia, palpitations, tachycardia, vasodilation or facial flush, abdominal pain, nausea, vomiting, amnesia, anxiety, nervousness, ataxia, confusion, depersonalization, dizziness, euphoria, hallucinations, paranoid reaction, somnolence, abnormal thinking.1 4 5 6 8 10 11 12 17 26

Interactions for Marinol

No formal drug interaction studies to date.1 26 Enzyme inhibition and induction potential of dronabinol and its active metabolite have not been fully elucidated.1 26

Metabolized principally by CYP2C9 and CYP3A4.1 26

Drugs Affecting Hepatic Microsomal Enzymes

CYP2C9 or CYP3A4 inhibitors: Potential increased systemic exposure to dronabinol and/or its active metabolite; monitor for adverse effects.1 26

CYP2C9 or CYP3A4 inducers: Potential decreased systemic exposure to dronabinol and/or its active metabolite; monitor for reduced efficacy.1 26

Protein-bound Drugs

Potential for displacement of other protein-bound drugs and increased adverse effects.1 26 Monitor for possible increased adverse effects, particularly with drugs that have a narrow therapeutic index and during initiation or dosage increases of dronabinol.1 26

Specific Drugs and Foods

Drug or food

Interaction

Comments

Alcohol

Possible additive drowsiness and CNS depression1 23 26

Amiodarone

CYP2C9 inhibitors potentially can increase systemic exposure to dronabinol and/or its active metabolite1 26

Monitor for dronabinol adverse effects1 26

Amphotericin B

Possible displacement of amphotericin B from plasma proteins and increased adverse effects1 26

Monitor for amphotericin B adverse effects, particularly during initiation or dosage increases of dronabinol1 26

Anticholinergic agents (e.g., antihistamines, atropine, scopolamine)

Possible additive CNS depressant and adverse cardiac effects (e.g., tachycardia)1 26

Avoid concomitant use of drugs associated with cardiac effects similar to those of dronabinol1 26

Antidepressants, tricyclic (e.g., amitriptyline, amoxapine, desipramine)

Possible additive cardiac effects (e.g., tachycardia, hypertension) and CNS depression1 26

Avoid concomitant use of drugs associated with cardiac effects similar to those of dronabinol1 26

Antifungals, azoles (e.g., fluconazole, ketoconazole, itraconazole)

Inhibitors of CYP2C9 (fluconazole) or CYP3A4 (ketoconazole, itraconazole) potentially can increase systemic exposure to dronabinol and/or its active metabolite1 26

Monitor for dronabinol adverse effects1 26

CNS depressants (e.g., anticholinergic agents, antihistamines, barbiturates, benzodiazepines, buspirone, lithium, muscle relaxants, opiates, scopolamine, TCAs)

Possible additive drowsiness and CNS depression1 26

Possible decreased barbiturate clearance23 30

Pentobarbital: Increased elimination half-life of pentobarbital by 4 hours1 26

Cyclosporine

Possible displacement of cyclosporine from plasma proteins and increased adverse effects1 26

Monitor for cyclosporine adverse effects, particularly during initiation or dosage increases of dronabinol1 26

Disulfiram

Dronabinol oral solution: Disulfiram-like reactions may occur due to alcohol content26

Reversible hypomanic reaction reported in a disulfiram-treated patient who smoked marijuana30

Dronabinol oral solution: Concomitant use contraindicated; allow at least 14 days between discontinuance of disulfiram and initiation of dronabinol oral solution and at least 7 days between discontinuance of dronabinol oral solution and initiation of disulfiram26

Fluoxetine

Manic reaction reported in a fluoxetine-treated patient after smoking marijuana30 34

Grapefruit

CYP3A4 inhibitors potentially can increase systemic exposure to dronabinol and/or its active metabolite1 26

Monitor for dronabinol adverse effects1 26

HIV protease inhibitors (e.g., ritonavir)

CYP3A4 inhibitors potentially can increase systemic exposure to dronabinol and/or its active metabolite1 26

Increased plasma dronabinol concentrations predicted with concomitant use of ritonavir25

No effect observed on plasma concentrations of HIV protease inhibitors with smoked (marijuana) or oral cannabinoids (dronabinol)2

Monitor for dronabinol adverse effects1 26

Reduction in dronabinol dosage may be necessary if used concomitantly with ritonavir; caution advised25

Macrolides (clarithromycin, erythromycin)

CYP3A4 inhibitors potentially can increase systemic exposure to dronabinol and/or its active metabolite1 26

Monitor for dronabinol adverse effects1 26

Metronidazole

Dronabinol oral solution: Disulfiram-like reactions may occur due to alcohol content26

Dronabinol oral solution: Concomitant use contraindicated; allow at least 14 days between discontinuance of metronidazole and initiation of dronabinol oral solution and at least 7 days between discontinuance of dronabinol oral solution and initiation of metronidazole26

Naltrexone

Enhanced effects of oral delta-9-THC observed during opiate receptor blockade18 24

Sympathomimetic agents (e.g., amphetamines)

Possible additive hypertension, tachycardia, and other cardiotoxicity1 26

Avoid concomitant use of drugs associated with cardiac effects similar to those of dronabinol1 26

Warfarin

Possible displacement of warfarin from plasma proteins and increased adverse effects1 26

Monitor for warfarin adverse effects, particularly during initiation or dosage increases of dronabinol1 26

Marinol Pharmacokinetics

Absorption

Bioavailability

About 90–95% absorbed after oral administration of dronabinol oral capsules, but only 10–20% of administered dose reaches systemic circulation because of first-pass hepatic metabolism and high lipid solubility.1 27

Bioequivalence demonstrated between a single 4.25-mg oral dose given as oral solution and a single 5-mg dose given as capsules under fasting conditions.27

Absorption from the oral solution appears to be more rapid than from the capsule.27 In a pharmacokinetic study, plasma concentrations detected within 15 minutes in all individuals following administration of oral solution compared with about 17% of individuals following administration of capsules.27

Peak plasma concentrations of dronabinol and its major active metabolite occur approximately 0.5–4 hours following oral administration of capsules or oral solution.1 26

Steady-state cannabinoid concentrations achieved within about 2 weeks following chronic oral administration.1 26

Onset

Approximately 0.5–1 hour after oral administration of capsules.1 26

Peak effect occurs 2–4 hours after oral administration of capsules.1 26

Duration

Appetite stimulant effect may persist ≥24 hours after oral administration.1 26

Psychoactive effects continue 4–6 hours after oral administration.1 26

Food

Administration of capsules with a high-fat, high-calorie meal delayed time to peak plasma concentrations by 4 hours and increased total exposure 2.9-fold; peak plasma concentration was unchanged.1

Administration of oral solution with a high-fat, high-calorie meal delayed time to peak plasma concentration by approximately 5 hours, decreased peak plasma concentration by approximately 20%, and increased total exposure approximately 2.5-fold.26

Special Populations

Twofold to threefold higher dronabinol exposures reported in poor CYP2C9 metabolizers.1 26 (See Pharmacogenomics and Effect of CYP2C9 Polymorphism under Cautions.)

Distribution

Extent

Volume of distribution: 10 L/kg (highly lipid soluble).1

Dronabinol may cross the placenta; cannabinoids detected in umbilical cord blood in pregnant women who reported prenatal use of cannabis (e.g., marijuana).1 26

Manufacturers state not known if dronabinol is distributed into milk.1 26 Delta-9-THC (the active component of dronabinol) reportedly distributes into milk.33

Plasma Protein Binding

Approximately 97% for dronabinol and its metabolites.1 26 (See Interactions.)

Elimination

Metabolism

Undergoes extensive first-pass hepatic metabolism, principally by hydroxylation, to active and inactive metabolites.1 26 Formation of the major active metabolite, 11-hydroxy-delta-9-THC, appears to be mediated primarily by CYP2C9.1 26 Dronabinol and 11-hydroxy-delta-9-THC are present in plasma in approximately equal concentrations.1

Elimination Route

Dronabinol and its metabolites are eliminated principally in feces (approximately 50%) and to a lesser extent in urine (approximately 10–15%) within 72 hours; <5% of an oral dose is recovered unchanged in feces.1 26 The principal excretory pathway appears to be the biliary system.1 26

Half-life

Biphasic; initial elimination half-life is about 4 hours, and terminal elimination half-life is 25–36 hours.1 2

Because of redistribution, dronabinol and its metabolites may be excreted at low concentrations for extended periods; dronabinol metabolites detected in urine and feces >5 weeks following single doses.1 26

Stability

Storage

Oral

Capsules

8–15ºC in tightly closed container; may refrigerate, but protect from freezing.1

Solution

2–8°C (may be exposed to 15–25°C).26 Can store at 25°C after opening.26 Discard unused portion 28 days after first opening.26

Actions

  • Exerts complex effects on CNS, including central sympathomimetic activity.1 8 17 18 20 26

  • Sympathomimetic activity may result in tachycardia and/or conjunctival injection.1 2 26 Effects on BP are inconsistent; orthostatic hypotension and/or syncope upon abrupt standing occasionally occurs.1 26

  • Exerts reversible effects on appetite, mood, cognition, memory, and perception; these effects appear to be dose related and exhibit considerable interpatient variability.1 26 Antiemetic and appetite stimulant effects may be caused in part by interaction with the cannabinoid receptor system including the cannabinoid 1 (CB1) receptors in the central and peripheral nervous system.1 8 17 26

  • Like other cannabinoids, may possess analgesic, antispasmodic, and muscle relaxant activity; however, further evaluation is necessary.3 20 21

  • May produce alterations in mental state similar to those of cannabis (marijuana).1 3 9 17 18 20 22 26 These effects may include changes in mood (e.g., euphoria, detachment, depression, anxiety, panic, paranoia), impairment in cognitive performance and memory, decreased ability to control drives and impulses, and alterations in the experience of reality (e.g., distortions in perception of objects and sense of time and distance, hallucinations).1 3 9 17 18 20 26

Advice to Patients

  • Importance of advising patients to read the patient information for capsules (e.g., Marinol) or oral solution (Syndros) and the instructions for use of oral solution before starting therapy with the drug.1 26

  • Importance of instructing patients and/or caregivers regarding proper dosing and administration of oral solution.26 Importance of instructing patients to drink a full glass of water (180–240 mL) with each dose of oral solution.26

  • Importance of informing patients that accidental ingestion of oral solution, which contains 50% dehydrated alcohol and 5.5% propylene glycol, may result in toxicity; importance of advising patients to seek immediate medical attention.26 Importance of instructing patients to store capsules and oral solution in a secure place1 26 to prevent possible theft,1 misuse, or accidental ingestion.26

  • Risk of adverse neuropsychiatric effects.1 26 Importance of informing patients that adverse psychiatric effects may occur, particularly in patients with a past psychiatric history or in those concurrently receiving other drugs that also are associated with psychiatric effects.1 26 Importance of also informing patients, particularly geriatric patients, that cognitive impairment or altered mental state may occur during dronabinol therapy, and to contact their clinician if any new or worsening psychiatric symptoms or signs and symptoms of cognitive impairment develop.1 26

  • Importance of advising patients to avoid driving, operating other dangerous machinery, or performing hazardous tasks during therapy until they are reasonably certain that dronabinol does not adversely affect them.1 26

  • Importance of alerting patients to the potential for additive CNS depression during concurrent use with alcohol or other CNS depressants, including benzodiazepines and barbiturates.1 26

  • Risk of hemodynamic instability, particularly in patients with cardiac disorders.1 26 Importance of advising patients to inform their clinician if they experience manifestations of hemodynamic instability, including hypotension, hypertension, syncope, or tachycardia, particularly following initiation or increasing the dosage of dronabinol.1 26

  • Risk of interaction with disulfiram or metronidazole.26 Importance of informing patients that concurrent use of dronabinol oral solution may cause a disulfiram-like reaction because of the alcohol content.26 Importance of advising patients not to take disulfiram- or metronidazole-containing products during treatment with dronabinol oral solution and for ≥7 days following discontinuance of the oral solution.26

  • Risk of seizures.1 26 Importance of advising patients to discontinue dronabinol therapy and immediately contact a clinician if they experience a seizure.1 26

  • Risk of multiple substance abuse.1 26 Importance of informing patients with a history of substance abuse or dependence, including marijuana and alcohol, that they may be more likely to abuse dronabinol.1 26 Importance of advising patients to inform their clinician if they develop substance abuse behaviors or conditions.1 26

  • Risk of paradoxical nausea, vomiting and abdominal pain.1 26 Importance of advising patients to report worsening nausea, vomiting, or abdominal pain to their clinician.1 26

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., disulfiram, metronidazole) and OTC drugs or herbal supplements (see Interactions), as well as concomitant illnesses (e.g., cardiovascular disease, seizures, psychiatric conditions, history of substance or alcohol abuse).1 26

  • Risk of fetal harm.1 26 Necessity of advising women of childbearing potential to avoid use of dronabinol during pregnancy.1 26 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 26 If pregnancy occurs, advise patient of potential risk to fetus.1 26

  • Importance of advising HIV-infected women with anorexia associated with weight loss not to breast-feed.1 26

  • Importance of advising women with nausea and vomiting associated with cancer chemotherapy not to breast-feed during dronabinol therapy and for 9 days after the last dose of the drug.1 26

  • Importance of informing patients of other important precautionary information.1 26 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Dronabinol preparations are subject to control under the Federal Controlled Substances Act of 1970.1 26 29

Dronabinol capsules are subject to control as a schedule III (C-III) drug.1 29

Dronabinol oral solution is subject to control as a schedule II (C-II) drug.26 29 (See Abuse Potential under Cautions.)

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Dronabinol

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, liquid-filled

2.5 mg*

Marinol (C-III)

AbbVie

5 mg*

Marinol (C-III)

AbbVie

10 mg*

Marinol (C-III)

AbbVie

Solution

5 mg/mL

Syndros (C-II)

Insys

AHFS DI Essentials™. © Copyright 2019, Selected Revisions November 5, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. AbbVie, Inc. Marinol (dronabinol) capsules prescribing information. North Chicago, Il; 2017 Aug.

2. Abrams DI, Hilton JF, Leiser RJ et al. Short-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebo-controlled clinical trial. Ann Intern Med. 2003; 139:258-66. http://www.ncbi.nlm.nih.gov/pubmed/12965981?dopt=AbstractPlus

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