Dronabinol

Prescription

Noms de marque : DRONABINOL

Forme Pharmaceutique

Capsule

Voie d'Administration

ORAL

Fabricant

American Health Packaging

About This Medication

11 DESCRIPTION Dronabinol is a cannabinoid designated chemically as (6aR,10aR)-6a,7,8,10a-Tetrahydro-6,6,9‑trimethyl-3-pentyl-6H-dibenzo[b,d]-pyran-1-ol. Dronabinol has the following empirical and structural formulas: C 21 H 30 O 2 (molecular weight = 314.46) Dronabinol, the active ingredient in dronabinol capsules, USP, is synthetic delta-9‑tetrahydrocannabinol (delta-9-THC). Dronabinol is a light yellow resinous oil that is sticky at room temperature and hardens upon refrigeration. Dronabinol is insoluble in water and is formulated in sesame oil. It has a pKa of 10.6 and an octanol-water partition coefficient: 6,000:1 at pH 7. Dronabinol capsule strengths are formulated with the following inactive ingredients: FD&C Yellow No. 6, gelatin, glycerin, purified water, sesame oil, titanium dioxide, iron oxide black Ingredients in imprint ink , shellac glaze , isopropyl alcohol , n-butyl alcohol , propylene glycol , and ammonium hydroxide. The 2.5 mg and 5 mg capsules also contain FD&C Blue No. 1 and FD&C Red No. 40. Structural Formula

Principes Actifs

Ingrédient	Dosage
Dronabinol	-

Indications et Utilisation

1 INDICATIONS AND USAGE DRONABINOL CAPSULES, USP are indicated in adults for the treatment of: anorexia associated with weight loss in patients with Acquired Immune Deficiency Syndrome (AIDS). nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. Dronabinol capsules are a cannabinoid indicated in adults for the treatment of: Anorexia associated with weight loss in patients with AIDS. (1) Nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. (1)

Comment ça marche

12.1 Mechanism of Action Dronabinol is an orally active cannabinoid which has complex effects on the CNS, including central sympathomimetic activity. Cannabinoid receptors have been discovered in neural tissues. These receptors may play a role in mediating the effects of dronabinol.

Posologie et Administration

2 DOSAGE AND ADMINISTRATION Anorexia Associated with Weight Loss in Adult Patients with AIDS (2.1) : The recommended adult starting dosage is 2.5 mg orally twice daily, one hour before lunch and dinner. See the full prescribing information for dosage titration to manage adverse reactions and to achieve desired therapeutic effect. Nausea and Vomiting Associated with Chemotherapy in Adult Patients Who Failed Conventional Antiemetics (2.2) : The recommended starting dosage is 5 mg/m 2 , administered 1 to 3 hours prior to the administration of chemotherapy, then every 2 to 4 hours after chemotherapy, for a total of 4 to 6 doses per day. Administer the first dose on an empty stomach at least 30 minutes prior to eating; subsequent doses can be taken without regard to meals. See the full prescribing information for dosage titration to manage adverse reactions and to achieve desired therapeutic effect. 2.1 Anorexia Associated with Weight Loss in Adult Patients with AIDS Starting Dosage The recommended adult starting dosage of dronabinol capsules is 2.5 mg orally twice daily, one hour before lunch and dinner. In elderly patients or patients unable to tolerate 2.5 mg twice daily, consider initiating dronabinol capsules at 2.5 mg once daily one hour before dinner or at bedtime to reduce the risk of central nervous system (CNS) symptoms [see Use in Specific Populations (8.5) ]. Dosing later in the day may reduce the frequency of CNS adverse reactions. CNS adverse reactions are dose-related [see Warnings and Precautions (5.1) ]; therefore, monitor patients and reduce the dosage as needed. If CNS adverse reactions of feeling high, dizziness, confusion, and somnolence occur, they usually resolve in 1 to 3 days and usually do not require dosage reduction. If CNS adverse reactions are severe or persistent, reduce the dosage to 2.5 mg in the evening or at bedtime. Dosage Titration If tolerated and further therapeutic effect is desired, the dosage may be increased gradually to 2.5 mg one hour before lunch and 5 mg one hour before dinner. Increase the dose of dronabinol capsules gradually in order to reduce the frequency of dose-related adverse reactions [see Warnings and Precautions (5.1) ]. Most patients respond to 2.5 mg twice daily, but the dose may be further increased to 5 mg one hour before lunch and 5 mg one hour before dinner, as tolerated to achieve a therapeutic effect. Maximum Dosage: 10 mg twice daily. 2.2 Nausea and Vomiting Associated with Cancer Chemotherapy in Adult Patients Who Failed Conventional Antiemetics Starting Dosage The recommended starting dosage of dronabinol capsules is 5 mg/m 2 , orally administered 1 to 3 hours prior to the administration of chemotherapy and then every 2 to 4 hours after chemotherapy, for a total of 4 to 6 doses per day. In elderly patients, consider initiating dronabinol capsules at 2.5 mg/m 2 once daily 1 to 3 hours prior to chemotherapy to reduce the risk of CNS symptoms [see Use in Specific Populations (8.5) ]. Administer the first dose on an empty stomach at least 30 minutes before eating. Subsequent doses can be taken without regard to meals [see Clinical Pharmacology (12.3) ]. The timing of dosing in relation to meal times should be kept consistent for each chemotherapy cycle, once the dosage has been determined from the titration process. Dosage Titration The dosage can be titrated to clinical response during a chemotherapy cycle or subsequent cycles, based upon initial response, as tolerated to achieve a clinical effect, in increments of 2.5 mg/m 2 . The maximum dosage is 15 mg/m 2 per dose for 4 to 6 doses per day. Adverse reactions are dose-related and psychiatric symptoms increase significantly at the maximum dosage [see Warnings and Precautions (5.1) ]. Monitor patients for adverse reactions and consider decreasing the dose to 2.5 mg once daily 1 to 3 hours prior to chemotherapy to reduce the risk of CNS adverse reactions.

Side Effects Overview

6 ADVERSE REACTIONS Most common adverse reactions (≥3%) are: abdominal pain, dizziness, euphoria, nausea, paranoid reaction, somnolence, thinking abnormal, and vomiting. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Rhodes Pharmaceuticals at 1-888-827-0616, or FDA at 1-800-FDA-1088, or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following serious adverse reactions are described below and elsewhere in the labeling. Neuropsychiatric Adverse Reactions [see Warnings and Precautions (5.1) ] Hemodynamic Instability [see Warnings and Precautions (5.2) ] Seizures [see Warnings and Precautions (5.3) ] Paradoxical Nausea, Vomiting, and Abdominal Pain [see Warnings and Precautions (5.5) ] Studies of AIDS-related weight loss included 157 patients receiving dronabinol capsules at a dose of 2.5 mg twice daily and 67 receiving placebo. Studies of nausea and vomiting related to cancer chemotherapy included 317 patients receiving dronabinol capsules and 68 receiving placebo. In the tables below is a summary of the adverse reactions in 474 patients exposed to dronabinol capsules in studies. Studies of different durations were combined by considering the first occurrence of events during the first 28 days. A cannabinoid dose-related "high" (easy laughing, elation, and heightened awareness) has been reported by patients receiving dronabinol capsules in both the antiemetic (24%) and the lower dose appetite stimulant clinical trials (8%). The most frequently reported adverse experiences in patients with AIDS during placebo-controlled clinical trials involved the CNS and were reported by 33% of patients receiving dronabinol capsules. About 25% of patients reported a CNS adverse reaction during the first 2 weeks and about 4% reported such a reaction each week for the next 6 weeks thereafter. Common Adverse Reactions The following adverse reactions were reported in clinical trials at an incidence greater than 1%. System Organ Class Adverse Reactions General Asthenia Cardiovascular Palpitations, tachycardia, vasodilation/facial flush Gastrointestinal Abdominal pain Actual incidence 3% to 10% , nausea , vomiting Central Nervous System Dizziness , euphoria , paranoid reaction , somnolence , thinking abnormal , amnesia, anxiety/nervousness, ataxia, confusion, depersonalization, hallucination Less Common Adverse Reactions The following adverse reactions were reported in clinical trials at an incidence less than or equal to 1%. System Organ Class Adverse Reactions General Chills, headache, malaise Cardiovascular Hypotension, conjunctival injection [see Clinical Pharmacology (12.2) ] Gastrointestinal Diarrhea, fecal incontinence, anorexia, hepatic enzyme elevation Musculoskeletal Myalgias Central Nervous System Depression, nightmares, speech difficulties, tinnitus Respiratory Cough, rhinitis, sinusitis Skin Flushing, sweating Sensory Vision difficulties 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of dronabinol capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. General disorders and administration site conditions: Fatigue Hypersensitivity reactions: Lip swelling, hives, disseminated rash, oral lesions, skin burning, flushing, throat tightness [see Contraindications (4) ] Injury, poisoning, and procedural complications: Fall [see Use in Specific Populations (8.5) ] Nervous system disorders: Seizures [see Warnings and Precautions (5.3) ], disorientation, movement disorder, loss of consciousness Psychiatric disorders: Delirium, insomnia, panic attack Vascular disorders: Syncope [see Warnings and Precautions (5.2) ]

Mises en Garde et Précautions

5 WARNINGS AND PRECAUTIONS Neuropsychiatric Adverse Reactions : May cause psychiatric and cognitive effects and impair mental and/or physical abilities. Avoid use in patients with a psychiatric history. Monitor for symptoms and avoid concomitant use of drugs with similar effects. Inform patients not to operate motor vehicles or other dangerous machinery until they are reasonably certain that dronabinol capsules do not affect them adversely. (5.1) Hemodynamic Instability : Patients with cardiac disorders may experience hypotension, hypertension, syncope or tachycardia. Avoid concomitant use of drugs with similar effects and monitor for hemodynamic changes after initiating or increasing the dosage of dronabinol capsules. (5.2) Seizures and Seizure-like Activity : Weigh the potential risk versus benefits before prescribing dronabinol capsules to patients with a history of seizures, including those requiring anti-epileptic medication or with other factors that lower the seizure threshold. Monitor patients and discontinue if seizures occur. (5.3) Multiple Substance Abuse : Assess risk for abuse or misuse in patients with a history of substance abuse or dependence, prior to prescribing dronabinol capsules and monitor for the development of associated behaviors or conditions. (5.4) Paradoxical Nausea, Vomiting, or Abdominal Pain : Consider dose reduction or discontinuation, if worsening of symptoms while on treatment. (5.5) 5.1 Neuropsychiatric Adverse Reactions Psychiatric Adverse Reactions Dronabinol has been reported to exacerbate mania, depression, or schizophrenia. Significant CNS symptoms followed oral doses of 0.4 mg/kg (28 mg per 70 kg patient) of dronabinol capsules in antiemetic studies. Prior to initiating treatment with dronabinol capsules, screen patients for a history of these illnesses. Avoid use in patients with a psychiatric history or, if the drug cannot be avoided, monitor patients for new or worsening psychiatric symptoms during treatment. Also, avoid concomitant use with other drugs that are associated with similar psychiatric effects. Cognitive Adverse Reactions Use of dronabinol capsules has been associated with cognitive impairment and altered mental state. Reduce the dose of dronabinol capsules or discontinue use of dronabinol capsules if signs or symptoms of cognitive impairment develop. Elderly patients may be more sensitive to the neurological and psychoactive effects of dronabinol capsules [see Use in Specific Populations (8.4 , 8.5) ]. Hazardous Activities Dronabinol capsules can cause and may impair the mental and/or physical abilities required for the performance of hazardous tasks such as driving a motor vehicle or operating machinery. Concomitant use of other drugs that cause dizziness, confusion, sedation, or somnolence such as CNS depressants may increase this effect (e.g., barbiturates, benzodiazepines, ethanol, lithium, opioids, buspirone, scopolamine, antihistamines, tricyclic antidepressants, other anticholinergic agents, muscle relaxants). Inform patients not to operate motor vehicles or other dangerous machinery until they are reasonably certain that dronabinol capsules do not affect them adversely. 5.2 Hemodynamic Instability Patients may experience occasional hypotension, possible hypertension, syncope, or tachycardia while taking dronabinol capsules [see Clinical Pharmacology (12.2) ]. Patients with cardiac disorders may be at higher risk. Avoid concomitant use of other drugs that are also associated with similar cardiac effects (e.g., amphetamines, other sympathomimetic agents, atropine, amoxapine, scopolamine, antihistamines, other anticholinergic agents, amitriptyline, desipramine, other tricyclic antidepressants). Monitor patients for changes in blood pressure, heart rate, and syncope after initiating or increasing the dosage of dronabinol capsules. 5.3 Seizures Seizure and seizure-like activity have been reported in patients receiving dronabinol. Weigh this potential risk against the benefits before prescribing dronabinol capsules to patients with a history of seizures, including those receiving anti-epileptic medication or with other factors that can lower the seizure threshold. Monitor patients with a history of seizure disorders for worsened seizure control during dronabinol capsules therapy. If a seizure occurs, advise patients to discontinue dronabinol capsules and contact a healthcare provider immediately. 5.4 Multiple Substance Abuse Patients with a history of substance abuse or dependence, including marijuana or alcohol, may be more likely to abuse dronabinol capsules as well. Assess each patient's risk for abuse or misuse prior to prescribing dronabinol capsules and monitor patients with a history of substance abuse during treatment with dronabinol capsules for the development of these behaviors or conditions. 5.5 Paradoxical Nausea, Vomiting, or Abdominal Pain Nausea, vomiting, or abdominal pain can occur during treatment with synthetic delta-9‑tetrahydrocannabinol (delta-9-THC), the active ingredient in dronabinol capsules. In some cases, these adverse reactions were severe (e.g., dehydration, electrolyte abnormalities) and required dose reduction or drug discontinuation. Symptoms are similar to cannabinoid hyperemesis syndrome (CHS), which is described as cyclical events of abdominal pain, nausea, and vomiting in chronic, long-term users of delta-9-THC products. Because patients may not recognize these symptoms as abnormal, it is important to specifically ask patients or their caregivers about the development of worsening of nausea, vomiting, or abdominal pain while being treated with dronabinol capsules. Consider dose reduction or discontinuing dronabinol capsules if a patient develops worsening nausea, vomiting, or abdominal pain while on treatment.

Contre-indications

4 CONTRAINDICATIONS Dronabinol capsules are contraindicated in patients with a history of a hypersensitivity reaction to dronabinol or sesame oil. Reported hypersensitivity reactions to dronabinol capsules include lip swelling, hives, disseminated rash, oral lesions, skin burning, flushing, and throat tightness [see Adverse Reactions (6.2) ]. History of a hypersensitivity reaction to dronabinol or sesame oil (4)

Pharmacocinétique

12.3 Pharmacokinetics Absorption Dronabinol (delta-9-THC) is almost completely absorbed (90 to 95%) after single oral doses. Due to the combined effects of first pass hepatic metabolism and high lipid solubility, only 10 to 20% of the administered dose reaches the systemic circulation. Concentrations of both parent drug and its major active metabolite (11-hydroxy-delta-9-THC) peak at approximately 0.5 to 4 hours after oral dosing and decline over several days. The pharmacokinetics of dronabinol after single doses (2.5, 5, and 10 mg) and multiple doses (2.5, 5, and 10 mg given twice a day) have been studied in healthy subjects. Summary of Multiple-Dose Pharmacokinetic Parameters of Dronabinol in Healthy Subjects (n=34; 20 to 45 years) under Fasted Conditions Mean (SD) PK Parameter Values Twice Daily Dose C max ng/mL Median T max (range), hr AUC (0-12) ng∙hr/mL C max : maximum observed plasma concentration; T max : time to maximum observed plasma concentration; AUC (0-12) : area under the plasma concentration-time curve from 0 to 12 hours. 2.5 mg 1.32 (0.62) 1.00 (0.50-4.00) 2.88 (1.57) 5 mg 2.96 (1.81) 2.50 (0.50-4.00) 6.16 (1.85) 10 mg 7.88 (4.54) 1.50 (0.50-3.50) 15.2 (5.52) A slight increase in dose proportionality on mean C max and AUC (0-12) of dronabinol was observed with increasing dose over the dose range studied. Effect of Food: In a published study, the effect of food on the pharmacokinetics of dronabinol was studied by concomitant dosing of dronabinol capsules with a high-fat (59 grams of fat, approximately 50% of total caloric content of the meal), high calorie meal (approximately 950 calories). An appreciable food effect was observed, resulting in a 4-hour delay in mean T max and 2.9-fold increase in total exposure (AUC inf ), but C max was not significantly changed [see Dosage and Administration (2.2) ]. Distribution Dronabinol has an apparent volume of distribution of approximately 10 L/kg, because of its lipid solubility. The plasma protein binding of dronabinol and its metabolites is approximately 97% [see Drug Interactions (7.4) ]. Elimination The pharmacokinetics of dronabinol can be described using a two-compartment model with an initial (alpha) half-life of about 4 hours and a terminal (beta) half-life of 25 to 36 hours. Values for clearance average about 0.2 L/kg-hr, but are highly variable due to the complexity of cannabinoid distribution. Metabolism Dronabinol undergoes extensive first-pass hepatic metabolism, primarily by hydroxylation, yielding both active and inactive metabolites. Dronabinol and its principal active metabolite, 11‑hydroxy-delta-9-THC, are present in approximately equal concentrations in plasma. Published in vitro data indicates that CYP2C9 and CYP3A4 are the primary enzymes in the metabolism of dronabinol. CYP2C9 appears to be the enzyme responsible for the formation of the primary active metabolite [see Clinical Pharmacology (12.5) ]. Excretion Dronabinol and its biotransformation products are excreted in both feces and urine. Biliary excretion is the major route of elimination with about half of a radiolabeled oral dose being recovered from the feces within 72 hours as contrasted with 10 to 15% recovered from urine. Less than 5% of an oral dose is recovered unchanged in the feces. Due to its re-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. In a study of dronabinol capsules involving AIDS patients, urinary cannabinoid/creatinine concentration ratios were studied bi-weekly over a six-week period. The urinary cannabinoid/creatinine ratio was closely correlated with dose. No increase in the cannabinoid/creatinine ratio was observed after the first two weeks of treatment, indicating that steady-state cannabinoid levels had been reached. This conclusion is consistent with predictions based on the observed terminal half-life of dronabinol. Drug Interaction Studies Formal drug-drug interaction studies have not been conducted with dronabinol. The enzyme inhibition and induction potential of dronabinol and its active metabolite are not completely understood. Published data showed an increase in the elimination half-life of pentobarbital by 4 hours when concomitantly dosed with dronabinol [see Warnings and Precautions (5.1) ].

Frequently Asked Questions

1 INDICATIONS AND USAGE DRONABINOL CAPSULES, USP are indicated in adults for the treatment of: anorexia associated with weight loss in patients with Acquired Immune Deficiency Syndrome (AIDS). nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. Dronabinol capsules are a cannabinoid indicated in adults for the treatment of: Anorexia associated with weight loss in patients with AIDS. (1) Nausea and vomiting associated with cancer chemotherapy in patients who have …

2 DOSAGE AND ADMINISTRATION Anorexia Associated with Weight Loss in Adult Patients with AIDS (2.1) : The recommended adult starting dosage is 2.5 mg orally twice daily, one hour before lunch and dinner. See the full prescribing information for dosage titration to manage adverse reactions and to achieve desired therapeutic effect. Nausea and Vomiting Associated with Chemotherapy in Adult Patients Who Failed Conventional Antiemetics (2.2) : The recommended starting dosage is 5 mg/m 2 , administered 1 to 3 hours …

5 WARNINGS AND PRECAUTIONS Neuropsychiatric Adverse Reactions : May cause psychiatric and cognitive effects and impair mental and/or physical abilities. Avoid use in patients with a psychiatric history. Monitor for symptoms and avoid concomitant use of drugs with similar effects. Inform patients not to operate motor vehicles or other dangerous machinery until they are reasonably certain that dronabinol capsules do not affect them adversely. (5.1) Hemodynamic Instability : Patients with cardiac disorders may experience hypotension, hypertension, syncope or tachycardia. Avoid …

4 CONTRAINDICATIONS Dronabinol capsules are contraindicated in patients with a history of a hypersensitivity reaction to dronabinol or sesame oil. Reported hypersensitivity reactions to dronabinol capsules include lip swelling, hives, disseminated rash, oral lesions, skin burning, flushing, and throat tightness [see Adverse Reactions (6.2) ]. History of a hypersensitivity reaction to dronabinol or sesame oil (4)

Dronabinol is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

Similar Capsule Products

Quetiapine

Metyrapone

Lonafarnib

Deferiprone

Succimer

Oxaprozin

Browse all Capsule products →

References & Data Sources

• DailyMed — Dronabinol drug label (National Library of Medicine)
• openFDA — Dronabinol label data (U.S. Food & Drug Administration)
• RxNorm — RXCUI 197635 (NLM Normalized Drug Names)
• NDC Directory — Dronabinol (FDA National Drug Code)

Avertissement Médical

Les informations sur cette page sont destinées à des fins éducatives uniquement et ne doivent pas être utilisées en remplacement d'un avis médical professionnel, d'un diagnostic ou d'un traitement.

Consultez toujours votre médecin ou tout autre professionnel de santé qualifié pour toute question relative à une condition médicale ou à un médicament.

Sources des données : DailyMed (NLM), openFDA, MFDS