dronabinol 10 MG Oral Capsule
WARNINGS
Patients receiving treatment with Dronabinol Capsules should be specifically warned not to drive, operate machinery, or engage in any hazardous activity until it is established that they are able to tolerate the drug and to perform such tasks safely.
DRUG INTERACTIONS
Drug Interactions In studies involving patients with AIDS and/or cancer, Dronabinol Capsules has been co-administered with a variety of medications (e.g., cytotoxic agents, anti-infective agents, sedatives, or opioid analgesics) without resulting in any clinically significant drug/drug interactions.
Although no drug/drug interactions were discovered during the clinical trials of Dronabinol Capsules, cannabinoids may interact with other medications through both metabolic and pharmacodynamic mechanisms.
Dronabinol is highly protein bound to plasma proteins, and therefore, might displace other protein-bound drugs.
Although this displacement has not been confirmed in vivo , practitioners should monitor patients for a change in dosage requirements when administering dronabinol to patients receiving other highly protein-bound drugs.
Published reports of drug/drug interactions involving cannabinoids are summarized in the following table.
CONCOMITANT DRUG CLINICAL EFFECT(S) Amphetamines, cocaine, other sympathomimetic agents Additive hypertension, tachycardia, possibly cardiotoxicity Atropine, scopolamine, antihistamines, other anticholinergic agents Additive or super-additive tachycardia, drowsiness Amitriptyline, amoxapine, desipramine, other tricyclic antidepressants Additive tachycardia, hypertension, drowsiness Barbiturates, benzodiazepines, ethanol, lithium, opioids, buspirone, antihistamines, muscle relaxants, other CNS depressants Additive drowsiness and CNS depression Disulfiram A reversible hypomanic reaction was reported in a 28 y/o man who smoked marijuana; confirmed by dechallenge and rechallenge Fluoxetine A 21 y/o female with depression and bulimia receiving 20 mg/day fluoxetine × 4 wks became hypomanic after smoking marijuana; symptoms resolved after 4 days Antipyrine, barbiturates Decreased clearance of these agents, presumably via competitive inhibition of metabolism Theophylline Increased theophylline metabolism reported with smoking of marijuana; effect similar to that following smoking tobacco
OVERDOSAGE
Signs and symptoms following MILD Dronabinol Capsules intoxication include drowsiness, euphoria, heightened sensory awareness, altered time perception, reddened conjunctiva, dry mouth and tachycardia; following MODERATE intoxication include memory impairment, depersonalization, mood alteration, urinary retention, and reduced bowel motility; and following SEVERE intoxication include decreased motor coordination, lethargy, slurred speech, and postural hypotension.
Apprehensive patients may experience panic reactions and seizures may occur in patients with existing seizure disorders.
The estimated lethal human dose of intravenous dronabinol is 30 mg/kg (2100 mg/ 70 kg).
Significant CNS symptoms in antiemetic studies followed oral doses of 0.4 mg/kg (28 mg/70 kg) of Dronabinol Capsules.
Management A potentially serious oral ingestion, if recent, should be managed with gut decontamination.
In unconscious patients with a secure airway, instill activated charcoal (30 to 100 g in adults, 1 to 2 g/kg in infants) via a nasogastric tube.
A saline cathartic or sorbitol may be added to the first dose of activated charcoal.
Patients experiencing depressive, hallucinatory or psychotic reactions should be placed in a quiet area and offered reassurance.
Benzodiazepines (5 to 10 mg diazepam po ) may be used for treatment of extreme agitation.
Hypotension usually responds to Trendelenburg position and IV fluids.
Pressors are rarely required.
DESCRIPTION
Dronabinol is a cannabinoid designated chemically as ( 6aR-trans )-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: Dronabinol, the active ingredient in Dronabinol Capsules, is synthetic delta-9-tetrahydrocannabinol (delta-9-THC).
Delta-9-tetrahydrocannabinol is also a naturally occurring component of Cannabis sativa L.
(Marijuana).
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.
Capsules for oral administration: Dronabinol Capsules are supplied as oval, soft gelatin capsules containing either 2.5 mg, 5 mg, or 10 mg dronabinol.
Each Dronabinol Capsule strength is formulated with the following inactive ingredients: 2.5 mg capsule contains gelatin, glycerin, sesame oil, titanium dioxide, SDA 35A alcohol, propylene glycol, black iron oxide, polyvinyl acetate phthalate, purified water, isopropyl alcohol, polyethylene glycol, and ammonium hydroxide; 5 mg capsule contains iron oxide red, iron oxide black, gelatin, glycerin, sesame oil, titanium dioxide, SDA 35A alcohol, propylene glycol, polyvinyl acetate phthalate, purified water, isopropyl alcohol, polyethylene glycol, and ammonium hydroxide; 10 mg capsule contains iron oxide red, iron oxide yellow, gelatin, glycerin, sesame oil, titanium dioxide, SDA 35A alcohol, propylene glycol, black iron oxide, polyvinyl acetate phthalate, purified water, isopropyl alcohol, polyethylene glycol, and ammonium hydroxide.
Chemical Structure
CLINICAL STUDIES
Clinical Trials Appetite Stimulation The appetite stimulant effect of Dronabinol Capsules in the treatment of AIDS-related anorexia associated with weight loss was studied in a randomized, double-blind, placebo-controlled study involving 139 patients.
The initial dosage of Dronabinol Capsules in all patients was 5 mg/day, administered in doses of 2.5 mg one hour before lunch and one hour before supper.
In pilot studies, early morning administration of Dronabinol Capsules appeared to have been associated with an increased frequency of adverse experiences, as compared to dosing later in the day.
The effect of Dronabinol Capsules on appetite, weight, mood, and nausea was measured at scheduled intervals during the six-week treatment period.
Side effects (feeling high, dizziness, confusion, somnolence) occurred in 13 of 72 patients (18%) at this dosage level and the dosage was reduced to 2.5 mg/day, administered as a single dose at supper or bedtime.
Of the 112 patients that completed at least 2 visits in the randomized, double-blind, placebo-controlled study, 99 patients had appetite data at 4-weeks (50 received Dronabinol Capsules and 49 received placebo) and 91 patients had appetite data at 6-weeks (46 received Dronabinol Capsules and 45 received placebo).
A statistically significant difference between Dronabinol Capsules and placebo was seen in appetite as measured by the visual analog scale at weeks 4 and 6 (see figure ).
Trends toward improved body weight and mood, and decreases in nausea were also seen.
After completing the 6-week study, patients were allowed to continue treatment with Dronabinol Capsules in an open-label study, in which there was a sustained improvement in appetite.
Figure Antiemetic Dronabinol Capsules treatment of chemotherapy-induced emesis was evaluated in 454 patients with cancer, who received a total of 750 courses of treatment of various malignancies.
The antiemetic efficacy of Dronabinol Capsules was greatest in patients receiving cytotoxic therapy with MOPP for Hodgkin’s and non-Hodgkin’s lymphomas.
Dronabinol Capsule dosages ranged from 2.5 mg/day to 40 mg/day, administered in equally divided doses every four to six hours (four times daily).
As indicated in the following table, escalating the Dronabinol Capsules dose above 7 mg/m 2 increased the frequency of adverse experiences, with no additional antiemetic benefit.
Dronabinol Capsules Dose: Response Frequency and Adverse Experiences Nondysphoric events consisted of drowsiness, tachycardia, etc.
(N = 750 treatment courses) Dronabinol Capsules Dose Response Frequency (%) Adverse Events Frequency (%) Complete Partial Poor None Nondysphoric Dysphoric 7 mg/m 2 33 31 36 13 58 28 Combination antiemetic therapy with Dronabinol Capsules and a phenothiazine (prochlorperazine) may result in synergistic or additive antiemetic effects and attenuate the toxicities associated with each of the agents.
HOW SUPPLIED
Dronabinol Capsules are available containing 2.5 mg, 5 mg or 10 mg of dronabinol.
The 2.5 mg capsule is an opaque off-white soft gelatin capsule printed with INS in black ink.
They are available as follows: NDC 0378-8170-91 bottles of 60 capsules The 5 mg capsule is an opaque maroon or brown soft gelatin capsule printed with INS in white ink.
They are available as follows: NDC 0378-8171-91 bottles of 60 capsules The 10 mg capsule is an opaque tan to tan-orange soft gelatin capsule printed with INS in black ink.
They are available as follows: NDC 0378-8172-91 bottles of 60 capsules
GERIATRIC USE
Geriatric Use Clinical studies of Dronabinol Capsules in AIDS and cancer patients did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
In general, dose selection for an elderly patient should be cautious usually starting at the low end of the dosing range, reflecting the greater frequency of falls, decreased hepatic, renal, or cardiac function, increased sensitivity to psychoactive effects and of concomitant disease or other drug therapy.
INDICATIONS AND USAGE
Dronabinol Capsules is indicated for the treatment of: 1.
anorexia associated with weight loss in patients with AIDS; and 2.
nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.
PREGNANCY
Pregnancy Pregnancy Category C Reproduction studies with dronabinol have been performed in mice at 15 to 450 mg/m 2 , equivalent to 0.2 to 5 times maximum recommended human dose (MRHD) of 90 mg/m 2 /day in cancer patients or 1 to 30 times MRHD of 15 mg/m 2 /day in AIDS patients, and in rats at 74 to 295 mg/m 2 (equivalent to 0.8 to 3 times MRHD of 90 mg/m 2 in cancer patients or 5 to 20 times MRHD of 15 mg/ m 2 /day in AIDS patients).
These studies have revealed no evidence of teratogenicity due to dronabinol.
At these dosages in mice and rats, dronabinol decreased maternal weight gain and number of viable pups and increased fetal mortality and early resorptions.
Such effects were dose dependent and less apparent at lower doses which produced less maternal toxicity.
There are no adequate and well-controlled studies in pregnant women.
Dronabinol should be used only if the potential benefit justifies the potential risk to the fetus.
NUSRING MOTHERS
Nursing Mothers Use of Dronabinol Capsules is not recommended in nursing mothers since, in addition to the secretion of HIV virus in breast milk, dronabinol is concentrated in and secreted in human breast milk and is absorbed by the nursing baby.
INFORMATION FOR PATIENTS
Information for Patients Patients receiving treatment with Dronabinol Capsules should be alerted to the potential for additive central nervous system depression if Dronabinol Capsules is used concomitantly with alcohol or other CNS depressants such as benzodiazepines and barbiturates.
Patients receiving treatment with Dronabinol Capsules should be specifically warned not to drive, operate machinery, or engage in any hazardous activity until it is established that they are able to tolerate the drug and to perform such tasks safely.
Patients using Dronabinol Capsules should be advised of possible changes in mood and other adverse behavioral effects of the drug so as to avoid panic in the event of such manifestations.
Patients should remain under the supervision of a responsible adult during initial use of Dronabinol Capsules and following dosage adjustments.
DOSAGE AND ADMINISTRATION
Appetite Stimulation Initially, 2.5 mg Dronabinol Capsules should be administered orally twice daily (b.i.d.), before lunch and supper.
For patients unable to tolerate this 5 mg/day dosage of Dronabinol Capsules, the dosage can be reduced to 2.5 mg/day, administered as a single dose in the evening or at bedtime.
If clinically indicated and in the absence of significant adverse effects, the dosage may be gradually increased to a maximum of 20 mg/day Dronabinol Capsules, administered in divided oral doses.
Caution should be exercised in escalating the dosage of Dronabinol Capsules because of the increased frequency of dose-related adverse experiences at higher dosages.
(See PRECAUTIONS .
) Antiemetic Dronabinol Capsules are best administered at an initial dose of 5 mg/m 2 , given 1 to 3 hours prior to the administration of chemotherapy, then every 2 to 4 hours after chemotherapy is given, for a total of 4 to 6 doses/day.
Should the 5 mg/m 2 dose prove to be ineffective, and in the absence of significant side effects, the dose may be escalated by 2.5 mg/m 2 increments to a maximum of 15 mg/m 2 per dose.
Caution should be exercised in dose escalation, however, as the incidence of disturbing psychiatric symptoms increases significantly at maximum dose.
(See PRECAUTIONS .
)