Pill Identifier App

Dronabinol (Systemic)


VA CLASSIFICATION
Primary: GA609
Secondary: GA753

Note: Controlled substance classification—

Note: Controlled substance classification


U.S.—Schedule III{15}

Canada—N
Commonly used brand name(s): Marinol.

Another commonly used name is
delta-9-tetrahydrocannabinol (THC).
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antiemetic—

appetite stimulant—

Indications

Accepted

Nausea and vomiting, cancer chemotherapy–induced (prophylaxis) —Dronabinol is indicated in selected patients for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy {14}when other antiemetic medications are not effective. {01}{04}{12}{15}

Anorexia, AIDS-associated (treatment)—Dronabinol is indicated for the treatment of anorexia associated with weight loss in patients with acquired immunodeficiency syndrome (AIDS). {04}{12}{14} {15}Tachyphylaxis and tolerance to some effects of dronabinol develop with chronic use; unlike cardiovascular and subjective adverse central nervous system (CNS) effects, the appetite stimulant effects of dronabinol have been sustained for up to 5 months in AIDS patients receiving doses ranging from 2.5 to 20 mg per day. {04}{12}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    A cannabinoid. {01} {04}
Molecular weight—
    314.47 {11}

pKa—
    10.6 {04} {12}

Mechanism of action/Effect:

The exact mechanism of action of dronabinol is not known. Cannabinoid receptors in neural tissues may mediate the effects of dronabinol and other cannabinoids. {04} {12} Animal studies with other cannabinoids suggest that dronabinol's antiemetic effects may be due to inhibition of the vomiting control mechanism in the medulla oblongata. {06} {07} {08}


Other actions/effects:

Central sympathomimetic activity {01} {04} may result in tachycardia and/or conjunctival injection. {04} {12} Dose-related reversible effects on appetite, mood, cognition, memory, and perception also occur, subject to great interpatient variability. {04} {12}

Absorption:

Although dronabinol is 90 to 95% absorbed after administration of single oral doses, only 10 to 20% reaches the systemic circulation, due to first-pass hepatic metabolism and high lipid solubility. {04} {12}

Distribution:

Apparent volume of distribution is approximately 10 liters per kilogram (L/kg). {04} {12}

Distributed into human breast milk. {01} {04}

Protein binding:

Very high (97%). {04} {12}

Biotransformation:

Extensive first-pass hepatic metabolism, primarily by microsomal hydroxylation, yields both active and inactive metabolites. Dronabinol and its principal active metabolite, 11-OH-delta-9-THC, are present in approximately equal concentrations in plasma. {12}

Half-life:


Elimination:

Alpha phase: 4 hours. {01} {04} {12}

Terminal (beta) phase: 25 to 36 hours. {01} {04} {12}


Time to peak concentration:

2 to 4 hours. {04} {12}

Duration of action:

Psychoactive effects—4 to 6 hours. {04}

Appetite stimulant effects—24 hours or longer. {04}

Elimination:
    Primarily fecal {01} {04} (biliary) {12} {13}; approximately 50% of an oral dose appears in the feces (less than 5% as unchanged drug) {12} and 10 to 15% in the urine (either as unchanged drug or as metabolite) within 72 hours. {01} {04} {12} {13}
    Following single dose administration, low levels of dronabinol metabolites are detectable in the urine and feces for more than 5 weeks. {12}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to other marijuana products or sesame oil may be sensitive to this preparation also. {01} {04} {13}

Carcinogenicity

Studies to evaluate the carcinogenic potential of dronabinol have not been performed. {01} {04}

Mutagenicity

Dronabinol was not shown to be mutagenic in an Ames test. {04}

Pregnancy/Reproduction
Fertility—
In a long-term study in rats at doses 0.3 to 1.5 times the maximum recommended human dose (MRHD) in cancer patients or 2 to 10 times the MRHD in AIDS patients, a decrease in seminal fluid volume, as well as reduced ventral prostate, seminal vesicle, and epididymal weights were reported. Decreases in spermatogenesis, number of developing germ cells, and number of Leydig cells in the testes were also observed. However, sperm count, mating success, and testosterone levels were not affected. The significance of these animal findings for use in humans is not known. {04} {12}

Pregnancy—
Adequate and well-controlled studies in humans have not been done. {04}

Reproduction studies in mice (at doses 0.2 to 5 times the MRHD in cancer patients and 1 to 30 times the MRHD in AIDS patients) and in rats (at doses 0.8 to 3 times the MRHD in cancer patients and 5 to 20 times the MRHD in AIDS patients) have revealed no evidence of teratogenicity. {04} {12} However, dose-dependent effects of dronabinol, including decreased maternal weight gain and number of viable pups, and increased fetal mortality and early resorptions were observed. {04} {12}

FDA Pregnancy Category C. {04} {12}

Breast-feeding

Use is not recommended since dronabinol is distributed into and concentrated in human breast milk {01} {04} {12} and is absorbed by the nursing infant {04} {12}.

Pediatrics

No information is available on whether the risk of dronabinol-induced adverse effects is increased in children. However, because of this medication's psychoactive effects and potential for dependence, it should be used as an antiemetic with caution,{12}after less toxic alternatives have been considered and found ineffective. Recommended doses should not be exceeded, and children should be carefully monitored during therapy. {04} {12}

Safety and efficacy of dronabinol for use in the treatment of AIDS-associated anorexia has not been established. {04} {12}


Geriatrics


Studies performed in a limited number of patients up to 82 years of age have not demonstrated geriatrics-specific problems that would limit the usefulness of dronabinol in the elderly. However, because of this medication's psychoactive effects and potential for dependence and withdrawal effects, {09}therapy could be more troublesome in the elderly and should be used with caution,{12}after less toxic alternatives have been considered and found ineffective. Recommended doses should not be exceeded, and the elderly patient should be carefully monitored during therapy. {02}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Alcohol {01} {12} or
» Central nervous system (CNS) depression-producing medications, other {01} {12} (see Appendix II)    (concurrent use may potentiate the CNS-depressant effects of either these medications or dronabinol)


Anticholinergics {04} (see Appendix II) or
Antihistamines {04}    (additive or super-additive tachycardia may occur with concurrent use)


CNS stimulation-producing medications, other (see Appendix II), especially:
Amphetamines {12}
Cocaine{12} and
Sympathomimetic agents {12}    (additive hypertension, tachycardia, and possible cardiotoxicity may occur with concurrent use)


Apomorphine {10}    (prior administration of dronabinol may decrease the emetic response to apomorphine; also, concurrent use may potentiate the CNS-depressant effects of either apomorphine or dronabinol)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Bipolar disorder (manic or depressive states) {01} {12} {13} or
» Psychosis {01} {12}    (symptoms may be exacerbated)


» Cardiac disorders {01} {04} {12} {13}    (dronabinol may cause cardiac effects, including occasional hypotension, hypertension, syncope, and tachycardia)


» Drug abuse or dependence, history of, including acute alcoholism {01} {12} {13}    (increased risk of dronabinol abuse and dependence)


Hypersensitivity to dronabinol {01} {04} {13} or sesame oil {04} {13}
Hypertension {01}    (increase in sympathomimetic activity may exacerbate condition)



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Blood pressure determinations and
Cardiac function monitoring    (recommended for early detection of tachycardia and changes in blood pressure, especially in patients with hypertension or cardiac disease {10})




Side/Adverse Effects

Note: Following abrupt withdrawal of dronabinol, an abstinence syndrome manifested by irritability, insomnia, and restlessness was observed within 12 hours in volunteers receiving dosages of 210 mg per day for 12 to 16 consecutive days {04} {12}; approximately 24 hours later, the withdrawal syndrome intensified with such symptoms as hot flashes, sweating, rhinorrhea, loose stools, hiccups, and anorexia {01} {04} {12}. Withdrawal symptoms dissipated gradually over the next 48 hours. {04} {12} Electroencephalographic changes consistent with the hyperexcitation effects of drug withdrawal were recorded in patients after abrupt discontinuation. {04} {12}
Sleep disturbances, which continued for several weeks after discontinuation of high-dose dronabinol therapy, have been reported. {04} {12}
Although chronic abuse of cannabis has been associated with decreases in motivation, cognition, judgment, and perception, no such decrements in psychological, social, or neurological status have been associated with the administration of dronabinol for therapeutic purposes. {04} {12} In an open-label study in patients with AIDS who received dronabinol for up to 5 months, no abuse, diversion, or systematic change in personality or social functioning was observed, even in those patients with a history of drug abuse. {04} {12}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
CNS effects{12}{13} (amnesia [memory loss]; changes in mood; confusion; delusions; feelings of unreality; hallucinations [seeing, hearing, or feeling things that are not there]; mental depression; nervousness or anxiety)
    
palpitations{12} (fast or pounding heartbeat)
    
tachycardia{01}{13} (fast or pounding heartbeat)


Note: The above side/adverse effects may also be symptoms of overdose.
An initial tachycardia may be followed by normal sinus rhythm and then bradycardia. These effects may disappear when tolerance develops after continued use. {01}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Ataxia{01}{12} (clumsiness or unsteadiness)
    
dizziness{01}{12}{13}
    
drowsiness{01}{12}{13}
    
euphoria{12} (false sense of well-being)
    
nausea{04}{12}
    
trouble thinking{01}{13}
    
vomiting{04}

Incidence less frequent or rare
    
Asthenia{12} (unusual tiredness or weakness)
    
blurred vision or any changes in vision{01}{12}
    
dryness of mouth{01}{13}
    
flushing of face{12}{13}
    
orthostatic hypotension{01}{13} (feeling faint or lightheaded, especially when getting up from a lying or sitting position)
    
restlessness{01}





Overdose
For specific information on the agents used in the management of dronabinol overdose, see:
   • Charcoal, Activated (Oral-Local) monograph; and/or
   • Diazepam in Benzodiazepines (Systemic) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Mild intoxication
    
Heightened sensory awareness{12} (change in your sense of smell, taste, sight, sound, or touch)
    
altered time perception{12} (change in how fast you think time is passing)
    
drowsiness{12}
    
dryness of mouth{12}
    
euphoria{12} (false sense of well-being)
    
reddened conjunctiva{12} (redness of eyes)
    
tachycardia (fast or pounding heartbeat)

Moderate intoxication
    
Memory impairment{12} (being forgetful)
    
mood changes{12}
    
reduced bowel motility{12} {04}(constipation)
    
urinary retention{12} (problems in urinating)

Severe intoxication
    
Decreased motor coordination{12}
    
lethargy{12} (unusual drowsiness or dullness; feeling sluggish)
    
orthostatic hypotension{12}
    
panic reaction{12}
    
seizures{12}
    
slurred speech{04}{12}


Treatment of overdose
Overdose may occur either with therapeutic doses or with higher, nontherapeutic doses {01}. Recommended treatment includes:

To decrease absorption—Gut decontamination, if ingestion is recent. {04} Activated charcoal may be administered to unconscious patients (30 to 100 grams in adults, 1 to 2 grams per kilogram of body weight in infants) via a nasogastric tube; saline cathartic or sorbitol may be added to the first dose of charcoal {12}.

Specific treatment—Treatment of hypertension or hypotension, if necessary. {01} Hypotension usually responds to Trendelenburg position and administration of IV fluids. Pressors are rarely required. {04} {12} Benzodiazepines (5 to 10 mg of diazepam orally) may be used to treat extreme agitation. {04} {12} Patients with depressive, hallucinatory, or psychotic reactions should be placed in a quiet environment and offered reassurance {12} {13}.

Monitoring—Observation of patient in a quiet environment. {01} {13} Continuous blood pressure monitoring. {01} Cardiac monitoring.

Supportive care—Supportive therapy. {01} {13} Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Dronabinol (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to marijuana products or sesame oil

Pregnancy—No studies in humans; increased risk of fetal mortality and resorptions in animal studies with doses many times the usual human dose





Breast-feeding—Not recommended; distributed into human breast milk





Use in children—Caution recommended because of psychoactive effects and potential for developing dependence and withdrawal effects






Use in the elderly—Caution recommended because of psychoactive effects and potential for developing dependence and withdrawal effects
Other medications, especially CNS depressants
Other medical problems, especially bipolar disorder, cardiac disorders, drug or alcohol abuse or dependence, or psychosis

Proper use of this medication
» Importance of not taking more medication than the amount prescribed because of danger of overdose

» Proper dosing
Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
» Avoiding use of alcohol or other CNS depressants during therapy {01}

» Caution if dizziness, drowsiness, lightheadedness, or false sense of well-being occurs {01}

» Caution when getting up suddenly from a lying or sitting position

» Suspected overdose: Getting emergency help at once


Side/adverse effects
Signs of potential side effects, especially CNS effects, palpitations, and tachycardia


General Dosing Information
Because of the potential for abuse and risk of diversion, the amount of dronabinol dispensed should be limited to the amount necessary for the period between clinic visits. {04} {12}

Patients should remain under the supervision of a responsible adult during initial use of dronabinol and following dosage adjustments. {04} {12} Also, patients taking dronabinol should be advised of possible changes in mood and other adverse behavioral effects of the medication, so that occurrence of such effects will not be alarming. {04} {12}

Psychological and physical dependence may occur with high doses or chronic administration of dronabinol {01}; an abstinence syndrome may be precipitated when dronabinol is discontinued (see Side/Adverse effects ). {01} However, this is very unlikely to occur with therapeutic doses and short-term use of dronabinol.


Oral Dosage Forms

DRONABINOL CAPSULES USP

Usual adult and adolescent dose
Antiemetic
Oral, 5 mg per square meter of body surface area one to three hours prior to chemotherapy and every two to four hours following chemotherapy, for a total of four to six doses a day. {01} {04} {05} {12} {13}{14}{15}

Note: The dose may be increased by increments of 2.5 mg per square meter of body surface area if the initial dose is ineffective and side effects are not significant. {01} {04} {05} {12} {13}Caution should be exercised in dose escalation because the incidence of psychiatric symptoms increases significantly at maximum doses. {14}{15}


Appetite stimulant
Oral, initially 2.5 mg two times a day, before lunch and supper. {04} {12}{14}{15} Patients unable to tolerate this dose may be given 2.5 mg a day, administered as a single dose in the evening or at bedtime. {04} {12} {14}{15}The dose may be increased, if clinically indicated and in the absence of significant adverse effects, to a maximum of 20 mg a day; however, the incidence of psychiatric symptoms increases significantly at maximum doses. {04} {12}{14}{15}


Usual adult prescribing limits
Antiemetic
15 mg per square meter of body surface area per dose. {01} {04} {05} {12}{14}{15}

Appetite stimulant
20 mg a day. {04} {12}{14}{15}


Usual pediatric dose
Antiemetic
See Usual adult and adolescent dose. {01} {04} {05}

Note: Caution is advised because of the psychoactive effects of dronabinol. {04} {12}


Appetite stimulant
Safety and efficacy have not been established. {04} {12}


Usual geriatric dose
See Usual adult and adolescent dose. {01} {04}

Note: Caution is advised because of the psychoactive effects of dronabinol. {04} {12}


Strength(s) usually available
U.S.—


2.5 mg (Rx) [Marinol (sesame oil)]


5 mg (Rx) [Marinol (sesame oil)]


10 mg (Rx) [Marinol (sesame oil)]

Canada—


2.5 mg (Rx) [Marinol (sesame oil)]


5 mg (Rx) [Marinol (sesame oil)]


10 mg (Rx) [Marinol (sesame oil)]

Packaging and storage:
Store between 8 and 15 °C (46 and 59 °F), in a well-closed container. Protect from freezing. {04}

Auxiliary labeling:
   • Refrigerate.
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • May be habit-forming.

Note: Controlled substance in the U.S. and Canada.




Revised: 01/06/2003



References
  1. Marinol package insert (Roxane—US), Rev 4/86.
  1. Synthetic marijuana for nausea and vomiting due to cancer chemotherapy. Med Lett Drugs Ther 1985 Nov 22; 27(701): 97-8.
  1. Devine ML, Dow GJ, Greenberg BR, Holsten DW, Icaza L, Jue PY, et al. Adverse reactions to delta-9-tetrahydrocannabinol given as an antiemetic in a multicenter study. Clin Pharm 1987 Apr; 6: 319-22.
  1. Marinol package insert (Roxane—US), Rev 12/92, Rec 1/21/93.
  1. Marinol product monograph (Boehringer Ingelheim—Canada). In: Krough CME, editor. CPS Compendium of pharmaceuticals and specialities. 27th ed. Ottawa: Canadian Pharmaceutical Association; 1992: 649-50.
  1. Medical Sciences Bulletin 1986 Jun; 8(10).
  1. Ward A, Holmes B. Nabilone: a preliminary review of its pharmacological properties and therapeutic use. Drugs 1985 Aug; 30(2): 127-44.
  1. London SW, McCarthy LE, Borison HL. Suppression of cancer chemotherapy-induced vomiting in the cat by nabilone, a synthetic cannabinoid. Proc Soc Exp Biol Med 1979; 160: 437-40.
  1. Reviewer comment, 6/28/93.
  1. Reviewers' consensus, 1993.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: United States Pharmacopeial Convention Inc; 1997. p. 258.
  1. Marinol product monograph (Roxane—US), Rev 6/96. In: PDR Physicians' desk reference. 52nd ed. 1998. Montvale, NJ: Medical Economics Company; 1998. p. 2544-6.
  1. Marinol product monograph (Sanofi—Canada), Rev 1996. In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialities. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 941-2.
  1. Product Information: Marinol, delta-9-tetrahydrocannabinol. Sanofi–Synthelabo Canada (licensed from Unimed), Markham, Ontario, Canada, (PI revised 4/2000) reviewed 2/2001.
  1. Product Information: Marinol®, dronabinol (delta-9-tetrahydrocannabinol). Unimed Pharmaceuticals (Marinol formerly distributed by Roxane), Deerfield, IL, (PI revised 1/2001) reviewed 2/2001.
Hide
(web2)