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Prescription pot! The important part that is of interest to my nuro is

that the duration of action for psychoactive effects is 4 to 6 hours. His

information is about how long the appetite/nausia effect lasts and he is

unaware of the above information. That is all explained below and on the

referenced web site

..

http://www.druglibrary.org/schaffer/hemp/medical/marinol1.htm

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DRCNet Library | Schaffer Library | Hemp (Marijuana) | Medical Information

MARINOL

(dronabinol*)

Capsules

(Warning: May be habit forming)

The USAN name for delta-9-tetrahydrocannabinol (THC).

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Dronabinol is a cannabinoid designated chemically as

(6aR-trans)-6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]py

ran-l-ol. Dronabinol has the following empirical and structural formulas:

Dronabinol, delta-9-tetrahydrocannabinol (delta-9-THC), is

naturally-occurring and has been extracted from Cannabis saliva L.

(marijuana).

Dronabinol is also chemically synthesized and 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: Marinol is supplied as round, soft

gelatin capsules containing either 2.5 mg, 5 mg, or 1 0 mg dronabinol. Each

Marinol capsule is formulated with the following inactive ingredients:

sesame oil, gelatin, glycerin, methylparaben, propylparaben, and titanium

dioxide.

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CLINICAL PHARMACOLOGY

Dronabinol is an orally active cannabinoid which, like other cannabinoids,

has complex effects on the central nervous system (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 and other cannabinoids.

Pharmacodynamics: Dronabinol-induced sympathomimetic activity may result in

tachycardia and/or conjunctival injection. Its effects on blood pressure

are inconsistent, but occasional subjects have experienced orthostatic

hypotension and/or syncope upon abrupt standing.

Dronabinol also demonstrates reversible effects on appetite, mood,

cognition, memory, and perception. These phenomena appear to be

dose-related, increasing in frequency with higher dosages, and subject to

great interpatient variability

After oral administration, dronabinol has an onset of action of

approximately 0.5 to 1 hours and peak effect at 2 to 4 hours. Duration of

action for psychoactive effects is 4 to 6 hours, but the appetite stimulant

effect of dronabinol may continue for 24 hours or longer after

administration.

Tachyphylaxis and tolerance develop to some of the pharmacologic effects of

dronabinol and other cannabinoids wth chronic use, suggesting an indirect

effect on sympathetic neurons. In a study of the pharmacodynamics of

chronic dronabinol exposure, healthy male volunteers (N = 12) received 210

mg/day dronabinol, administered orally in divided doses, for 16 days. An

initial tachycardia induced by dronabinoi was replaced successively by

normal sinus rhythm and then bradycardia. A decrease in supine blood

pressure, made worse by standing, was also observed initially. These

volunteers developed tolerance to the cardiovascular and subjective adverse

CNS effects of dronabinol within 12 days of treatment initiation.

Tachyphylaxis and tolerance do not, however, appear to develop to the

appetite stimulant effect of Marinol. In studies involving patients with

Acquired Immune Deficiency Syndrome (AIDS), the appetite stimulant effect

of Marinol has been sustained for up to five months in clinical trials, at

dosages ranging from 2.5 mg/day to 20 mg/day.

Pharmacokinetics:

Absorption and Distribution: Marinol (dronabinol) 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. Dronabinol has a

large apparent volume of distribution, approximately 10 L/kg, because of

its lipid solubility. The plasma protein binding of dronabinol and its

metabolites is approximately 97%.

The elimination phase 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. Because of its large volume of

distribution, dronabinol and its metabolites may be excreted at low levels

for prolonged periods of time.

Metabolism: Dronabinol undergoes extensive first-pass hepatic metabolism,

primarily by icrosomal hydroxylation, yielding both active and inactive

metabolites. Dronabinol and its principal active metabolite,

11-OH-delta-9-THC, are present in approximately equal concentrations in

plasma. Concentrations of both parent drug and metaboiite peak at

approximately 2 to 4 hours after oral dosing and decline over several days.

Values to clearance average about 0.2 L/kg-hr, but are highly variable due

to the complexity of cannabinoid distribution.

Elimination: 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.

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 Marinol involving AIDS patients, urinary

cannabinoid/creatinine concentration ratios were studied biweekly 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.

Special Populations: The pharmacokinetic profile of Marinol has not been

investigated in either pediatric or geriatric patients.

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CLINICAL TRIALS

Appetite Stimulation: The appetite stimulant effect of Marinol (dronabinol)

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 Marinol 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 Marinol appeared

to have been associated with an increased frequency of adverse experiences,

as compared to dosing later in the day. The effect of Marinol 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.

As compared to placebo, Marinol treatment resulted in a statistically

significant improvement in appetite as measured by visual analog scale (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 Marinol in an open-label study, in which there was a

sustained improvement in appetite.

Antiemetic: Marinol (dronabinol) treatment ofchemotherapy-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

Marinol was greatest in patients receiving cytotoxic therapy with MOPP for

Hodgkin's and non-Hodgkin's lymphomas. Marinol dosages ranged from 2.5

mg/day to 4O mg/day administered in equally divided doses every four to six

hours(four times daily). As indicated in the following table, escalating

the Marinol dose above 7 mg/m2 increased the frequency of adverse

experiences, with no additional antiemetic benefit.

Marinol Dose:Response Frequency and Adverse Experiences *

(N = 750 treatment courses)

Response Frequency (%) Adverse Events Frequency (%)

Marinol Dose Complete Partial Poor None Nondysphoric Dysphoric

<7 mg/m2 36 32 32 23 65 12

>7 mg/m2 33 31 6 13 58 28

*Nondysphoric events consisted of drowsiness, tachycardia, etc.

Combination antiemetic therapy with Marinol and a phenothiazine

(prochlorperazine) may result in synergistic or additive antiemetic effects

and attenuate the toxicities associated with each of the agents.

INDIVIDUALIZATION OF DOSAGES

The pharmacologic effects of Marinol (dronabinol) are dose-related and

subject to considerable interpatient variability. Therefore, dosage

individualization is critical in achieving the maximum benefit of Marinol

treatment.

Appetite Stimulation: In the clinical trials, the majority of patients were

treated with 5 mg/day Marinol, although the dosages ranged from 2.5 to 20

mg/day. For an adult:

1. Begin with 2.5 mg before lunch and 2.5 mg before supper. If CNS symptoms

(feeling high, dizziness, confusion, somnolence) do occur, they usually

resolve in 1 to 3 days with continued dosage.

2. If CNS symptoms are severe or persistent, reduce the dose to 2.5 mg

before supper. if symptoms continue to be a problem, taking the single dose

in the evening or at bedtime may reduce their severity.

3. When adverse effects are absent or minimal and further therapeutic

affect is desired, increase the dose to 2.5 mg before lunch and 5 mg before

supper or 5 and 5 mg. Although most patients respond to 2.5 mg twice daily,

10 mg twice daily has been tolerated in about half of the patients in

appetite stimulation studies.

The pharmacologic effects of Marinol are reversible upon treatment

cessation.

Antiemetic: Most patients respond to 5 mg three or four times daily. Dosage

may be escalated during a chemotherapy cycle or at subsequent cycles, based

upon initial results. Therapy should be initiated at the lowest recommended

dosage and titrated to clinical response. Administration of Marinol with

phenothiazines, such as prochlorperazine, has resulted in improved efficacy

as compared to either drug alone, without additional toxicity.

Pediatrics: Marinol is not recommended for AIDS-related anorexia in

pediatric patients because it has not been studied in this population. The

pediatric dosage for the treatment of chemotherapy-induced emesis is the

same as in adults. Caution is recommended in prescribing Marinol for

children because of the psychoactive effects.

Geriatrics: Caution is advised in prescribing Marinol in elderly patients

because they are generally more sensitive to the psychoactive effects of

drugs. In antiemetic studies, no difference in tolerance or efficacy was

apparent in patients > 55 years old.

INDICATIONS AND USAGE

Marinol (dronabinol) is indicated for the treatment of:

anorexia associated with weight loss in patients with AIDS; and

nausea and vomiting associated with cancer chemotherapy in patients who

have failed to respond adequately to conventional antiemetic treatments.

CONTRAINDICATIONS

Marinol (dronabinol) is contraindicated in any patient who has a history of

hypersensitivity to any cannabinoid or sesame oil.

WARNINGS

Marinol (dronabinol) is a medication with a potential for abuse. Physicians

and pharmacists should use the same care in prescribing and accounting for

Marinol as they would with morphine or other drugs controlled under

Schedule II (CII) of the Controlled Substances Act.

Because of the risk of diversion, it is recommended that prescriptions be

limited to the amount necessary for the period between clinic visits.

Patients receiving treatment with Marinol 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.

PRECAUTIONS

General: The risk/benefit ratio of Marinol (dronabinol) use should be

carefully evaluated in patients with the following medical conditions

because of individual variation in response and tolerance to the effects of

Marinol.

Marinol should be used with caution in patients with cardiac disorders

because of occasional hypotension, possible hypertension, syncope, or

tachycardia (see CLINICAL PNARMACOLOGY).

Marinol should be used with caution in patients with a history of substance

abuse, including alcohol abuse or dependence, because they may be more

prone to abuse Marinol as well. Multiple substance abuse is common and

marijuana, which contains the same active compound, is a frequently abused

substance.

Marinol should be used with caution and careful psychiatric monitoring in

patients with mania, depression, or schizophrenia because Marinol may

exacerbate these illnesses.

Marinol should be used with caution in patients receiving concomitant

therapy with sedatives, hypnotics or other psychoactive drugs because of

the potential for additive or synergistic CNS effects.

Marinol should be used with caution in pregnant patients, nursing mothers,

or pediatric patients because it has not been studied in these patient

populations.

Marinol should be used with caution for treatment of anorexia and weight

loss in elderly patients with AIDS because they may be more sensitive to

the psychoactive effects and because its use in these patients has not been

studied.

Information for Patients: Patients receiving treatment with Marinol

(dronabinol) should be alerted to the potential for additive central

nervous system depression if Marinol is used concomitantly with alcohol or

other CNS depressants such as benzodiazepines and barbiturates.

Patients receiving treatment with Marinol 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 Marinol 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 Marinol and following dosage

adjustments.

Drug Interactions: In studies involving patients with AIDS and/or cancer,

Marinol (dronabinol) 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 Marinol, 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 sym- Additive hypertension, tachycardia,

pathomimetic agents possibly cardiotoxicity

Atropine, scopolamine, antihistamines, Additive or super-additive

tachycardia, other anticholinergic agents drowsiness

Amitriptyline, amoxapine, desipramine, Additive tachycardia, hypertension,

other tricyclic antidepressants drowsiness

Barbiturates, benzodiazepines, ethanol, Additive drowsiness and CNS

lithium, opioids, buspirone, antihista- depression mines, muscle relaxants,

other CNS depressants

Disuffiram 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 X 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

Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenicity

studies have not been performed with dronabinol. Mutagenicity testing was

negative in an Ames test. In a long-term study (77 days) in rats, oral

administration of dronabinol at doses of 30 to 150 mg/m2 , equivalent to

0.3 to 1.5 times maximum recommended human dose (MRHD) of 90 mg/m2/day in

cancer patients or 2 to 10 times MRHD of 15 mg/m2/day in AIDS patients,

reduced ventral prostate, seminal vesicle and epididymal weights and caused

a decrease in seminal fluid volume. Decreases in spermatogenesis, number of

developing germ cells, and number of Leydig cells in the testis were also

observed. However, sperm count, mating success and testosterone levels were

not affected. The significance of these animal findings in humans is not

known.

Pregnancy: Pregnancy Category C. Reproduction studies with dronabinol have

been performed in mice at 15 to 450 mg/m2 equivalent to 0.2 to 5 times

maximum recommended human dose (MRHD) of 90 mg/m2/day in cancer patients or

1 to 30 times MRHD of 15 mg/m2/day in AIDS patients, and in rats at 74 to

295 mg/m2 (equivalent to 0.8 to 3 times m of 90 mg/m2 in cancer patients or

5 to 20 times MRHD of 15 mg/m2/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.

Nursing Mothers: Use of Marinol 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.

ADVERSE REACTIONS

Adverse experiences information summarized in the tables below was derived

from well-controlled clinical trials conducted in the US and US territories

involving 474 patients exposed to Marinol (dronabinol). Studies of

AIDS-related weight loss included 157 patients receiving dronabinol at a

dose of 2.5 mg twice daily and 67 receiving placebo. Studies of different

durations were combined by considering the first occurrence of events

during the first 28 days. Studies of nausea and vomiting related to cancer

chemotherapy included 317 patients receiving dronabinol and 68 receiving

placebo.

A cannabinoid dose-related " high " (easy laughing, elation and heightened

awareness) has been reported by patients receiving Marinol in both the

antiemetic (24%) and the lower dose appetite stimulant clinical trials (8%)

(see CLINICAL TRIALS).

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 Marinol. About 25% of patients

reported a minor CNS adverse event during the first 2 weeks and about 4%

reported such an event each week for the next 6 weeks thereafter.

PROBABLY CAUSALLY RELATED: Incidence greater than 1%. Rates derived from

clinical trials in AIDS-related anorexia (N = 157) and chemotherapy-related

nausea (N = 317). Rates were generally higher in the antiemetic use (given

in parentheses).

Body as a whole: Asthenia.

Cardiovascular: Palpitations, tachycardia, vasodilation/facial flush.

Digestive: Abdominal pain*, nausea*, vomiting*.

Nervous system: (Amnesia), anxiety/nervousness, (ataxia), confusion,

depersonalization, dizziness*, euphoria*, (hallucination), paranoid

reaction*, somnolence*, thinking abnormal*.

*Incidence of events 3% to 10%

PROBABLY CAUSALLY RELATED: Incidence less than 1%.

Event rates derived from clinical trials in AIDS-related anorexia (N=157)

and chemotherapy-related nausea (N = 317).

Cardiovascular: Conjunctivitis*, hypotension*.

Digestive: Diarrhea*, fecal incontinence.

Musculoskeletal: Myalgias.

Nervous system: Depression, nightmares, speech difficulties, tinnitus.

Skin and Appendages: Flushing*.

Special senses: Vision difficulties.

*Incidence of events 0. 3% to 1 %.

CAUSAL RELATIONSHIP UNKNOWN: Incidence less than 1%.

The clinical significance of the association of these events with Marinol

treatment is unknown, but they are reported as alerting information for the

clinician.

Body as a whole: Chills, headache, malaise.

_Digestive: Anorexia, hepatic enzyme elevation

Respiratory: Cough, rhinitis, sinusitis.

Skin and Appendages: Sweating.

DRUG ABUSE AND DEPENDENCE

Marinol (dronabinol) is one of the psychoactive compounds present in

cannabis, and is abusable and controlled Schedule II (CII) under the

Controlled Substances Act. Both psychological and physiological dependence

have been noted in healthy individuals receiving dronabinol, but addiction

is uncommon and has only been seen after prolonged high dose

administration.

Chronic abuse of cannabis has been associated with decrements in

motivation, cognition, judgement, and perception. The etiology of these

impairments is unknown, but may be associated with the complex process of

addiction rather than an isolated effect of the drug. No such decrements in

psychological, social or neurological status have been associated with the

administration of Marinol for therapeutic purposes.

In an open-label study in patients with AIDS who received Marinol for up to

five months, no abuse, diversion or systematic change in personality or

social functioning were observed despite the inclusion of a substantial

number of patients with a past history of drug abuse.

An abstinence syndrome has been reported after the abrupt discontinuation

of dronabinol in volunteers receiving dosages of 210 mg/day for 12 to 16

consecutive days. Within 12 hours after discontinuation, these volunteers

manifested symptoms such as irritability, insomnia, and restlessness. By

approximately 24 hours post-dronabinol discontinuation, withdrawal symptoms

intensified to include " hot flashes " , sweating, rhinorrhea, loose stools,

hiccoughs and anorexia.

These withdrawal symptoms gradually dissipated over the next 48 hours.

Electroencephalographic changes consistent with the effects of drug

withdrawal (hyperexcitation) were recorded in patients after abrupt

dechallenge. Patients also complained of disturbed sleep for several weeks

after discontinuing therapy with high dosages of dronabinol.

OVERDOSAGE

Signs and symptoms following MILD Marinol (dronabinol) 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 Marinol.

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.

DOSAGE AND ADMINISTRATION

Appetite stimulation: Initially, 2.5 mg Marinol (dronabinol) should be

administered orally twice daily (b.i.d.), before lunch and supper. For

patients unable to tolerate this 5 mg/day dosage of Marinol, 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 Marinol, administered in divided oral doses. Caution should be

exercised in escalating the dosage of Marinol because of the increased

frequency of dose-related adverse experiences at higher dosages (see

PRECAUTIONS).

Antiemetic: Marinol is best administered at an initial dose of 5 mg/m2,

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/m2 dose prove to be ineffective, and in the absence of

significant side effects, the dose may be escalated by 2.5 mg/m2 increments

to a maximum of 15 mg/m2 per dose. Caution should be exercised in dose

escalation, however, as the incidence of disturbing psychiatric symptoms

increases significantly at maximum dose (see PRECAUTIONS).

SAFETY AND HANDLING

Marinol (dronabinol) should be packaged in a well-closed container and

stored in a cool environment between 8' and 15'C (46' and 59'F). Protect

from freezing. No particular hazard to health care workers handling the

capsules has been identified.

Access to abusable drugs such as Marinol presents an occupational hazard

for addiction in the health care industry. Routine procedures for handling

controlled substances developed to protect the public may not be adequate

to protect health care workers. Implementation of more effective accounting

procedures and measures to appropriately restrict access to drugs of this

class may minimize the risk of self-administration by health care providers.

HOW SUPPLIED

MARINOL CAPSULES (dronabinol solution In sesame oil in soft gelatin

capsules)

2.5 mg white capsules (identified RL).

NDC 0054-2601-11: Bottles of 25 capsules.

NDC 0054-2601-21: Bottles of 60 capsules.

NDC 0054-2601-25: Bottles of 100 capsules.

5 mg dark brown capsules (identified RL).

NDC 0054-2602-11: Bottles of 25 capsules.

NDC 0054-2602-25: Bottles of 100 capsules.

10 mg orange capsules (Identified RL).

NDC 0054-2603-11: Bottles of 25 capsules.

MARINOL is a registered trademark of Unimed Pharmaceuticals, Inc. and is

marketed by Roxane Laboratories, Inc. under license from Unimed

Pharmaceuticals, Inc.

Manufactured by Banner Gelatin Products Corporation, Chatsworth CA 91311

DEA ORDER FORM REQUIRED

Caution: Federal law prohibits dispensing without prescription.

Roxane Laboratories, Inc.

Columbus, OH 43216

Revised December 1994

References:

1. Chlebowski RT, Grosvenor MB, Bernhard NH, et al: Am J Gastroenterol

1989;84(10):1288-1293.

2. Ott M, Lembcke B, Fischer H, et al: Am J Clin Nutr 1993;57:15-19.

3. Kotler DP, Tierney AR, Wang J, et al: Am J Clin Nutr 1989;50:444-447.

4. Gorbach SL, Knox TA, Roubenoff R: Nutr Rev 1993;51(8):226-234.

5. Data on file, Roxane Laboratories, Inc.

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