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ve been associated with the administration of
MARINOL Capsules for therapeutic purposes.


In an open-label study in patients with AIDS who received MARINOL Capsules for up to five
months, no abuse, diversion or systematic change
in personality or social functioning were observed
despite the inclusion of a substa
ntial number of patients with a
past history of drug abuse.

An abstinence syndrome has been reported afte
r 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 disconti
nuation, withdrawal symptoms intensified to
include ﬁhot flashesﬂ, sweating, rhinorrh
ea, loose stools, hiccoughs and anorexia.

These withdrawal symptoms gradually dissipate
d 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 di
sturbed sleep for several weeks after discontinuing
therapy with high dosages of dronabinol.
OVERDOSAGE
Signs and symptoms following MILD MARINOL Caps
ules intoxication include drowsiness, euphoria,
heightened sensory awareness, altered time pe
rception, reddened conjun
ctiva, dry mouth and
tachycardia; following MODERATE intoxication in
clude memory impairment
, depersonalization,
mood alteration, urinary retenti
on, and reduced bowel motility; and following SEVERE intoxication
include decreased motor coordination, lethar
gy, 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 fo
llowed oral doses of 0.4 mg/kg (28 mg/70 kg) of
MARINOL Capsules.

Management: A potentially serious oral ingestion, if
recent, should be managed with gut
decontamination. In unconscious pa
tients with a secure airway, instill activated charcoal (30 to 100 g
in adults, 1 to 2 g/kg in infants) via a nasogastri
c 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 of
fered 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 Capsules should be administered orally twice
daily (b.i.d.), before lunch and supper. For patie
nts unable to tolerate this 5 mg/day dosage of
MARINOL 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 MARINOL Capsules, administered in
NDA 18-651/S-025 and S-026
Page 13
divided oral doses. Caution should be exercised
in escalating the dosage of MARINOL Capsules
because of the increased frequency of dose-relate
d adverse experiences at higher dosages. (See
PRECAUTIONS.
) Antiemetic:
MARINOL Capsules is 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 dos
e escalation, however, as the incidence of
disturbing psychiatric symptoms increases significantly at maximum dose. (See
PRECAUTIONS.
) Storage Conditions

ve been associated with the administration of

MARINOL Capsules for therapeutic purposes.

In an open-label study in patients with AIDS who received MARINOL Capsules for up to five

months, no abuse, diversion or systematic change

in personality or social functioning were observed

despite the inclusion of a substa

ntial number of patients with a

past history of drug abuse.

An abstinence syndrome has been reported afte

r 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 disconti

nuation, withdrawal symptoms intensified to

include ﬁhot flashesﬂ, sweating, rhinorrh

ea, loose stools, hiccoughs and anorexia.

These withdrawal symptoms gradually dissipate

d 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 di

sturbed sleep for several weeks after discontinuing

therapy with high dosages of dronabinol.

OVERDOSAGE

Signs and symptoms following MILD MARINOL Caps

ules intoxication include drowsiness, euphoria,

heightened sensory awareness, altered time pe

rception, reddened conjun

ctiva, dry mouth and

tachycardia; following MODERATE intoxication in

clude memory impairment

, depersonalization,

mood alteration, urinary retenti

on, and reduced bowel motility; and following SEVERE intoxication

include decreased motor coordination, lethar

gy, 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 fo

llowed oral doses of 0.4 mg/kg (28 mg/70 kg) of

MARINOL Capsules.

Management: A potentially serious oral ingestion, if

recent, should be managed with gut

decontamination. In unconscious pa

tients with a secure airway, instill activated charcoal (30 to 100 g

in adults, 1 to 2 g/kg in infants) via a nasogastri

c 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 of

fered 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 Capsules should be administered orally twice

daily (b.i.d.), before lunch and supper. For patie

nts unable to tolerate this 5 mg/day dosage of

MARINOL 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 MARINOL Capsules, administered in

NDA 18-651/S-025 and S-026

Page 13

divided oral doses. Caution should be exercised

in escalating the dosage of MARINOL Capsules

because of the increased frequency of dose-relate

d adverse experiences at higher dosages. (See

PRECAUTIONS.

) Antiemetic:

MARINOL Capsules is 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 dos

e escalation, however, as the incidence of

disturbing psychiatric symptoms increases significantly at maximum dose. (See

PRECAUTIONS.

) Storage Conditions