Note: Descriptions are shown in the official language in which they were submitted.
CA 02432945 2004-04-06
1
TITLE OF THE INVENTION
USE OF DOXYLAMINE SUCCINATE AND PYRIDOXINE HYDROCHLORIDE FOR PROPHYLAXIS
AND TREATMENT OF POST-SURGICAL VOMITING
FIELD OF THE INVENTION
The present invention relates to pharmaceutical compositions and their use for
the prophylaxis and treatment of post-surgical vomiting. More specifically,
the
present invention relates to a newly discovered indication for a known drug.
The
drug comprises Doxylamine Succinate and Pyridoxine Hydrochloride (vitamin
B6). This drug is currently marketed in Canada under the registered trademark
DiclectincJ.
BACKGROUND OF THE INVENTION
Post-operative vomiting is an important problem and from a patient
standpoint, one of the most commonly reported and distressing post-operative
complication. Patients commonly report post-operative vomiting as a greater
source of discomfort than pain.
From a clinical standpoint, post-operative vomiting is troublesome and
requires the presence of clinical staff to ensure that patients do not choke
or
otherwise harm themselves. In many surgical interventions it is clinically
important that patients do not vomit and cause strain on stitches. Ruptured
stitches, especially when stitches are internal, can lead to hemorrhage, which
can
in turn lead to further surgery and in general terms leads to a setback in
patient
recovery.
Thus from the standpoint of both patients and clinicians, the control of
post-operative vomiting is essential.
Financially, the control of post-operative vomiting is also important.
Industrialized society outpatient surgery is common and the importance of
being
able to send patients home without an overnight stay is financially
attractive.
Thousands of day surgeries are performed everyday in most countries of the
world. Thus, millions of such operations are completed each year. As a
societal
cost, post-operative vomiting slows recovery, return to productive activities
and
uses up valuable health care resources.
CA 02432945 2003-07-10
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Many anesthetists currently use prophylactic anti-vomiting drugs such as
metoclopramide, chloropromazine, diphenhydramine, dimenhydrinate, meclizine,
cyclizine before or during surgery. However, it is common not to use anti-
vomiting
drugs at all due to either poor efficacy of current agents or troublesome side-
effects such as dystonic reactions and somnolence.
Since the 1950's it has been known to use the drug now sold as Diclectin~
as an anti-nauseant and anti-emetic for the treatment of hyperemesis
gravidarum
among pregnant women (Brent, 1983).
Hyperemesis gravidarum is an extreme form of nausea and vomiting
encountered during pregnancy. Up to now, there has been a belief that
Diclectin~
was effective because it would safely control symptoms of the hormonal and
physiological upheaval causing nausea and vomiting during pregnancy. Indeed,
systematic and randomized clinical trials have consistently demonstrated the
safety and efficacy of Diclectin~ in a pregnancy setting (Jewell. 1993).
It has also previously been shown that Diclectin~ may be efficacious in
curbing nausea in terminal disease situations when hormonal and physiological
functions are greatly disrupted by disease and side effects caused by potent
drugs
such as anti-cancer drugs (Canadian Patent 2,139,896).
However, it has been unknown and unproven that Diclectin~ could be used
as an anti-emetic in a general population setting undergoing standard surgical
interventions. Such discovery is of great practical significance considering
the
large number of such surgical interventions and the fact that post-surgical
vomiting
is an important drawback to rapid recovery.
In light of the foregoing, there remains a constant need for new post-
operative anti-vomiting drugs which are safe, efficacious and which exhibit
few or
mild side-effects.
SUMMARY OF THE INVENTION
The inventors have overcome the deficiencies of the prior art by providing
the use of a known drug for the new indication of prophylaxis and treatment of
CA 02432945 2003-07-10
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post-surgical vomiting. In one aspect of the present invention, there is
provided
the use of Doxylamine Succinate and Pyridoxine Hydrochloride for reducing post-
surgical vomiting. The Doxylamine Succinate and Pyridoxine Hydrochloride can
be used before, during and/or after surgery. In particular embodiments, the
Doxylamine Succinate and Pyridoxine Hydrochloride can be used after surgery at
regular intervals. Doxylamine Succinate and Pyridoxine Hydrochloride can also
be
used before and/or during surgery but not after surgery.
In certain aspects of this invention, Doxylamine Succinate and Pyridoxine
Hydrochloride can be used orally. When Doxylamine Succinate and Pyridoxine
Hydrochloride are used orally, they can be formulated in a delayed release
formulation. The orally delayed release formulation can be enterically coated.
In another embodiment, Doxylamine Succinate and the Pyridoxine
Hydrochloride can be formulated in a pharmaceutically acceptable carrier.
In specific aspects of this invention, at least about 10 mg of Doxylamine
Succinate and at least about 10 mg of Pyridoxine Hydrochloride can be given to
the patient to reduce, prevent or treat post-surgical vomiting. In other
embodiment,
at least about 20 mg of Doxylamine Succinate and at least about 20 mg of
Pyridoxine Hydrochloride can be given to a patient.
In particular embodiments, the patient is a woman. The surgery can be
performed on an outpatient basis.
In still another aspect of this invention, Doxylamine Succinate and
Pyridoxine Hydrochloride can be given before anesthesia is induced in the
patient.
In other embodiments, Doxylamine Succinate and Pyridoxine Hydrochloride can be
used on an evening prior to surgery, a morning of the day of surgery and/or
immediately after surgery.
Doxylamine Succinate can be used before, at substantially the same time
or after Pyridoxine Hydrochloride is administered to the patient.
In more specific aspects of this invention, there is provided a method of
treating, preventing or reducing post-surgical vomiting comprising pre-
operative
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and or peri-operative administration of a therapeutically effective amount of
Doxylamine Succinate and Pyridoxine Hydrochloride. In one embodiment, the
Doxylamine Succinate and Pyridoxine Hydrochloride are used by administering to
the patient Diclectin~. Diclectin~ is an anti-vomiting drug that is currently
marketed in Canada. Optionally, the method also includes the further step of
post-
operative administration of the same drug. In a preferred embodiment,
Diclectin~
will be used pre and/or peri-operatively such as prior to induction of
anesthesia or
concurrently with anesthesia and/or post-operatively.
A "patient" or "subject", as used herein, may be an animal. Preferred
animals are mammals, including but not limited to humans, pigs, cats, dogs,
rodents, horses, cattle, sheep, goats and cows. Preferred patients and
subjects
are humans.
"Reducing post-surgical vomiting" means any measurable decrease of post
surgical-vomiting. Similarly, "reducing" means any measurable decrease or
complete inhibition of post-surgical vomiting.
The words "a" and "an", as used in this specification, including the claims,
denotes "one or more." Specifically, the use of "comprising", "having", or
other
open language in claims that claim a combination or use employing "an object",
denotes that "one or more of the object" may be employed in the claimed use or
combination.
Other objects, advantages and features of the present invention will
become more apparent upon reading the following non-restrictive description of
preferred embodiments included throughout this specification and the example
provided below.
DESCRIPTION OF THE PREFERRED EMBODIMENT
A. Diclectin~
Diclectin~ is an anti-nauseant approved for use during pregnancy. It is
currently sold in Canada in delayed release formulation containing 10 mg of
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Doxylamine Succinate (an antihistamine) and 10 mg of Pyridoxine Hydrochloride
(Vitamin B6).
Doxylamine Succinate has the following chemical formula:
CH3
N ~
OCH2CH2N(CH3)2
5 Pyridoxine Hydrochloride has the following chemical formula:
C
.HCI
HO~ ~ ~CH20H
H20H
It has now been shown, against prior art expectations that pre, and/or peri-
operative and/or post-operative use of Diclectin~ reduces the incidence of
post-
operative vomiting in patients undergoing surgery such as elective
laparoscopic
tubal ligation. This newly discovered indication can be described as the use
of
Diclectin~ in the prophylaxis and treatment of post-operative vomiting.
2. Combination Therapy
In order to increase the effectiveness of the present invention, it may be
desirable to combine the administration Doxylamine Succinate and Pyridoxine
Hydrochloride with other known drugs, compounds, agents, and methods effective
in the preventing or reducing vomiting, including post-surgical vomiting.
Drugs that
may be used in combination with the present invention include, but are not
limited
to, metoclopramide, chloropromazine, diphenhydramine, dimenhydrinate,
meclizine and cyclizine.
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This process may involve administering the combination of Doxylamine
Succinate and Pyridoxine Hydrochloride with other agents) to the patient at
the
same time, for example, using a single composition or pharmacological
formulation
that includes Doxylamine Succinate, Pyridoxine Hydrochloride and an additional
anti-vomiting agent or drug. In other embodiments of this invention, the
combination can be separated into two distinct compositions or formulations
given
at the same time, wherein one composition includes Doxylamine Succinate and
Pyridoxine Hydrochloride and the second composition includes a known anti-
vomiting agent or agents. The second agent therapy may precede or follow the
administration of Doxylamine Succinate and Pyridoxine Hydrochloride to the
patient by intervals ranging from minutes to weeks.
The exact schedule of treatment with Doxylamine Succinate and Pyridoxine
Hydrochloride combination therapy and the second agent is determined in large
part by the pharmacokinetic or pharmacodynamic properties of Doxylamine
Succinate and Pyridoxine Hydrochloride and the second agents.
In embodiments where the other agent and Doxylamine Succinate and
Pyridoxine Hydrochloride combination therapy are used separately to the
subject,
one may wish that a significant period of time does not expire between the
time of
each delivery, such that the second agent and the Doxylamine Succinate and
Pyridoxine Hydrochloride combination therapy would be able to exert an
advantageously combined effect on the subject. In such instances, it is
contemplated that one may administer to the subject with both modalities
within
about 12-24 h of each other and, more preferably, within about 6-12 h of each
other. In some situations, it may be desirable to extend the time period for
treatment significantly, however, where several days (2, 3, 4, 5, 6 or 7) to
several
weeks (1, 2, 3, 4, 5, 6, 7 or 8) lapse between the respective administrations.
Various combinations may be employed, the Doxylamine Succinate and
Pyridoxine Hydrochloride combination therapy is "A" and the second agent is
"B":
A/B/A B/A/B B/B/A A/A/B A/B/B B/A/A A/B/B/B B/A/B/B
B/B/B/A B/B/A/B A/A/B/B A/B/A/B A/B/B/A B/B/A/A B/A/B/A
B/A/A/B A/A/A/B B/A/A/A A/B/A/A A/A/B/A
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3. Formulations and Routes of Administrations
Pharmaceutical compositions of the present invention include Doxylamine
Succinate and Pyridoxine Hydrochloride. The phrases "pharmaceutical or
pharmacologically acceptable" refers to molecular entities and compositions
that
do not produce an adverse, allergic or other untoward reaction when used on an
animal, such as, for example, a human. The preparation of a pharmaceutical
composition comprising Doxylamine Succinate and Pyridoxine Hydrochloride will
be known to those of skill in the art in light of the present disclosure, as
exemplified
by Remington's Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990.
Moreover, for animal (e.g., human) administration, it will be understood that
preparations should meet sterility, pyrogenicity, general safety and purity
standards
as required by FDA Office of Biological Standards.
"Therapeutically effective amounts" are those amounts effective to produce
beneficial results, particularly with respect to treating post-surgical
vomiting in a
patient. Such amounts may be initially determined by reviewing the published
literature, by conducting in vitro tests or by conducting metabolic studies in
healthy
experimental animals.
As used herein, "pharmaceutically acceptable carrier" includes any and all
solvents, dispersion media, coatings, surfactants, antioxidants, preservatives
(e.g.,
antibacterial agents, antifungal agents), isotonic agents, absorption delaying
agents, salts, preservatives, drugs, drug stabilizers, gels, binders,
excipients,
disintegration agents, lubricants, sweetening agents, flavoring agents, dyes,
such
like materials and combinations thereof, as would be known to one of ordinary
skill
in the art (Remington's, 1990). Except insofar as any conventional carrier is
incompatible with the active ingredient, its use in the therapeutic or
pharmaceutical
compositions is contemplated.
The compositions of the present invention may comprise different types of
carriers depending on whether it is to be used in solid, liquid or aerosol
form, and
whether it need to be sterile for such routes of administration as injection.
The
present invention can be used intravenously, intradermally, intraarterially,
intraperitoneally, intralesionally, intracranially, intraarticularly,
intraprostaticaly,
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intrapleurally, intratracheally, intranasally, intravitreally, intravaginally,
intrarectally,
topically, intratumorally, intramuscularly, intraperitoneally, subcutaneously,
subconjunctival, intravesicularlly, mucosally, intrapericardially,
intraumbilically,
intraocularally, orally, topically, locally, inhalation (e.g., aerosol
inhalation),
injection, infusion, continuous infusion, localized perfusion bathing target
cells
directly, via a catheter, via a lavage, in cremes, in lipid compositions
(e.g.,
liposomes), or by other method or any combination of the forgoing as would be
known to one of ordinary skill in the art (Remington's, 1990).
The actual dosage amount of a composition of the present invention
administered to a patient can be determined by physical and physiological
factors
such as body weight, severity of condition, the type of disease being treated,
previous or concurrent therapeutic interventions, idiopathy of the patient and
on the
route of administration. The practitioner responsible for administration will,
in any
event, determine the concentration of active ingredients) in a composition and
appropriate doses) for the individual subject.
In certain embodiments, pharmaceutical compositions may comprise, for
example, at least about 0.1 % of an active compound. In other embodiments, the
an active compound may comprise between about 2% to about 75% of the weight
of the unit, or between about 25% to about 60%, for example, and any range
derivable therein. In other non-limiting examples, a dose may also comprise
from
about 1 microgramlkg/body weight, about 5 microgram/kg/body weight, about
10 microgram/kg/body weight, about 50 microgram/kg/body weight, about
100 microgram/kg/body weight, about 200 microgram/kg/body weight, about
350 microgram/kg/body weight, about 500 microgram/kg/body weight, about
1 milligram/kg/body weight, about 5 milligram/kg/body weight, about
10 milligram/kg/body weight, about 50 milligram/kg/body weight, about
100 milligram/kg/body weight, about 200 milligram/kg/body weight, about
350 milligram/kg/body weight, about 500 milligram/kg/body weight, to about
1000 mg/kg/body weight or more per administration, and any range derivable
therein. In non-limiting examples of a derivable range from the numbers listed
herein, a range of about 5 mg/kg/body weight to about 100 mg/kg/body weight,
CA 02432945 2003-07-10
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about 5 microgram/kg/body weight to about 500 milligram/kg/body weight, etc.,
can
be used, based on the numbers described above.
In any case, the composition may comprise various antioxidants to retard
oxidation of one or more component. Additionally, the prevention of the action
of
microorganisms can be brought about by preservatives such as various
antibacterial and antifungal agents, including but not limited to parabens
(e.g.,
methylparabens, propylparabens), chlorobutanol, phenol, sorbic acid,
thimerosal or
combinations thereof.
The compositions may be formulated into a composition in a free base,
neutral or salt form. Pharmaceutically acceptable salts, include the acid
addition
salts, e.g., those formed with the free amino groups of a proteinaceous
composition, or which are formed with inorganic acids such as for example,
hydrochloric or phosphoric acids, or such organic acids as acetic, oxalic,
tartaric or
mandelic acid. Salts formed with the free carboxyl groups can also be derived
from inorganic bases such as for example, sodium, potassium, ammonium,
calcium or ferric hydroxides; or such organic bases as isopropylamine,
trimethylamine, histidine or procaine.
In certain embodiments, the compositions are prepared for administration
by such routes as oral ingestion. In these embodiments, the solid composition
may comprise, for example, solutions, suspensions, emulsions, tablets, pills,
capsules (e.g., hard or soft shelled gelatin capsules), sustained time release
formulations, buccal compositions, troches, elixirs, suspensions, syrups,
wafers, or
combinations thereof. Oral compositions may be incorporated directly with the
food of the diet. Preferred carriers for oral administration comprise inert
diluents,
assimilable edible carriers or combinations thereof. In other aspects of the
invention, the oral composition may be prepared as a syrup or elixir. A syrup
or
elixir, and may comprise, for example, at least one active agent, a sweetening
agent, a preservative, a flavoring agent, a dye, a preservative, or
combinations
thereof.
In certain embodiments, an oral composition may comprise one or more
binders, excipients, disintegration agents, lubricants, flavoring agents, and
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combinations thereof. In certain embodiments, a composition may comprise one
or more of the following: a binder, such as, for example, gum tragacanth,
acacia,
cornstarch, gelatin or combinations thereof; an excipient, such as, for
example,
dicalcium phosphate, mannitol, lactose, starch, magnesium stearate, sodium
5 saccharine, cellulose, magnesium carbonate or combinations thereof; a
disintegrating agent, such as, for example, corn starch, potato starch,
alginic acid
or combinations thereof; a lubricant, such as, for example, magnesium
stearate; a
sweetening agent, such as, for example, sucrose, lactose, saccharin or
combinations thereof; a flavoring agent, such as, for example peppermint, oil
of
10 wintergreen, cherry flavoring, orange flavoring, etc.; or combinations
thereof the
foregoing. When the dosage unit form is a capsule, it may contain, in addition
to
materials of the above type, carriers such as a liquid carrier. Various other
materials may be present as coatings or to otherwise modify the physical form
of
the dosage unit. For instance, tablets, pills, or capsules may be coated with
shellac, sugar or both.
In embodiments where the composition is in a liquid form, a carrier can be a
solvent or dispersion medium comprising but not limited to, water, ethanol,
polyol
(e.g., glycerol, propylene glycol, liquid polyethylene glycol, etc), lipids
(e.g.,
triglycerides, vegetable oils, liposomes) and combinations thereof. The proper
fluidity can be maintained, for example, by the use of a coating, such as
lecithin; by
the maintenance of the required particle size by dispersion in carriers such
as, for
example liquid polyol or lipids; by the use of surfactants such as, for
example
hydroxypropylcellulose; or combinations thereof such methods. In many cases,
it
will be preferable to include isotonic agents, such as, for example, sugars,
sodium
chloride or combinations thereof.
In other embodiments, one may use eye drops, nasal solutions or sprays,
aerosols or inhalants in the present invention. Such compositions are
generally
designed to be compatible with the target tissue type. In a non-limiting
example,
nasal solutions are usually aqueous solutions designed to be used in the nasal
passages in drops or sprays. Nasal solutions are prepared so that they are
similar
in many respects to nasal secretions, so that normal ciliary action is
maintained.
Thus, in preferred embodiments, the aqueous nasal solutions usually are
isotonic
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or slightly buffered to maintain a pH of about 5.5 to about 6.5. In addition,
antimicrobial preservatives, similar to those used in ophthalmic preparations,
drugs, or appropriate drug stabilizers, if required, may be included in the
formulation. For example, various commercial nasal preparations are known and
include drugs such as antibiotics or antihistamines.
Additional formulations which are suitable for other modes of administration
include suppositories. Suppositories are solid dosage forms of various weights
and shapes, usually medicated, for insertion into the rectum, vagina or
urethra.
After insertion, suppositories soften, melt or dissolve in the cavity fluids.
In
general, for suppositories, traditional carriers may include, for example,
polyalkylene glycols, triglycerides or combinations thereof. In certain
embodiments, suppositories may be formed from mixtures containing, for
example,
the active ingredient in the range of about 0.5% to about 10%, and preferably
about 1 % to about 2%.
Sterile injectable solutions are prepared by incorporating the active
compounds in the required amount in the appropriate solvent with various of
the
other ingredients enumerated above, as required, followed by filtered
sterilization.
Generally, dispersions are prepared by incorporating the various sterilized
active
ingredients into a sterile vehicle which contains the basic dispersion medium
and/or the other ingredients. In the case of sterile powders for the
preparation of
sterile injectable solutions, suspensions or emulsion, the preferred methods
of
preparation are vacuum-drying or freeze-drying techniques which yield a powder
of
the active ingredient plus any additional desired ingredient from a previously
sterile-filtered liquid medium thereof. The liquid medium should be suitably
buffered if necessary and the liquid diluent first rendered isotonic prior to
injection
with sufficient saline or glucose. The preparation of highly concentrated
compositions for direct injection is also contemplated, where the use of DMSO
as
solvent is envisioned to result in extremely rapid penetration, delivering
high
concentrations of the active agents to a small area.
The composition should be stable under the conditions of manufacture and
storage, and preserved against the contaminating action of microorganisms,
such
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12
as bacteria and fungi. It will be appreciated that exotoxin contamination
should be
kept minimally at a safe level, for example, less that 0.5 ng/mg protein.
EXAMPLES
The following example is included to demonstrate new and inventive
methods of the inventor and preferred embodiments of the invention. It should
be
appreciated by those of skill in the art that the techniques disclosed in the
example
which follows represent techniques discovered by the inventor to function well
in
the practice of the invention and, thus, can be considered to constitute
preferred
modes for its practice. However, those of skill in the art should, in light of
the
present disclosure, appreciate that many changes can be made in the specific
embodiments which are disclosed and still obtain a like or similar result
without
departing from the spirit and scope of the invention.
Example 1
Materials and Methods: The present invention is evidence in a
randomized, stratified, double-blind, placebo-controlled study as described in
the
following paragraphs. In the study, a total of 146 patients were recruited. Of
the
146 patients enrolled in the study, 14 patients cancelled surgery. Others were
removed from the study because of unavailable data, withdrawn consent or break
in protocol. Thus, out of 146 patients, the data from 102 patients was
considered.
In the study, 102 women who underwent day surgery (tubal ligation),
Diclectin~ or placebo were used in a randomized, stratified, double-blind
manner.
Patients were stratified according to the timing of their menstrual cycle such
that at
least 30% of the patients were in day 0-8 of their menstrual cycle. In each
case,
patients were given, either a placebo or Diclectin~ dosage units, each unit
containing about 10 mg of Doxylamine Succinate (an antihistamine) and about 10
mg of Pyridoxine Hydrochloride (Vitamin B6) at specified time intervals. More
specifically, patients were instructed to take 2 pills with fluid before
retiring to bed
on the night prior to surgery. Upon awakening the morning of surgery, they
took 1
more tablet with a sip of water, and any other pre-operative medications as
instructed by their anesthesiologist (no pre-operative anti-emetics). The
fourth
tablet was taken post-operatively, before discharge form the short stay unit.
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For the tubal ligation, patients received a standard anesthetic with no pre-
operative anti-emetics. Induction of anesthesia consisted of propofol (1-3
mg/kg)
plus an opioid dose equivalent to fentanyl 102 ug/kg. Muscle relaxation was
achieved with rocuronium (0.6 mg/kg) or vecuronium (0.1 mg/kg) at the
discretion
of the attending anesthesiologist. Anesthesia was maintained with nitrous
oxide
(70%), oxygen (30%), and isoflurane (0.5-1.5%). Patients received volumed
cycled mechanical ventilation. Muscle relaxation was monitored by peripheral
nerve stimulator and, at the end of surgery, was reversed with neostigmine
(50 ug/kg) and glycopyrrolate (10 ug/kg). Patients were transferred post-
operatively to the recovery room, and transferred to the short stay unit until
ready
for discharge home.
Post-operatively, there were 3 periods of observation in different venues.
The first observation period was in the Post Anesthetic Care Unit (PACU) and
outcomes were recorded by the PACU nurse.
The second observation period was in the Short Stay Unit (SSU), and
outcomes were recorded by the SSU nurse. Those 2 periods covered the time
from 0-6 hours.
The third period spanned the time from hospital discharge until 24 hours
post-operatively (6-24 hours); data were collected for this period using
interviewer-
administered telephone follow-up by the principal investigator.
The outcomes were measured during each of the 3 post-operative
observation periods included incidence of nausea, incidence of vomiting,
possible
side-effects including headache, epigastric discomfort, dizziness, or
drowsiness,
and administration of post-operative rescue anti-emetic drugs.
Patient symptoms of nausea and vomiting were measured separately in this
trial. Nausea was recorded as absent (0), mild (1 ), moderate (2), or severe
(3).
Vomiting was recorded as absent (0), vomited once (1 ), vomited more than once
(2). A priori, it was determined that a difference in one point would
represent a
clinically important difference to patients.
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14
For statistical calculations Chi square analysis was used to compare the
proportions of patients in each group with these symptoms. Two sided
significance
test was used and p<0.05 was set as the barrier indicating complete
statistical
significance.
Results: The results are shown in Table 1 below:
TABLE 1
AI location
TIME FRAME OUTCOME p-value
DICLECTIN~ PLACEBO
N=50 N=52
Nausea 12/50 (24%) 10/51 (19.6%)0.593
Vomiting 2/50 (4%) 4/51 (7.8%) 0.678
PACU
>_ 1 dose of
anti-
10/50 (20%) 10151 (19.6%)0.885
emetic given
Nausea 20150 (40%) 16151 (31.4%)0.365
Vomiting 9/49 (18.4%) 9/52 (17.3%) 0.889
SSU
>_ 1 dose of
anti-
7/50 (14%) 10/52 (19.2%)0.479
emetic given
Nausea 14150 (28%) 15148 (31.3%)0.725
Vomiting 5/50 (10%) 12/48 (25%) 0.04995
6-24 HRS
.
>_ 1 dose of
anti-
1/50 (2%) 2148 (4.2%) 0.292
emetic given
Functional Return to usual
1.510 4.065 0.098
Outcome activities
(days)
Significance of Results: In this randomized double-blind placebo-
controlled trial, it was clearly demonstrated that Diclectin~ significantly
reduced the
incidence of post-operative vomiting.
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As an effective agent for preventing post-operative vomiting, Diclectin~ is
an attractive alternative to medications currently given either
prophylactically or to
treat vomiting in post-op recovery areas.
Diclectin~ is preferably provided as an oral delayed release formulation.
5 Because it does not require an injection, Diclectin~ can be easily ingested
by
patients pre-operatively and after discharge from hospital.
Known anti-emetics given intravenously may be efficacious in preventing in-
hospital nausea and vomiting but will have worn off by the time patients are
home.
In the study reported above in Table 1, it was shown that Diclectin~
significantly
10 reduced the occurrence of post-operative vomiting even after hospital
discharge
during the first 24 hours at home.
Also shown in Table 1 is the trend of an accelerated return to normal
activities and work associated with Diclectin~. This is also a significant
finding. A
return to work after 1.5 days on Diclectin~ is a strong benefit in comparison
to 4.1
15 days for patients on placebo.
*************************
All of the compositions and/or methods disclosed and claimed herein can
be made and executed without undue experimentation in light of the present
disclosure. While the compositions and methods of this invention have been
described in terms of preferred embodiments, it will be apparent to those of
skill in
the art that variations may be applied to the compositions and/or methods and
in
the steps or in the sequence of steps of the method described herein without
departing from the concept, spirit and scope of the invention.
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16
REFERENCES
The following references, to the extent that they provide exemplary
procedural or other details supplementary to those set forth herein.
Brent, Teratology, 27:283-286, 1983.
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