U.S. patent application number 12/945480 was filed with the patent office on 2011-03-10 for pharmaceutical dosage form bearing pregnancy-friendly indicia.
This patent application is currently assigned to Duchesnay Inc.. Invention is credited to Gordana Atanackovic, Eric Gervais, Raymond Hebert.
Application Number | 20110059026 12/945480 |
Document ID | / |
Family ID | 4171184 |
Filed Date | 2011-03-10 |
United States Patent
Application |
20110059026 |
Kind Code |
A1 |
Gervais; Eric ; et
al. |
March 10, 2011 |
PHARMACEUTICAL DOSAGE FORM BEARING PREGNANCY-FRIENDLY INDICIA
Abstract
A pharmaceutical dosage form comprising at least one active
ingredient and destined for administration to pregnant women. The
pharmaceutical dosage form bears pregnancy-friendly indicia apt to
improve patient compliance with medically recommended dosage
regimen resulting in improved product effectiveness. The
pregnancy-friendly indicia is also apt to diminish the incidence of
erroneous dispensing of or erroneous ingestion of pharmaceutical
dosage forms not intended for pregnant women. Also disclosed is a
method for achieving improved patient compliance resulting in
improved product effectiveness. Also disclosed is a method for
diminishing the incidence of erroneous dispensing of or erroneous
ingestion of dosage forms not intended for pregnant women. Said
methods comprising providing a pharmaceutical dosage form, intended
for use by pregnant women, bearing pregnancy-friendly indicia apt
to graphically distinguish dosage forms intended to be used during
pregnancy from others.
Inventors: |
Gervais; Eric; (Laval,
CA) ; Atanackovic; Gordana; (Dollard-des-Ormeaux,
CA) ; Hebert; Raymond; (IIe Bizard, CA) |
Assignee: |
Duchesnay Inc.
Laval
CA
|
Family ID: |
4171184 |
Appl. No.: |
12/945480 |
Filed: |
November 12, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11384584 |
Mar 20, 2006 |
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12945480 |
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10611803 |
Jul 1, 2003 |
7560122 |
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11384584 |
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Current U.S.
Class: |
424/10.2 |
Current CPC
Class: |
A61K 31/4402 20130101;
A61K 31/4415 20130101; A61K 45/06 20130101; A61K 31/4402 20130101;
A61K 9/2072 20130101; A61K 31/44 20130101; A61K 31/4415 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101 |
Class at
Publication: |
424/10.2 |
International
Class: |
A61K 9/44 20060101
A61K009/44 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 5, 2002 |
CA |
CA/2,392,486 |
Claims
1. A patient dosage regimen compliance improving pharmaceutical
dosage form destined for administration to pregnant women, said
pharmaceutical dosage form containing one or more vitamin
supplement or drug, said pharmaceutical dosage form further
comprising a graphical representation of a pregnant woman applied
to the outer surface of the dosage form, said graphical
representation being visible to the naked eye.
2. The patient dosage regimen compliance improving pharmaceutical
dosage form in accordance with claim 1 wherein the dosage form is a
tablet.
3. The patient dosage regimen compliance improving pharmaceutical
dosage form in accordance with claim 1 wherein said pharmaceutical
dosage form contains a vitamin supplement.
4. The patient dosage regimen compliance improving pharmaceutical
dosage form in accordance with claim 3 wherein the dosage form is a
tablet.
5. The patient dosage regimen compliance improving pharmaceutical
dosage form in accordance with claim 3 wherein said vitamin
supplement comprises folic acid.
6. The patient dosage regimen compliance improving pharmaceutical
dosage form in accordance with claim 5 wherein the dosage form is a
tablet.
7. The patient dosage regimen compliance improving pharmaceutical
dosage form in accordance with claim 1, wherein the vitamin
supplement comprises vitamins or minerals.
8. The patient dosage regimen compliance improving pharmaceutical
dosage form in accordance with claim 1 wherein said pharmaceutical
dosage form consists of a vitamin supplement.
9. The patient dosage regimen compliance improving pharmaceutical
dosage form in accordance with claim 8 wherein the dosage form is a
tablet.
10. The patient dosage regimen compliance improving pharmaceutical
dosage form in accordance with claim 8 wherein said vitamin
supplement comprises folic acid.
11. The patient dosage regimen compliance improving pharmaceutical
dosage form in accordance with claim 10 wherein the dosage form is
a tablet.
12. The patient dosage regimen compliance improving pharmaceutical
dosage form in accordance with claim 1 wherein the graphical
representation being visible to the naked eye is that shown in FIG.
1.
13. The patient dosage regimen compliance improving pharmaceutical
dosage form in accordance with claim 12 wherein the dosage form is
a tablet.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. application Ser.
No. 11/384,584, filed Mar. 20, 2006, which is a divisional of U.S.
application Ser. No. 10/611,803, filed Jul. 1, 2003 (which issued
as U.S. Pat. No. 7,560,122), which claims priority to Canadian
patent Application No. CA 2,392,486, filed Jul. 5, 2002. The
contents of all of the above-referenced applications are
incorporated by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to pharmaceutical dosage forms
intended for use during pregnancy.
BACKGROUND OF THE INVENTION
[0003] During pregnancy a variety of medical conditions require
treatment with therapeutic agents. For instance, in Canada,
excessive nausea and vomiting, possibly leading to hyperemesis
gravidarum, are routinely treated with the prescription drug
Diclectin.RTM. which contains a mixture in equal amounts of two
active ingredients, namely pyridoxine HCl and doxylamine
succinate.
[0004] Other conditions, pre-existing or developed during
pregnancy, for example: diabetes, hypertension, blood cloths,
depressive illness and heart disease are also commonly treated with
prescription drugs.
[0005] In the case of pre-existing medical conditions numerous
studies have shown that women have a tendency to abruptly stop
taking their medications upon learning of the pregnancy, due to the
perceived fear of birth defects.sup.1. In many cases, the risk to
the health of the expectant mother and her baby is much higher if
she stops or reduces her treatment than if she keeps taking the
required medications.
[0006] Because of this perceived risk of harm to the fetus,
otherwise known as the teratogenic risk, it is common for expectant
mothers to discontinue taking a prescribed drug or to voluntarily
diminish the prescribed dosage regimen. This often leads to dosage
levels below therapeutic ranges in turn leading patients and the
medical community to incorrectly conclude that a particular drug is
clinically ineffective.
[0007] Discontinuing or altering drug therapy, often against
competent medical prescription, may have grave consequences indeed.
The health of the expectant mother and vicariously of the fetus may
be put at great risk because of poor compliance with competent
medical prescription. In many instances, the teratogenic risks must
be weighed against the risk of catastrophic illness or worsening
condition on the part of the expectant mother.
[0008] Even discounting the particular problem of patient
compliance during pregnancy, drug therapy patient compliance is a
widespread and difficult problem in the medical community.
Non-compliance with prescribed drug dosage regimen is a huge health
problem for patients in general. For example, it is estimated that
less than 25% of outpatients will complete a 10 day course of
antibiotic therapy for a strep throat or otitis media.
[0009] Matsui.sup.2 described that non-compliance with prescribed
medication regimens may take many forms, including failure to fill
the prescription, incorrect dosage, improper dosing interval, and
premature discontinuation of the drug. Of course, the problem of
non-compliance is magnified during pregnancy due to the importance
of fetal safety..sup.3
[0010] Whenever women delay or discontinue use of medications
during pregnancy due to fears related to fetal safety, the result
may be a worsening of the condition and hospitalisation with use of
multiple drug therapy. Furthermore, depending of the underlying
condition, the worsening of the condition has serious consequences
even including suicidal ideation. Einarson showed in her
study.sup.1 on abrupt discontinuation of psychotropic drugs during
pregnancy due to teratogenic fears, that 70.3% of women reported
physical and psychological adverse effects to the point that 29.7%
reported suicidal ideation (one third of them were
hospitalised).
[0011] Despite these appalling statistics, the perception of the
expectant mother remains shrouded by well-known errors of the past
such as the widely publicized cases of thalidomide-induced fetal
malformations. The graphic evidence of birth defects attributed to
Thalidomide exposure during early pregnancy has left a
teratogenicity stigma on all medications. Hence, it is commonly
thought that all medications are to be avoided during pregnancy. In
the study entitled "Prevention of Unnecessary Pregnancy
Terminations by Counselling Women of Drug, Chemical, and Radiation
Exposure During the First Trimester", (1990).sup.4, Koren showed
that pregnant women exposed to drugs that are known to be non
teratogenic, still perceive that their born-to-be baby has a 24%
chance to suffer a major birth defect. This is about the same risk
as an intra-uterine exposure to Thalidomide.
[0012] Scientific studies aimed at measuring the risk of drugs
during pregnancy and patient education and counseling have so far
been at the forefront of efforts to achieve better patient
compliance with medical prescription.
[0013] However, even in the case of drugs having an extensively
demonstrated record of fetal innocuousness, such as Diclectin.RTM.
used to curb nausea and vomiting, the perception of latent risk
remains. This perception of risk is of course carried over from the
negative experiences of thalidomide which was also prescribed for
nausea and vomiting during pregnancy and which was also provided as
an oral dosage form. However, in reality, the active ingredient
thalidomide and the active ingredients of Diclectin.RTM., namely
pyridoxine HCl and doxylamine succinate are completely unrelated.
The risk perception carried-over from thalidomide is made apparent
from patient compliance inquiries. Patient compliance with a
medically prescribed dosage regimen of Diclectin.RTM. is clearly
below what is recommend in the medical profession.
[0014] Even physicians and pharmacists are anxious about their
liability associated with prescription or dispensing of medications
to pregnant women. In the study by Pole.sup.5, it was shown that
even health care professionals, after reading four different labels
(all of them stating that drug is safe to be used in pregnancy),
have evaluated these labels, as bearing a residual risk. They were
unable to fully perceive or accept that medication is safe to be
used in pregnancy. Patients, physicians and pharmacists are also
worried about erroneous ingestion or dispensing of drugs not
intended for use during pregnancy.
[0015] Despite the enormous volume of scientific evidence
supporting Diclectin.RTM. harmlessness to the fetus, pregnant women
persistently do not follow their physician's recommendation as to
the adherence to Diclectin.RTM. dosage regimen. In most cases,
women voluntarily reduce the dosage by half. In fact, they do not
comply with the proper dosage regimen for Diclectin.RTM. to the
point that some woman and some physicians believe that the
medication is not effective. Therefore, non-compliance often
results in a perception of product effectiveness failure.
[0016] Due to non-compliance with medical prescription, patients
using less than prescribed amounts of Diclectin.RTM. will often
find themselves in sub-therapeutic state. This prevents the
medication from being effective and may aggravate the mother's
condition to the point of developing hyperemesis gravidarum (HG).
HG is the most severe end of nausea and vomiting during pregnancy,
when a pregnant woman suffers from loss of more than 5% of her
pre-pregnancy body weight, dehydration, acid-base disturbances,
ketonuria and electrolyte imbalance. At this stage, physicians use
intravenous medications that are often not recognised for safe use
during pregnancy in order to control maternal condition. The use of
these medications poses an unnecessary risk to the fetus. If this
last resort medication appears to be ineffective due to the
deterioration of the woman's condition, a therapeutic abortion may
even be considered.sup.6.
[0017] In order to diminish potential for birth defects a vitamin
intake is now medically recommended during pregnancy. For example,
clinical evidence shows that taking folic acid before conception
and during the first trimester of pregnancy may prevent up to 72%
of the congenital abnormalities spina bifida and anencephaly.sup.7.
Despite this, pregnant women are generally non compliant with
recommended folic acid intake treatment thus putting an unborn
child at an increased risk of major birth defect.
[0018] The situation is even worse if pregnant woman has been on a
drug therapy that interferes with folic acid receptors (e.g.,
phenobarbital, phenytoin, carbamazepine, valproic acid). In this
case, a pregnant woman is even at greater risk for having a baby
with birth defect if she is not compliant.
[0019] Thus there remains an important need for innovative
solutions to achieve better patient compliance of vitamins or drugs
recommended for use during pregnancy.
OBJECTS OF THE INVENTION
[0020] An object of the present invention is therefore to provide
an improved oral dosage form for, inter alia, achieving better
patient compliance with vitamins or drugs intended for use during
pregnancy.
[0021] Another object is to provide a method for improving patient
compliance of pregnant women by diminishing their perception of
teratogenic risk and by direct implication to improve product
effectiveness of dosage forms containing at least one active
ingredient and intended for use by pregnant women.
[0022] A further object is to provide a method for diminishing the
incidence of erroneous ingestion by pregnant women or of erroneous
dispensing by pharmacists of therapeutic agents not prescribed to
said pregnant women.
SUMMARY OF THE INVENTION
[0023] More specifically, in accordance with the present invention,
there is provided a pharmaceutical dosage form comprising at least
one active ingredient, such as for example a vitamin supplement or
a synergistic combination of pyridoxine HCl and doxylamine
succinate, and destined for administration to pregnant women, the
pharmaceutical dosage form bearing pregnancy-friendly indicia. In a
preferred embodiment the pregnancy-friendly indicia is in the shape
of a graphical illustration of a pregnant woman applied to the
dosage form itself or to its packaging. In a most preferred
embodiment, the dosage form is destined for oral
administration.
[0024] Also provided is a method of diminishing the perception of
teratogenic risk among pregnant women taking a pharmaceutical
dosage form containing at least one active ingredient. The method
comprising providing said pharmaceutical dosage form bearing
pregnancy-friendly indicia, preferably in the shape of a graphical
illustration of a pregnant woman applied to the dosage form itself
or to its packaging.
[0025] Also provided is a method of improving patient compliance of
pregnant women with medically recommended dosage regimen of at
least one active ingredient. The method comprising providing a
pharmaceutical dosage form bearing pregnancy-friendly indicia.
Improving patient compliance also leads to improved product
effectiveness because product effectiveness is linked to patient
compliance. Thus, the method of the present invention also leads to
improved product effectiveness.
[0026] Also provided is method of diminishing the incidence of
erroneous ingestion by pregnant women or of erroneous dispensing by
pharmacists of therapeutic agents not prescribed to said pregnant
women. The method comprising providing a pharmaceutical dosage form
comprising at least one active ingredient prescribed to said
pregnant women, the dosage form bearing pregnancy-friendly indicia
apt to graphically distinguish dosage forms intended to be used
during pregnancy from others.
[0027] Other objects, advantages and features of the present
invention will become more apparent upon reading of the following
non-restrictive description of preferred embodiments thereof, given
by way of example only with reference to the accompanying
drawing.
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] FIG. 1 is a pictorial representation of an improved oral
dosage form in accordance with the present invention and bearing a
visible indicia apt to achieve improved patient compliance.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0029] The main object of the present invention is therefore to
provide an improved oral dosage form for achieving better patient
compliance with drugs prescribed for use during pregnancy. This
objective is surprisingly and effectively achieved by applying
pregnancy-friendly indicia on the dosage form. Dosage form is
understood to encompass its packaging. By "pregnancy-friendly"
indicia is meant any graphical or textual representation apt to be
easily recognized as indicative of a safe medication for taking
during pregnancy.
[0030] In a most preferred embodiment, the pregnancy-friendly
indicia are a graphical representation of the profile of a pregnant
woman having a hand resting on her stomach region. Such graphical
representation is illustrated in FIG. 1 and has a particularly
comforting effect on expectant mothers and have been statistically
shown to substantially lower the perception of teratogenic risk and
consequently lead to elevated patient compliance. Such evidence is
presented in the examples provided below.
Example 1
[0031] A study was conducted with 12 pregnant women. This study was
aimed at testing if pregnancy-friendly indicia such as the indicia
illustrated in FIG. 1 may have a positive impact by reducing the
perception of teratogenic risk of a drug taken during pregnancy,
and if it is the case, which kind of design is most effective in
improving patient compliance.
[0032] Different designs of pregnancy-friendly indicia were printed
on tablets. This aim was to ascertain if, when used, those indicia
would increase the patients' confidence in taking the tablet during
pregnancy by reducing the perception of teratogenic risk.
Diminishing the perception of teratogenic risk would consequently
improve patient compliance and as a result achieve better treatment
effectiveness.
[0033] The study revealed while all pregnancy-friendly indicia are
helpful at diminishing the perception of teratogenic risk, the most
preferred graphical representation is that of FIG. 1. The graphical
representation shown in FIG. 1 would indicate in a clear and
precise fashion that the medication has been specifically designed
for the pregnant woman.
[0034] This surprising positive effect on patient compliance would
of course translate itself in the effectiveness of a vitamin or
drug treatment and a concurrent reduction of medical complications
for the pregnant woman and the fetus.
Example 2
[0035] To further validate the findings disclosed in Example 1, an
observational, prospective survey on pregnant women in family
practice offices and obstetrician offices was conducted. The
statistical tool used for measuring the objective of the study (how
reassured about fetal safety woman feels taking one or the other
tablet once prescribed to them) was a validated scientific tool for
subjective measurements: a visual analog scale (VAS) from 1-5 (1
being the least safe and 5 being the most safe). Patients were told
that the prescribed drug, in tablet form, was safe for use in
pregnancy and were asked to label on the VAS how reassured about
fetal safety they felt when taking the tablet. They were shown two
different tablets, one plain white and the other white with the
illustration of FIG. 1 applied to the tablet.
[0036] Data was collected from 132 pregnant women and the results
are shown in the table below:
Test: Dual-Sample Assuming Equal Variances
[0037] Teratogenic Risk Perception on Scale of 1 to 5 with 1 being
Greatest Risk Perception.
TABLE-US-00001 Plain Tablet with pregnancy- White friendly indicia
tablet as per Figure 1 Observations 132 132 Mean Risk 2.5227 3.6969
Perception Variance 1.2132 1.3120 P(T <= t) one-tail P <
0.0001
[0038] The study clearly showed superiority of the tablet with a
printed pregnant woman concerning the perception of the teratogenic
risk (results were statistically significant with P<0.0001). The
P value of 0.0001 signifies that the result of this study as
1/10,000 chance to be the result of chance only. If we repeat this
study 10,000 times, in 9,999 cases, the same results would be
obtained. Usually P<0.05 is recognized as medically
significant.
[0039] Thus, in the sample group of 132 pregnant women, 23.4% felt
more reassured about the fetal safety of taking the tablet with a
printed pregnant woman as shown in FIG. 1, than a plain white
tablet.
[0040] Of course, these results would translate themselves directly
into improved patient compliance by a margin of at least 23.4%.
Thus, a strong conclusion emerges that the presence of
pregnancy-friendly indicia on a vitamin or drug to be taken during
pregnancy will significantly reduce teratogenic risk perception and
by the same token improve patient compliance with prescribed dosage
regimen.
[0041] Although the present invention has been described
hereinabove by way of preferred embodiments thereof, it can be
modified, without departing from the spirit and nature of the
subject invention as defined in the appended claims. More
specifically, the exact appearance of pregnancy-friendly indicia is
variable with the understanding that some indicia will induce
greater patient compliance than others. Also, it is to be
understood that although examples were given in relation to oral
tablets, other pharmaceutical dosages forms are of course covered
by the present invention. Thus, pregnancy-friendly indicia may
appear on the actual dosage form, such as tablet, sugar coated
tablet, sublingual tablet, caplet, capsule, gel capsule, chewable
tab, pill, suppository, powder, vial, ampoule, pre-filled syringe,
nasal spray, pastille, syrup, drops, vaginal ovule, subcutaneous
implant, transdermal gel, transdermal patch, transmucausal strip,
pouch, or may also appear on the packaging and labeling of the
dosage form.
REFERENCES
[0042] 1. Einarson A., Selby P., Koren G., Abrupt discontinuation
of psychotropic drugs during pregnancy: fear of teratogenic risk
and impact of counseling, J. psychiatry Neurosci 2001; 26(1): 44-48
[0043] 2. Matsui D., Drug compliance in pediatrics: Clinical and
research issues. Ped Clin N Amer 1997; 44(1):1-14 [0044] 3. Anke
M., et al., Questions about drugs: how do pregnant women solve
them? Pharm world Sci 1994 Dec. 2; 16(6):254-9; [0045] and [0046]
Olesen C., Sondergaard C., Do Pregnant Women Report Use of
Dispensed Medications?, Epidemiology 2001; 12(5):497-501 [0047] 4.
Koren G., Pastuszak A., Prevention of Unnecessary Pregnancy
Terminations by Counselling Women on Drug, Chemical, and Radiation
Exposure During the First Trimester, Teratology 1990; 41(6):657-61
[0048] 5. Pole M., Einarson A., Pairaudeau N.& al., Drug
Labeling and Risk Perceptions of Teratogenicity: A Survey of
Pregnant Canadian Women and Their Health Professionals, J. Clin.
Pharmacol. 2000; 40: 573-577 [0049] 6. Mazzotta P., Stewart D.,
Koren G., Magee L A. Factors associated with elective termination
of pregnancy among Canadian and American women with nausea and
vomiting of pregnancy. J. Psychosom Obstet. Gynecol. 2001;
22(1):7-12 [0050] 7. Czeizel A E, Dudas I: Prevention of the first
occurance of neural tube defects by periconceptional vitamin
supplementation. N Eng J Med 1992; 327:1832-1835; [0051] and [0052]
Pastuszak A., Bhatia D., Okotore B., Koren G., The Effectiveness of
Preconceptional Counseling on Women's Compliance with Folic Acid
Supplementation, Maternal-Fetal Toxicology, A Clinician's Guide,
Third-Edition, 2001:141-149
* * * * *