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Naproxen, paracetamol and pamabrom versus paracetamol, pyrilamine and

pamabrom in primary dysmenorrhea: a randomized, double-blind clinical trial

Article  in  Medwave · October 2016

DOI: 10.5867/medwave.2016.09.6587

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Research article
Medwave 2016 Oct;16(9):6587 doi: 10.5867/medwave.2016.09.6587

Naproxen, paracetamol and pamabrom versus

paracetamol, pyrilamine and pamabrom in primary
dysmenorrhea: a randomized, double-blind clinical trial
Autores: Mario I. Ortiz [1 ], Gabriela Murguía-Cánovas [2 ], Laura C. Vargas-López [1], Rodolfo
Silva[3], Mario González-de la Parra [4 ]

Affiliation:
[1] Área Académica de Medicina del Instituto de Ciencias de la Salud de la Universidad Autónoma del
Estado de Hidalgo, Pachuca, Hidalgo, México
[2] Universidad del Futbol y Ciencias del Deporte, San Agustín Tlaxiaca, Hidalgo, México
[3] Laboratorios Liomont S.A. de C.V. Ciudad de México, México
[4] Biokinetics, S.A. de C.V., Ciudad de México, México

E-mail: [email protected]

Citation: Ortiz M , Murguía-Cánovas G , Vargas-López LC , Silva R , González-de la Parra M .

Naproxen, paracetamol and pamabrom versus paracetamol, pyrilamine and pamabrom in primary
dysmenorrhea: a randomized, double-blind clinical trial.Medwave 2016 Oct;16(9):6587 doi:
10.5867/medwave.2016.09.6587
Submission date: 15/5/2016
Acceptance date: 12/9/2016
Publication date: 24/10/2016
Origin: not requested
Type of review: reviewed by three external peer reviewers, double-blind

Key Words: naproxen, paracetamol, pamabrom, primary dysmenorrhea, pyrilamine

Abstract
INTRODUCTION
Dysmenorrhea is caused by the discharge of prostaglandins into the uterine tissue; therefore, non-
steroidal anti-inflammatory drugs (NSAIDs) are the established initial therapy for dysmenorrhea.
Dysmenorrhea therapy may include the administration of drug monotherapy or combination therapy.
However, clinical scientific evidence on the efficacy of medications with two or three drugs combined is
scarce or nonexistent.

OBJECTIVE
To evaluate and compare the efficacy and safety of two oral fixed-dose combinations for the relief of
the symptoms of primary dysmenorrhea among Mexican women. One of the combinations is widely used
in Mexico (paracetamol, pyrilamine and pamabrom) and the selected comparison was a medication with
naproxen sodium, paracetamol and pamabrom based on the pathophysiology of primary dysmenorrhea.

METHODS
This was a single-centre, double blind, experimental, parallel group, randomized trial. Female patients
with primary dysmenorrhea, older than 17 years and with pain intensity greater than 45 mm on a visual
analogue scale, were included. The patients were then randomized to receive tablets with naproxen
sodium, paracetamol and pamabrom or tablets with paracetamol, pyrilamine and pamabrom for one
menstrual cycle. Patient evaluations of symptomatology and pain intensity were recorded throughout
one menstrual period. Descriptive and inferential statistical analyses were utilized.

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 RESULTS
An intention-to-treat population of 91 women, with a mean age of 21.3 ± 3.2 years, received
paracetamol, pyrilamine and pamabrom tablets, and 98 participants, with a mean age of 21.0 ± 3.2
years, received naproxen sodium, paracetamol and pamabrom tablets. The participants’ assessments
of pain on the Visual Analogue Scale during the menstrual cycle demonstrated a significant reduction in
both treatment groups (p<0.05). There is no significant difference in efficacy between both groups
(p>0.05).

CONCLUSIONS
The results showed that both drug combinations were not different in reducing dysmenorrheic pain.
Likewise, both treatments were well tolerated. Therefore, both treatments may be used for the
treatment of primary dysmenorrhea.

Introduction

Dysmenorrhea is a chronic, cyclic pelvic pain associated medication containing two or three different drugs, which
with menstruation and may be associated with nausea, have different, but complementary action
vomiting, diarrhea, headache, fatigue, back pain, and mechanisms [9],[10]. What is expected of such
dizziness. The prevalence of dysmenorrhea ranges from combinations is causing better pain relief at lower doses
20% to 90% [1],[2],[3]. Primary dysmenorrhea (PD) is (synergism) and fewer adverse reactions. For example, our
suggested to be caused by the release of prostaglandins group demonstrated that the most common medications
into the uterine tissue [3],[4],[5]. Prostaglandins are prescribed by physicians and used in self-medication to
derivatives of arachidonic acid metabolism by the enzyme treat dysmenorrheic pain in Mexican students were the
cyclooxygenase (COX). Nonsteroidal anti-inflammatory medications Syncol® (a combination of paracetamol
drugs (NSAIDs) are a group of chemically different drugs, [analgesic], pamabrom [diuretic] and pyrilamine
which inhibit cyclooxygenase enzyme causing a decrease in [antihistamine H1]) and Buscapina Compositum® (a
prostaglandin synthesis [5]. Nonsteroidal anti- combination of metamizole [NSAID] plus butylhyoscine
inflammatory drugs have anti-inflammatory, analgesic and [antimuscarinic]) [1],[2].
antipyretic effects. A very recent meta-analysis showed
that nonsteroidal anti-inflammatory drugs are more It is important to note that clinical scientific evidence on the
effective than placebo in reducing pain in women with efficacy of medications with two or three drugs combined
primary dysmenorrhea [5]. Therefore, nonsteroidal anti- (for example, paracetamol with naproxen sodium) is scarce
inflammatory drugs such as naproxen, diclofenac, or missing [1],[2],[6]. Therefore, well designed studies are
ibuprofen among others, are the initial established therapy mandatory to assess the effectiveness of medications that
for primary dysmenorrhea [1],[2],[3],[4],[5]. contain a combination of several drugs and are commonly
used in the management of primary dysmenorrhea in some
Oral contraceptives, analgesic-antipyretic such as countries.
paracetamol, among other drugs are other pharmacological
therapeutic options for the treatment of pain in women with Therefore, the objective of the present study was to
primary dysmenorrhea [1],[2],[3],[4]. However, its evaluate the efficacy and safety of two medications with
effectiveness in relieving pain in patients with primary different drug combinations: a) naproxen sodium +
dysmenorrhea is controversial [3],[6],[7],[8]. Some paracetamol + pamabrom (NPP; tested medication), and b)
studies demonstrated the ability of paracetamol to paracetamol + pyrilamine + pamabrom (PPP; medication
decrease the production of F2αprostaglandin in menstrual of reference) on primary dysmenorrhea in Mexican women;
fluid and symptoms in women with primary dysmenorrhea and in particular demonstrate non-inferiority of the tested
[7],[8]. However, meta-analysis studies showed that medication compared to the reference one.
paracetamol was less effective than nonsteroidal anti-
inflammatory drugs and as effective as placebo in relieving Methods
pain in patients with this condition [3],[5].
Participants
Although nonsteroidal anti-inflammatory drugs are the best According to the health legislation of Mexico, first of all, the
choice for pain relief in patients with primary study protocol was reviewed and approved by a local Ethics
dysmenorrhea; there is evidence showing that these drugs Committee (Universidad del Fútbol y Ciencias del Deporte,
administered alone may lead to therapeutic failure or to a Hidalgo, Mexico). After that, the same study protocol was
weak analgesic effect [1],[2],[3],[5]. Furthermore, clinical submitted for review and approval by independent Ethics
studies of patients with primary dysmenorrhea found that and Research Committees pertaining to the Federal
nonsteroidal anti-inflammatory drugs have more Commission for the Protection against Sanitary Risk
gastrointestinal and neurological adverse reactions than (COFEPRIS, Mexico). The study was conducted in
placebo [3],[5]. Therefore, another treatment option for accordance with the Declaration of Helsinki.
primary dysmenorrhea is the administration of a

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Recruitment was performed from students of equipped. The study medications were provided in opaque
the Universidad Autónoma del Estado de Hidalgo, Mexico. white polyethylene bottles, labeled with letter "A" or "B",
The inclusion criteria were an agreement to participate in and were sufficient for 3 days of treatment (nine identical
the research work and a signed informed consent, age over tablets per bottle for each of the medications; initiating
17 years, satisfactory health, negative urine pregnancy test treatment 24 hours before menstruation and up to 48 hours
and, primary dysmenorrhea screened by a physician who after starting menstruation). During the final evaluation,
also obtained a medical history and performed a physical the participants returned their empty bottles.
examination. Each woman had a history of primary
dysmenorrhea, and reported it as painful menstruation in Primary efficacy measures
the previous four months with pain intensity greater The primary efficacy measure was the menstrual pain
than 45 mm on a visual analogue scale. intensity reported in the patient’s case reports prior to
taking the first dose of the study medication, which
The exclusion criteria were: patients with dysmenorrhea occurred at regular intervals (every eight hours), after the
secondary to organic pathology, chronic degenerative first dose and at the end of the study (72 hours). Pain
diseases and use of nonsteroidal anti-inflammatory drugs intensity was determined by the visual analogue scores of
or oral contraceptives within three months prior to study pain severity (0 mm = no pain, 100 mm = unbearable
entry. Patients with active peptic ulcer(s) or any pain).
gastrointestinal disease associated with clinically significant
blood loss within the last two years. Secondary efficacy measures included

Study design A) The proportion of the patients who at the end of the
This was a single-centre, double blind, prospective, treatment period reported a reduction of their baseline pain
experimental, parallel group, randomized study. by at least 50%.
B) Symptoms of dysmenorrhea were evaluated and
Randomization and blinding reported in the patient’s case reports prior to taking the
A database with the names of the participants in first dose of study medication and at the end of the study
spreadsheets Microsoft Excel 2010 was completed. (72 hours).
Participants were numbered from 1 to 200. According to the C) The patient’s global evaluation of the study medication
experimental design, two groups of participants (group "A" was performed at the end of the study. Patients assessed
for naproxen sodium, paracetamol and pamabrom of 100 the response to their study medication as: satisfactory
participants and another group "B" for paracetamol, response, moderate response, poor response and no
pyrilamine and pamabrom of 100 participants) were response to treatment.
established. A random numbers scheme was performed
with Microsoft Excel 2010. Each participant was randomly Treatment safety
assigned to receive its respective treatment to either "A" or Participants were informed to call or go to the principal
"B". Randomization and allocation was concealed to investigator in the presence of any suspected adverse event
statistical and clinical evaluators. The two medications produced by the medications throughout the study period.
(naproxen, paracetamol and pamabrom or paracetamol, No adverse event report was received before the final study
pyrilamine and pamabrom) were packed in bottles and visit. A clinical interrogatory and complete physical
labeled "A" (100 bottles) or "B" (100 bottles). Identification examination at the final evaluation were performed.
codes of the medications were also hidden to statistical and Adverse events were reported by the patients and were
clinical evaluators. The opening of the identification codes recorded in case report forms by the researchers. Adverse
was performed when the capture and verification of all data events were registered, evaluated and classified according
from the case report forms and diaries of patients was to the event start date, severity, relationship to study
completed. medication, action and treatment, outcome and end date of
the event.
Pharmacological intervention phase
Once the participants were included, a checklist was used Statistical analysis
to collect the demographic data, menstrual history, and Assuming a hypothesis of non-inferiority, the sample size
past medical and reproductive histories. Participants were was determined using a computerized software package
randomly divided into two groups: a group that received nQuery Advisor®, version 7.0. A sample size of 174
tablets orally with a combination of naproxen sodium (220 participants was estimated to provide 80% power, with a
mg), paracetamol (300 mg), and pamabrom (25 mg) margin of non-inferiority of 10 mm [11] between two
(naproxen, paracetamol and pamabrom group, Analgen groups in the evaluation of pain relief, using a visual
FEM®, Laboratorios Liomont, S.A. de C.V, Distrito Federal, analogue scale of 100 mm and assuming a significance level
Mexico) three times a day for one menstrual cycle and of 0.025 and a standard deviation of 23.4 mm. With a
another group that received tablets orally with a projected dropout rate of 10%, a minimum of 200
combination of paracetamol (500 mg), pamabrom (25 mg) participants (100 per each treatment) were estimated to be
and pyrilamine (15 mg) (paracetamol, pamabrom and required.
pyrilamine group, Syncol®, Laboratorios Sanfer, S. A. de An analysis of the efficacy data was accomplished on the
C.V., Estado de Mexico, Mexico) three times a day for one intention-to-treat population, which is defined as all of the
menstrual cycle. Study medications were properly randomized patients who fulfilled the inclusion criteria, had

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completed the treatments for the menstrual cycle and had using the Fisher’s exact test. For all of the statistical tests,
one complete evaluable cycle the type I error was fixed at 5% (α = 0.05). Stata® version
13 was used to generate all of the graphics and most of the
In the present study, parametric statistical analysis was analysis described in this report. NCSS 9® (NCSS, LLC.
applied to the scores of pain intensity from the visual Kaysville, Utah, United States) was used for the repeated-
analogue, because several sources of information measures ANOVA.
concerning statistical analysis of data obtained with this
scale justify their use [12],[13],[14],[15]. Results

The pain intensity scores were analyzed using a repeated- Sociodemographic and clinical characteristics of both
measures ANOVA with the treatment group as a between- groups
subject factor, time as a within-subject factor and the Two hundred patients were included in the study, and the
interaction between the treatment group and time. patients were randomly assigned to the naproxen,
paracetamol and pamabrom group (100 patients) or the
The degrees of freedom of the F statistical associated with paracetamol, pamabrom and pyrilamine group (100
the effects of the treatment group and the interaction were patients). Nonetheless, 11 randomized participants who
corrected (statistical test more conservative) using the met the inclusion criteria and received their bottle of
epsilon estimated (sphericity) of Greenhouse-Geisser, medicine could not be incorporated into the analysis of the
because this is a relatively small sample size and for intention-to-treat population; 10 were removed (without
deviations to the sphericity assumption applicable to data from an evaluable complete cycle, because the
repeated measures ANOVA [16]. patients did not return, nor could be reached, personally or
by telephone) and one due to protocol deviation (not
The primary comparison to assess efficacy was pain meeting a level of initial pain greater than 45 mm) (Figure
intensity mean difference between the global (72-hour 1). Consequently, there were 189 participants (naproxen,
period) means of the treatment groups. The efficacy paracetamol and pamabrom group: n = 98 and
measures recorded in categorical scale (symptoms of paracetamol, pamabrom and pyrilamine group: n = 91)
dysmenorrhea and patient’s global evaluation of the study included in the intent-to-treat population. The baseline
medication) were analyzed using the Fisher’s exact test. demographic, clinical data and dysmenorrheic symptoms of
Sociodemographic continuous variables were analyzed both groups are shown in Tables 1 and 2.
using the t-test and the categorical variables were analyzed

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Figure 1. Flow diagram for randomized participants.

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 Table 1. Sociodemographic and clinical data of the 189 patients according to group.

Table 2. Baseline characteristics of symptomatology in dysmenorrheic young women, who reported the
presence of symptoms: NPP (98 patients) and PPP (91 patients)

Primary efficacy

Pain intensity
reduced the pain intensity over time (P<0.001). A
Figure 2 shows the pain intensity vs. time profiles for both
statistically significant reduction of pain intensity in both
treatment groups. The results of the repeated-measures
groups was observed after the first eight hours of treatment
ANOVA indicated that both treatment groups significantly
(P<0.01) (Figure 2).

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 Figure 2. Effect of naproxen, paracetamol and pamabrom or paracetamol, pamabrom and pyrilamine on the
Pain Intensity (PI) in women with primary dysmenorrhea.

The estimated mean difference between the group global Secondary efficacy endpoints
means (NPP-PPP) was 3.25 mm, 95% CI (-1.49 mm, 7.99
mm, and p = 0.1779), and the global means (95% CI) for The proportion of patients who reported a pain
each treatment group were 37.87 mm(34.58 and 41.15) reduction by at least 50%
and 34.62 mm (31.20 and 38.03), respectively. Thus, This proportion of patients was 80.6% (79/98) in the
there was not a significant difference between the naproxen, paracetamol and pamabrom group and 87.9%
treatment groups. This result allows us to conclude that the (80/91) in the paracetamol, pamabrom and pyrilamine
tested medication (NPP) is not inferior to the medication of group. There was not a significant association between the
reference (PPP) because the upper value of 95% CI of the treatment groups, regardless of whether the patients
difference means (7.99 mm) was below the non-inferiority achieved a pain reduction of at least 50%, with respect to
margin of 10 mm used for determining the sample size for the baseline conditions (p = 0.2318).
this study.
Post-treatment symptoms of dysmenorrhea
Table 3 shows the post-treatment symptoms of
dysmenorrhea by the treatment group. There was no
significant association between the treatment group and
the post-treatment symptoms of dysmenorrhea.

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 Table 3. Symptoms in women with dysmenorrhea at the end of treatment.

Patient’s global evaluation of the treatment naproxen, paracetamol and pamabrom and paracetamol,
effectiveness pamabrom and pyrilamine groups (Table 4). Nevertheless,
Most women rated the effectiveness of their treatment as a there was no significant association (p = 0.7096) between
“moderate response” and “satisfactory response” in both the patient’s global evaluation and the treatment groups.

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 Tabla 4. End clinical response to treatment.

Safety findings The clinical use of combinations of analgesic and/or

During the study period and of the 200 women in the safety nonsteroidal anti-inflammatory drugs has increased
population, 2 (2.0%) patients experienced 3 adverse
events during the paracetamol, pamabrom and pyrilamine significantly in the last decades. The purpose is to associate
treatment and 4 (4.0%) women experienced five adverse two or three drugs with different mechanisms of action to
events during the naproxen, paracetamol and pamabrom achieve a synergistic interaction, yielding a sufficient
treatment. The most commonly reported adverse events in analgesic effect with low doses and therefore reduce the
the study were headache (one case) and abdominal pain intensity and incidence of untoward effects [9],[10].
(two cases) in the paracetamol, pamabrom and pyrilamine Previous studies have demonstrated the effectiveness of
group. However, somnolence (one case), headache (one paracetamol in alleviating the symptoms caused by primary
case), dizziness (one case), increased thirst (one case) and dysmenorrhea [7],[8].
diarrhea (one case) were reported in the naproxen,
paracetamol and pamabrom group. No serious adverse There is evidence that paracetamol is a weak inhibitor of
events were reported in this study. prostaglandin synthesis [17]. The ability of paracetamol to
decrease the production of prostaglandins F2α in menstrual
Discussion fluid and the symptoms in women with primary
dysmenorrhea has been previously demonstrated [9],[10].
Medications and alternative treatments are the main Likewise, paracetamol inhibits spinal cord nitric oxide
therapeutic strategies to alleviate the signs and symptoms synthesis and reinforces the serotonergic descending
caused by primary dysmenorrhea. Nonsteroidal anti- inhibitory pain pathways [18],[19]. Experimental data
inflammatory drugs are the first drugs of choice in the shows that the paracetamol metabolite N-
treatment of primary dysmenorrhea, which is supported by arachidonoylaminephenol inhibits the uptake and
findings that have shown that prostaglandins are the main degradation of anandamide, which is reported to mediate
substances involved in the pathogenesis of primary the analgesic action of acetaminophen via the CB1 receptor
dysmenorrhea [3],[4],[7]. Patients suffering from primary [20]. It is likely that these paracetamol are involved in it
dysmenorrhea usually do not go to the physician for care. ability to reduce pain in patients with primary
Instead, they resort to non-drug remedies and self- dysmenorrhea.
medication. Several studies have found an important
therapeutic failure or a small analgesic effect of On the other hand, it has been reported that histamine
nonsteroidal anti-inflammatory drugs [1],[2],[3],[5]. produces contractile activity of pregnant human uterine
Therefore, it is necessary to resort to other therapeutic strips, and this effect was blocked by the H1 histamine
measures to eliminate or ameliorate the symptoms that receptor antagonist pyrilamine [21],[22]. Recently, our
women experience with primary dysmenorrhea. In our group demonstrated that pyrilamine was able to block the
study and according to the analysis of the primary and contractile effect induced by KCl (60 mM) in non-pregnant
secondary efficacy variables, we found that the medications human uterine strips, and it was suggested that this effect
with the naproxen, paracetamol and pamabrom was through a mechanism different to the antagonism of
combination and the paracetamol, pamabrom and the H1 receptors [23]. It is possible that the analgesic effect
pyrilamine combination significantly reduced pain intensity induced by the paracetamol, pamabrom and pyrilamine mix
in a period of 72 hours (p <0.0001). In addition, no was due to the synergist effect between the different action
significant difference was found in the other secondary mechanisms of paracetamol and pyrilamine mentioned
efficacy measures between the two treatment groups (p> above. This is supported by the findings that low
0.05). concentrations of the paracetamol-pyrilamine combinations
interact synergistically to relax the uterine tissue[23] and

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therefore this association may represent a therapeutic probable activation of the action mechanisms of
advantage for the clinical treatment of primary paracetamol and pamabrom mentioned above.
dysmenorrhea.
With the experimental design used in this study, it is not
Alternatively, pamabrom, chemically 2-amino-2-methyl- possible to determine superiority or inferiority of individual
propanol 8-bromo theophylline, is a weak diuretic that is drugs versus any of the combinations. In this sense, it
effective in treating primary dysmenorrhea and would be of great importance to perform another clinical
premenstrual syndrome [24]. Theophylline, the active study in which the effectiveness and safety of any of the
xanthine derivative of pamabrom, has been shown to combinations (e.g. naproxen, paracetamol and pamabrom)
alleviate the angina-like chest pain induced by adenosine, were compared versus naproxen and paracetamol
post-dural puncture headache and pain during individually. Another limitation of this study is that a
experimental ischemia in humans [25],[26],[27]. There is placebo group was not included to determine the intrinsic
experimental evidence to suggest that the analgesic efficacy of both medications. This was because in its
activities produced by theophylline involve planning the use of placebo, being a study related to pain,
phosphodiesterase and adenosine receptors [25],[26]. was not considered as ethical. In addition, patients were
Taken together, it is possible to suggest that the selected within a range of age and other physiological
pamabrom-induced pharmacological effects were included conditions, according to inclusion and exclusion criteria of
with the activities produced for paracetamol and pyrilamine the protocol so that the results of this study may not be
in the efficacy produced for the paracetamol, pamabrom generalizable to the entire target population.
and pyrilamine mix observed in the present study. The real
participation of the different action mechanisms of each Conclusions
drug of the paracetamol, pamabrom and pyrilamine mix
requires future elucidation. The results show that both drug combinations were not
different in reducing the dysmenorrheic pain, therefore the
Naproxen and naproxen sodium are very potent analgesic medication tested (naproxen, paracetamol and pamabrom)
and anti-inflammatory drugs that are used for treating is not inferior to the medication of reference (paracetamol,
painful conditions such as arthritis and gout [28],[29]. The pamabrom and pyrilamine). For this reason, we suggest
anti-inflammatory and analgesic properties of naproxen that the drug combinations naproxen, paracetamol and
have been attributed to the inhibition of cyclooxygenase pamabrom and paracetamol, pamabrom and pyrilamine are
and the consequent inhibition of prostaglandin effective and safe options for the treatment of primary
biosynthesis [28]. dysmenorrhea.

The analgesic efficacy of naproxen in women with primary Notes

dysmenorrhea has been previously demonstrated. From the editor
Marjoribanks et al. [5] published a meta-analysis to The authors originally submitted this article in Spanish and
compare nonsteroidal anti-inflammatory drugs used in the English. The Journal has not copyedited the English
treatment of primary dysmenorrhea. The authors found version.
that naproxen was significantly more effective than the
placebo in producing moderate to excellent relief of Acknowledgement
dysmenorrheic pain (OR 3.67, 95 % IC: 2.94 to 4.58). In This research and its publication were supported by
the same study, it was found that naproxen was Laboratorios Liomont, S.A. de C.V. Federal, Mexico.
significantly more effective than paracetamol in decreasing
the symptomatology of primary dysmenorrhea [5]. Conflicts of interest
The authors completed the ICMJE conflicts of interest
In a previous study, we demonstrated that the self declaration form, and declare having received funds
medication of naproxen was statistically more effective in from Laboratorios Liomont, S.A. Ciudad de México, Mexico
alleviating dysmenorrheic pain than the paracetamol, for the completion of this report. Mario I. Ortiz is a worker
pamabrom and pyrilamine mix (P=0.006) or the over-the- of the Universidad Autónoma del Estado de Hidalgo,
counter medication with metamizole (a nonsteroidal anti- Pachuca, Mexico; Gabriela Murguía-Cánovas is a worker of
inflammatory drug) plus butylhyoscine bromide the Universidad del Futbol y Ciencias del Deporte, Pachuca,
(P=0.004) [1]. Hidalgo, Mexico; Rodolfo Silva is a worker of Laboratorios
Liomont, S.A. Ciudad de México, Mexico; Mario González-
In our study, the paracetamol dose (300 mg) employed in de la Parra is a worker of Biokinetics, S.A. de C.V., Ciudad
the naproxen, paracetamol and pamabrom mix was less de México, Mexico. Forms can be requested to the
than the paracetamol dose (500 mg) used in the responsible author or the editorial direction of the Journal.
paracetamol, pamabrom and pyrilamine combination.
Based on these results, we suggest that the analgesic effect Ethical aspects
produced by the naproxen, paracetamol and pamabrom According to the health legislation of Mexico, first of all, the
combination could be synergistic. In addition, we propose study protocol was reviewed and approved by a local Ethics
that the efficacy of the naproxen, paracetamol and Committee (Universidad del Futbol y Ciencias del Deporte,
pamabrom combination in our study was due to the ability Hidalgo, Mexico). After that, the same study protocol was
of naproxen to inhibit prostaglandin biosynthesis and the submitted for review and approval by independent Ethics

www.medwave.cl 10 doi: 10.5867/medwave.2016.09.6587

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Author address:
[1] Área Académica de Medicina del Instituto de Ciencias de la Salud
Universidad Autónoma Del Estado de Hidalgo
Eliseo Ramírez Ulloa 400
Colonia Doctores
Pachuca
Hidalgo
México

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