Azole Antifungal Consumption in Community Pharmacy Sales in Mainland Portugal: Trend Analysis from 2014 to 2023

Abstract

Background/Objectives: Excessive or inadequate use of antimicrobial drugs may lead to the emergence of resistant strains. For this reason, it is important to monitor consumption indicators to assess drugs’ utilization over time. This study aimed to analyze the consumption of medically prescribed azole antifungal drugs in mainland Portugal from 2014 to 2023, focusing on those directed to genital infections: fluconazole, isoconazole, itraconazole, and sertaconazole. Methods: For each drug, the evaluated parameters were the total number of packages, number of packages per 1000 inhabitants, defined daily dose (DDD) per 1000 inhabitants per day, and total costs. For this purpose, we used data from community pharmacies’ sales, which are available through INFARMED (the Portuguese national authority on medicines and health products). Results: Several trends emerged from data analysis. The COVID-19 pandemic negatively affected the consumption of all azole antifungal drugs included in this study. However, after 2020, fluconazole and sertaconazole consumption has been increasing. In the specific case of fluconazole, there was an increase in expenditure, although the total number of packages suffered a decrease over the 10-year study period. Additionally, the defined daily dose (DDD) per 1000 inhabitants per day for fluconazole and itraconazole was lower compared to estimates from the last available survey (2009). Conclusions: Although our findings represent a lesser pressure on fungi, further monitoring is needed to better understand the evolution of fluconazole and itraconazole consumption over time, particularly due to the trends observed in this study.

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Academic Editors: Max Carlos
Ramírez-Soto and Alexandro Bonifaz
Received: 5 December 2024
Revised: 27 December 2024
Accepted: 1 January 2025
Published: 4 January 2025
Citation: Moura, S.; Duarte, P.;
Oliveira, A.S.; Martinez-de-Oliveira, J.;
Palmeira-de-Oliveira, A.; Rolo, J.
Azole Antifungal Consumption in
Community Pharmacy Sales in
Mainland Portugal: Trend Analysis
from 2014 to 2023. Antibiotics 2025,14,
33. https://doi.org/10.3390/
antibiotics14010033
Copyright: © 2025 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
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(https://creativecommons.org/
licenses/by/4.0/).
Article
Azole Antifungal Consumption in Community Pharmacy Sales
in Mainland Portugal: Trend Analysis from 2014 to 2023
Sofia Moura 1,2,3,4 , Paulo Duarte 5, Ana Sofia Oliveira 1,2,4 , JoséMartinez-de-Oliveira 2,4,
Ana Palmeira-de-Oliveira 1,2,4,6 and Joana Rolo 1,2,4,*
1
Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal; sofia.moura@ubi.pt (S.M.);
ana_g2s@hotmail.com (A.S.O.); apo@fcsaude.ubi.pt (A.P.-d.-O.)
2CICS-UBI—Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilhã, Portugal;
jmo@fcsaude.ubi.pt
3Department of Clinical Pathology, Santarém District Hospital, Lezíria Local Healthcare Unit,
2005-177 Santarém, Portugal
4RISE-Health, Faculdade das Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal
5NECE—Research Centre for Business Sciences, Faculty of Human and Social Sciences, University of
Beira Interior, 6200-209 Covilhã, Portugal; pduarte@ubi.pt
6Labfit, Health Products Research and Development Lda, 6200-284 Covilhã, Portugal
*Correspondence: joanarolo@fcsaude.ubi.pt
Abstract: Background/Objectives: Excessive or inadequate use of antimicrobial drugs
may lead to the emergence of resistant strains. For this reason, it is important to monitor
consumption indicators to assess drugs’ utilization over time. This study aimed to analyze the
consumption of medically prescribed azole antifungal drugs in mainland Portugal from 2014
to 2023, focusing on those directed to genital infections: fluconazole, isoconazole, itracona-
zole, and sertaconazole. Methods: For each drug, the evaluated parameters were the total
number of packages, number of packages per 1000 inhabitants, defined daily dose (DDD) per
1000 inhabitants per day, and total costs. For this purpose, we used data from community
pharmacies’ sales, which are available through INFARMED (the Portuguese national authority
on medicines and health products). Results: Several trends emerged from data analysis.
The COVID-19 pandemic negatively affected the consumption of all azole antifungal drugs
included in this study. However, after 2020, fluconazole and sertaconazole consumption has
been increasing. In the specific case of fluconazole, there was an increase in expenditure,
although the total number of packages suffered a decrease over the 10-year study period.
Additionally, the defined daily dose (DDD) per 1000 inhabitants per day for fluconazole
and itraconazole was lower compared to estimates from the last available survey (2009).
Conclusions: Although our findings represent a lesser pressure on fungi, further monitoring
is needed to better understand the evolution of fluconazole and itraconazole consumption
over time, particularly due to the trends observed in this study.
Keywords: fluconazole; isoconazole; itraconozole; Portugal; sertaconazole
1. Introduction
Fungal infections are a growing public health threat, yet they receive far less attention
than bacterial and viral diseases and depend on fewer resources worldwide. One of the
mechanisms to fight these types of infections is the use of antifungal drugs. Although
essential in the medical armamentarium, antifungals must be used rationally to avoid the
emergence of resistant strains [1].
Antibiotics 2025,14, 33 https://doi.org/10.3390/antibiotics14010033

Antibiotics 2025,14, 33 2 of 11
Azole antifungal drugs are utilized to fight different types of fungi, such as yeast infections,
like Vulvovaginal Candidosis and Cryptococcosis, and mold infections, like Aspergillosis [
2
].
Azoles are a class of antifungal agents that inhibit lanosterol 14 alpha-demethylase, which is
crucial for the biosynthesis of ergosterol, an essential component of fungal cell membranes. Cell
membrane disruption affects its permeability, leading to cell lysis and death [3].
Resistance to azole antifungal drugs can vary significantly depending on the species of
fungus, geographic origin, and the pharmacological profile of the specific azole in use. For
example, Aspergillus spp. and Candida krusei isolates are intrinsically resistant to fluconazole.
At the same time, resistance rates can differ from region to region in part due to the amounts
of azoles present in the environment, for example, in agricultural practices [4].
Five azole antifungal drugs (clotrimazole, fluconazole, itraconazole, miconazole, and
voriconazole) are listed in the World Health Organization Model List of Essential Medicines [
5
].
Their availability and cost vary widely across countries. While fluconazole is widely available,
others are less readily available. In 2018, itraconazole and fluconazole were among the
systemic antifungal drugs more commonly used in middle- and high-income countries [6].
Within Europe, Portugal was the third country with the highest consumption of outpa-
tient systemic antimycotic and antifungal use in 2009, presenting 0.43 and 0.32 defined daily
dose (DDD) per 1000 inhabitants per day for itraconazole and fluconazole, respectively [
7
].
Azevedo et al. [
8
] conducted a trend analysis regarding azole antifungal drug consumption
in Portugal from 2003 to 2013 and concluded that azole sales under medical prescription
were very high. In 2013, fluconazole and itraconazole were the most consumed among
azoles subject to medical prescription sold in community pharmacies [8].
With a special focus on azole antifungal drugs used to treat Vulvovaginal Candidosis,
the goal of this study is to conduct a trend analysis of fluconazole, isoconazole, itraconazole,
and sertaconazole community pharmacies’ sales in mainland Portugal from 2014 to 2023.
Understanding antifungal drugs’ consumption patterns is important to assess and interpret
the future emergence of antifungal resistance.
2. Results
2.1. Number of Packages Sold
From 2014 to 2023, fluconazole presented the highest number of packages sold in main-
land Portugal, followed by sertaconazole, itraconazole, and isoconazole (Table 1). During this
period, the most prescribed fluconazole package was the one containing two capsules of 150
mg each, and for itraconazole, it was the one with 32 capsules of 100 mg each. Regarding
sertaconazole, the cream was the most prescribed pharmaceutical form. As for isoconazole
vaginal cream, there was a decrease in sales by 98.48% during the same period.
Figure 1shows the total number of packages sold in each Portuguese Regional Health
Administration (North, Centre, Lisbon and Tagus Valley, Alentejo, and Algarve). Overall,
these regions presented similar consumption patterns, such as the most sold azole antifun-
gal drug being fluconazole, followed by sertaconazole, itraconazole and finally isoconazole.
Additionally, all regions showed a decrease in fluconazole, isoconazole, and itraconazole
consumption in 2020. The exception was sertaconazole that only presented a decrease in
the regions North and Algarve.
As shown in Figure 2, the overall trend for fluconazole shows an accentuated decrease
(by 14.79%) in consumption in 2020 compared to the previous year, with a rapid increase in the
following years. Comparing the number of packages sold between 2014 and 2023, the difference
was
−
1.23 per 1000 inhabitants. A decrease in sales between 2019 and 2020 was also observed for
isoconazole, itraconazole, and sertaconazole, which were36.25%, 17.43%, and 1.04%, respectively.
All azole antifungal drugs included in this study were less consumed in 2023 compared to 2014.
Nonetheless, after 2020, sertaconazole and especially fluconazole were on a rising path.

Antibiotics 2025,14, 33 3 of 11
Table 1. Number of packages sold in community pharmacies in mainland Portugal for fluconazole, isoconazole, itraconazole, and sertaconazole between 2014 and 2023.
Year
Active Substance/
Pharmaceutical Form Strength
Pack Size
2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 TOTAL
Fluconazole
Capsule 50 mg 7 34,915 34,500 32,747 30,983 31,459 31,984 28,677 30,579 32,539 34,636 323,019
Capsule 100 mg 14 13,618 13,855 14,034 14,660 15,757 16,176 14,859 15,852 16,904 17,408 153,123
Capsule 150 mg 1 37,292 40,071 40,784 35,107 41,777 51,429 35,750 40,026 46,305 51,493 420,034
Capsule 150 mg 2 287,648 273,161 260,727 252,821 246,975 238,558 208,458 220,523 243,195 260,189
2,492,255
Capsule 200 mg 7 14,391 15,314 15,599 14,795 15,753 15,867 13,663 14,960 16,374 17,773 154,489
Capsule 200 mg 14 17,449 16,683 17,406 18,158 18,181 18,748 17,054 18,722 21,155 23,580 187,136
Powder for oral
suspension 10 mg/mL 35 mL 1780 1548 1474 902 4 0 0 0 0 0 5708
Powder for oral
suspension 40 mg/mL 35 mL 2084 2343 1943 2486 2788 2846 2165 2014 2175 1937 22,781
TOTAL 409,177 397,475 384,714 369,912 372,694 375,608 320,626 342,676 378,647 407,016
3,758,545
Isoconazole
Vaginal cream 10 mg/g 40 g 11,139 8946 9349 8854 8716 7869 5020 4995 319 169 65,376
Itraconazole
Capsule 100 mg 4 15,615 14,627 13,208 11,981 11,558 8721 4794 4826 5097 5272 95,699
Capsule 100 mg 15 13,217 13,020 11,944 11,625 11,711 10,456 9286 9663 9353 9541 109,816
Capsule 100 mg 16 13,713 12,430 12,382 11,688 11,769 13,872 11,975 13,302 13,654 9917 124,702
Capsule 100 mg 28 35,677 34,172 31,872 31,004 27,597 20,390 18,250 19,028 18,996 13,551 250,537
Capsule 100 mg 32 38,665 33,886 33,133 31,271 29,024 31,397 25,729 27,369 27,919 34,258 312,651
Oral solution 10 mg/mL 150 mL 1705 1525 1456 1512 1326 1393 1251 1374 1171 1578 14,291
TOTAL 118,592 109,660 103,995 99,081 92,985 86,229 71,285 75,562 76,190 74,117 907,696
Sertaconazole
Cream 20 mg/g 30 g 97,631 97,132 96,599 93,051 68,587 46,536 54,002 66,553 75,387 80,510 775,988
Cutaneous powder 20 mg/g 30 g 19,251 20,049 21,502 21,994 18,964 19,542 16,503 20,048 23,424 25,617 206,894
Cutaneous solution 20 mg/mL 30 mL 18,006 17,080 16,638 16,626 19,898 17,487 14,069 14,443 14,181 14,687 163,115
Pessary 300 mg 1 36,193 35,758 33,533 30,505 27,967 20,988 19,006 20,633 20,848 20,356 265,787
TOTAL 171,081 170,019 168,272 162,176 135,416 104,553 103,580 121,677 133,840 141,170
1,411,784

Antibiotics 2025,14, 33 4 of 11
Antibiotics 2025, 14, x FOR PEER REVIEW 4 of 11
Figure 1. Consumption of uconazole, isoconazole, itraconazole, and sertaconazole by number of
packages and by Regional Health Administration (A—North, B—Centre, C—Lisbon and Tagus Val-
ley, D—Alentejo, and E—Algarve) between 2014 and 2023.
As shown in Figure 2, the overall trend for uconazole shows an accentuated de-
crease (by 14.79%) in consumption in 2020 compared to the previous year, with a rapid
increase in the following years. Comparing the number of packages sold between 2014
and 2023, the dierence was −1.23 per 1000 inhabitants. A decrease in sales between 2019
and 2020 was also observed for isoconazole, itraconazole, and sertaconazole, which were
36.25%, 17.43%, and 1.04%, respectively. All azole antifungal drugs included in this study
were less consumed in 2023 compared to 2014. Nonetheless, after 2020, sertaconazole and
especially uconazole were on a rising path.
Figure 2. Consumption of uconazole, isoconazole, itraconazole, and sertaconazole by number of
packages per 1000 inhabitants in community pharmacies in mainland Portugal between 2014 and
2023.
Figure 1. Consumption of fluconazole, isoconazole, itraconazole, and sertaconazole by number of
packages and by Regional Health Administration (A—North, B—Centre, C—Lisbon and Tagus Valley,
D—Alentejo, and E—Algarve) between 2014 and 2023.
Antibiotics 2025, 14, x FOR PEER REVIEW 4 of 11
Figure 1. Consumption of uconazole, isoconazole, itraconazole, and sertaconazole by number of
packages and by Regional Health Administration (A—North, B—Centre, C—Lisbon and Tagus Val-
ley, D—Alentejo, and E—Algarve) between 2014 and 2023.
As shown in Figure 2, the overall trend for uconazole shows an accentuated de-
crease (by 14.79%) in consumption in 2020 compared to the previous year, with a rapid
increase in the following years. Comparing the number of packages sold between 2014
and 2023, the dierence was −1.23 per 1000 inhabitants. A decrease in sales between 2019
and 2020 was also observed for isoconazole, itraconazole, and sertaconazole, which were
36.25%, 17.43%, and 1.04%, respectively. All azole antifungal drugs included in this study
were less consumed in 2023 compared to 2014. Nonetheless, after 2020, sertaconazole and
especially uconazole were on a rising path.
Figure 2. Consumption of uconazole, isoconazole, itraconazole, and sertaconazole by number of
packages per 1000 inhabitants in community pharmacies in mainland Portugal between 2014 and
2023.
Figure 2. Consumption of fluconazole, isoconazole, itraconazole, and sertaconazole by number of packages
per 1000 inhabitants in community pharmacies in mainland Portugal between 2014 and 2023.

Antibiotics 2025,14, 33 5 of 11
2.2. Defined Daily Dose (DDD) per 1000 Inhabitants per Day
Table 2provides the estimated DDD per 1000 inhabitants per day between 2014 and
2023. Until 2020, the azole antifungal drug with the highest DDD per 1000 inhabitants per
day was itraconazole, ranging from 0.380 to 0.235 in 2014 and 2020, respectively. Since 2021,
we have observed a shift with fluconazole, which presents higher values for this indicator.
For fluconazole, the lowest estimate was 0.233 in 2020, and the highest was 0.292 in 2023.
Since 2020, there has been a steady increase of approximately 0.02 for this indicator.
Table 2. Fluconazole, isoconazole, and itraconazole DDD per 1000 inhabitants per day between 2014
and 2023.
Year Fluconazole Isoconazole Itraconazole
2014 0.271 0.002 0.380
2015 0.266 0.002 0.349
2016 0.262 0.002 0.333
2017 0.261 0.002 0.320
2018 0.265 0.002 0.297
2019 0.266 0.001 0.279
2020 0.233 0.001 0.235
2021 0.250 0.001 0.249
2022 0.274 0.000 0.249
2023 0.292 0.000 0.246
2.3. Total Costs
During the 10-year period of this study, the highest expenditure observed was with
fluconazole, followed by itraconazole, sertaconazole, and isoconazole (Figure 3). Costs
with fluconazole varied from €3,529,335.79 in 2020 to €4,523,052.76 in 2023. Fluconazole
expenditure in 2023 represented an increase of 11.68% when compared to 2014.
Antibiotics 2025, 14, x FOR PEER REVIEW 5 of 11
2.2. Dened Daily Dose (DDD) per 1000 Inhabitants per Day
Table 2 provides the estimated DDD per 1000 inhabitants per day between 2014 and
2023. Until 2020, the azole antifungal drug with the highest DDD per 1000 inhabitants per
day was itraconazole, ranging from 0.380 to 0.235 in 2014 and 2020, respectively. Since
2021, we have observed a shift with uconazole, which presents higher values for this
indicator. For uconazole, the lowest estimate was 0.233 in 2020, and the highest was 0.292
in 2023. Since 2020, there has been a steady increase of approximately 0.02 for this indica-
tor.
Table 2. Fluconazole, isoconazole, and itraconazole DDD per 1000 inhabitants per day between 2014
and 2023.
Year
Fluconazole
Isoconazole
Itraconazole
2014
0.271
0.002
0.380
2015
0.266
0.002
0.349
2016
0.262
0.002
0.333
2017
0.261
0.002
0.320
2018
0.265
0.002
0.297
2019
0.266
0.001
0.279
2020
0.233
0.001
0.235
2021
0.250
0.001
0.249
2022
0.274
0.000
0.249
2023
0.292
0.000
0.246
2.3. Total Costs
During the 10-year period of this study, the highest expenditure observed was with
uconazole, followed by itraconazole, sertaconazole, and isoconazole (Figure 3). Costs
with uconazole varied from € 3,529,335.79 in 2020 to € 4,523,052.76 in 2023. Fluconazole
expenditure in 2023 represented an increase of 11.68% when compared to 2014.
Figure 3. Total costs of uconazole, isoconazole, itraconazole, and sertaconazole from community
pharmacies’ sales in mainland Portugal between 2014 and 2023.
3. Discussion
When analyzing the data, our aention was particularly drawn to the decrease in
community consumption of all studied azole antifungal drugs during 2020. This decrease
may be a consequence of the COVID-19 pandemic. During this year, some non-COVID-
19 clinical activity was suspended or postponed due to the pressure on healthcare
Figure 3. Total costs of fluconazole, isoconazole, itraconazole, and sertaconazole from community
pharmacies’ sales in mainland Portugal between 2014 and 2023.
3. Discussion
When analyzing the data, our attention was particularly drawn to the decrease in
community consumption of all studied azole antifungal drugs during 2020. This decrease
may be a consequence of the COVID-19 pandemic. During this year, some non-COVID-19
clinical activity was suspended or postponed due to the pressure on healthcare institutions

Antibiotics 2025,14, 33 6 of 11
to respond to increased respiratory symptoms [
9
]. This led to fewer medical appointments
in many medical specialties [
10
], from which one may assume fewer prescriptions of drugs.
On the other hand, in the absence of medical appointments’ availability, patients may
have looked for antifungal drugs that were not subject to medical prescription, such as
clotrimazole, econazole, fenticonazole, and nistatin. Another possible explanation for this
decrease in consumption may be a lower prevalence of infections due to reduced opportu-
nities for human contact due to the implementation of non-pharmaceutical interventions,
such as lockdowns where gatherings and meetings were banned and public spaces were
closed. This reduction in infection rates could have led to an overall decrease in consump-
tion of broad-spectrum antibiotics, which is a main risk factor associated with recurrent
Vulvovaginal Candidosis [11].
Additionally, infection control measures were promoted, such as frequent hand wash-
ing, reduction of facial touch, and physical distancing [
12
]. Due to these restriction mea-
sures, fewer fungal infections may have occurred, which led to a decrease in the need
to use azole antifungal drugs. These findings highlight how public health emergencies
can disrupt standard prescribing patterns, affecting overall antifungal drug usage trends.
Future studies should explore the impact of similar disruptions on other drug classes.
Health systems can use these insights to adapt prescribing practices and ensure essential
services during crises.
After 2020, some azole antifungal drugs included in this study started an ascending
trend in consumption, such as fluconazole and sertaconazole. Regarding fluconazole,
the number of packages per 1000 inhabitants sold in 2023 was lower compared to 2014;
however, the consumption of certain package sizes, such as the 150 mg capsule, increased.
For example, the fluconazole pack with two capsules of 150 mg each presented a decrease
in consumption, but the one with one capsule of 150 mg increased from 37,292 packages in
2014 to 51,493 in 2023. One may feel tempted to conclude that this could point to a shift
in less severe fungal infections, where one capsule is often sufficient to fight the infection,
or a change in the type of fungal infection, for example, Vulvovaginal Candidosis can be
treated with one capsule of 150 mg. In contrast, other fungal infections could take weeks of
treatment. This study does not provide sufficient data to draw a conclusion, as multiple
packages may be used for a single fungal infection.
Another trend noticed was the accentuated decrease in isoconazole vaginal cream
consumption by 98.48% from 2014 to 2023. We wonder if this reflects a medical preference
or if there is another reason for this decrease. The International Society for the Study of
Vulvovaginal Disease indicates isoconazole vaginal suppository as one of the available treat-
ment options for patients with uncomplicated Vulvovaginal Candidosis (mild symptoms);
however, it does not mention vaginal cream [11].
This study estimates that fluconazole and itraconazole DDD per 1000 inhabitants per
day are lower than 2009 levels, as reported by Adriaenssens et al. [
7
]. In 2009, fluconazole
and itraconazole DDD per 1000 inhabitants per day were 0.32 and 0.43, respectively. Our
findings show a lower DDD per 1000 inhabitants per day for both drugs in 2023. This
decrease could represent a lesser antimicrobial pressure on fungi, which is a good sign for
the maintenance of antifungal effectiveness, as excessive use could lead to the emergence of
resistant strains. As seen in other indicators, after 2020, there was also an increase in DDD
per 1000 inhabitants per day for fluconazole and itraconazole. However, the evolution of
this indicator in these two drugs was different. Fluconazole presented a rapid increase,
surpassing the estimate at the beginning of this study period, 0.292 in 2023 compared to
0.271 in 2014. As for itraconazole, there was a modest increase; however, the highest value
was estimated to be in 2014. Further monitoring of these indicators is needed to better
understand the evolution of these drugs’ consumption over the next years. Comparing our

Antibiotics 2025,14, 33 7 of 11
indicators with global consumption of antifungal agents in 65 middle- and high-income
countries [
6
], Portugal presented a higher fluconazole DDD per 1000 inhabitants per day.
In 2018, the global fluconazole consumption was 0.2296 DDD per 1000 inhabitants per
day, while in Portugal, it was 0.265. Regarding itraconazole, Pathadka et al. [
6
] showed an
increase in DDD per 1000 inhabitants per day during their study period, which is contrary
to the trend shown in our study. In 2018, the global consumption of itraconazole was
0.324 DDD per 1000 inhabitants per day, while in Portugal, it was 0.297.
Monitoring consumption trends is important to understand the emergence of re-
sistance patterns. In Portugal, several studies report resistance to azole antifungal
drugs
[13–28]
, which need to be carefully interpreted in terms of species, type of sam-
ples, provenience, and time period. The most recent ones showed different percentages
of resistance to fluconazole and itraconazole. A study published by Azevedo et al. [
13
]
found that 3.9% of yeasts isolated from the oral cavity, gut, and breastmilk were resistant to
fluconazole. Rolo et al. [
14
] showed that 46% of vaginal Candida spp. isolates were resistant
to fluconazole. Simões-Silva et al. [
15
] reported that all oral Candida isolates identified in
their study were susceptible to fluconazole and resistant to itraconazole. Sabino et al. [
16
]
conducted a trend analysis and found that, between 2012 and 2019, 4.4% of Aspergillus
fumigatus sensu stricto isolates were resistant to itraconazole. Focusing only on Vulvovagi-
nal Candidosis isolates, considering the same region in Portugal, two consecutive studies
have revealed that C. albicans isolates collected between 2009 and 2014 had a fluconazole
resistance rate of 61% [
14
], while isolates collected between 2019 and 2022 had a fluconazole
resistance rate of 8.9% [
17
]. On the other hand, at the same time period, the fluconazole
resistance rate among C. glabrata isolates increased from 3% in the first study to 53% in
the second study. It would be interesting to verify if this trend is statistically significant
and related to our findings in the current study. Further research is needed to consolidate
these findings.
As for costs related to azole antifungal drugs included in the current study, fluconazole
expenditure increased by 11.68% between 2014 and 2023. Although there was a decrease
in the total number of packages sold, this increase can be explained by the fact that sev-
eral types of packages presented a rise in sales. For example, the fluconazole pack size
containing one capsule of 150 mg increased sales by 38.08% and suffered a growth of
5.36% per package during the 10-year study period. Given that Portugal has a higher
fluconazole consumption rate than other countries, future research should investigate the
reasons behind this trend and assess whether these patterns correlate with unique epidemi-
ological factors or prescribing behaviors within Portugal. Furthermore, it highlights the
importance of healthcare policymakers considering pricing, accessibility, and the economic
burden of antifungal medications on public health budgets. Another perspective on this
finding would be the need to implement additional measures to prevent a possible rise
in fluconazole resistance like, for instance, expanding the availability of generic drugs in
the community, reducing inappropriate consumption by raising public awareness with
campaigns on the prudent use of antifungals, investment in diagnostics and surveillance
to track resistance trends, the inclusion of major fungal diseases in the Portuguese list of
notifiable diseases or cross-sectional collaboration between healthcare, agriculture, and
policymakers in Portugal.
The main limitations of this study are the following. First, the data used in this study
includes only sales in community pharmacies and only for medically prescribed drugs.
It would be interesting to analyze data on over-the-counter azole antifungal drugs and
observe if their consumption patterns were alike. On the other hand, the dataset did
not include the consumption of medically prescribed azole antifungal drugs in hospi-
tals. Since studies report increased fungal infections during the COVID-19 pandemic in

Antibiotics 2025,14, 33 8 of 11
hospitals
[29–31]
, the decrease in azole antifungal drugs in 2020 should be interpreted
cautiously. Second, the Portuguese Law on Epidemiological Surveillance of Communi-
cable Diseases [
32
] does not include fungal infections. Although there are local studies
on the prevalence of these types of infections and their resistance patterns [
13
–
28
], as we
mentioned previously in this discussion, there are no data at a national level. For this
reason, we could not correlate the indicators used in this study with prevalence and azole
resistance patterns over the 10-year study period. Nonetheless, this study shows the trends
of azole antifungal drugs community pharmacies’ sales over 10 years, which is important
to understand consumption patterns. These data are crucial for determining the need for
antifungal stewardship to address the emergence of resistance.
4. Materials and Methods
4.1. Study Design
This study is a trend analysis of fluconazole, isoconazole, itraconazole, and serta-
conazole community pharmacies’ sales in mainland Portugal from 2014 to 2023. These
antifungal drugs were selected for inclusion since these are the most used drugs to treat
genital infections caused by fungi [13].
4.2. Data Source
The analysis is based on the data provided by INFARMED—National Authority
of Medicines and Health Products, I.P., a Portuguese government agency. The dataset
includes only sales of medically prescribed drugs subject to government reimbursement
in community pharmacies, which means that the administration of this type of drug in
hospital healthcare was not included. The dataset was limited to drugs sold in mainland
Portugal, excluding the Azores and Madeira islands.
The estimated number of inhabitants in Portugal per year was obtained from Statistics
Portugal [33].
4.3. Data Analysis
Our focus was on azole antifungal drugs used to treat Vulvovaginal Candidosis.
Therefore, only fluconazole (capsule and powder for oral suspension), isoconazole (vaginal
cream), itraconazole (capsule and oral solution), and sertaconazole (cream, cutaneous
powder, cutaneous solution, and pessary) were included in this study. For each of these
drugs, the evaluated parameters were the total number of packages, number of packages
per 1000 inhabitants, DDD per 1000 inhabitants per day, and total costs.
We conducted a descriptive analysis of the total number of packages sold by pharma-
ceutical form, strength, pack size, and year for each azole antifungal drug. Additionally,
the total number of packages sold was presented by each Regional Health Administration
(that includes each geographic region in mainland Portugal). Since we observed the same
trends across geographic regions, we focused on estimating DDD per 1000 inhabitants
per day for the whole Portuguese population. We estimated the number of packages per
1000 inhabitants for each antifungal drug, dividing the total number of packages sold by
the population size, and multiplying by 1000. This indicator was calculated for each year
of the study period. DDD was estimated as defined by the World Health Organization
Collaborating Centre for Drug Statistics Methodology [
34
]. To calculate the indicator DDD
per 1000 inhabitants per day, the annual number of DDD was divided by the popula-
tion size and the number of days. Finally, the result was multiplied by 1000. DDD per
1000 inhabitants per day was estimated for fluconazole, isoconazole, and itraconazole.
Sertaconazole was excluded from this particular evaluation since there is no available DDD

Antibiotics 2025,14, 33 9 of 11
for this drug. Finally, we computed the retail price, in euros, for each azole antifungal drug
by year.
5. Conclusions
Continued surveillance of antifungal usage trends in Portugal is critical, as is education
among healthcare providers regarding conservative prescribing practices. The study’s
findings support the need for ongoing monitoring of antifungal usage in Portugal to detect
shifts in prescribing practices and guide antifungal stewardship initiatives. Additional
research on patient adherence, alternative therapies, and resistance patterns would provide
valuable insights for clinical guidelines and public health strategies.
Author Contributions: Conceptualization, S.M., J.R. and A.S.O.; methodology, S.M. and J.R.; formal
analysis, S.M. and P.D.; validation, J.M.-d.-O.; writing—original draft preparation, S.M.; writing–-review
and editing, A.P.-d.-O., A.S.O., J.M.-d.-O., P.D. and J.R.; supervision, A.P.-d.-O. and J.R. All authors
have read and agreed to the published version of the manuscript.
Funding: This research was funded by Fundação para a Ciência e a Tecnologia, Portugal, grant
numbers UIDB/00731/2020 and UIDB/04630/2020-DOI: 10.54499/UIDP/04630/2020.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Restrictions apply to the availability of these data. Data were obtained
from INFARMED.
Acknowledgments: The authors wish to acknowledge INFARMED—National Authority of Medicines
and Health Products, I.P. for providing data for this study.
Conflicts of Interest: The authors declare no conflicts of interest.
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