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ORIGINAL RESEARCH
Inclusion of Potentially Inappropriate Medicines
for the Older Adults in the Brazilian Consensus in
Accordance with International Criteria
Andréa Pecce Bento
1
, Leonardo Costa Pereira
2
, Kerolyn Ramos Garcia
1
, Luiz Fernando Ramos Ferreira
3
,
Emília Vitória da Silva
1
, Margô Karnikowski
1
1
Sciences and Health Technologies Program, University of Brasilia, Brasilia, DF, Brazil;
2
Physical Education, University UNIEURO, Brasilia, DF, Brazil;
3
Academic League of Project Management, Florence College, São Luis, Maranhão, Brazil
Correspondence: Margô Karnikowski, University Campus, s/n, Metropolitan Center, Brasília, DF, 72220-275, Brazil, Tel/Fax +5 613107 8418,
Email margounb@gmail.com
Aim: The use of potentially inappropriate medications (PIM) can impair the safety and effectiveness of pharmacotherapy in the older
adults. Thus, several countries have lists and criteria to indicate these drugs, in order to promote the safety of prescription and the
rational use of drugs in geriatric practice.
Objective: This study sought to contribute to the inclusion of PIM for the older adults in the Brazilian criterion (BCPIM/2016) –
current list used in Brazil and reference in Latin American countries – through expert approval, comparing convergences with
international AGS lists BEERS/2019, STOPP/START/2015, PRISCUS/2010 and EU (7)-PIM List/2015.
Methods: This is a critical analysis of potentially inappropriate medications for use in the older adults present in the list of Brazilian criteria,
together with their absence of some drugs that are on international lists (BEERS/2019; Priscus/2010; Stopp/Start/2015; EU7-PIM list/2015).
This study was subdivided in 6 stages: selection of national criteria, classication of drugs according to Anatomic Therapeutic Chemical,
comparison between BCPIM/2016 with international lists, selection of drugs not included in the Brazilian list, selection of experts for
evaluation and suggestions about drugs not included in the Brazilian list and the synthesis of the analysis carried out by the specialists.
Results: We cataloged 66 drugs marketed in Brazil that are on international lists, but not in the Brazilian consensus, of which 24 were
validated by experts as necessary for inclusion in this consensus, considering the risks and benets in health care for the older adults.
However, the lists have divergences and similarities between them. We observed that eight drugs were common to all criteria studied,
mainly related to the nervous system.
Conclusion: The results suggest the need for periodic validation of PIM against research clinics, new drugs and the inclusion of this
agenda by the Ministry of Health in the revision of the National List of Essential Drugs and other Clinical Protocols and Therapeutic
Prescription Guidelines for the older adults.
Keywords: list of potentially inappropriate drugs, seniors, aging, side effects, drug-related adverse reactions
Introduction
Functional changes and homeostasis usually appear naturally due to the senescence physiology and impact on pharma-
cokinetics and pharmacodynamics, with the potential to inuence the drug therapy safety and effectiveness.
1,2
One of the senility processes designs, characterized by a gradual and pathological decline in all body systems
functioning, has determined the highest frequency of frailty and comorbidities and, by consequence, the polypharmacy in
the older adults. The long-lived population is one of the largest consumers of drugs
3
and studies have shown that the use
of inappropriate medications is prevalent in older adults patients, as well as adverse reactions and drug interactions.
4
Thus, the peculiarities of the older adults organism referring to pharmacotherapy become them more exposed to
Drug-Related Problems – DRP and to Negative Results Associated with Medication – NMR, both responsible for
a signicant number of clinical admissions.
5,6
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Open Access Full Text Article
Received: 4 May 2021
Accepted: 15 July 2021
Published: 16 February 2022
In this context, Potentially Inappropriate Medicines (PIM) for the older adults arise. It is characterized by increasing the
risk of having adverse reactions compared to younger patients or also when they have no evidence-based indication.
6,7
According to Beer’s criteria, the PIM are dened as drugs with higher risk of intolerance related to adverse pharmacodynamics
or pharmacokinetics or drugs-disease interactions REF, and it is classied into three categories, those that should be avoided in
the older adults regardless of the clinical condition; those that should be avoided in the older adults with certain diseases,
which can be aggravated by such drugs; and those that should be used with care/caution in the older adults.
8
Several countries have been elaborated lists containing PIM for the older adults attempting to favor the prescription and
rational use of medicines in geriatric practice
9
e to keep them updated through constant reviews.
10
Among these lists are the
classication criteria of the American Geriatric Society (AGS) for the BEERS Criterion, version 2019;
11
Screening Tool of
Older Person’s Prescriptions (STOPP) Criterion Screening Tool to Alert to Right Treatment (START), 2015 version (STOPP/
START-2015);
12,13
the list of Germany; PRISCUS/2010
14
and the EU (7) -PIM List/2015,
15
FORTA (t for the Aged) List/
EURO-FORTA- 2018,
16
Taiwan-PIM/2019,
17
McLeod and IPET-Improving Prescribing in the older adults/2008.
18
In Brazil, the content validation of the Beers Criteria 2012 and STOPP 2006 resulted, in 2016, in the Brazilian
Consensus on Potentially Inappropriate Medicines for the Older adults (BCPIM/2016).
19
The present study aims to assess the selectivity of potentially inappropriate medications (PIM) to the older adults for
the Brazilian criterion according to the convergences with the international lists under the specialists’ validation.
Materials and Methods
Study Design
The study has a mixed method.
20
It is qualitative research once the modied Delphi technique
21
was used to establish
a strategy for systematized analysis of expert opinions and for the consensus on the drugs inclusion in BCPIM/2016,
19
which were absent in this list, but were contained in the criteria North American and European internationals. It is also
quantitative, cross-sectional study,
22
due to the use of frequencies and agreement indicator concerning the concomitant
presence of PIM in BCPIM/2016 with international lists.
Procedures
The research design is shown in Figure 1 and was carried out in six stages.
1st Stage – Selection of International Lists of Drugs Potentially Inappropriate for the Older Adults
In addition to the Brazilian Consensus on Potentially Inappropriate Medicines for the Older adults, 2016 (BCPIM/2016)
REF, the criteria (Figure 1) identied by the literature as the best known and most used in the United States and Europe
today, applicable to regulatory studies, were selected, in their most current versions,
7
as follows: the EU (7) – PIM List
15
and the AGS Beers criteria.
11
The Screening Tool of Older Person’s Prescriptions (STOPP), Screening Tool to Alert to
Figure 1 Experimental study design.
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Right Treatment (START) and the German list PRISCUS/2010 (14) criteria were also included (12, 13) as these are
recent criteria and constantly pointed out in the literature as tools used to assess the PIM prescription and factors
associated with the use of PIM. This process was supported by a comprehensive literature search that occurred in the rst
half of 2019. As a tool to identify the guiding lists of PIM that would be used in this study, we consulted the following
bibliographic platforms for scientic research: PubMed, Lilacs, Scielo and Scopus. For searching in this database, the
next descriptors were used in Portuguese, English and Spanish languages: “List of Potentially Inappropriate Medicines”,
“Older adults”, “Aging”, “Side Effects”, “Drug-Related Adverse Reactions”.
2nd Stage – Survey of Drugs Potentially Inappropriate for the Older Adults Contained in the Lists
We determined which medications were potentially inappropriate for the older adults selected on the 1st Stage. The drugs
were listed in a database following the drug classication according to Anatomic Therapeutic Chemical (ATC).
23
3rd Stage – Agreement Indicator (BCPIM)
An analytical contrast measure was adopted in the relationships between the PIM contained in the ve criteria selected in
the 1st Stage through the agreement indicator (I). Thus, after identifying the total number of drugs listed in the different
criteria, we veried in what proportion two lists of drugs observed agreed among themselves, within the set of all drugs
present in both lists. Such indicator was obtained from the following formula:
I¼iLa;Lb
�
where
I= Agreement indicator between criteria a and b;
i
(La, Lb)
=Intersection between the criteria for PIM’s a (La) and b (Lb);
La =Number of drugs present in the criterion a;
Lb =Number of drugs present in the criterion b.
The agreement indicator is measured by a value ranging from 0 to 1. Thus, the indicator assumes zero if the lists in
the criteria are totally different, having no medicine in common. On the other hand, the closer to 1, the more similar the
lists assessed will be.
To dene the sum of the total number of drugs present in two PIM criteria subtracted from the intersection between
two criteria, the variable Єwas established, as described below:
P¼La þLb I La;Lbð Þ
where:
ϵ = Discordance between two lists;
I= Agreement indicator between criteria a and b;
i
(La, Lb)
=Intersection between the criteria for PIM’s a (La) and b (Lb);
La =Number of drugs present in the criterion a;
Lb =Number of drugs present in the criterion b.
4th Stage – Determination of PIM Use in Older Adults in the Lists Selected in Step 1 with the Possibility of
Being Included in BCPIM/2016
We veried how many and which were the drugs commercialized in Brazil that were concurrently included in the other
lists studied and were not part of BCPIM/2016. We consulted the website of the National Health Surveillance Agency
(ANVISA) to nd out which of these drugs were marketed in the country.
24
5th Stage – Criteria for Selection of Specialists, Adapted Ferhing Scale
With the analysis of PIM absences in BCPIM/2016, the casuistry was questioned and the etiology of these absences was
investigated according to the experts’ knowledge. Then, experts from different regions of the country were sought, based
on curriculum analysis, in a research on the National Council for Scientic and Technological Development - CNPq
website. Those who reached a score of >5 were eligible according to the Fehring scale adapted.
25
After accepting to
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participate voluntarily to the study, they answered all research-related forms. The exclusion criteria of this group of
experts were not to reaching a score >5, according to the adapted Fehring scale,
25
or failing to answer any of the forms.
6th Stage – Application of Method Delphi for Content Validation Regarding the Reasons for Non-Inclusion of
MPI Use in Older Adult at BCPIM/2016
Two questionnaires were prepared: the rst to investigate the experts’ sociodemographic prole; and, the second,
containing a list of PIMs that were not included in BCPIM/2016, even though they were commercialized in Brazil and
were part of any of the lists investigated. This instrument was applied through an interactive process in Google forms,
containing a semi-structured questionnaire and the Informed Consent Form, according to the modied Delphi
technique
26
This technique recommends obtaining the greatest consensus in a group of people, carefully selected, on
a given topic and can occur in several rounds.
26
In our study, two rounds were carried out.
The rst question was intended to consult experts about their inclusion or not in BCPIM/2016. In the second round,
experts were asked to justify the drugs that they choose to not include in the consensus. After obtaining these
justications, a content analysis was carried out, dened by Rocha as a set of investigation techniques in the study of
communication analysis, to understand the objectives of prescription practices in the eld of science, choosing directions
that ensure legitimacy, leading us to observe an assumption, a conception of science, without losing its heterogeneity,
27
in
order to reect why the questioned drugs are not BCPIM/2016.
19
According to the articulation of these elements, which
characterize the content analysis approach the meaning production refers to a deduction, that is, to reach a signicance
about the non-inclusion of these drugs. In Content Analysis, the answers written means the subject’s expression, where
the research seeks to categorize the units of text that are repeated, inferring an expression that represents them.
29
For that,
we categorized the answers given by the specialists and counted the repetitions of the same.
Ethical Aspects
This research was approved by the Research Ethics Committee of the Faculty of Ceilândia at the University of Brasília,
under protocol number 3.317.495.
Statistical Analysis
To perform the data analysis, we used the software Statistical Package for the Social Sciences (SPSS), version 22. The
categorical variables data were presented in absolute and/or relative frequencies. For discrimination of comparison
measures, the relative prevalence were observed.
Results
Eighteen specialists agreed to participate in the study, being: eight geriatricians, six clinical pharmacists and four nurses.
Regarding the degree, ten were specialists, three were masters and four PhD. As for the geographical distribution by
residence, three were from the Northeast, four from the Southeast, six from the Midwest and ve from the South Brazil.
The Agreement Indicator between BCPIM/2016 and the other criteria established in this study for Potentially
Inappropriate Medications for the older adults ranged from 0.2 to 0.3 (Table 1).
Table 1 Indicator of Agreement Between BCPIM/2016 and the Criteria for BEERS/2019, STOPP/START/2015,
PRISCUs2010, EU (7)-PIM/2015
Criteria i
(La, Lb)
La Lb ЄI
BCPIM/2016 x BEERS/2019 80 193 149 262 0, 30
BCPIM/2016 x EU (7)-PIM/2015 43 193 65 215 0, 2
BCPIM/2016 x PRISCUS/2010 60 193 94 227 0, 26
BCPIM/2016 x START/STOPP/2015 62 193 114 245 0, 25
Notes:La - number of drugs present in the BCPIM/2016; Lb - number of drugs present in the other studied criteria; i
(La, Lb)
- intersection between
consensus A (La) and B (Lb); Є- sum of the number of drugs present in the two lists minus the intersection between the lists; I – frequency of agreement
between lists.
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A total of 337 Potentially Inappropriate Medicines were found for use in the older adults in the ve criteria, excluding
repetitions. We observed that eight of these drugs were common in all the studied criteria, and, according to Anatomic
Therapeutic Chemical (ATC),
23
they belong to the nervous system (n=4), cardiovascular system (n=2), digestive and
metabolic systems (n=2) classes. The reasons for which they were inserted, as well as precautions for use and therapeutic
alternatives are described (Table 2).
We found that a total of 144 drugs, present in at least one of the international criteria surveyed, were not part of the
criteria of BCPIM/2016. Of these, 78 drugs were not commercialized in Brazil. Among the 66 drugs marketer in the
country that could be included in BCPIM/2016 once they are described in at least one of the other international criteria-
12 have action on the digestive and metabolic system, four on the hematological system, 18 on the cardiovascular system,
four on the genital-urinary system and sex hormones, seven in the skeletal muscle system, 18 in the central nervous
system and three in the respiratory system (Table 3).
Table 2 Justication, Precautions When Using, Therapeutic Alternatives and Characteristics of Impropriety for the Use of
Medications in the Older Adults Included Concurrently in the Criteria for BEERS/2019, STOPP/START /2015, PRISCUS/2010, EU (7)-
PIM/2015, and Brazilian Consensus on Potentially Inappropriate Medicines for the Older Adults – BCPIM/2016
Classication
ATC
Medicines Justication for Avoiding Use Precautions When Using Therapeutic
Alternatives*
T: Nervous
system
I,II,III,IV,
V
Amitriptyline
a
Anticholinergic effects dry
mouth, constipation, orthostatic
hypotension, cardiac arrhythmias,
restlessness drowsiness.
2
Monitoring of anticholinergic
effects, assessing the risk of falls.
Selective serotonin
reuptake inhibitors
(citalopram or sertraline)
I,II,III,IV,V
Diazepam
a
Risk of falls due to the effect of
muscle relaxation, agitation,
irritability, cognitive decline,
depression.
2
Monitoring cognitive function,
testing gait pattern, starting with the
lowest dose possible and using the
shortest time possible.
Shorter-acting
benzodiazepines such as
zolpidem.
I,II,III,IV,
V
Hydroxyzine
c
Decline in cognitive performance,
electrocardiographic changes.
2
Monitoring of anticholinergic
effects, assessing the risk of falls.
Non-sedative, non-
cholinergic antihistamines
such as loratadine.
I,II,III,IV,
V
Promethazine
c
Mental confusion and sedation.
2
Monitoring cognitive function,
testing gait pattern, starting with the
lowest dose possible and using the
shortest time possible.
Non-sedative, non-
cholinergic antihistamines
such as loratadine.
C: Device
Cardiovascular
I,II,III,IV,V
Digoxin
c
High risk of poisoning.
2
Calculate the dose according to
lean body mass and be based on
kidney function.
For heart failure use
diuretics, for tachycardia
use Beta blockers (except
propranolol and sotalol).
I,II,III,IV,V
Nifedipine
c
Risk of myocardial ischemia
c
Risk of hypotension
2
Lower initial doses, half the usual
dose
Other antihypertensive
drugs such as amlodipine,
selective beta blockers,
diuretics.
A: Digestive
and Metabolic
System
I,II,III,IV,
V
Glibenclamide
c
Risk of prolonged hypoglycemia
2
Use more conservative initial doses
and maintenance.
Diet, metformin (<2 times
X850mg/day).
I,II,III,IV,
V
Metoclopramide
c
Peripheral arterial ow worsens,
extrapyramidal effects such as
tardive dyskinesia, increased risk
in frail older adults.
2
Use for a short time in low doses,
can be used in palliative care.
Domperidone, if there is no
contraindication for use.
Notes:Quality of evidence [
a
High,
b
Low,
c
Intermediate]; Strength of precaution [
1
Strong,
2
Weak]; Lists [
I
BCPIM/2016,
II
BEERS,
III
PRISCUS/2010,
IV
EU (7)-PIM/2015,
V
STOPP/
START/2015]; *Experts.
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Health experts agreed on a percentage of 60% or more regarding the inclusion of these 66 PIM in BCPIM/2016
(Figure 2).
There was 100% validation among experts regarding the inclusion of 24 of these drugs in the BCPIM/2016 (Table 4).
In the content analysis, we stratied seven categories of different justications most cited for the non-inclusion of PIM
in BCPIM/2016, as follows: the low frequency of PIM use among the older adults (n = 5); the prescription could be carried
out depending on the clinical condition (n = 25); more scientic evidence would be required for drug inclusion (n = 5); ADR
is independent of age (n = 19); the low frequency of RAM (n = 11); present low side effect (n = 8); and it is not a medication
for continuous use (n = 5).
Discussion
Worldwide, European and North American lists containing medications potentially inappropriate for the older adults have
been used by prescribers to subsidize them in pharmacotherapy.
30
This difference in health determinants may explain the
fact that the international lists assessed in this work show a convergence of, at most, 30% in relation to BCPIM-2016.
Although BCPIM-2016 was based on the Beers/2012 and STOPP/2006 Criteria, there are 262 discrepant drugs with
Beers/2019 and 245 discrepant drugs with STOPP/START/2015. Part of these differences occurred due to the use, in this
research, of updated versions of the lists and because few of the PIMs are not marketed in Brazil. These stand out need
for constant review of PIM lists.
The ATC (24) Classication System have a proposal consistent with the Brazilian perspective, as in STOPP/START/
2015 and Eu (7) PIM/2015. Thus, medicines are divided into different groups according with the organ or system on
which they act, paying attention to physical, pharmacological and therapeutic properties. Thus, it is easy to monitor NRM
(Negative results associated with the medication), PNRD (Prevention and resolution of negative drugs-associated results)
and ADR (Adverse drug reactions). However, although the use of PIM is related to increased morbidity and mortality, the
prescription of these drugs in older adults patients remains very common.
31
Of the eight drugs that appeared on all the lists in our study, the predominant class was the Central Nervous System,
which encompasses the highest percentage of drugs that theoretically cause the most negative results for patients,
especially in the older adults.
32
Brain aging causes structural and functional changes and there is a compromise in the
Table 3 Potentially Inappropriate Medicines for the Older Adults Commercialized in Brazil, Which are Not Included in BCPIM/2016,
but are Described in at Least One of the Criteria BEERS/2019, PRISCUS/2010, EU (7)–PIM/2015 eSTOPP&START/2015
Class ATC* PIM**
A: Digestive and Metabolic
System
Bisacodyl
1
, Sacred Cascara
1
, Diphenoxylate
I,III
, Glimepiride
I
, Insulin
I
, Fast-acting Insulin
I
, Metformin
II
, Sodium
Picosulfate
IV
, Sene
IV
, Sitagliptin
IV
, Fiber supplement
II
, Vitamin D
II
.
B: Blood and hematopoietic
organs
Cilostazol
I
, Dabigatran
I
, Prasugrel
I,III
, Ferrous Sulphate
I,IV
.
C: Cardiovascular System Amlodipine
II
, Bisoprolol
II
, Captopril
II,III
, Chlortalidone
III,IV
, Disopyramide
I
, Osmotic diuretics
II
, Dronedarone
I
,
Enalapril
II
, Felodipine
II
, Guanabenz
I
, Guanfacina
I
, Hydrochlorothiazide
II
, Lisinopril
II
, Metoprolol
II
,
Pentoxifylline
III,IV
, Ramipril
II
, Rilmenidine
IV
, Trimetazidine
IV
.
G: Genito-urinary tract and sex
hormones
Megestrol
I
, Oxybutynin
I
, Tamsulosin
II
, Testosterone
I
.
M: Skeletal Muscle System Alendronate
II
, Baclofen
I,II,III
, Chlorzoxazone
I
, Phenylbutazone
III
, Isoxsuprine
I
, Strontium Ranelate
IV
, Calcium
supplement
II
.
N: Nervous system Zoledronic acid
I,II
, Belladonna alkaloids
I
, Amphetamine
I,III
, Carbamazepine
IV
, Chlorazepate
I,II
, Codeine
phosphate
II
, Ginkgo biloba
II
, L-Dopa
III
, Mirtazapine
I
, Naltrexone
IV
, Nicergoline
III
, Oxcarbazepine
I,II
, Piracetam
III,
IV
, Pramipexole
III
, Rivaroxabam
I
, Timolol
IV
, Tranilciproomina
III
, Trazodone
IV
.
R: Respiratory System Dexbronpheniramine
I,III
, Dimethindene
III
, Ipratropium
II
.
Notes:*ATC. Anatomical Therapeutic Chemical; **PIM: [I: Beers, II: Stopp/Start, III:PRISCUS and IV: EU (7)/PIM].
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preservation of brain white matter in senescence.
33
This fact justies the greater risk of delirium, cognitive decline
34
and
difculties with postural reexes in the older adults under the use of medications that have a sedative and anticholinergic
action.
35,36
Still, regarding the drugs in all the researched lists, we highlight those that are part of the cardiovascular system, such
as digoxin and nifedipine,
37
as they are associated with the risk of intoxication, ischemia and orthostatic hypotension.
38
In the same way, it is possible to mention those drugs that act in the digestive and metabolic system, because they present
a risk that the adverse effects become greater than the therapeutic ones in face of the pharmacokinetic alterations that
occur in senescence, such as glibenclamide and metoclopramide.
39,40
In this study, of the 66 drugs that were at least in one of the international lists surveyed, but were not included in
BCPIM/2016, 16 were included in the National List of Essential Medicines-RENAME,
40
with no reference to dealing
with potentially inappropriate drugs for use in the older adults. A list of essential drugs, materialized through RENAME
and the State Relations of Essential Medicines (RESME) and the Municipal Relations of Essential Medicines
(REMUME), are guiding lists for the acquisition, prescription and use of medicines, especially in the Unied Health
System (SUS).
41
Since these lists contain PIM, their prescription and use could increase their risk for this age group. The increased risk
of inadequate prescription may compromise the pharmacotherapy directed to the older adults, especially to those with
low income, who depend exclusively on the Unied Health System (SUS). There is a need, therefore, to use evidence-
based criteria for the elaboration of summaries with a lower percentage of PIM for the older adults in these essential drug
lists.
When consulted, the experts unanimously agreed that of the 66 drugs on at least one of the international lists, 24 of
them should be present at BCPIM/2016. It is important to highlight that the lowest percentage of agreement among the
specialists about include the 66 drugs in the BCPIM/2016 was 66.7%.
Figure 2 Percentage of validation among experts regarding the inclusion in BCPIM/2016 of the PIMs contained in at least one of the criteria BEERS/2019; STOPP-START/2015;
PRISCUS/2010; o EU (7)-PIM List/2015.
Notes: Central Nervous System: 1-Zoledronic acid, 2-Belladonna alkaloids, 3-Amphetamines, 4-Carbamazepine, 5-Clorazepate, 6-codeine phosphate, 7-Ginkgo biloba,
8-L-dopa, 9-Mirtazapine, 10 -Naltrexone, 11-Nicergoline, 12-Oxcarbazepine, 13-Piracetam, 14-Pramipexole, 15-Rivaroxaban, 16-Timolol, 17-Tranylcypromine and 18-
Trazodone; Cardiovascular System: 19-Amlodipine, 20-Bisoprolol, 21-Captopril, 22-Chlorthalidone, 23-Disopyramide, 24-Osmotic diuretic, 25-Dronedarone, 26-Enalapril,
27-Felodipino, 28-Guanabens, 29-Guanfacine, 30- Hydrochlorothiazide, 31-Lisinopril, 32-Metoprolol, 33-Pentoxifylline, 34-Ramipril, 35-Rilmenidine, 36-Trimetazidine;
Digestive and Metabolic System: 37-Bisacodyl, 38-Sacred Cascara, 39-Diphenoxylate, 40-Glimepiride, 41-Insulin, 42-Fast-acting Insulin, 43-Metformin, 44-Sodium
Picosulfate, 45-Senne, 46-Sitagliptin, 47-Fiber supplement and 48-Vitamin D; Skeletal Muscle System: 49-Alendronate, 50-Baclofen, 51-Chlorzoxazone, 52-Phenylbutazone,
53-Isoxsuprine, 54-Strontium Ranelate and 55-Calcium supplement; Blood and Hematopoietic Organs: 56-Cilostazol, 57-Dabigatran, 58-Prasugrel and 59-Ferrous Sulphate;
Genitourinary System and Sex Hormones: 60-Megestrol, 61-Oxybutynin, 62-Tamsulosin and 63-Testosterone; Respiratory System: 64-Dexbronferinamine, 65-
Demethindene and 66-Ipratropium.
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Table 4 Medicines with 100% Validation by Experts Regarding Their Inclusion in the BCPIM/2016
Class ATC* Medicines** Justicative for Prescription with Caution to the Older Adults
A: Metabolic Digestive
System
Glimepiride
I
Prolonged hypoglycemia in the older adults
11
Fast-acting
insulin
I
Higher risk of hypoglycemia without improving control of hyperglycemia
11
Sodium
Picosulfate
III
Adverse events include abdominal pain, uid and electrolyte imbalance, and
hypoalbuminemia.
15
Sene
III
Adverse events include abdominal pain, uid and electrolyte imbalance, and hypoalbuminemia.
May worsen intestinal dysfunction
15
Sitagliptin
III
Risk of hypoglycemia, dizziness, headache and peripheral changes, edema
15
Diphenoxylate
I,II,
III
For drug treatment of Alzheimer’s dementia: acetylcholinesterase inhibitor
14,15
B: Blood and
hematopoietic organs
Prasugrel
II
Ventricular ulcers and duodenal blood clotting disorders
14
C: Cardiovascular System Bisoprolol
IV
The risk of adverse reactions is greater than the potential benets. When used for a short
time, may cause marked postural hypotension, falls and injuries
12,13
Dysopyramine
I
It has more potent negative inotropic properties compared to other antiarrhythmic agents and
has signicant anticholinergic side effects
11
Guanabenz
I
High risk of adverse effects on the CNS; They can cause bradycardia and orthostatic
hypotension; Not routinely recommended in hypertension
11
Guanfacina
I
High risk of adverse effects on the CNS; They can cause bradycardia and orthostatic
hypotension; Not routinely recommended in hypertension.
11
Metoprolol
I
It can exacerbate or cause respiratory depression. Possible cognitive decline and adverse
events
12,13
Rilmenidine
III
Risk of falling due to orthostatic hypotension
15
Trimetazidine
III
May cause or aggravate parkinsonian symptoms (tremors, akinesia, hypertonia)
15
G: Genito-urinary tract
and sex hormones
Megestrol
I
Increased risk of thrombotic events and possibly death; Minimal effect on weight
11
Tamsulosin
IV
Increased risk of dementia
12,13
M: Skeletal Muscle System Chlorzoxazone
I
Causes drowsiness and dizziness, there are other drugs with less reactions
11
Isoxosuprine
I
Lack of effectiveness or security
11
Phenylbutazone
IV
Higher risk of bleeding, ulceration or gastrointestinal perforation, especially in the older adults.
It should not be used in the older adults due to the risk of blood dyscrasia in the older adults.
May cause bone marrow depression, severe hematological adverse effects
12,13
Strontium
ranelate
III
Higher risk of venous thromboembolism in people temporarily or permanently immobilized.
Assess the need for continued therapy for patients over 80 years of age with increased risk of
thromboembolism
15
N: Nervous system Carbamazepine
III
Adverse events such as confusion and agitation, atrioventricular block and bradycardia
15
Nicergolina
II
No recommendations allowed for the treatment of vascular dementia. Ineffective treatment
for dementia and moderate risk of side effects (postural hypotension, fall) with no proven
efcacy
14
OxcarbazepineI
IV
Ability to produce ataxia, impaired psychomotor function, syncope and additional falls
11,13
(Continued)
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Fiber supplements were the ones that obtained the lowest validation percentage among specialists for inclusion in
CBPIM/2016 and, among the justications, is that older adults patients often have constipation, and ber is well indicated
and can assist in the proper intestinal functioning, causing no potential damage. These factors are corroborated by the
literature.
42
Insoluble bers have limited fermentation in the large intestine and are not soluble in water, which leads to
an increase in the feces volume and activate the release of hormones involved in food intake regulation in the intestine.
43
However, for ber supplements, mentioned in the Stopp/Start criterion,
44
they recommend discontinuity in case of
prophylaxis, once soluble bers are viscous and easily fermentable in the large intestine, which can delay gastric
emptying and affect the secretion and insulin action.
45
Adapting a list of medications to the national reality has unprecedented signicance, as it makes possible to analyze
the pharmacotherapy risks for the older adults in real time. Thus, after the experts’ analysis, we found that the number of
drugs belonging to the classes of Cardiovascular System (n = 7) and Digestive and Metabolic Systems (n = 6) was higher
compared with other classes when the agreement to be part of BCPIM/2016 was 100%. Experts reported that
cardiovascular drugs can cause bradycardia, orthostatic hypotension, respiratory depression or its exacerbation, cognitive
decline, and risk of falls. In the digestive and metabolic system experts claimed that the drugs can increase intestinal
motility, aggravate intestinal dysfunction, and increase the risk of hypoglycemia, abdominal pain, dizziness, headaches
and peripheral changes. All these ndings are corroborated for the scientic literature.
46
As for the drugs that act on the skeletal muscle system, the experts’ suggestions for inclusion in BCPIM/2016 cause
adverse reactions including risk of bleeding, ulcerations or gastrointestinal perforations, severe adverse effects, ther-
apeutic insecurity, blood dyscrasia, bone marrow depression, and situations corroborated by scientic evidence.
47
Those who act on the respiratory system, experts emphasized that many antihistamines, with or without prescription,
have potent anticholinergic properties, claiming that there are non-anticholinergic drugs as an option for older adults
patients. Studies have shown that inhaled corticosteroids (IC) at low doses can produce good results, have few adverse
systemic effects and are safe in the older adults, showing signicantly positive changes in airway inammation.
48
Conclusion
This study aimed to contribute to the older adults healthcare by determining the PIM in the international criteria most
cited in the literature compared to CBPIM/2016.
Drugs that are absent from the Brazilian list, but included in international criteria, can provide health professionals
with a better evaluation of the risks and benets when prescribing PIM in the older adults, identifying the causes of the
PIM adverse effects, and seeking pharmacotherapeutic options for this age population. Thus, it will be possible to
contribute to the prescription and responsible use of medicines by the Brazilian population of older adults, as well as to
help other researchers to update the criteria of their own countries by sharing the methodology used in the present study.
The results allowed to reect on the relevance of considering the specicities of pharmacotherapy for the older adults
and the need for constant review of CBPIM/2016 in view of the knowledge generated by the research. Thus, we veried
the possibility of expanding the Brazilian list by at least 24 PIM distributed in the several human body systems according
with the unanimous consensus of specialists.
However, the clinical decision is the prerogative of the prescriber who, in agreement with the patient, denes the best
therapy, respecting the individual response of each patient, as well as the various variables that can inuence clinical
Table 4 (Continued).
Class ATC* Medicines** Justicative for Prescription with Caution to the Older Adults
R: Respiratory System Dimethindenee
II
All over-the-counter and many prescription antihistamines can have potent anticholinergic
properties. Many coughs and cold preparations are available without antihistamines and are
safer substitutes for the older adults. Non-anticholinergic antihistamines are preferred in older
adults patients in the treatment of allergic reactions. Muscarinic blocking agents there is
conict, sedation
14
Notes: *ATC. Anatomical Therapeutic Chemical, **[
I
BEERS/2019,
II
PRISCUS/2010,
III
EU (7)-PIM/2015,
IV
STOPP/START/2015].
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outcomes. Thus, clinical judgment is fundamental in individualizing the medical prescription, according to the patient’s
circumstances and treatment objectives.
We emphasize the importance that should be attributed to the health professional when making the prescription,
assessing the risks and benets for the older adults population. This knowledge that medication can bring to the patient
must be very clear and having an appropriate list for the older adults Brazilian population is essential to health.
Acknowledgments
This work received support from the research’s members of University of Aging/University of Brasilia (UniSER/UnB),
from Education and Human Aging Institute (IEEH) and from the research group – Human aging determinants from
National Council for Scientic and Technological Development – CNPQ. We also thank Mr. Mateus de Castro for his
contribution in the development of the third stage of this work.
Disclosure
The authors have no conicts of interest to disclose.
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