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Pharmacists' interventions on 2 years of drug monitoring in an oncology

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Article  in  Journal of Oncology Pharmacy Practice · October 2021

DOI: 10.1177/10781552211041037

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Original Article

J Oncol Pharm Practice

1–9
Pharmacists’ interventions on 2 years of © The Author(s) 2021
Article reuse guidelines:
drug monitoring in an oncology pediatric sagepub.com/journals-permissions
DOI: 10.1177/10781552211041037
inpatient ward journals.sagepub.com/home/opp

Rafaela Dall Agnol1 , Maitê T dos Santos2 ,

Mariana B Michalowski3 and Lídia Einsfeld1

Abstract
Background: In oncology, pharmacists contribute to safety and effectiveness of drug treatment, identifying, preventing
and forwarding solutions to drug-related problems (DRPs). However, it is still necessary to elucidate the profile of drug-
related problems in pediatric cancer treatment to contribute to guide clinical pharmacy activities.
Methods: A retrospective cross-sectional study was conducted. Records on Excel® spreadsheets of 2 years of pharma-
ceutical assistance were analyzed regarding the prescriptions of chemotherapy for hospitalized patients aged 0–19 years.
Data on age, sex, cancer diagnosis, protocol and drugs prescribed were collected. Causes and types of DRPs and
pharmacists’ interventions as their rate of acceptance were measured according to PCNE V 9.0.
Results: Drug-related problems were identified for 84 patients, in 5.3% of analyzed prescriptions. Leukemias, patients
aged 0–4 years and male sex were associated with higher rates of drug-related problems. The BFM 2009 protocol for
acute lymphocytic leukemia treatment had the highest frequency of prescriptions with drug-related problems. Main
drug-related problems were related to effectiveness (49.2%) and safety (33.2%), with most of them due to drug selection
and dose. Rate of acceptance of interventions was 92.2% and 90.6% of drug-related problems were fully resolved.
Mercaptopurine and filgrastim were the drugs most associated with drug-related problems. Oral antineoplastic agents
represented 36% of the prescriptions with drug-related problems.
Conclusion: The high rate of acceptance of pharmacist interventions demonstrates the relevance of the pharmacist par-
ticipation in the care of hospitalized pediatric patients undergoing chemotherapy. Pharmacists need to take attention to
cases of necessity of drug prescription, intervening with other health professionals. Special attention to oral chemother-
apy is required.

Keywords
Clinical pharmacist, drug-related problems, oncology, antineoplastic chemotherapy protocol, pediatric
Date received: 15 April 2021; revised: 2 August 2021; accepted: 3 August 2021

Background drug-related problems (DRPs).6–8 “A DRP is an event or cir-

Childhood cancer, although rare when compared to neo-
plasms in adults, is a leading cause of death among children
and adolescents aged 0–19 years.1,2 It presents its own
histological characteristics and distinct clinical behavior,2,3
with antineoplastic chemotherapy being the main treatment
since it benefits patients with regard to a decrease in
chances of metastases and disease recurrence.4 Therapeutic
results are improved and a less toxicity profile is observed
when different chemotherapy drugs are used in combination
(polychemotherapy regimens) in appropriate doses, chrono-
logical sequence of administration and well-established
treatment protocols.5
However, this complex treatment approach added to the
clinical vulnerability of cancer patients makes chemotherapy
one of the most common drug treatments associated with
cumstance involving drug therapy that actually or potentially
interferes with desired health outcomes.” According to the
Pharmaceutical Care Network Europe Classification, PCNE
1
Pharmacy Service, Clinical Pharmacy Section, Hospital de Clínicas de
Porto Alegre, Brazil
2
Postgraduate Program in Child and Adolescent Health, Federal University
of Rio Grande do Sul, Brazil
3
Department of Pediatrics, Federal University of Rio Grande do Sul and
Pediatric Oncology Service, Hospital de Clínicas de Porto Alegre, Brazil
Corresponding author:
Rafaela Dall Agnol, Pharmacist Resident in Onco-Hematology, Pharmacy
Service, Clinical Pharmacy Section, Hospital de Clínicas de Porto Alegre,
Brazil.
Email: rafa_dall_agnol@hotmail.com
2 Journal of Oncology Pharmacy Practice 0(0)
V9.0, a DRP does not always occur, but it is important to iden-
tify the causes that could lead to a DRP to prevent or resolve it.
The cause is a fact, an attitude or lack of attitude that leads up
to the occurrence of a potential or real problem, being a DRP a
consequence of more than one cause.9
Pediatric patients are at increased risk of suffering from
DRPs, due to prolonged treatment regimens, polyche-
motherapy, scheduled administration of medicines, the
need for frequent dose adjustments and the risk of tox-
icity.7,10 Decreased renal and liver function are also respon-
sible for a higher risk of occurrence.11 Therefore, drug
therapy in pediatric oncology requires intense monitoring.12
A method that can contribute to prevent or to resolve
the occurrence of DRPs is the development of clinical phar-
macy services (CPS), in which clinical pharmacists partici-
pate systematically and continuously in the conduction of
antineoplastic chemotherapy protocols. In this work
process, the pharmacist monitors the need for dose indi-
vidualization and the risk related to narrow therapeutic
index drugs and performs interventions to other health pro-
fessionals, patients and caregivers, in search for prevention
and solutions for adverse drug reactions, drug interactions,
physical-chemical incompatibilities,10,12,13 in addition to
other causes of DRPs.
Several studies have demonstrated the role of CPS and
the results of pharmacists’ interventions in the prevention
and resolution of DRPs, particularly in oncology,6–8,10,14
contributing to security and efficacy of patient treatment.
However, it is still necessary to elucidate the problems
with the greatest impact associated with children and ado-
lescents undergoing antineoplastic treatment to contribute
to guide pharmacists acting in this work field. Therefore,
the present study aimed to evaluate CPS focused on the
drug monitoring and review of chemotherapy protocols pre-
scriptions in a pediatric oncology ward of a university
hospital.
Methods
This retrospective cross-sectional study was conducted in
the Pediatric Oncology Unit of a university hospital, the
Hospital de Clínicas de Porto Alegre, in Brazil. This
inpatient unit has 24 beds for pediatric patients assisted
by Pediatric Oncology and Pediatric Hematology teams,
with approximately 90% of patients being attended by the
Brazilian Public Unified Health System (SUS).
Records of clinical pharmacy activities on drug monitor-
ing and pharmacist interventions performed from July 2017
to June 2019 were analyzed, emerging from the evaluation
of prescriptions of chemotherapy protocols for all hospita-
lized children and adolescents aged 0–19 years.
Prescriptions reviews were previously performed by a
staff clinical pharmacist and a resident pharmacist, on a
daily basis schedule, in the morning shift, (except for week-
ends and holidays). Parameters evaluated included:
characteristics of the patient (type of cancer, age, weight,
height and body surface area (BSA)), chemotherapy proto-
col, drug necessity and indication, treatment duration,
dosage, pharmaceutical form, dose (considering deviations
greater than 10% for more or less), timing of administration,
order and range of administration among medications, route
of administration, time of intravenous infusion, physical-
chemical incompatibilities, drug interactions and availabil-
ity and logistics of drugs in the institution. During the
prescription analysis process, pharmacists accessed and
reviewed the original chemotherapy protocols documents
and databases such as UpToDate® and Micromedex
Solutions®.
After evaluating the prescription, if a drug-related
problem (potential or manifested) was detected, the
pharmacist intervened with medical and nursing teams or
another responsible health professional and caregivers, to
refer to the best conduct for prevention or solution of DRPs.
The evaluations of antineoplastic prescriptions were
registered on the patient’s electronic medical records.
Spreadsheets on Microsoft Office Excel program® were
used as a tool to record patients and prescriptions’ informa-
tion, DRP identified and the pharmacists’ interventions at
the time of prescription evaluation. Confidentiality was pre-
served given that the data registration was decoded by a
serial number which could not allow patient identification.
From these records, variables collected for the study
were: patients’ age, sex, diagnosed neoplasm, chemother-
apy protocol in use by the patient at the time of the interven-
tion and the drug involved in the intervention. DRPs, their
causes, types and acceptability of pharmacists’ interven-
tions and final status of the DRP were also collected and
classified through the proposal of the Foundation
Pharmaceutical Care Network Europe version 9.00,9 the
classification PCNE V 9.0.
It was considered for inclusion and data analysis only
prescriptions of antineoplastic drugs and filgrastim,
mesna, calcium folinate, dexrazoxane and sodium bicar-
bonate (supportive therapy components provided in chemo-
therapy protocols) evaluated by a clinical pharmacist
Interventions made at the patient discharge, from chemo-
therapy drugs and filgrastim prescribed for home therapy
were also included. Only pharmacists’ interventions per-
formed for chemotherapy and supportive therapy prescrip-
tions mentioned above were considered in this study.
Supportive therapy prescriptions, except for filgrastim,
were considered linked to chemotherapy drugs prescrip-
tions for the calculation of total prescriptions, such as the
associations between doxorubicin and dexrazoxane,
calcium folinate and methotrexate and, cyclophosphamide
and mesna.
Exclusion criteria were prescriptions and pharmaceutical
interventions related to prescriptions of antiemetics, antial-
lergens, antibiotics and all other drugs used during hospital-
ization which were not part of chemotherapy protocols, as
Dall Agnol et al. 3

well as chemotherapy cycles performed on an outpatient Results

basis or for intrathecal administration in the Outpatient
Surgical Centre. Corticosteroids were also excluded from
this study analysis. Although they were part of drug
monitoring, we were not able to statistically analyze corti-
costeroids related interventions, given the nature of the dis-
pensing systems, in which they are prescribed separated
from other chemotherapy drugs in our institution.
This study was approved by the Research Ethics
Committee of the Hospital de Clínicas de Porto Alegre,
under project number 2018-0694. The information obtained
was submitted to specific statistical analysis using the
Software SPSS 18.0 for Windows (Illinois, USA).
Descriptive statistics were used in order to present data
regarding absolute and relative frequency. The equality of
proportions of categorical variables was analyzed by
Pearson’s chi-square test or Fisher’s exact test Statistical
tests were performed for a significance level of α = 0.05.
Epidemiological data
In a 2-year period, the chemotherapy protocols of 194
patients admitted to the Pediatric Oncology Unit were eval-
uated, totaling 7267 chemotherapy prescriptions. Clinical
pharmacists evaluated 4573 prescriptions, reaching 62.9%
of total prescriptions during the study period. DRPs were
detected in 5.3% of prescriptions (n = 244). Among the
patients admitted during the study period, 43.3% (n = 84)
received a pharmacist intervention of any kind.
Most of the patients in the study were aged 0–4 years and
male (Table 1) despite the fact that statistical results have
shown no association between age and sex and the occur-
rence of DRPs.
Regarding diagnostic groups, most patients were diag-
nosed with leukaemias, myeloproliferative diseases or mye-
lodysplastic diseases. Most patients in this group presented

Table 1. Demographics characteristics of patients and prescriptions taking chemotherapy protocols and followed by clinical
pharmacists.

Patients Prescriptions

Without With Without With

DRPs DRPs p value DRPs DRPs p value

Total (n) 110 84 4329 244

Age (n (%)) 0 to 4 years 46 (41.8) 32 (38.1) 1932 (44.2) 117 (48.0)
5 to 9 years 26 (23.6) 22 (26.2) 1183 (27.3) 62 (25.4)
0.949a 0.247a
10 to 14 years 18 (16.4) 15 (17.9) 734 (17.0) 32 (13.1)
15 to 19 years 20 (18.2) 15 (17.9) 480 (11.1) 33 (13.5)
Sex (n (%)) Male 64 (58.2) 57 (67.9) 2802 (64.7) 160 (65.6)
0.168a 0.787a
Female 46 (41.8) 27 (32.1) 1527 (35.3) 84 (34.4)
Diagnostic group Leukaemias, myeloproliferative diseases, 26 (23.6) 44 (52.4)b 2552 (59.0) 157 (64.3)
(n (%)) and myelodysplastic diseases
Lymphomas and reticuloendothelial 20 (18.2) 6 (7.1)b 382 (8.8) 17 (7.0)
neoplasms
Malignant bone tumors 8 (7.3) 11 (13.1) 338 (7.8) 27 (11.1)
<0.001a 0.055a
Neuroblastoma and other peripheral 15 (13.6) 5 (6.0)b 331 (7.6) 11 (4.5)
nervous cell tumors
CNS and miscellaneous intracranial and 7 (6.4) 10 (11.9)b 255 (5.9) 14 (5.7)
intraspinal neoplasms
Others 34 (30.9)b 8 (9.5) 471 (10.9) 18 (7.4)
15 b
Protocol (n (%)) BFM 2009 7 (6.4) 26 (31.0) 1567 (36.2) 81 (33.2)
Interfant-0616 0 (0.0) 3 (3.6)b 246 (5.7) 18 (7.4)
UKALL17 0 (0.0) 1 (1.2)b c 75 (1.7) 17 (7.0)b
<0.001 <0.001a
GBTO18 3 (2.7) 5 (6.0) 110 (2.5) 14 (5.7)b
EsPhALL19 1 (0.9) 1 (1.2) 125 (2.9) 12 (4.9)
Others 99 (90.0) 48 (57.1) 2206 (51.0)b 102 (41.8)
DRPs: drug-related problems; CNS: central nervous system; BFM 2009: Berlin-Frankfurt-Münster Study Group 200915; Interfant-06: International
Collaborative Treatment Protocol for Infants under One Year with Acute Lymphoblastic or Biphenotypic Leukaemia16; UKALL: Medical Research Council
for United Kingdom Childhood Acute Lymphoblastic Leukaemia17; GBTO: Brazilian Osteosarcoma Treatment Group18; EsPhALL: European intergroup
study on post-induction treatment of Ph + ALL.19
a
Pearson’s chi-square test.
b
Adjusted residual >1.96.
c
Fisher’s exact test.
4 Journal of Oncology Pharmacy Practice 0(0)

at least one prescription with DRPs showing a positive Table 3. Causes of DRPs (n = 292).
association with the occurrence of DRPs. Also, leukemia
Causes of DRPs* Total (n (%))
represented 64.3% of prescriptions with DRPs. The
second diagnostic group with the highest number of Drug selection 152 (52.0)
patients and prescriptions with DRPs was lymphomas and No or incomplete drug treatment in spite of 93 (31.7)
reticuloendothelial neoplasms (Table 1). existing indication
It was prescribed 82 chemotherapy protocols being found Inappropriate combination of drugs 26 (8.9)
DRPs in prescriptions of 38 of them. A greater number of Drug within protocol but otherwise 23 (7.8)
contraindicated
causes of DRPs were identified for the first-line acute
No indication for drug 6 (2.0)
lymphocytic leukemia (ALL) treatment protocol, the
Duplication of therapeutic group or active 3 (1.0)
Berlin-Frankfurt-Münster Study Group Version 2009 (BFM ingredient
2009),15 counting for 31.0% of the patients with prescriptions Inappropriate drug according to protocol 1 (0.3)
with DRPs. Also draws attention to the patients treated with Drug form 3 (1.0)
the Interfant-0616 protocol used for treating ALL children Inappropriate drug form 3 (1.0)
under 1 year of age. Only 3 patients were treated with this Dose 54 (18.5)
protocol and for all of them were identified at least one pre- Drug dose too high 23 (7.8)
scription with DRPs. In addition to leukemia protocols, the Drug dose too low 16 (5.5)
first-line osteosarcoma treatment protocol of the Brazilian Dosage regimen too frequent 7 (2.4)
Osteosarcoma Treatment Group, GBTO18 (5.7%; n = 14) Dosage regimen not frequent enough 3 (1.0)
Dose timing instructions wrong, unclear or 5 (1.7)
was among the protocols most involved with DRPs.
missing
Treatment duration 7 (2.4)
Duration of treatment too short 5 (1.7)
Drug-related problems Duration of treatment too long 2 (0.7)
Problems related to treatment effectiveness were the most Dispensing 10 (3.4)
frequent type of DRPs found, followed by those related to Prescribed drug not available at the institution 10 (3.4)
treatment safety, as shown in Table 2. Drug use process 30 (10.3)
Drug administered via wrong route 19 (6.5)
Inappropriate time of administration or dosing 11 (3.8)
Causes of DRPs intervals
Patient transfer related 18 (6.1)
Among the total of 292 causes of DRPs recorded, a higher Patient has not received the necessary 13 (4.4)
number was related to drug selection, of which 31.7% were medication at discharge from the hospital
related to lack or incomplete drug treatment in spite of exist- Discharge information about medication 5 (1.7)
ing indication (mainly referring to cases of the need for drug incomplete or missing
prescription). It was also found higher numbers of causes of Other 18 (6.2)
DRPs according to the inappropriate combination of drugs Inadequate dilution of parenteral drugs 8 (2.7)
and of drug dose too high (Table 3). Drug logistics in the institution 7 (2.4)
Prescription with incomplete information 2 (0.7)
Prescribed dose with an inadequate unit of 1 (0.3)
Drugs measurement

Forty-six different drugs were prescribed. Filgrastim (n = *DRPs: drug-related problems.

785 (17.2%)), cytarabine (n = 620 (13.6%)), mercaptopurine
Table 2. Drug-related problems (DRPs).
DRP
1.1 Treatment effectiveness
No effect of drug treatment
Untreated symptoms or indication
2.1 Treatment safety
Adverse drug event (possibly) occurring
3.1 Other
Problems with cost-effectiveness of the
treatment
Unnecessary drug treatment
(n = 545 (11.9%)), etoposide (n = 364 (8.0%)) and vincris-
tine (n = 298 (6.5%)) were the most prescribed drugs.
Interventions were performed for a total of 39 drugs.
Total (n (%))
Mercaptopurine (15.2%), filgrastim (14.3%) and methotrex-
120 (49.2) ate (8.2%), regardless of the administration route, presented
25 (10.2) the higher frequencies of prescriptions with causes of
95 (38.9) DRPs (Figure 1).
81 (33.2) For mercaptopurine, the most common cause of DRP was
81 (33.2) related to lack of or incomplete drug treatment in spite of an
36 (14.8) existing indication (34%; n = 16), drug dose too low (17.0%;
17 (7.0) n = 8) and treatment duration (5.4%; n = 2). The main causes
of DRPs recorded for filgrastim were also related to drug
26 (10.7)
selection: 56.4% (n = 22) was related to the fact that it was
Dall Agnol et al.
Figure 1. Frequency of drugs with a drug-related problem detected and categories causes.
not prescribed even with indication and 12.8% (n = 5) for
drugs prescribed without indication. Regarding methotrex-
ate, 33.3% (n = 8) of interventions was performed according
to lack of treatment or incomplete treatment and 29.2% (n =
7) of inappropriate combinations of drugs.
Remarkably, among the 244 prescriptions with causes of
DRPs, 36% (n = 89) were related to oral antineoplastic
drugs (tretinoin, cyclophosphamide, dasatinib, hydro-
xyurea, imatinib, mercaptopurine, methotrexate, mitotane,
temozolomide and thioguanine). Also, 16.8% was related
to chemotherapy prescribed at the time of hospital dis-
charge for home use.
Pharmacists’ interventions
According to the types of causes of DRPs identified, phar-
macists’ interventions were performed, suggesting the most
convenient solution to the prescriber or other professionals.
One intervention was performed for each prescription with
causes of DRPs and 88.1% of the interventions (n = 215)
were related to proposing to the prescriber some change
in the prescription. Overall, interventions were accepted
and fully implemented in 92.2% of cases. From the inter-
ventions performed with the prescriber, 99.1% were
accepted (87.3% of total). In 7.3% of total cases, the imple-
mentation is unknown, although the intervention was
accepted, for example, the previous orientation for con-
comitant administration of methotrexate and sodium bicar-
bonate through the same venous access in a weekend.
Interventions in which the pharmacist provided instructions
5
about correct drug use were those directed both to the
physician and to the nursing staff (Figure 2).
Final status of the DRP
Regarding the final status of the DRP, 90.6% (n = 221)
were fully resolved. From these, 35.7% were related to
safety and 48.4% to treatment effectiveness (Figure 3).
Discussion
Our study was the first in our country to describe character-
istics and results of clinical pharmacy activities of inpatient
oncology pediatric ward, identifying patients who are more
exposed to the risk of developing DRPs and guide pharma-
cist drug monitoring and interventions to prevent and solve
those problems.
Identification of DRPs depends on the intensity at which
CPSs are performed.10 A study in Brazil demonstrated that
without the presence of a clinical pharmacy service, DRPs
were identified in only 0.9% of chemotherapy prescriptions.
After structuring this activity, the identification of DRPs
doubled (2%).10 In another similar study, DRPs were iden-
tified in 12.6% of prescriptions considering chemotherapy
and supportive therapy for results calculation.8 A study
conducted only with chemotherapy administered intraven-
ously in onco-pediatrics found a rate of 6.9% of prescrip-
tions with DRPs.20
In our study, even with the review of only 62.9% of the
total prescriptions, 43.3% of patients had prescriptions with
6 Journal of Oncology Pharmacy Practice 0(0)

Figure 2. Pharmacists’ interventions and acceptability (PCNE V 9.0).

DRPs and at least one cause of DRPs was identified in 5.3%
of the antineoplastic prescriptions analyzed. Probably, a
higher number of DRPs would be identified if the clinical
pharmacy unit expanded its services from the actual busi-
ness schedule. In addition, results for DRPs could be
even more expressive if it were also analyzed interventions
performed for other classes of drugs, such as corticosteroids
and other supportive therapies.
Most patients with DRPs were aged 0–4 years, male sex
and diagnosed with leukaemias. It was not found a positive
correlation between sex and the finding of DRPs, being sex
not considered a significant risk factor for DRPs in children,
since hormonal and physiological differences are not well
established in this population.20,21 Patients aged 0–4 years
and males are the main population characteristics recorded
worldwide for childhood cancer and leukemias are the most
common cancer in children and adolescents.2 Our results
show that patients diagnosed with leukemias are more
exposed to the risk of developing DRPs which arises the
urgency of pharmacists focusing their attention on these
patients.
Four of the five most prescribed and related-to-DRPs pro-
tocols were used to treat some type of leukemias. Protocols
requiring prescription of more than 3 antineoplastic drugs

Figure 3. Final status of DRPs (PCNE V 9.0). DRPs: drug-related problems.

Dall Agnol et al.
per cycle are at increased risk of DRPs.22 The BFM 2009
presented the highest rate of patients with DRPs. This proto-
col uses different combinations between asparaginase,
anthracyclines, vinca alkaloids, alkylating agents, antimeta-
bolic agents and corticosteroids over two years of
duration.15 Other protocols with polychemotherapy combi-
nations, the Interfant-0616 and the UKALL17 are also
presented as risk factors for the occurrence of DRPs. The
causes of DRPs identified for these protocols that draw
most attention were: cumulative dose and treatment time
of mercaptopurine, dose adaptations and frequency of
administration of pegaspargase due to the unavailability of
erwinase in the institution and the interval of administration
between vincristine and pegaspargase which needs to be at
least 12 h to minimize the risk of neurotoxicity.23
The types of causes of DRPs identified were similar to
those of other studies. In Turkey, a study that considered
chemotherapy and supportive therapy found a higher
number of causes of DRPs associated with drug selection
(41.4%) especially for cases where treatment would not
be prescribed even if it was indicated (18.7%).6 Kucuk
et al. also found a higher number of causes of DRPs
related to drug selection (22.6%) in a study with protocols
that associate immunotherapy and chemotherapy.24 In the
area of pediatric oncology, among the most common
problems found, 42% were related to drug selection, dose
and route of administration.25
Drug selection can be affected by the complexity of
administration of each chemotherapy cycle and patient clin-
ical performance. Factors such as infectious processes,
hematological cell count, renal, hepatic, cardiac function,
drug toxicity, nutrition, concomitant use of medications26
also may contribute to changes in drug selection and their
occurrence must be monitored by the clinical pharmacists.
By identifying causes of dose too high, dosage regimen
too frequent, contraindicated or inappropriate drugs and
inappropriate combinations of drugs, pharmacists contribu-
ted to prevent the occurrence of DRPs related to safety.
Overdose, unnecessary doses, and prolonged chemotherapy
time increase the risk of serious adverse events such as
neutropenia, anemia, thrombocytopenia, typhlitis, mucosi-
tis, nephrotoxicity, hepatotoxicity, cardiotoxicity, and
neurotoxicity.27,28 On the other hand, clinical pharmacists’
detection of causes of DRPs related to drug dose too low, no
or incomplete drug treatment in spite of existing indication,
dosage regimen not frequent enough and very short treat-
ment time, contributed to avoid or solve DRPs of treatment
effectiveness. Treatment-effectiveness DRPs may result in
neoplasm recurrence.29,30
Pharmacists must remember that children and adoles-
cents present constant alteration of BSA, intrinsically
related to growth. In addition, issues related to nutrition,
such as inadequate protein supply,31 and use of corticoster-
oids also influence body development.32 Chemotherapy
drugs have a narrow therapeutic index and small deviations
7
can easily lead to subtherapeutic doses or increased chances
of toxicity.26 Therefore, attention is needed to update doses
in prescribing a new chemotherapy cycle or even during a
cycle, according to the patient’s performance.15,20,29 This
helps to clarify the expressive record of causes of
dose-related DRPs in our study.
Not all cycles of chemotherapy protocols are conducted
in an inpatient ward, but those that are, have greater com-
plexity and risk of toxicity. Otherwise, the advent of oral
chemotherapy has enabled cancer treatment at home and,
generally, in hospitalization, administration of oral chemo-
therapy occurs during short periods.15 Even though, our
results found that 36% of prescriptions with causes of
DRPs were related to drugs administered orally.
Mercaptopurine, an oral chemotherapy, was the drug with
the greatest number of causes of DRPs.
It is known that pediatric patients are at increased risk for
DRPs due to the unavailability of different oral pharmaceut-
ical formulations, especially liquids.33 Mercaptopurine is
used in the treatment of ALL34 being available in
Brazilian market as 50 mg tablets and its dose should be cal-
culated individually according to BSA,15,16,34 which will
not always correspond to taking an entire daily tablet.
Fortunately, it can be considered mercaptopurine cumu-
lative dose throughout a cycle and an extemporaneous for-
mulation of mercaptopurine can be prepared to allow dose
fractionation.15,34 This enables the allocation on specific
days of a week of a sum of doses that would be very low
in relation to drug form or else allows the administration
of the entire tablet to adolescents or children who are
already able to swallow it. However, despite the alternatives
mentioned, our results show that attention is needed at the
dates of administration, duration of each cycle and
changes in BSA. We can exemplify it by the higher fre-
quency of interventions related to no or incomplete drug
treatment in spite of existing indication, very short treat-
ment time and drug dose too low.
Myelosuppression is the most important chemotherapy
adverse effect leading up to bleeding and infection.
Appropriate prophylaxis with filgrastim contributes to redu-
cing the risk of febrile neutropenia, which is an oncology
emergency.29,35 Febrile neutropenia has as consequences
prolonged hospitalization and additional treatments,
delays of cycles beginning and reduction of chemotherapy
doses with impairment of desired clinical outcomes.29,35 In
our study from the total causes of DRPs found for filgras-
tim, 56.4% were related to lack of prescription on the elec-
tronic hospital system. All interventions performed for this
drug were accepted, showing the importance of pharmacists
in preventing or minimizing adverse effects. Pharmacists
need to properly analyze the results of laboratory tests,
such as leukogram, to detect adverse effects and drug
effectiveness.
Interventions performed and implementation (92.2%) by
other professionals had high acceptance when compared to
8 Journal of Oncology Pharmacy Practice 0(0)
other studies (from 59.5% to 88.3% of acceptability and
implementation).6,21,24 Consequently, interventions accept-
ability had repercussions on the final status of DRPs being
90.6% of them fully resolved. Some points contribute to
explain these results: the pharmacists in our study have
their clinical activities focused exclusively on pediatric
oncology and hematology patients and have an important
proximity to the multidisciplinary team; daily, they partici-
pate in multidisciplinary rounds, attend the hospitalization
unit and interact directly with nursing and medical teams,
being a reference with regard to drug use; they provide
direct care to the patient, such as through drug reconcili-
ation at all times of care transition and guidance for hospital
discharge; in addition, they interact with other health team
professionals besides physicians and nurses, such as nutri-
tionists, social workers and psychologists, which contri-
butes to the expanded knowledge of patient’s health and
social status, assisting in the evaluation and optimization
of pharmacotherapy.
Conclusion
Our results may contribute to guide the work of clinical
pharmacists in the drug monitoring in the pediatric onco-
hematology field aiming at the efficacy and safety of
chemotherapy treatment. Younger children and diagnosed
with leukemias, correct drug selection and dose are critical
points in the use of antineoplastic drugs. It is understood
that adaptations of days of administration and doses of
oral antineoplastic drugs can be made to optimize pharma-
cotherapy and pharmacists need to pay special attention to
these drugs contributing to treatment success. The expres-
sive volume of interventions for filgrastim, mainly related
to treatment need, shows that pharmacists need to focus
on chemotherapy’s adverse effects. The high acceptability
and implementation of pharmacists’ interventions shows
that this professional can play a very important role in the
multidisciplinary team, in conducting chemotherapy proto-
cols, preventing and forwarding relevant solutions for
DRPs.
As limitations of this study, it can be cited that it was a
retrospective analysis with no control group and that it was
analyzed only DRPs involved with chemotherapy drugs, fil-
grastim and support therapy prescribed in combination with
specific chemotherapy drugs. In relation to the clinical
pharmacist activities analyzed, it can be observed that pre-
scription review needs to be expended to weekends and
during all day in order to increase the identification of cir-
cumstances that actually or potentially interferes with
desired health outcomes.
Acknowledgements
The Author(s) declare(s) that there is no conflict of interest
This research received no specific grant from any funding
agency in the public, commercial, or not-for-profit sectors.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship and/or publication of this article.
ORCID iDs
Rafaela Dall Agnol https://orcid.org/0000-0002-3889-7656
Maitê Telles Santos https://orcid.org/0000-0003-4013-4233
Mariana Bohns Michalowski https://orcid.org/0000-0002-
9482-0776
Lídia Einsfeld https://orcid.org/0000-0002-5222-233X
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