RESEARCH ARTICLE

Role of clinical pharmacists to prevent drug interactionsin cancer outpatients: a single-centre experience

Carmen Lopez-Martin • Margarita Garrido Siles •

Julia Alcaide-Garcia • Vicente Faus Felipe

Received: 1 June 2014 / Accepted: 3 October 2014

� Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2014

Abstract Background Cancer patients are especially

vulnerable to drug interactions, which may alter the effi-

cacy and toxicity of treatment, leading to severe clinical

consequences. Objective Determine the incidence of such

interactions in patients receiving chemotherapy, as well as

to identify the drugs most frequently involved, investigate

the influence of the pharmacist’s interventions and verify

the degree of acceptance of pharmacist’s recommendations

by the medical team. Setting The oncology department of a

Spanish tertiary hospital. Methods During 3 months, all the

drug interactions in the regular combined with treatment

for cancer were analysed using two databases, and rec-

ommendations were made when clinically significant

interactions (CSI) were identified. Main outcome measure

Incidence of CSI in oncology outpatients; drugs involved

in CSI. Results Of the 75 patients included, 31 (41 %)

presented CSI. Most interactions were among drugs

included in the patient’s usual treatment. The principal

drug groups involved in CSI were cytostatic agents, an-

tiemetics and antidepressants. The hospital pharmacist

intervened on 20 occasions (35 % of the patients present-

ing drug interactions). These interventions mainly focused

on recommendations to modify or discontinue drug pre-

scriptions, and were followed in 94 % of cases. Conclusion

The incidence of drug interactions in cancer patients is

high, and they most often involve medications to treat

comorbid conditions. The pharmacist, as a member of the

multidisciplinary team, can contribute significantly by

checking the treatment prescribed and detecting interac-

tions, to reduce medication-related problems and to opti-

mise drug therapy for these patients.

Keywords Cancer � Chemotherapy � Drug interactions �Interventions � Pharmacist � Regular medication � Spain

Impacts of findings on practice

• Detection of drug interactions in oncology patients is a

fundamental aspect in the management of the phar-

macotherapy in these patients

• A systematically conducted review of all the patient

treatments is essential to avoid drug interactions

• Pharmacists should participate in multidisciplinary

teams in hospital

Introduction

Cancer patients are at high risk of suffering drug interac-

tions, due to the large numbers of drugs required to treat

their pathology, including antitumoral agents and sup-

portive therapy (antiemetics, analgesics, antibiotics and

others) [1, 2]. Moreover, most patients diagnosed with

cancer are aged over 65 years and often present comor-

bidities that require drug therapy. This factor greatly

increases the number of drugs prescribed and therefore

increases the risk of drug interactions. Additionally, the

organic deterioration that accompanies the tumour process,

together with the impact of ageing, affects liver and kidney

functions and thus the metabolism and clearance of drugs,

potentially increasing their toxicity [3].

C. Lopez-Martin (&) � M. Garrido Siles � V. Faus Felipe

Pharmacy Department, Hospital Costa del Sol, Marbella,

Malaga, Spain

e-mail: carmen_lopez_martin@hotmail.com

J. Alcaide-Garcia

Oncology Department, Hospital Costa del Sol, Marbella,

Malaga, Spain

123

Int J Clin Pharm

DOI 10.1007/s11096-014-0029-4

Drug interactions can be classified into three types:

pharmacokinetic, pharmacodynamic and pharmaceutical.

A pharmacokinetic interaction occurs when a drug alters

the absorption, distribution, metabolism and/or excretion

of another. A well-known pharmacokinetic mechanism is

the interaction with the cytochrome P450 family. The

pharmacodynamic interaction occurs when two drugs

have similar mechanisms of action, for example when

two active substances compete for the same biological/

physiological receptor or molecular target, in vivo. A

pharmaceutical interaction may result from physical or

chemical incompatibilities between two different drugs

[4]. Regardless of the type of interaction, drug interac-

tions may compromise treatment efficacy or increase

drug toxicity, with serious clinical consequences (they

can result in under/overdosing, the pharmacological

effect can be boosted or the drugs can became com-

pletely ineffective). Many studies have reported inter-

actions between the drugs used in chemotherapy and/or

antineoplastic treatment and supportive therapy, or the

drugs used in routine clinical treatment [3, 4]. However,

very few have examined the prevalence of drug inter-

actions in cancer patients undergoing chemotherapy and

their relevance [2, 5, 6].

Another important aspect is the use of complementary

and alternative medicine. Previous studies have highlighted

the frequent use of this type of medicine by cancer patients

[7], and on many occasions, the oncologist is unaware that

such therapies are being used. Tuna et al. [8] found that

over 76 % of patients do not inform their doctor of the use

of these therapies, and McCune et al. [9] estimated that

among the population being treated with cytostatic agents

and alternative medicine, at least 27 % are at risk of clin-

ically significant interactions (CSI).

The presence of interactions between cancer therapy

(antitumoral agents and supportive therapy) and the

patient’s usual treatment, including alternative medicine,

can affect the efficacy and toxicity of chemotherapy and

even the treatment prescribed for other pathologies. The

ability to predict potential interactions has important

implications for the success of drug therapy and the

enhanced quality of life of cancer patients [10]. Therefore,

a systematic review of the medication regimen before

starting chemotherapy should be part of the patient care

process [11].

Aims of the study

The aims of this study were to determine the incidence of

CSI in cancer patients undergoing chemotherapy, the drugs

involved, the influence of the hospital pharmacists’ rec-

ommendations regarding the interactions detected and the

degree of acceptance of these recommendations by the

medical team. As a secondary objective, we examined

patients’ usual treatment and assessed the discrepancies

observed between the latter and the findings of their

medical reports.

Ethical approval

Ethical approval was not necessary as this study did not

involve changes in routine clinical practice. Previous to

data collection for the study, interactions between patients’

regular treatment and chemotherapy (including supportive

therapy) were being checked. If any CSI were detected, the

oncologist was contacted to make the appropriate

modifications.

Methods

This was a prospective study to perform a systematic

analysis of all aspects of patient treatment in order to detect

potential CSI. This review included both the regular

medication–alternative medicine and that prescribed for

cancer pathologies, comprising cytostatic agents, hormone

therapy and supportive therapy.

Oncology outpatients starting chemotherapy at our

hospital for 3 months and referred to pharmacy service

were enrolled, regardless of stage of disease.

Details about chemotherapy and supportive therapy

were obtained from the electronic prescription programme

Oncofarm�. Clinical data (gender, patient age and diag-

nosis) were extracted from Doctor� medical records soft-

ware. The patients’ usual treatment was identified through

personal interviews at the hospital’s outpatient pharmacy

service, at the start of cancer therapy, and from the corre-

sponding medical report. In case of discrepancies, the usual

treatment was verified personally with the patient, by ref-

erence to the personal health e-record system of the

Andalusian Health Service (Diraya�).

Discrepancies between the usual treatment and that

specified in the patient’s medical report were recorded.

Interactions were analysed using two databases of pro-

ven structural quality [12]: Lexi-interact� [13] and Bot-

plus� [14]. A CSI are defined as one classified as category

D or X in Lexi-interact� and as category Red in Bot-plus�.

When CSI were identified, we consulted the procedure to

prevent the CSI detected from databases described previ-

ously. When it was found that some modifications were

required to prevent the CSI (i.e. withdrawal or modification

of a drug prescription), the oncology specialist was con-

tacted in person or by telephone to make the corresponding

recommendation.

Int J Clin Pharm

123

A data-collection form was designed, on which the

following variables were recorded: age, cancer diagnosis,

chemotherapy, supportive care, usual care, alternative

medicine treatment, number of drugs in usual treatment,

number of discrepancies between usual treatment and the

data recorded on the medical report, CSI according to Bot-

plus� and Lexi-interact� (drugs involved and number of

interactions), number of category C interactions according

to Lexi-interact�, number of interactions per type of

treatment (cancer treatment, usual treatment, supportive

therapy or alternative medicine treatment), recommenda-

tions made by the pharmacy service and level of

acceptance.

In Lexi-interact�, category D interactions are defined as

those which are of proven clinical significance, requiring

the physician to decide whether the benefits of using both

drugs outweigh the risks of the interaction. Specific actions

should be undertaken (such as close monitoring, dose

changes or the use of alternative therapies) to ensure a

beneficial outcome or to minimise the resulting toxicity.

For drugs with category X interactions, the risk usually

outweighs the benefits, and therefore, the association of

these drugs is considered contraindicated. Lexi-interact�

defines category C interactions as those with proven, sig-

nificant clinical implications in which the benefit of using

both drugs generally outweighs the risk. Appropriate

monitoring is required to identify the possible negative

effects of the interaction, and dose adjustments are only

necessary for a minority of patients. In Bot-plus�, category

Red interactions arise from drug combinations that should

be avoided, with extensive evidence underlying this

recommendation.

A descriptive analysis of the study variables was made,

and measures of central tendency and dispersion (SD) were

calculated for the quantitative variables and frequency dis-

tribution for the qualitative ones. Chi-square test was used to

compare qualitative variables (or Fisher’s exact test) and the

t test of Student’s for quantitative variables. Analysis with a

P value \ 0.05 was considered statistically significant. Sta-

tistical analysis was performed using SPSS� version 17.0.

Results

We analysed data collected from 75 patients, 52 % of

whom were male. Mean age was 59 (SD 13.9 years). The

most frequent cancer diagnoses were lung (23 %) and

breast carcinoma (21 %). Demographic characteristics are

shown in Table 1.

Analysis of the patients’ usual treatment revealed an

average consumption of 4.6 drugs per patient (SD 3.2).

Discrepancies were found between the usual treatment and

that described in the corresponding medical report in 58 %

of the patients treated for chronic pathologies. With respect

to alternative medicines, 8 % of patients were using them

and the oncologist was unaware of that use in 89 % of cases.

Clinically significant interactions were present in 41 %

of patients, and there were 61 category Red or D interac-

tions. The mean number of CSI per patient was 1.7 (SD

1.5) according to Lexi-interact� and 1.4 (SD 0.6) according

to Bot-plus�. The percentage of patients with a CSI was

35 % according to Lexi-interact� and 27 % according to

Bot-plus�. 80.3 % of the CSI were related to treatment

toxicity and 19.7 % to efficacy. Description of CSI found

involving anticancer drugs, supportive care drugs and

treatment for chronic diseases are detailed in Tables 2, 3

and 4, respectively.

In relation to the detection of minor interactions, 85 %

of these patients presented category C interactions,

according to Lexi-interact �, with a mean number of 4.9

(SD 4.7) interactions per patient.

In order to identify the potential risk factors for the

occurrence of CSIs, univariate analyses were performed.

The gender and the number of drugs were associated with

higher risk for CSIs. No statistically significant association

was found for age, BMI, tumour type, cancer severity or

presence of comorbidities (Table 1).

Most of the CSI identified took place between drugs

included in the patient’s usual treatment. Table 5 shows the

interactions obtained, per drug type (treatment for chronic

diseases, cancer treatment or supportive treatment).

The drug classes most commonly involved in CSI were

cytostatic agents, antiemetics and antidepressants (Table 6).

The drug groups that most frequently interacted were cyto-

static–cytostatic (11.4 %), antiemetic–antidepressant (9.8 %),

nonsteroidal anti-inflammatory drugs (NSAID)-NSAID (5 %)

and NSAID-diuretic (5 %).

The pharmacy service intervened in all cases when CSI

were detected. In 20 of these, which affected 35 % of

patients, the physician was informed about the interaction.

In 45 % of the latter cases, the drug prescribed was chan-

ged (45 % antiemetics, 22 % hypolipemiants, 11 % proton

pump inhibitors, 11 % antidepressives, 11 % others), in

40 % the medication was discontinued (57 % NSAIDs,

29 % Beta blockers, 14 % others) and in 15 % the dosage

was modified (separation in time of drugs involved: 67 %

antiacids, 33 % antiemetics). Sixty-three percentage of

these CSI were related to treatment toxicity and 37 % to

efficacy. The mechanism of the interactions previously

described was pharmacodynamic (pD) in 47 % of cases

and pharmacokinetic (pK) in the 53 % (50 % Cytochrome

P450-mediated).

The pharmacy service intervened in 83 % of cases when

patients used alternative medicine. The withdrawal of at

least one drug while the patient was receiving chemother-

apy was advised in every case. This recommendation

Int J Clin Pharm

123

affected to 60 % of all the alternative medicines. In cases

when sufficient information was not available on the

interaction between the alternative medicine and the che-

motherapy, the withdrawal of the former was recom-

mended. The pharmacist’s recommendations were

accepted in 94 % of cases.

Discussion

Cancer patients are especially susceptible to drug interac-

tions, due, among other factors, to the high number of

drugs needed to treat the tumour process, the toxicity

induced by antineoplastic agents, and the symptoms and

syndromes related to the tumour, as well as the patient’s

own comorbidities [6]. However, few studies have focused

on the question of drug interactions in these patients [4, 6,

15].

Limited papers published regarding to drug interactions

in oncology patients focus on the incidence of interactions,

and some of them describe the drugs involved. However,

no references were found in which interventions are made

to prevent the interactions detected. In addition to this,

most of published studies include patients over 70 or pal-

liative patients.

In terms of the average number of drugs that form part

of the patient’s usual treatment, our results were similar to

that reported elsewhere [3, 4, 6, 16].

Table 1 Demographic

characteristics and risk factors

for clinically significant

interactions (CSI)

CSI clinically significant

interactions, COPD chronic

obstructive pulmonary disease

Total No CSI CSI P

n % n % n %

Sex

Male 39 52 29 70.7 12 29.3 0.036

Female 36 48 15 44.1 19 55.9

Age

Media—SD 59.7 13.9 59.0 15.0 60.6 12.5 0.620

BMI

Media—SD 26.8 5.2 27.4 5.1 25.9 5.4 0.226

No. of drugs

Media—SD 4.6 3.2 3.9 3.0 5.6 3.4 0.020

Cancer type

Gastrointestinal 17 22.7 12 70.6 5 29.4 0.292

Lung 17 22.7 11 64.7 6 35.3

Breast 16 21.3 9 56.3 7 43.8

Head and neck 5 6.7 1 20.0 4 80.0

Genito-urinary 14 18.7 9 64.3 5 35.7

Other 6 8.0 2 33.3 4 66.7

Severity

Nonmetastatic 25 35.2 19 76.0 6 24.0 0.124

Metastatic 46 64.8 25 54.3 21 45.7

Diabetes

No 65 86.7 38 58.5 27 41.5 1.000

Yes 10 13.3 6 60.0 4 40.0

Hypertension

No 49 65.3 33 67.3 16 32.7 0.064

Yes 26 34.7 11 42.3 15 57.7

Asthma/COPD

No 68 90.7 40 58.8 28 41.2 1.000

Yes 7 9.3 4 57.1 3 42.9

Heart disease

No 63 84.0 38 60.3 25 39.7 0.537

Yes 12 16.0 6 50.0 6 50.0

Dyslipidemia

No 56 74.7 35 62.5 21 37.5 0.375

Yes 19 25.3 9 47.4 10 52.6

Int J Clin Pharm

123

Regarding the use of alternative medicine, the preva-

lence in the sample was relatively low. In other studies, this

parameter varies considerably depending on the source

consulted, ranging from 15 to 90 % [3, 8, 9, 16]. However,

we would like to emphasise that in our study, in a high

proportion of cases, the oncologist was unaware that the

patient was using alternative medicine products.

Discrepancies between the patient’s usual treatment and

the information contained in the medical report were

present in fewer patients than reported in previous studies

(76 %) [3], but the large proportion of patients for whom

the medical report does not fully detail the treatment being

received highlights the importance of drug reconciliation.

Drug reconciliation process represents an important

Table 2 Clinically significant interactions (CSI) found involving anticancer drugs

Interaction n Mechanism of CSI Description

Etoposide–glucosamine 1 pD Glucosamine may diminish the cytotoxic effect of etoposide by reducing the

expression of topoisomerase II

Taxane derivatives–platinum

derivatives

6 pk (decrease in drug

clearance)

Platinum derivatives may enhance the myelosuppressive effect of Taxane

derivatives

Pemetrexed–NSAIDs 3 pk (decrease in drug

clearance)

NSAIDs may increase the serum concentration of pemetrexed

Capecitabine–SSRIs 1 pK (p450 inhibition) Capecitabine may decrease the metabolism of fluoxetine

Doxorubicin–SSRIs 1 pK (p450 inhibition) Paroxetine may increase the serum concentration of doxorubicin

Cyclophosphamide/fluorouracil–

hydrochlorothiazide

4 Unknown Thiazide diuretics may enhance the adverse/toxic effect of

cyclophosphamide/fluorouracil

Fluorouracil–cisplatin 2 Unknown Fluorouracil may enhance the adverse/toxic effect of cisplatin (cardiotoxicity

mainly)

Fluorouracil–antidiabetics 1 pK (p450 inhibition) Fluorouracil may decrease the metabolism of gliclazide

Cisplatin–ciprofloxacin 1 pk (decrease in

absorption)

Pharmacologic effects of ciprofloxacin may be decreased by cisplatin

Doxorubicin–cinacalcet 1 pK (p450 inhibition) Cinacalcet may increase the serum concentration of doxorubicin

pD pharmacodynamic, pk pharmacokinetic, p450 cytochrome P450, NSAID nonsteroidal anti-inflammatory agents, SSRI selective serotonin

reuptake inhibitor

Table 3 Clinically significant interactions (CSI) found involving supportive care drugs

Interaction n Mechanism of CSI Description

Metoclopramide–digoxin 1 pk (decrease in absorption) Metoclopramide may decrease the serum concentration of digoxin

Metoclopramide–SSRIs 3 pD Metoclopramide may enhance the adverse/toxic effect of SSRIs

Metoclopramide–risperidone 1 pD Metoclopramide may enhance the adverse/toxic effect of

antipsychotics. Development of neuroleptic malignant syndrome or

extrapyramidal reactions is a potential risk of this combination

Corticosteroids–NSAIDs 2 pD and pK (protein binding

sites)

Corticosteroids may enhance the adverse/toxic effect of NSAID

Corticosteroids–nifedipine 1 pk (p450 induction) Dexamethasone may decrease the serum concentration of nifedipine

Corticosteroids–antacids 1 pk (decrease in absorption) Antacids may decrease the serum concentration of corticosteroids

Granisetron–amitriptyline 1 pD This combination can prolong QT interval

Corticosteroids–phenytoin 1 pk (p450 induction) Phenytoin may increase the metabolism of dexamethasone

Corticosteroids–acetylsalicylic

acid

1 pk (decrease in drug clearance) Salicylates may enhance the adverse/toxic effect of corticosteroids.

These specifically include gastrointestinal ulceration and bleeding.

Corticosteroids may decrease the serum concentration of salicylates

Fosaprepitant–corticosteroids 1 pk (p450 inhibition) Fosaprepitant may increase the serum concentration of corticosteroids

Granisetron–SSRIs 1 pD This combination can prolong QT interval

pD pharmacodynamic, pk pharmacokinetic, p450 cytochrome P450, NSAID nonsteroidal anti-inflammatory agents, SSRI selective serotonin

reuptake inhibitor

Int J Clin Pharm

123

strategy to reduce medication errors. The Joint Commis-

sion recommends that healthcare organisations consider

creating a process for reconciling medications at all inter-

faces of care as a National Patient Safety Goal [17]. On the

other hand, public pharmacists have set up several activi-

ties to review the patient’s drug list, i.e. The Medicines Use

Review and Prescription Intervention Service [18]. How-

ever, in Hospital Pharmacy setting, drug reconciliation is

still a challenge for the next years.

The incidence of interactions and the average number of

CSI per patient obtained were consistent with the data

previously published. Girre et al. [15] reported an average

of 1.4 interactions per patient, while Van Leeuwen et al.

[11] found that nearly 60 % of patients experienced at least

one potential interaction. The data reported in the literature

regarding the impact of drug interactions in cancer patients

vary depending on the interaction database consulted [19]

and the criteria applied with respect to the severity of

interactions. For example, Lees et al. [3] reported that

92 % of patients suffered moderate–severe interactions.

Popa et al. [20] identified potential interactions in 75 % of

patients, but other authors have obtained lower figures,

around 30–45 % [6, 15, 21]. Van Leeuwen et al. [22]

obtained potential drug–drug interactions in 46 % of

patients treated with oral anticancer drugs (16 % with

major interactions). The incidence of CSI obtained in our

study was also dependent on the database consulted and the

Table 4 Clinically significant interactions (CSI) found involving drug treatment for chronic diseases

Interaction n Mechanism of CSI Description

Atorvastin–diltiazem 2 pk (p450 inhibition) Atorvastatin may increase the serum concentration of diltiazem.

Diltiazem may increase the serum concentration of atorvastatin

Digoxin–spironolactone 1 pD Spironolactone may increase the serum concentration of digoxin

Digoxin–diltiazem 1 pk (decrease in drug clearance) Diltiazem may increase the serum concentration of digoxin

Acetylsalicylic acid–NSAIDs 3 pk (protein binding sites) NSAIDs may enhance the adverse/toxic effect of salicylates. An

increased risk of bleeding may be associated with use of this

combination. NSAIDs may diminish the cardioprotective effect

of salicylates. Salicylates may decrease the serum concentration

of NSAIDs

SSRIs–dextromethorphan 2 pD and pk (p450 inhibition) SSRIs may enhance the serotonergic effect of dextromethorphan.

SSRIs may increase the serum concentration of

dextromethorphan

Furosemide–NSAIDs 4 pD NSAIDs may diminish the diuretic effect of loop diuretics

Furosemide–risperidone 1 Unknown Loop diuretics may enhance the adverse/toxic effect of risperidone

Clopidogrel–omeprazole 1 pK (p450 inhibition) Omeprazole may diminish the antiplatelet effect of clopidogrel

Beta blockers–antidiabetics 2 pD Beta blockers may enhance the adverse/toxic effect of

antidiabetics (hypoglycaemia)

Iron–antacids 1 pk (decrease in absorption) Antacids may decrease the serum concentration of iron

Cyproheptadine–SSRIs 1 pD Cyproheptadine may diminish the therapeutic effect of SSRIs

NSAIDs–SSRIs 1 pD NSAID may diminish the therapeutic effect of SSRIs

Omeprazole–benzodiazepines 2 pK (p450 inhibition) Omeprazole may decrease the metabolism of benzodiazepines

Allopurinol–enalapril 1 Unknown Enalapril may enhance the potential for allergic or hypersensitivity

reactions to allopurinol

Ciprofloxacin–benzodiazepines 1 pK (p450 inhibition) Ciprofloxacin may decrease the metabolism of bromazepam

Beta blockers–doxazosin 1 pD Beta blockers may enhance the orthostatic hypotensive effect of

alpha1-blockers

Omeprazole–SSRIs 1 pK (p450 inhibition) Omeprazol may increase the serum concentration of citalopram

pD pharmacodynamic, pk pharmacokinetic, p450 cytochrome P450, NSAID nonsteroidal anti-inflammatory agents, SSRI selective serotonin

reuptake inhibitor

Table 5 Clinically significant interactions (CSI), per type of treat-

ment and database consulted

Type of treatment Lexi-interact� Bot-plus�

Chronic diseases Patients with CSI 10 (32 %) 11 (44 %)

CSI n (%) 18 (44 %) 15 (52 %)

Cancer Patients with CSI 11 (36 %) 8 (32 %)

CSI n (%) 11 (28 %) 8 (27 %)

Supportive Patients with CSI 10 (32 %) 6 (24 %)

CSI n (%) 11 (28 %) 6 (21 %)

Total Patients with CSI 31 (100 %) 25 (100 %)

CSI n (%) 40 (100 %) 29 (100 %)

CSI clinically significant interactions

Int J Clin Pharm

123

severity considered. We agree with Wong et al. [19] when

they point out that this fact reflects the need for more

studies to standardise the definitions and classifications of

drugs interactions. However, from our point of view, once

we know that the incidence of drug interactions in oncol-

ogy patients is high, our efforts should be directed to try to

prevent their consequences.

In this study, the number of drugs used concomitantly

has been identified as a risk factor for the occurrence of

CSIs. It is reasonable that an increasing number of drugs

used is associated with an increased risk of CSIs and is in

agreement with other studies [22]. Statistically significant

association between gender and CSI presence should not be

considered as certain cancer types only occur in men or

women (i.e. breast cancer which is highly prevalent in our

sample). It would be interesting to develop further studies

with a larger sample size, in order to obtain more homo-

geneous groups and to perform multivariate logistic

regression analyses to identify the potential risk factors for

the occurrence of CSIs.

Most of drugs involved in the interactions detected in

cancer patients are those used to treat comorbidities [4, 21].

Lees et al. [3] found that 32 % of interactions took place in

chronic treatment, a figure that is somewhat lower than that

obtained in our study. The review by Riechelmann et al. [6]

described a study in which interactions involving antineo-

plastic agents accounted for 13 % of all interactions, rather

fewer than the number obtained in our own study. How-

ever, interactions affected more frequently (87 % of cases)

usual treatment and supportive therapy, which is in line

with the data obtained in our study. The drugs most com-

monly involved in the interactions found in cancer patients

(antidepressants, antiemetics, anticoagulants, antihyper-

tensives, anticonvulsants and corticosteroids) [4, 6, 21],

coincide to a large degree with those identified in our

study.

The hospital pharmacy service intervened in 35 % of the

cases in which cancer patients presented significant drug

interactions. To the best of our knowledge, no previous

study has described such interventions in this field. In the

interactions that did not require the oncologist to be

informed either concerned potential interactions, appro-

priate modifications had been made to prevent such inter-

actions (by means such as the separation in time of the

drugs involved, dosage adjustments and ensuring the cor-

rect order of infusion).

Some examples of pharmacy service interventions were

the interaction between naproxen–pemetrexed and etopo-

side–glucosamine.

Naproxen–pemetrexed interaction: NSAID as naproxen

may increase the serum concentration of pemetrexed. The

combination of these two drugs was associated with a 20 %

increase in pemetrexed area under the curve, 15 % increase

in pemetrexed mean maximum serum concentration and

pemetrexed clearance decreased an average of 16 %.

NSAID may interfere with renal elimination of pemetrexed

resulting in drug toxicity. Patients with mild to moderate

renal impairment (estimated creatinine clearance

45–79 ml/min) should avoid NSAID with longer half-lives,

such as naproxen, for 5 days before, the day of and 2 days

following pemetrexed. NSAID with short half-lives should

be avoided for 2 days before, the day of and 2 days fol-

lowing pemetrexed [13]. When this interaction was

detected, the patient showed moderate renal impairment

and he was taking naproxen daily. Pharmacy service con-

tacted with the oncologist suggesting avoid naproxen for

5 days before, the day of and 2 days following pemetrexed.

The recommendation was accepted, and we explained the

patient the reasons why he should not take naproxen during

the days mentioned.

Etoposide–glucosamine interaction: glucosamine coad-

ministration with etoposide may result in loss of etoposide

activity. Glucosamine appears to reduce expression of

topoisomerase II (the mechanism of action of etoposide is to

inhibit the enzyme topoisomerase II). Consequently, it is

suggested to avoid the administration of glucosamine in

patients treated with etoposide [14]. Pharmacy service

informed the patient and oncologist about the consequences

of this interaction, and glucosamine was discontinued.

Most interventions related to the use of alternative med-

icine were to recommend the interruption of such treatment.

In many cases, there are no previous studies to confirm the

absence of significant interactions; furthermore, the few

Table 6 Drug groups involved in the clinically significant interac-

tions (CSI) detected

Drug groups Percentage of total CSI (%)

Cytostatic agents 24.3

Antiemetics 11.3

Antidepressives 10.4

NSAIDs 9.6

Diuretics 6.1

Antihypertensives 4.3

Proton pump inhibitors 3.5

Antidiabetics 2.6

Cardiotonics 2.6

Corticoids 2.6

Hypolipemiants 1.7

Antiarrhythmic agents 1.7

Antibiotics 1.7

Beta blockers 1.7

Antipsychotics 1.7

Others 14.2

CSI clinically significant interactions

Int J Clin Pharm

123

studies that have been made of medicinal plants are short

case study series, with small sample sizes and low meth-

odological quality [23]. Moreover, alternative medicine

products often contain more than one active component and

are commonly of an undefined and variable composition.

Finally, there is no established pharmacovigilance system in

place to report the side effects of these products [23]. For all

these reasons, when there was no conclusive evidence in the

literature, it was recommended that the alternative treatment

should be discontinued, at least while the patient was

undergoing chemotherapy.

The degree of acceptance by the attending physician after

communication of the need for treatment modification was

very high. The fact that the pharmacist is a member of the

hospital multidisciplinary oncology team could have con-

tributed to obtain the high rate of interventions acceptance.

Detection of interactions in oncology patients plays a

key role in the management of the pharmacotherapy in

these patients. Not only by the high incidence found, but

also by the consequences they may have. Clinical phar-

macists are uniquely trained in therapeutics and provide

comprehensive drug management to patients and members

of the healthcare team. In addition to this, their demon-

strated capacity to review the patient’s drug list and their

knowledge about detection and management of interactions

make the pharmacist as the most qualified professional to

develop this task.

The role of clinical pharmacists differs from that of

traditional pharmacists in that they work directly with

healthcare professionals and patients to provide services

not simply associated with dispensing of drugs. Therefore,

the detection of interactions in oncology patients could be a

great contribution for the development of pharmaceutical

care in oncology patients and could facilitate the integra-

tion of the clinical pharmacist as a member of the multi-

disciplinary team. However, further studies are needed to

establish the incidence and impact of drug interactions in

oncology patients in order to professionals realise the

magnitude and importance of this topic.

Conclusions

Cancer patients present a high risk of drug interactions that

may compromise the efficacy and safety both of the cancer

therapy and of the treatment of comorbidities. Interventions

must be done in order to prevent or minimise the conse-

quences of interactions. For this reason, it is of funda-

mental importance to review and analyse all patient

treatments, before the start of chemotherapy, in order to

detect potential interactions. Frequently, oncologists are

unaware of the patient complete treatments. The pharma-

cist, as a member of the multidisciplinary team treating

cancer patients, can contribute by performing a systematic

review of the treatment, detection of interactions and

making recommendations, to reduce medication-related

problems and optimise drug therapy in these patients.

Funding None.

Conflicts of interest The authors have no conflicts of interest to

declare.

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