Dominique Levêque

University of Strasbourg, Strasburg, Alsace, France

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Publications (108)225.26 Total impact

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  • Annales Pharmaceutiques Françaises 01/2015; DOI:10.1016/j.pharma.2014.12.002
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    Annales Pharmaceutiques Françaises 01/2015;
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    ABSTRACT: Clinical pharmacists are contributing to safe medication use by providing comprehensive management to patients and medical staff. However, little is known regarding their impact in oncology. The aim of this study was to document and evaluate the role of clinical pharmacy services in a hematology/oncology department. A prospective, descriptive, observational study was carried out from May 2012 to May 2013. Medication reviews concerning hospitalized adult cancer patients were performed twice a week. Medication problems, pharmaceutical interventions and acceptance rate by the oncologists were recorded by a clinical pharmacist. A total of 4,393 prescriptions (including chemotherapy and support) of 489 adult cancer patients (mean age=63 years) were analyzed. The pharmacist identified 552 drug-related problems (12.6% of the prescriptions) primarily related to anti-infective agents (59.5%). Medication problems included inappropriate medications (20.6%), untreated indications (14.8%), inappropriate administrations (14.1%), underdosing (11.7%), drug-drug interactions (14.3%), lack of monitoring (9.6%), overdosing (8.9%), administration omissions (3.5%) and side-effects (2.5%). Interventions (n=552) led to treatment discontinuation (26.2%), drug dosing adjustments (21.5%), drug additions (16.9%), alternate routes of administration (11.7%), replacement of a drug by another one (10.7%), therapeutic drug monitoring (10.3%) and optimizing administration (2.6%). Most (96%) of the interventions were accepted and implemented by the medical staff. The integration of clinical pharmacy services resulted in drug-specific interventions in 12.6 % of the prescriptions of hospitalized adult patients with cancer. Medication problems mostly concerned anti-infective agents. The intervention acceptance rate by oncologists was high. The outcome of care in the hematology/oncology inpatient setting remains to be measured. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 01/2015; 35(1):457-60. · 1.87 Impact Factor
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    ABSTRACT: Oral anticancer agents and particularly kinase inhibitors are subject to pharmacokinetic drug interactions in relation to absorption and elimination phases. Interacting factors are food, fruit juices, cigarette smoke, acid-reducing agents and inducers/inhibitors. Some anticancer agents are inducers and/or inhibitors and can also perpetrate drug interactions. This review emphasizes the mechanisms of pharmacokinetic drug interactions involving oral anticancer agents. Copyright © 2014 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
    Bulletin du cancer 12/2014; 102(1). DOI:10.1016/j.bulcan.2014.11.001 · 0.64 Impact Factor
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    ABSTRACT: We herein report the case of a male patient with acute myeloid leukemia with fatal outcome attributable to pharmacokinetics of pegfilgrastim.
    Anticancer research 11/2014; 34(11):6747-8. · 1.87 Impact Factor
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    ABSTRACT: The medication iatrogenic events are responsible for nearly one iatrogenic event in five. The main purpose of this prospective multicenter study is to determine the effect of pharmaceutical consultations on the occurrence of medication adverse events during hospitalization (MAE). The other objectives are to study the impact of age, of the number of medications and pharmaceutical consultations on the risk of MAE. The pharmaceutical consultation is associated to a complete reassessment done by both a physician and a pharmacist for the home medication, the hospital treatment (3days after admission), the treatment during chemotherapy, and/or, the treatment when the patient goes back home. All MAE are subject to an advice for the patient, additional clinical-biological monitoring and/or prescription changes. Among the 318 patients, 217 (68%) had 1 or more clinically important MAE (89% drug-drug interaction, 8% dosing error, 2% indication error, 1% risk behavior). The patients have had 1121 pharmaceutical consultations (3.2±1.4/patient). Thus, the pharmaceutical consultations divided by 2.34 the risk of MAE (unadjusted incidence ratio, P≤0.05). Each consultation decreased by 24% the risk of MAE. Moreover, adding one medication increases from 14 to 30% as a risk of MAE on the population. Pharmaceutical consultations during the hospital stay could reduce significantly the number of medication adverse effects. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    Annales Pharmaceutiques Françaises 11/2014; 72(6):440-50.
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    ABSTRACT: Introduction Our current development strategy integrates clinical pharmacy activities prioritized in surgical services. Patients in these services are typically risk patients: transfers, multiple prescribers, frequent medication change, pharmacotherapeutic risk classes. Patients and methods Three clinical pharmacy activities (admission reconciliation, pharmaceutical analysis, participation doctors round) have been developed in orthopaedic surgery and neurosurgery. Pharmacists prospectively recorded data describing their activities: number of reconciliations and analyzed requirements and time required to achieve them. Data on pharmaceutical interventions were recorded on the basis ActIP®. The clinical significance of interventions was retrospectively rated by a team of two pharmacists and two physicians on the scale adapted Hatoum et al. Results Four thousand five hundred pharmaceutical analysis and 248 reconciliations were conducted. One hundred and fifty-six pharmaceutical interventions were issued. The average acceptance rate was 80%. A total of 5.8% of pharmaceutical interventions have been listed with a very significant clinical importance and 48.1% with at least significant clinical importance. The activities and documentation required pharmaceutical average daily time (senior pharmacist, resident and external pharmacist) about 6 hours. Discussion and conclusion Other studies, including comparative and medico-economic, must be conducted to support these results. Nevertheless, the indicators obtained attend a better readability of the clinical importance of the activities performed by clinical pharmacists and this particularly in surgical services, both by prescribers and authorities.
    Annales Pharmaceutiques Françaises 09/2014; 73(2). DOI:10.1016/j.pharma.2014.09.001
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    ABSTRACT: Most of oral targeted therapies are tyrosine kinase inhibitors (TKIs). Oral administration generates a complex step in the pharmacokinetics (PK) of these drugs. Inter-individual PK variability is often large and variability observed in response is influenced not only by the genetic heterogeneity of drug targets, but also by the pharmacogenetic background of the patient (e.g. cytochome P450 and ABC transporter polymorphisms), patient characteristics such as adherence to treatment and environmental factors (drug–drug interactions). Retrospective studies have shown that targeted drug exposure, reflected in the area under the plasma concentration–time curve (AUC) correlates with treatment response (efficacy/toxicity) in various cancers. Nevertheless levels of evidence for therapeutic drug monitoring (TDM) are however heterogeneous among these agents and TDM is still uncommon for the majority of them. Evidence for imatinib currently exists, others are emerging for compounds including nilotinib, dasatinib, erlotinib, sunitinib, sorafenib and mammalian target of rapamycin (mTOR) inhibitors. Applications for TDM during oral targeted therapies may best be reserved for particular situations including lack of therapeutic response, severe or unexpected toxicities, anticipated drug–drug interactions and/or concerns over adherence treatment. Interpatient PK variability observed with monoclonal antibodies (mAbs) is comparable or slightly lower to that observed with TKIs. There are still few data with these agents in favour of TDM approaches, even if data showed encouraging results with rituximab, cetuximab and bevacizumab. At this time, TDM of mAbs is not yet supported by scientific evidence. Considerable effort should be made for targeted therapies to better define concentration–effect relationships and to perform comparative randomised trials of classic dosing versus pharmacokinetically-guided adaptive dosing.
    European Journal of Cancer 08/2014; 50(12). DOI:10.1016/j.ejca.2014.04.015 · 4.82 Impact Factor
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    ABSTRACT: The medication iatrogenic events are responsible for nearly one iatrogenic event in five. The main purpose of this prospective multicenter study is to determine the effect of pharmaceutical consultations on the occurrence of medication adverse events during hospitalization (MAE). The other objectives are to study the impact of age, of the number of medications and pharmaceutical consultations on the risk of MAE. The pharmaceutical consultation is associated to a complete reassessment done by both a physician and a pharmacist for the home medication, the hospital treatment (3 days after admission), the treatment during chemotherapy, and/or, the treatment when the patient goes back home. All MAE are subject to an advice for the patient, additional clinical-biological monitoring and/or prescription changes. Among the 318 patients, 217 (68%) had 1 or more clinically important MAE (89% drug-drug interaction, 8% dosing error, 2% indication error, 1% risk behavior). The patients have had 1121 pharmaceutical consultations (3.2 ± 1.4/patient). Thus, the pharmaceutical consultations divided by 2.34 the risk of MAE (unadjusted incidence ratio, P ≤ 0.05). Each consultation decreased by 24% the risk of MAE. Moreover, adding one medication increases from 14 to 30% as a risk of MAE on the population. Pharmaceutical consultations during the hospital stay could reduce significantly the number of medication adverse effects.
    Annales Pharmaceutiques Françaises 07/2014; DOI:10.1016/j.pharma.2014.05.003
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    ABSTRACT: Most anticancer drugs are characterised by a steep dose-response relationship and narrow therapeutic window. Inter-individual pharmacokinetic (PK) variability is often substantial. The most relevant PK parameter for cytotoxic drugs is the area under the plasma concentration versus time curve (AUC). Thus it is somewhat surprising that therapeutic drug monitoring (TDM) is still uncommon for the majority of agents. Goals of the review were to assess the rationale for more widely used TDM of cytotoxics in oncology. There are several reasons why TDM has never been fully implemented into daily oncology practice. These include difficulties in establishing appropriate concentration target ranges, common use of combination chemotherapies for many tumour types, analytical challenges with prodrugs, intracellular compounds, the paucity of published data from pharmacological trials and 'Day1=Day21' administration schedules. There are some specific situations for which these limitations are overcome, including high dose methotrexate, 5-fluorouracil infusion, mitotane and some high dose chemotherapy regimens. TDM in paediatric oncology represents an important challenge. Established TDM approaches includes the widely used anticancer agents carboplatin, busulfan and methotrexate, with 13-cis-retinoic acid also recently of interest. Considerable effort should be made to better define concentration-effect relationships and to utilise tools such as population PK/PD models and comparative randomised trials of classic dosing versus pharmacokinetically guided adaptive dosing. There is an important heterogeneity among clinical practices and a strong need to promote TDM guidelines among the oncological community.
    European journal of cancer (Oxford, England: 1990) 05/2014; 50(12). DOI:10.1016/j.ejca.2014.04.014 · 4.82 Impact Factor
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    [Show abstract] [Hide abstract]
    ABSTRACT: Therapeutic drug monitoring (TDM) can be defined as the measurement of drug in biological samples to individualise treatment by adapting drug dose to improve efficacy and/or reduce toxicity. The cytotoxic drugs are characterised by steep dose-response relationships and narrow therapeutic windows. Inter-individual pharmacokinetic (PK) variability is often substantial. There are, however, a multitude of reasons why TDM has never been fully implemented in daily oncology practice. These include difficulties in establishing appropriate concentration target, common use of combination chemotherapies and the paucity of published data from pharmacological trials. The situation is different with targeted therapies. The large interindividual PK variability is influenced by the pharmacogenetic background of the patient (e.g. cytochrome P450 and ABC transporters polymorphisms), patient characteristics such as adherence to treatment and environmental factors (drug-drug interactions). Retrospective studies have shown that targeted drug exposure correlates with treatment response in various cancers. Evidence for imatinib currently exists, others are emerging for compounds including nilotinib, dasatinib, erlotinib, sunitinib, sorafenib and mammalian target of rapamycin (mTOR) inhibitors. Applications for TDM during oral targeted therapies may best be reserved for particular situations including lack of therapeutic response, severe or unexpected toxicities, anticipated drug-drug interactions and concerns over adherence treatment. There are still few data with monoclonal antibodies (mAbs) in favour of TDM approaches, even if data showed encouraging results with rituximab and cetuximab. TDM of mAbs is not yet supported by scientific evidence. Considerable effort should be made for targeted therapies to better define concentration-effect relationships and to perform comparative randomised trials of classic dosing versus pharmacokinetically-guided adaptive dosing.
    European journal of cancer (Oxford, England: 1990) 05/2014; 50(12). DOI:10.1016/j.ejca.2014.04.013 · 4.82 Impact Factor
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    ABSTRACT: Clinical pharmacy has been developed and evaluated in various medical hospital activities. Reviews conducted in this area reported a higher value of this discipline. In surgical services, evenly adverse drug events may occur, so clinical pharmacy activities must also help to optimize the management of drug's patient. The objectives of this literature review is to determine the profile of clinical pharmacy activities developed in surgical services and identify indicators. The research was conducted on Pubmed® database with the following keywords (2000–2013), “surgery”, “pharmacy”, “pharmacist”, “pharmaceutical care”, “impact” and limited to French or English papers. Studies dealing on simultaneously medical and surgical areas were excluded. Twenty-one papers were selected. The most frequently developed clinical pharmacy activities were history and therapeutic drug monitoring (antibiotics or anticoagulants). Two types of indicators were identified: activity indicators with the number of pharmaceutical interventions, their description and clinical signification, the acceptance rate and workload. Impact indicators were mostly clinical and economic impacts. The development of clinical pharmacy related to surgical patients is documented and appears to have, as for medical patients, a clinical and economical value.
    Annales Pharmaceutiques Françaises 05/2014; DOI:10.1016/j.pharma.2013.12.011
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    ABSTRACT: Clinical pharmacy has been developed and evaluated in various medical hospital activities. Reviews conducted in this area reported a higher value of this discipline. In surgical services, evenly adverse drug events may occur, so clinical pharmacy activities must also help to optimize the management of drug's patient. The objectives of this literature review is to determine the profile of clinical pharmacy activities developed in surgical services and identify indicators. The research was conducted on Pubmed(®) database with the following keywords (2000-2013), "surgery", "pharmacy", "pharmacist", "pharmaceutical care", "impact" and limited to French or English papers. Studies dealing on simultaneously medical and surgical areas were excluded. Twenty-one papers were selected. The most frequently developed clinical pharmacy activities were history and therapeutic drug monitoring (antibiotics or anticoagulants). Two types of indicators were identified: activity indicators with the number of pharmaceutical interventions, their description and clinical signification, the acceptance rate and workload. Impact indicators were mostly clinical and economic impacts. The development of clinical pharmacy related to surgical patients is documented and appears to have, as for medical patients, a clinical and economical value.
    Annales Pharmaceutiques Françaises 05/2014; 72(3):152-163.
  • Dominique Leveque, Amina Delpeuch, Benedicte Gourieux
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    ABSTRACT: Clinical pharmacy (or clinical pharmacy services) aims to contribute to safe medication use by providing comprehensive management to patients and medical staff, both in the community and the hospital. In oncology, these services include comprehensive medication reviews integrating chemotherapy, supportive care and ambulatory treatment for co-morbidities, medication information for the medical staff and patients, therapeutic drug monitoring (anticancer agents, anti-infective agents, immunosuppressive drugs in recipients of allogeneic stem cell transplantation), supportive care counseling (nutritional support, pain management, chemotherapy side-effects prophylaxis and treatment), elaboration of therapeutic guidelines, optimal use of economic resources. With regard to new anticancer agents, pharmacists both in the community and in hospitals are faced with a growing body of complex information as well as the development of ambulatory treatment (oral agents, subcutaneous administration). Clinical pharmacists with oncology training have the potential to optimize drug use both in the hospital and the community. With the understanding and recognition of drug interactions and side-effects, pharmacists can provide timely interventions and information to health providers, as well as counseling to patients.
    Anticancer research 04/2014; 34(4):1573-8. · 1.87 Impact Factor
  • Dominique Levêque
    The Lancet Oncology 02/2014; 15(2):e51. DOI:10.1016/S1470-2045(14)70004-X · 24.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Therapeutic drug monitoring (TDM) can be defined as the measurement of drug in biological samples to individualise treatment by adapting drug dose to improve efficacy and/or reduce toxicity. The cytotoxic drugs are characterised by steep dose–response relationships and narrow therapeutic windows. Inter-individual pharmacokinetic (PK) variability is often substantial. There are, however, a multitude of reasons why TDM has never been fully implemented in daily oncology practice. These include difficulties in establishing appropriate concentration target, common use of combination chemotherapies and the paucity of published data from pharmacological trials. The situation is different with targeted therapies. The large interindividual PK variability is influenced by the pharmacogenetic background of the patient (e.g. cytochrome P450 and ABC transporters polymorphisms), patient characteristics such as adherence to treatment and environmental factors (drug–drug interactions). Retrospective studies have shown that targeted drug exposure correlates with treatment response in various cancers. Evidence for imatinib currently exists, others are emerging for compounds including nilotinib, dasatinib, erlotinib, sunitinib, sorafenib and mammalian target of rapamycin (mTOR) inhibitors. Applications for TDM during oral targeted therapies may best be reserved for particular situations including lack of therapeutic response, severe or unexpected toxicities, anticipated drug–drug interactions and concerns over adherence treatment. There are still few data with monoclonal antibodies (mAbs) in favour of TDM approaches, even if data showed encouraging results with rituximab and cetuximab. TDM of mAbs is not yet supported by scientific evidence. Considerable effort should be made for targeted therapies to better define concentration–effect relationships and to perform comparative randomised trials of classic dosing versus pharmacokinetically-guided adaptive dosing.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Most anticancer drugs are characterised by a steep dose–response relationship and narrow therapeutic window. Inter-individual pharmacokinetic (PK) variability is often substantial. The most relevant PK parameter for cytotoxic drugs is the area under the plasma concentration versus time curve (AUC). Thus it is somewhat surprising that therapeutic drug monitoring (TDM) is still uncommon for the majority of agents. Goals of the review were to assess the rationale for more widely used TDM of cytotoxics in oncology. There are several reasons why TDM has never been fully implemented into daily oncology practice. These include difficulties in establishing appropriate concentration target ranges, common use of combination chemotherapies for many tumour types, analytical challenges with prodrugs, intracellular compounds, the paucity of published data from pharmacological trials and ‘Day1 = Day21’ administration schedules. There are some specific situations for which these limitations are overcome, including high dose methotrexate, 5-fluorouracil infusion, mitotane and some high dose chemotherapy regimens. TDM in paediatric oncology represents an important challenge. Established TDM approaches includes the widely used anticancer agents carboplatin, busulfan and methotrexate, with 13-cis-retinoic acid also recently of interest. Considerable effort should be made to better define concentration–effect relationships and to utilise tools such as population PK/PD models and comparative randomised trials of classic dosing versus pharmacokinetically guided adaptive dosing. There is an important heterogeneity among clinical practices and a strong need to promote TDM guidelines among the oncological community.
  • Source
    Médecine et Maladies Infectieuses 01/2013; 43(1). DOI:10.1016/j.medmal.2012.11.006 · 0.91 Impact Factor

Publication Stats

737 Citations
225.26 Total Impact Points

Institutions

  • 1996–2015
    • University of Strasbourg
      • Institut de Bactériologie
      Strasburg, Alsace, France
  • 2001–2012
    • CHRU de Strasbourg
      • Pôle Pharmacie-pharmacologie
      Strasburg, Alsace, France
  • 1993–2008
    • Institut de France
      Lutetia Parisorum, Île-de-France, France
  • 1998
    • Centre Hospitalier Universitaire de Limoges
      Limages, Limousin, France
  • 1997
    • IHU de Strasbourg
      Strasburg, Alsace, France