Jean-Christophe Poutrain

Drug interactions between antihypertensive drugs and non‐steroidal anti‐inflammatory agents: a descriptive study using the French Pharmacovigilance database

Drug–drug interactions (DDIs) between antihypertensive drugs and non‐steroidal anti‐inflammatory drugs (NSAIDs) can lead to adverse drug reactions (ADRs). Guidelines are available to help prescribers deal with these drug associations, but their implementation is not well evaluated. The aims of this study were to assess the prevalence of NSAIDs exposure in patients treated with antihypertensive drugs, using the French Pharmacovigilance database, and explore the ADRs related to DDIs between antihypertensive drugs and NSAIDs. Over the 11, 442 notifications of ADRs recorded in this database in patients treated with oral antihypertensive drugs between 2008 and 2010, 517 (4.5 and 95% CI: 4.1–4.9) also included exposure to NSAIDs. These subjects were more frequently women, took more drugs in general, and were younger and less frequently treated with antiplatelet drugs. In 24.2% of them (125 patients), a DDI between NSAIDs and antihypertensive drugs was potentially the cause of the reported ADR. Acute renal failure caused by DDIs between NSAIDs and angiotensin‐converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or diuretics was the most frequently reported ADR (20.7%). Finally, in the French Pharmacovigilance database, around one‐fourth of associations NSAIDs + antihypertensive drugs are associated with a ‘serious’ ADR (mainly acute renal failure), suggesting that this well‐known DDI is not enough taken into account by prescribers.

Effectiveness of drug tests in outpatients starting opioid substitution therapy

We aimed to assess the effectiveness of drug tests for treatment retention in outpatients starting opioid substitution therapy. A retrospective cohort was created from the data of the French health insurance system database for the Midi-Pyrenees region. Patients starting opioid substitution treatment (OST) were included and followed for 18 to 30 months. Two groups of patients were defined: the drug test group (at least one drug test reimbursement) and a control group (no drug test reimbursement). The cohort included 1507 patients. During follow-up, 39 subjects (2.6%) had at least one drug test reimbursement. Mean treatment retention was 207 days in the control group and 411 days in the drug test group (p < 0.001). With a multivariate Cox model, drug tests were associated with treatment retention: hazard ratio 0.55 (95% CI: 0.38-0.80). Use of a drug test in follow-up of opioid substitution treatment, although rarely prescribed, significantly improved treatment retention.

More on the "Triple Whammy": antihypertensive drugs, non-steroidal anti-inflammatory agents and acute kidney injury - a case/non-case study in the French pharmacovigilance database.

Abstract It has been suggested that the risk of acute kidney injury (AKI) increases with the number of drugs associated between non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme inhibitors (ACEis) [or angiotensin receptor blockers (ARBs)] and diuretics. We aimed to investigate whether the number of drugs associated between NSAIDs, ACEis, ARBs and diuretics was associated to disproportionate reporting of AKI in the French Pharmacovigilance Database. In reports of Adverse Drug Reactions (ADRs) recorded between 01 January 2008 and 31 December 2010, we selected patients whose medications included at least one oral antihypertensive drug. We used a case/non-case methodology. Cases were AKI and non-cases were all the remaining reports. Among the 11,442 ADR reports in patients under antihypertensive drug recorded in the French Pharmacovigilance Database, 837 ADRs were AKI (7.3%, 95% CI 6.8–7.8). AKI and the number of drugs associated were disproportionately reported (one drug alone: adjusted ROR 2.19, 95% CI: 1.65–2.89, two drugs: adjusted ROR 5.27, 95% CI: 4.00–6.94, three and more: adjusted ROR 16.46, 95% CI: 11.38–23.80). There was no significant association between NSAIDs’ half-lives and reporting of AKI (adjusted ROR = 0.54, 95% CI: 0.25–1.15). Given the widespread use of these hazardous drugs in general population, caution is needed when they are associated.

Which Adverse Events Are Related to Health Care during Hospitalization in Elderly Inpatients

Background: Adverse events result in longer hospital stays and increase costs and mortality. We aimed to assess incidence of adverse events occurring during hospitalization in a post-emergency unit and to describe their characteristics. Methods: All adverse events occurring in patients during their hospitalization in a post-emergency unit in a French university hospital (20 beds) were systematically and consecutively recorded from September 2009 to February 2011. Patients with adverse events were compared to up to three control patients, matched for date of admission +/- age in the same unit. Results: We identified 56 patients with 64 adverse events, giving an incidence of 3.0/100 patients admitted/year. Fifty-one adverse events were drug-related. Patients had a median age of 82.5 years with a male/female ratio of 1/1.4. They presented a median Charlson score of 1 and the median number of medications was 6. The drugs most frequently involved in drug-related events were nervous system drugs (47%) and anti-infectives (22%). In multivariate analysis, a Charlson score ≥ 2 was associated with the occurrence of adverse events (OR 0.4; 95% CI [0.21 - 0.80]). Conclusions: Systematic recording showed that adverse events were not rare in a post-emergency unit. Patients with comorbid conditions were less likely to present an adverse event, possibly because of greater precautions taken by the medical team.

Identifying competencies required for medication prescribing for general practice residents: a nominal group technique study

BackgroundTeaching of medication prescribing is a specific challenge in general practice curriculum. The aim of this study was to identify and rank the competencies required for prescribing medication for general practice residents in France.MethodsQualitative consensus study using the nominal group technique. We invited different stakeholders of the general practice curriculum and medication use in primary care to a series of meetings. The nominal group technique allowed for the quick development of a list of consensual and ranked answers to the following question: “At the end of their general practice curriculum, in terms of medication prescribing, what should residents be able to do?”.ResultsFour meetings were held that involved a total of 31 participants, enabling the creation of a final list of 29 ranked items, grouped in 4 domains. The four domains identified were ‘pharmacology’, ‘regulatory standards’, ‘therapeutics’, and ‘communication (both with patients and healthcare professionals)’. Overall, the five items the most highly valued across the four meetings were: ‘write a legible and understandable prescription’, ‘identify specific populations’, ‘prescribe the doses and durations following the indication’, ‘explain a lack of medication prescription to the patient’, ‘decline inappropriate medication request’. The ‘communication skills’ domain was the domain with the highest number of items (10 items), and with the most highly-valued items.ConclusionThe study results suggest a need for developing general practice residents’ communication skills regarding medication prescribing.

Patients’ Knowledge About Analgesic-Antipyretic Medications Purchased in Community Pharmacies: A Descriptive Study

ABSTRACT The objective of this study was to describe the level of knowledge about paracetamol (acetaminophen), ibuprofen, and aspirin of subjects who purchased nonprescription medications containing one of these drugs. We conducted this cross-sectional descriptive study in 42 community pharmacies located in southwestern France between July and November 2013. A six-item self-administered questionnaire was used. Participants were asked to identify the active ingredient contained in 14 brand-name analgesic-antipyretics, to state the maximum daily dose of paracetamol, ibuprofen, and aspirin, the recommended first-line analgesic, and precautions of use or contraindications for paracetamol, ibuprofen, and aspirin. Among 576 participants, the identification of paracetamol ranged from 58% (for Dafalgan or Efferalgan) to 90% (for Doliprane), the identification of ibuprofen from 34% (for Nureflex) to 63% (for Nurofen), and the identification of aspirin was 70% (for Aspegic). The maximum recommended daily dose of paracetamol, ibuprofen, and aspirin was known by 58.3%, 17.7%, and 19.3% of participants, respectively, whereas 6.8%, 17.2%, and 13.2% stated supratherapeutic daily doses. Paracetamol was correctly stated as the first-line analgesic-antipyretic by 76.2% of participants. Knowledge on major precautions of use or contraindications was poor (45.8% and 53.6% for ibuprofen and aspirin use during pregnancy, and 14.1% for concurrent use of anticoagulants and ibuprofen). Purchasers of nonprescription analgesic-antipyretics had poor knowledge on the medication they purchased.

Parenteral Anticoagulants Use in General Practice: A Cross-Sectional Study in South Western France

Using parenteral anticoagulants in compliance with their summaries of product characteristics (SPCs) and consensus guidelines is associated with decreased rates of adverse drug reactions. The objectives were to assess compliance of parenteral anticoagulants use with SPCs and 4 consensus guidelines in outpatients of general practice. A descriptive cross-sectional study was conducted among 112 teaching general practitioners’ offices, from May to October 2011. Among the 332 adult outpatients consecutively included, 108 (32.5%) had a parenteral anticoagulant therapy complying with SPCs for both indication and regimen. The rate of compliance increased when considering consensus guidelines (159 patients, 47.9%). Rate of adverse events was 5.4%, including 0.6% of serious adverse events. This study showed that the use of parenteral anticoagulants complies with indications and regimens of SPCs in only 1 of the 3 outpatients. Further studies should be conducted in primary care to explore reasons for such low compliance rates.