Assessment of drug-drug interaction in an elderly human immunodeficiency virus population: Comparison of 3 expert databases.

AIMS: Polypharmacy increase the risk of drug-drug interactions (DDIs) in the elderly population living with human immunodeficiency virus (HIV). Several expert databases can be used to evaluate DDIs. The aim of the study was to describe actual DDIs between antiretroviral drugs and comedications in an elderly population and to compare grading of the DDIs in 3 databases. METHODS: All treatments of HIV-infected subjects aged 65 years and older were collected in 6 French HIV centres. Summary of Product Characteristic (SPC), French DDI Thesaurus (THES), and Liverpool HIV DDI website (LIV) were used to define each DDI and specific grade. DDIs were classified in yellow flag interaction (undefined grade in SPC and THES or potential weak interaction in LIV), amber flag interaction (to be considered/precaution of use in SPC and THES and potential interaction in LIV) and red flag interaction (not recommended/contraindication in SPC and THES and do not administer/contraindication in LIV). RESULTS: Among 239 subjects included, 60 (25.1%) had at least 1 DDI for a total of 126 DDIs: 23/126 red flag DDIs were identified in 17 patients. All these 23 DDIs were identified in LIV. THES and SPC missed 6 and 1 red flag DDIs, respectively. Seven of 23 red flag DDIs were identified in the 3 databases concomitantly. CONCLUSION: Polypharmacy is frequent in this elderly HIV population leading to DDI in a quarter of the subjects. The discrepancies between databases can be explained by differences in analysis methods. A consensus between databases would be helpful for clinicians.

[Completeness of pharmacovigilance reporting in general medicine in France.] / Informativité des déclarations de pharmacovigilance en médecine générale en France.

INTRODUCTION: Spontaneous reporting remains one of the cornerstones of post-marketing drug safety surveillance. One of its main limitations is a lack of completeness.The main aim of this study was to assess the completeness of pharmacovigilance reports sent by general practitioners (GPs) to regional pharmacovigilance centers (RPC) reported in the French pharmacovigilance database (FPVD). Secondary aim was to identify factors associated with complete reports. METHOD: All adverse drugs reactions (ADRs) sent by GPs in France in 2015 were analyzed. According to information provided in ADR reports (ADR, date of occurrence, clinical description, drugs suspected, etc.), completeness was analyzed from “mandatory” criteria (age, gender, ADR and suspected drug(s)) and “non-mandatory” criteria (medical history, concomitant drugs, symptoms evolution and complementary exams) and classified as “well-documented”, “slightly-documented” or “poorly-documented”. RESULTS: In 2015, the FPVD contained 3,020 ADR reports realized by GPs. Only 16.4% of these reports were classified as “well-documented”, in accordance with study criteria. The most poorly documented items were concomitant drugs (41.4%) and complementary exams (37.4%). An association between a “well-documented” ADR report and its “seriousness” (OR = 3,02 [95% CI 2,44; 3,23], P < 10–3) and elderly compared to adults (OR = 1,76 [95% CI 1,42; 2,18], P < 10–3) or children (OR = 4,59 [95% CI 2,51; 8,39], P < 10–3). CONCLUSION: Our study shows that only one out of six ADR reports was “well-documented”. It appears to be important to promote pharmacovigilance to improve completeness of ADR reports.

A Severe Neonatal Lymphopenia Associated With Administration of Azathioprine to the Mother in a Context of Crohn's Disease.

Azathioprine is commonly used in Crohn's disease. It has been administered to many pregnant women over many years without significant side effects. However, pancytopenia and severe combined immune deficiency-like disease have been reported in infants whose mothers received azathioprine throughout pregnancy. Moreover, myelotoxicity has been described in patients being treated with azathioprine and having a low or absent thiopurine S-methyl transferase [TPMT] activity.Here, we describe the case of a newborn girl found to be highly lymphopenic [< 300 CD3+ T cells] after a positive newborn screening for severe combined immuno deficiency. The clinical examination was normal. The mother was treated with azathioprine throughout her pregnancy, without any reduction of the dose. It was shown that the mother was heterozygous for the 3A [TPMT] activity mutation and that the baby was homozygous for the same mutation; 6-thioguanine nucleotides were high (744 pmol/8.108 red blood cells [RBC]) in the mother and detectable in the infant [177 pmol/8.108 RBC].Although rare, this case illustrates the potential grave consequences of unsuspected TPMT homozygosity in a newborn of a mother receiving thiopurines during pregnancy. Because of the severity of the risk for the newborn, consideration should be given to performing maternal genetic testing and newborn routine blood count in cases of thiopurine treatment during pregnancy.

[MEOPA use practices in a university hospital: Which conformity?] / Pratiques d'utilisation du MEOPA dans un CHU : quelle conformité ?

INTRODUCTION: MEOPA (equimolar mixture of oxygen and nitrous oxide) is used for its analgesic and anxiolytic properties in order to obtain conscious sedation of the patient when performing painful care. It is subject to an enhanced pharmacovigilance and addictovigilance monitoring. In this context, it is important to dispose of hospital utilization data. This work aims to assess the compliance of the use of nitrous oxide regarding the recommendations of the summary of product characteristics, in a French university hospital (Nantes) and consider possible improvements. MATERIALS AND METHODS: Transversal descriptive study, conducted in 2014 with all health professionals using MEOPA. RESULTS: Two thousand thirty-four health professionals answered the questionnaire ; durations of administrations are in conformity and the premises are generally appropriate but almost 60% of professionals have the feeling of inhaling the drug. The systematization of the prescription (always or almost always prescribed for 67% of professionals) and traceability of use (always or almost always in the patient's file for 71% of professionals) are potential source of improvement, particularly since 18% of professional health reported "abuse demands" from patients. CONCLUSION: The formation and information of health professionals are major issues of good use of nitrous oxide.

Bacterial infections and NSAIDs exposure? Seek septic complications.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed. Some authors suggested a relationship between more severe infections and NSAIDs exposure, especially skin and soft tissue infections (SSTI). However, their impact during bacterial infections remains unclear. The aim of the study was to report the severity features of patients having bacterial infection who were exposed to NSAIDs prior to their hospitalisation. Cases of infected patients with these characteristics declared to the pharmacovigilance department of a French university hospital from 1 January 2011 to 31 December 2013 were retrospectively reviewed. Forty-one patients were included, mainly male (61%). Median age was 37years. No underlying disease was noted for 68% of cases. Ibuprofen was the most frequent drug (63%). Self-medication concerned 61% of cases. Respiratory tract, osteoarticular and SSTI were the most frequent infected sites. Patients suffered septic complications: dissemination of infection to more than one site (51%), suppuration (59%), and requirement for invasive procedures (32%). Eleven patients (27%) had severity criteria as usually defined (10 severe sepsis and 1 septic shock) and 30 did not. There was no significant difference regarding the rate of septic complications between the severe and non-severe group. Septic complications frequently occurred in patients with NSAIDs exposure, whether or not there was severe sepsis or shock. Further studies investigating the impact of NSAIDs in bacterial infections should consider the septic complications depicted here as clinically relevant endpoints. Moreover, clinicians should seek those complications in case of bacterial infections and NSAIDs use.

Anti-tumour necrosis factor alpha therapy and increased risk of de novo psoriasis: is it really a paradoxical side effect?

OBJECTIVES: Tumour necrosis factor (TNF) alpha inhibitors (infliximab, etanercept, adalimumab) revolutionised the treatment of autoimmune diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD) and plaque psoriasis. During these treatments, cutaneous adverse effects may occur like eczema, lupus, alopecia areata or psoriasis, which represents a paradoxical adverse effect. The aim of this study was to collect and to analyse characteristics and outcomes of psoriasis induced by anti-TNF alpha treatments. METHODS: A search in the French Pharmacovigilance Database was performed between January 2002 and September 2009 using the following terms 'infliximab', 'etanercept', 'adalimumab' combined with the term 'psoriasis'. A literature review was performed utilising PubMed Database and Google scholar using permutations of the following terms 'infliximab', 'etanercept', 'adalimumab', 'tumour necrosis factor-α inhibitor' combined with 'psoriasis', 'palmoplantar pustular psoriasis', palmoplantar pustulosis'. Certolizumab pegol and golimumab were approved only recently and so were not included in the search. RESULTS: We found 57 cases in the French Pharmacovigilance Database and 184 cases in the literature. It appeared that the eruptions are most often pustular lesions and occur mainly on palms and/or soles (33.3% in the French Pharmacovigilance Database and 42.9% in the literature), while palmoplantar pustular psoriasis represents only 1.7% of the psoriatic patients. The three anti-TNF-alpha are involved in the psoriasis induction. Half the cases appeared with infliximab. The patients affected by this adverse effect are mostly women aged between 40-50 years old. The time of onset of psoriasis is highly variable. Those patients treated for their psoriasis with TNF-alpha inhibitor developed a psoriasis induced by the treatment with a different localisation and a different morphology from the initial psoriasis while other patients had a recurrence of this side effect with two different TNF-alpha antagonists, then the psoriasis developed with the 2nd anti-TNF alpha is of the same type as the psoriasis developed with the first molecule. CONCLUSIONS: This suggests that psoriasis occurring during anti-TNF alpha therapy are de novo psoriasis and not an aggravation of a pre-existing psoriasis. To this day several hypotheses have been proposed to explain the mechanism of action. The occurrence of this adverse effect may call into question the continuation of the treatment which is nevertheless effective.