Drug-induced Sweet's syndrome: A case/non-case study in the French pharmacovigilance database.

AIMS: Sweet's syndrome is an acute febrile neutrophilic dermatosis first described in 1964 by Robert Douglas Sweet. The pathophysiological mechanism is not fully established; however, several cases of Sweet's syndrome have been reported following drug administration. METHODS: To investigate the existence of pharmacovigilance signals between drugs and the occurrence of Sweet's syndrome, we performed a case/non-case study on reports of 'acute febrile neutrophilic dermatosis' registered in the French pharmacovigilance database. Reporting odds ratio (ROR) with its 95% confidence interval were calculated. RESULTS: Amongthe 994 789 reports recorded in the database, 136 were Sweet's syndrome, of which 50.7% were men and the median age was 59 years (range 15-91). A total of 224 drugs were mentioned as suspects: 21.0% were antibacterials, 19.2% were antineoplastics and 12.1% were immunosuppressants. Median time to onset from drug initiation to the development of Sweet's syndrome was 15 days (range 1-1095). The highest RORs were observed with bortezomib (74.04 [40.8-134.2]), azacitidine (72.14 [29.4-176.9]), perfilgrastim (67.05 [21.2-211.6]), azathioprine (55.46 [34.8-88.4]) and bendamustine (35.84 [11.4-112.8]). CONCLUSIONS: Pharmacovigilance signals have been observed between the occurrence of Sweet's syndrome and colony-stimulating factors, immunosuppressants, antineoplastics and antibiotics. Clinicians should be aware of the potential associations with these drugs and should be encouraged to report any case of drug-induced Sweet's syndrome.

Trastuzumab-emtansine induced pleural and pericardial effusions.

INTRODUCTION: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate which combine trastuzumab (T), a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER2), and a cytotoxic molecule derived from maytansine (DM1). CASE REPORT: We report the first case of T-DM1-associated pleural and pericardial effusions three weeks after the second course of T-DM1 in a patient with breast cancer. Drug-induced pleural and pericardial effusions was implicated in the absence of other etiologies. The Naranjo Scale indicated a probable drug-induced adverse reaction.Management & outcome: The patient fully recovered after thoracentesis and discontinuation of T-DM1. The patient has reported no side effect after the sixth course of trastuzumab. DISCUSSION: To our knowledge, this is the first case in the literature of bilateral pleural and pericardial effusions in a patient treated with T-DM1. The successful initiation of treatment with trastuzumab following withdrawal of T-DM1 suggests that emtansine played a role in the development of bilateral pleural and pericardial effusions. We hypothesize that the patient's condition was a result of a local inflammatory reaction to emtansine by direct toxicity.

[COVID-19 and adenovirus vaccines: French experience of enhanced pharmacovigilance]. / COVID-19 et vaccins à adénovirus : expérience française de suivi renforcé de pharmacovigilance.

As part of the COVID-19 vaccination campaign, the National Agency for the Safety of Medicines and Health Products and all 31 regional pharmacovigilance centers were mobilized in an exceptional reinforced vaccine pharmacovigilance surveillance system. Concerning adenovirus vaccines, Vaxzévria® and Jcovden®, this national system, based on the daily analysis of notified cases of adverse events, has allowed the early identification of safety signals, some of which have been validated, others still under analysis, common to mRNA vaccines or more specific of adenovirus vaccines such as Vaccine Induced Immune Thrombocytopenia. Complementing european and international actions, this follow-up has contributed to a better definition of the safety profile of these vaccines and has led to redefine the vaccine strategy in our country. Although today these two vaccines have no longer place in the national vaccine strategy, they are still used in other countries, where the experience acquired could be useful and will contribute to fuel the reflection on future therapies involving viral vectors.

Beta-lactam-induced severe neutropaenia: a descriptive study.

The objectives of this study were to describe the characteristics and natural history of beta-lactam-induced severe neutropaenia and to evaluate the risk of recurrences after another beta-lactam readministration. Reports of pure agranulocytosis associated with a beta-lactam exposure within the 10 days preceding the neutropaenia were extracted from the French Pharmacovigilance Database over the year 2010. Cases with another evident cause or more likely attributable to another drug were excluded. Data were analyzed for demographics, clinical and biological features, prognosis factors, granulocyte colony stimulating factors administration and outcome. Sixty-two cases were included (median age: 65 years). The median duration of treatment before neutropaenia was 16 days. In 47% of cases, the diagnosis was made on a systematic blood cell count. The median neutrophil count at nadir was 0.125 × 109 /L, and bone marrow examination evidenced features of neutrophilic maturation arrest or aplasia in 21 patients, hyperplasia of granulopoietic cells in three and normal findings in five. Three patients developed severe sepsis. All but one recovered a normal blood cell count within 2-56 days after beta-lactam discontinuation. The last patient died from recurrent severe septic shock. No significant effect of granulocyte colony stimulating factor on the mean duration of haematological recovery was found. Among the 21 patients who later received another beta-lactam, two experienced recurrence of the neutropaenia after receiving a beta-lactam from another subfamily. Beta-lactam-induced agranulocytosis was usually observed after prolonged treatment, and severe complications are uncommon. In most patients, a subsequent treatment with another beta-lactam was well tolerated.

Safety profile of etifoxine: A French pharmacovigilance survey.

Etifoxine chlorhydrate is a benzoxazine derivative approved for the treatment of psychosomatic manifestations of anxiety since 1979. Previously labeled adverse drug reactions (ADRs) only include drowsiness, benign cutaneous reactions, and acute hypersensitivity reactions. The objectives were to examine recent data on etifoxine-related ADR by reviewing Individual Case Safety Reports (ICSRs) recorded in France especially unexpected ADRs. Etifoxine-related ICSRs were extracted from the French Pharmacovigilance database from 1 January 2000 to 30 April 2012 and data from the marketing authorization holder up to 31 December 2011 were also obtained. Of the 350 cases retained for analysis, 123 (35%) were considered serious. Dermatological or acute hypersensitivity reactions were the most frequent ADRs (59%) mainly isolated cutaneous eruptions. However, there were 24 cases of severe toxidermia (DRESS in 5, erythema multiforme in 10 and Stevens-Johnson syndrome in 5) with etifoxine as the most suspected drug in 11 patients, and seven cases of vasculitis or serum sickness-like reaction. Liver disorders were reported in 34 patients of whom 25 developed acute hepatitis with a cytolytic biological pattern in 16. Other unexpected ADRs included 16 reversible cases of metrorrhagia with positive rechallenge in 5, and three cases of biopsy-proven microscopic colitis of which one recurred after etifoxine re-administration. Although etifoxine has been marketed for more than 30 years, this survey identified a number of unexpected and sometimes serious ADRs, in particularly severe toxidermia and acute cytolytic hepatitis. A recent update of the French etifoxine summary of the product characteristics (SPC) was based on these findings.