Valérie Gras

Adverse drug reactions in patients with Alzheimer's disease and related dementia in France: a national multicentre cross‐sectional study

To assess the prevalence of adverse drug reactions (ADRs) occurring in patients with Alzheimers disease (AD) or other dementia in France.

Ulceration of the oral mucosa following direct contact with ferrous sulfate in elderly patients: a case report and a review of the French National Pharmacovigilance Database

Objective To report a series of cases of ulceration of the oral mucosa linked to direct contact with ferrous sulfate in elderly patients. Case summary The first case report concerns the occurrence of widespread oral ulceration in an 87-year-old woman with Alzheimer’s disease. The ulceration extended from the side of the tongue to the floor of the mouth. No clear explanation was found and various local treatments were ineffective. Once it was realized that the ferrous sulfate tablets (given as an iron supplement) were crushed prior to administration (due to the patient’s deglutition disorder), withdrawal of this treatment led to rapid resolution of the ulceration. Nine other cases of oral ulcerations associated with ferrous sulfate were identified in the French National Pharmacovigilance Database. All but one of the patients were over 80 years of age and the youngest patient (a 54-year-old) had dysphagia associated with facial paralysis. Discussion Only two other reports of oral ulceration due to ferrous sulfate have been published to date. Mucosal toxicity of ferrous sulfate (which is probably related to oxidative stress) has previously been reported for the hypopharynx, the esophageal lumen, and (after inhalation of a tablet) the tracheobronchial tree. Conclusion The mucosal toxicity of ferrous sulfate must be taken into account when deglutition disorders are present (as in elderly patients) and appropriate pharmaceutical formulations (such as syrups) should be administered to at-risk patients. The use of iron salts other than ferrous sulfate could be considered.

Cefixime-induced Oromandibular Dystonia in an Adult: A Case Report

INTRODUCTION Cefixime, a third-generation cephalosporin, is commonly used in different infections. Tolerance is pretty good even if some side effects can be frequent like digestive disorders. Other effects, not mentioned in the Summary of Product Characteristics, can occur. METHODS We report a case of recurrent, acute oromandibular dystonia in a cefixime-treated adult. CASE-REPORT After the third dose of cefixime, prescribed for a bronchial infection, a patient experienced a first episode of oromandibular dystonia. Then, after each ingestion, the same effects appeared. After the discontinuation of cefixime, there was no recurrence. The diagnosis of acute oromandibular dystonia has been confirmed by a neurologist. DISCUSSION Some cases of dystonia have been published with other β-lactams antibiotics and with cefixime but they concerned children. Different mechanisms are proposed to explain the occurrence of dystonia during a treatment with cefixime. They involved certain neurotransmitters like dopamine, acetylcholine or GABA. CONCLUSION Even if dystonia is not a side effect mentioned in the SPC, the drugs potential causal role must always be considered in case of involuntary contraction of muscles in a patient treated with cefixime or any other β-lactam antibiotics.

Tendinopathy after ofloxacin ear drops.

Fluoroquinolone antibiotics are commonly prescribed. These drugs are known to increase the risk of tendon injury, including rupture [1]. We report an unusual case of fluoroquinoloneinduced tendinopathy considering the route of administration. A 58-year-old man, with no relevant medical history, had experienced a first episode of tendinopathy in 2002 after taking five pills of ofloxacin 200 mg associated with corticosteroids for otitis. The complete recovery took 1 year. In October 2014, the patient consulted an ear/nose/throat specialist, who prescribed ofloxacin ear drops (1.5 mg per dose instilled in each ear bid) for bilateral external otitis. No canal or tympanic injury was seen. No other drug was taken. One hour after the third instillation, the patient experienced pain in both feet then pain in the Achilles tendons, knees, shoulders and wrists. The symptoms were similar to those presented in 2002. Ofloxacin was withdrawn after three instillations. The symptoms worsened over the following days and weeks. The pain was disabling, and the patient needed to use orthopaedic soles and crutches. Paracetamol and a short course of non-steroidal anti-inflammatory drug were prescribed. A rheumatologist was consulted 1 month later and no other cause was found, especially no underlying inflammatory disorder that could have been associated with tendinopathy. Ultrasonography of the Achilles tendons showed no inflammation and no Doppler anomaly. The patient felt better 7 weeks after the last dose of ofloxacin but was still using crutches. In January 2015, the walking distance without crutches was 4 m. The Summary of Product Characteristics (SmPC) of ear drop ofloxacin (French trade name: Oflocet auriculaire solution®) does not mention tendinopathy as a contraindication, precaution or side effect, whereas those for fluoroquinolones administrated orally, intravenously or by ocular routes do [2, 3]. Peak plasma concentrations after ear drop instillation mentioned in the SmPC are lower than or equal to 0.002 μg/ml 30 min after a single instillation (that is 10 drops of 0.3 % solution corresponding to 1.5 mg of ofloxacin) and between 0.002 and 0.012 μg/ml after repeated administrations (10 drops every 12 h for 7 days). These concentrations are similar to those of eye drop ciprofloxacin (French trade name Ciloxan collyre®) [3]. Our patient had no known risk factors for fluoroquinoloneinduced tendinopathy (renal failure, age greater than 60 years, concomitant or recent corticosteroid use, or organ transplant) except for serious ofloxacin-induced tendinopathy 12 years earlier. He had no special sporting activity. No other drug had been taken. We found no similar cases concerning fluoroquinolone ear drops in the literature. One case of Achilles tendinopathy after 14 days of treatment with ophthalmic moxifloxacin was published [4]. In the French Pharmacovigilance Database, we found one case of Achilles tendon injury in a 5-year-old boy 3 days after the administration of ofloxacin ear drops for otitis with an open tympanum. The recovery was quick, and negative rechallenge was seen after treatment for closed tympanum * Aurelie Grandvuillemin aurelie.grandvuillemin@chu-dijon.fr

Valvular Heart Disease Associated with Long-term Treatment by Methysergide: a Case Report

This case report concerns a woman treated continuously since at least 10 years by methysergide for cluster headache. The echocardiographic and histological features of the severe valve fibrosis presented by this patient are very similar to those described with 5 HT(2B) receptors agonistic drugs.