Ondansetron induced blindness: a pharmacovigilance database study.

BACKGROUND: Ondansetron is an antiemetic drug (AED) used to prevent and treat nausea and vomiting. The summary of product characteristics reports a rare risk of transient blindness primarily during IV injections, notably with the concomitant use of chemotherapeutic agents. We aimed to refine the characterization of ondansetron-induced blindness. RESEARCH DESIGN AND METHODS: We performed a descriptive and a case/non-case analysis using VigiBase®. Cases were defined as reports of adverse drug reactions (ADRs) related to blindness: amaurosis, amaurosis fugax, blindness. Non-cases were all other recorded reactions. Reporting risk of blindness-related ADRs was assessed using a disproportionality analysis and expressed as Reporting Odds Ratios (ROR). RESULTS: 138,315 ADRs were reported with AEDs, including 136 blindness-related ADRs, among them 44 (32.4%) with ondansetron. For ondansetron users, blindness-related ADRs occurred mainly on the first day. Out of the 25 patients with known outcomes, 18 (72.0%) were recovering or had recovered, 7 (28.0%) patients had not recovered There were no statistical differences in the number of cases for IV or oral users and for users or not of chemotherapeutic agents. Compared with other AEDs, ondansetron was associated with an increase in the reporting risk of blindness-related ADRs (ROR = 4.00 [2.79-5.72], p < 0.001). CONCLUSIONS: Rarely blindness can occur following intravenous or oral administration of ondansetron.

Early treatment with atorvastatin exerts parenchymal and vascular protective effects in experimental cerebral ischaemia.

BACKGROUND AND PURPOSE: From the clinical and experimental data available, statins appear to be interesting drug candidates for preventive neuroprotection in ischaemic stroke. However, their acute protective effect is, as yet, unconfirmed. EXPERIMENTAL APPROACH: Male C57Bl6/JRj mice were subjected to middle cerebral artery occlusion and treated acutely with atorvastatin (10-20 mg·kg(-1) day(-1) ; 24 or 72 h). Functional recovery (neuroscore, forelimb gripping strength and adhesive removal test) was assessed during follow-up and lesion volume measured at the end. Vasoreactivity of the middle cerebral artery (MCA), type IV collagen and FITC-dextran distribution were evaluated to assess macrovascular and microvascular protection. Activated microglia, leucocyte adhesion and infiltration were chosen as markers of inflammation. KEY RESULTS: Acute treatment with atorvastatin provided parenchymal and cerebral protection only at the higher dose of 20 mg·kg(-1) ·day(-1) . In this treatment group, functional recovery was ameliorated, and lesion volumes were reduced as early as 24 h after experimental stroke. This was associated with vascular protection as endothelial function of the MCA and the density and patency of the microvascular network were preserved. Acute atorvastatin administration also induced an anti-inflammatory effect in association with parenchymal and vascular mechanisms; it reduced microglial activation, and decreased leucocyte adhesion and infiltration. CONCLUSIONS AND IMPLICATIONS: Acute atorvastatin provides global cerebral protection, but only at the higher dose of 20 mg·kg(-1) ·day(-1) ; this was associated with a reduction in inflammation in both vascular and parenchymal compartments. Our results suggest that atorvastatin could also be beneficial when administered early after stroke.

[Systemic adverse effects of topical ocular instillation of atropine in two children]. / Effets systémiques des collyres mydriatiques atropiniques chez deux enfants.

A medication-related cause must be sought when unusual symptoms occur. Topical treatments, including eye drops, whose side effects are more common in exposed children, need to be verified. We report here the cases of two children who developed systemic symptoms after the administration of atropine-based mydriatic eye drops. A 6-month-old boy was admitted to the emergency department with acute urine retention lasting 36h. Investigations identified only eye drop treatment 3h before the onset of symptoms, with 2 drops of homatropine 1 %, as a cause. No other urinary retention was observed during the 1-year follow-up. A 2-year-old boy was admitted to the emergency department for drowsiness, thirst, and dry mouth 30min after the administration of three eye drops of atropine 1 % instead of atropine 0.3 % (error made by the pharmacy). Symptoms disappeared after 6h. Both observations highlight the possible side effects related to mydriatic eye drops. Indeed, because of small penetration of such medications in the eye, a high concentration of the active part of the medication is contained in each drop. In young children, at least 20 to 40 % of the volume of a drop drains into the nasolacrimal duct and thereby into the systemic circulation, without passage through the liver. A close national pharmacologic vigilance follow-up has been set up for atropine-based mydriatic eye drops in young children, who are the most exposed to systemic and potentially severe complications of these medications. We emphasize the appropriate procedure for the use of eye drops in young children to limit systemic passage, with only a 0.3 % maximum atropine concentration in infants, compression of the internal angle of the eye for at least 1min, and at least a 15-mins interval between two eye drop administrations.