Comparative safety profiles of intravitreal bevacizumab, ranibizumab and pegaptanib: the analysis of the WHO database of adverse drug reactions.

PURPOSE: The purpose of this study is to conduct a comparative analysis of the suspected adverse drug reactions (ADRs) associated with intravitreal bevacizumab, ranibizumab and pegaptanib in the WHO database in order to have a real-life information on these drugs, which now is only based on data coming from clinical trials. METHODS: ADR reports for intravitreal use of bevacizumab, ranibizumab and pegaptanib from January 2002 to December 2012 were selected from the WHO-VigiBase. Reporting odds ratio (ROR) with confidence interval of 95 % and p value was calculated. The analysis was performed for drug-reaction pairs. The Medical Dictionary for Regulatory Activities (MedDRA) terminology for ADRs was used. RESULTS: The analysis was performed on 3180 reports corresponding to 7753 drug-reaction pairs. Significant RORs for endophthalmitis and uveitis (1.90, 95 % confidence interval (CI) 1.48-2.43, and 10.62, 6.62-17.05, respectively) were retrieved for bevacizumab, and cerebrovascular accident and myocardial infarction produced significant ROR (1.54, 1.14-2.10 and 1.73, 1.18-2.53, respectively) for ranibizumab. Pegaptanib was significantly associated with visual impairment (1.98, 1.12-3.5, p = 0.02), nausea (3.29, 1.57-6.86, p < 0.001), vomiting (2.91, 1.2-7.07, p = 0.01) and drug hypersensitivity (8.75, 3.1-24.66, p < 0.001). CONCLUSIONS: Our data showed an elevated disproportionality for cardiovascular ADRs in patients treated with ranibizumab and for infective ocular reactions in those treated with bevacizumab. No relevant safety issues were identified for pegaptanib. These findings suggest bevacizumab as a suitable choice for AMD therapy due to its effectiveness similar to that of ranibizumab, its favourable safety profile and for its lower cost.

Use and safety profile of antiepileptic drugs in Italy.

OBJECTIVE: To analyse and discuss the use and the safety profile of individual antiepileptic drugs (AEDs) in Italy. METHODS: The AED safety data referred to the period January 1988-June 2005 and were obtained from the database of the Italian Interregional Group of Pharmacovigilance (GIF). This database collects all spontaneous reports of suspected adverse drug reactions (ADRs) from six Italian regions which are the main contributors to the Italian spontaneous reporting system. Individual AED consumption data (defined daily dose/1,000 inhabitants per day) in the GIF area and in the whole of Italy referred to the period January 2003-June 2005 and were derived from drug sales data (Institute for Medical Statistics Health). RESULTS: Phenobarbital was the most frequently used AED in the GIF area (4.26 DDD/1,000 inhabitants per day) followed by carbamazepine (1.97), valproic acid (1.33) and gabapentin (1.10). AED consumption in the whole of Italy showed a similar pattern. Gabapentin was the most frequently used AED among newer AEDs. In the GIF database 37,906 reports (up to June 2005) were present; 666 of them (1.76%) were associated with at least one AED (Anatomical Therapeutic Chemical code N03A). The AED with the highest number of reports was carbamazepine (208 reports) followed by phenobarbital (98), gabapentin (80), phenytoin (56), valproic acid (55), lamotrigine (51), oxcarbazepine (43) and vigabatrin (35). Use and toxicity profile were evaluated only for AEDs associated with at least 30 reports. Skin reactions were the most frequently reported ADRs, followed by haematological, general condition, hepatic, neurological and gastrointestinal adverse reactions. Phenobarbital, lamotrigine, carbamazepine and phenytoin had the highest percentage of skin reactions (69, 67, 60 and 54%, respectively). Many haematological reactions were reported for each AED; the highest percentage was related to valproic acid (25%). Vigabatrin was associated with the highest percentage of reactions related to hearing, vision and other senses (97%). Phenytoin and valproic acid had the highest percentage of hepatic reactions (30 and 20%), whereas gabapentin of nervous system, psychiatric, gastrointestinal and urinary reactions (26, 21, 21 and 14%, respectively) and phenobarbital of musculoskeletal reactions (13%). CONCLUSIONS: In Italy antiepileptic drug therapy appears to be still dominated by traditional drugs. Our analysis showed a different safety profile related to each AED. Some of the drug-adverse reaction associations discussed are not included in the Italian drug leaflets or have not been reported before in the literature.

Use of anti-asthmatic drugs in Italy: analysis of prescriptions in general practice in the light of guidelines for asthma treatment.

UNLABELLED: Our aim was to analyse anti-asthmatic drug utilisation in primary health care in a Northern Italian region in the light of guidelines for asthma treatment. METHODS: We collected all prescriptions for anti-asthmatic agents reimbursed in 1998 in six local health authorities (overall population: 1,909,192 inhabitants) of Emilia Romagna (Northern Italy). The asthmatic cohort was defined as the population of subjects aged 20-44 years receiving at least one prescription of an anti-asthmatic agent devoid of indications for transient respiratory diseases. In order to include routine users, the asthmatic cohort was restricted to those subjects with at least one prescription in the first quarter of 1998. Anti-asthmatic agents were classified according to their therapeutic role as follows: maintenance therapy for mild-moderate asthma (Mm); maintenance therapy for severe asthma (Ms); quick relief for mild attack (Qm) and quick relief for severe attack (Qs). RESULTS: The asthmatic cohort included 11,518 subjects; of these, 47% received only one prescription in 1998. The most frequent regimens were Mm+Qm (25%) and Qm alone (23%). Some regimens appeared not to be in accordance with international recommendations. The main reasons were lack of drugs for quick relief (36%), use of long-term beta(2)-adrenoceptor agonists (Ms drugs) without quick-relief or anti-inflammatory agents (10% of the cohort and 56% of the recipients of Ms drugs) and presence of fixed-dose combinations (27%). In 76% of the patients treated with Mm drugs (mainly inhaled steroids), the total amount of drugs prescribed over the 1-year period covered less than 150 days. CONCLUSIONS: The use of anti-asthmatic drugs in general practice in Italy does not seem to comply with the international recommendations especially with regard to the use of quick-relief agents. Active interventions to implement guidelines and monitor the choice of drug regimens are warranted.

[Myocardial perfusion evaluated with a 2-isotope technique. Experience with the first 1600 cases in Mexico]. / Perfusión miocárdica valorada con técnica de dos isótopos. Experiencia de los primeros 1600 casos en México.

SPECT has a high sensitivity for the diagnosis of coronary artery disease. Dual isotope protocol using rest thallium and stress MIBI was introduced in Mexico 4 years ago. This protocol reunite the advantages of both radiotracers for the study of myocardial perfusion. We present our experience of the first three years. One thousand six hundred patients were studied with suspected myocardial ischemia; 288 were excluded because of an absence of a proper follow up. In 895 of the 1312 patients a coronariography was performed. Images were evaluated by dividing the heart in 20 segments using a 5 points scale (0 = normal to 4 = absence of perfusion). It was considered a perfusion defect when a segment had a score greater or equal to 2 and the SPECT study was considered abnormal if two or more segments had a MIBI stress score equal or greater than 2. The global sensitivity for diagnosis of ischemia was 96.28%. Dual isotope method is appropriate for the diagnosis of ischemic heart disease. It has a high sensitivity and specificity for the recognition of global coronary disease and for specific coronary territories. This work constitutes the greatest series in Latin America that uses this diagnosis method.