Pierandrea Rende

Effects of glucocorticoids and tumor necrosis factor-alpha inhibitors on both clinical and molecular parameters in patients with Takayasu arteritis

Objective: To explore the effect of sequential treatment with glucocorticoid and tumor necrosis factor-alpha inhibitors in patients with Takayasu arteritis (TA). Materials and Methods: In five patients with TA, the effects of the sequential treatment with prednisone for 5-7 months and then with adalimumab (ADA) + methotrexate (MTX) or infliximab + MTX, or with ADA only, for 12 months on both clinical and laboratory findings were evaluated. Results: All treatments improved both symptoms and laboratory parameters without the development of side-effects. Conclusions: It was hypothesized that MMP-9 and neutrophil gelatinase-associated lipocalin could be markers of the response to the treatments.

A Comprehensive Safety Evaluation of Trabectedin and Drug-Drug Interactions of Trabectedin-Based Combinations

Trabectedin (Yondelis®) is a potent marine-derived antineoplastic drug with high activity against various soft tissue sarcoma (STS) subtypes as monotherapy, and in combination with pegylated liposomal doxorubicin (PLD) for the treatment of patients with relapsed platinum-sensitive ovarian cancer. This article reviews the safety and pharmacokinetic profiles of trabectedin. Records were identified using predefined search criteria using electronic databases (e.g. PubMed, Cochrane Library Database of Systematic Reviews). Primary peer-reviewed articles published between 1 January 2006 and 1 April 2014 were included. The current safety and tolerability profile of trabectedin, based on the evaluation in clinical trials of patients treated with the recommended treatment regimens for STS and recurrent ovarian cancer, was reviewed. Trabectedin as monotherapy or in combination with PLD, was not associated with cumulative and/or irreversible toxicities, such as cardiac, pulmonary, renal, or oto-toxicities, often observed with other common chemotherapeutic agents. The most common adverse drug reactions (ADRs) were myelosuppression and transient hepatic transaminase increases that were usually not clinically relevant. However, trabectedin administration should be avoided in patients with severe hepatic impairment. Serious and fatal ADRs were likely to be related to pre-existing conditions. Doxorubicin or PLD, carboplatin, gemcitabine, or paclitaxel when administered before trabectedin, did not seem to influence its pharmacokinetics. Cytochrome P450 (CYP) 3A4 has an important role in the metabolism of trabectedin, suggesting a risk of drug–drug interactions with trabectedin used in combination with other CYP3A4 substrates. Trabectedin has a favorable risk/efficacy profile, even during extended treatment in pretreated patients.

Retrospective evaluation of adverse drug reactions induced by antihypertensive treatment

The use of cardiovascular drugs is related to the development of adverse drug reactions (ADRs) in about 24% of the patients in the Cardiovascular Care Unit. Here, we evaluated the ADRs in patients treated with antihypertensive drugs. The study was conducted in two phases: In the first phase, we performed a retrospective study on clinical records of Clinical Divisions (i.e., Internal Medicine Operative Unit and Geriatric Operative Unit) from January 1, 2012 to December 31, 2012. Moreover from January 1, 2013 to March 30, 2013 we performed a prospective study on the outpatients attending the Emergency Department (ED) of the Pugliese-Ciaccio Hospital of Catanzaro, by conducting patient interviews after their informed consent was obtained. The association between a drug and ADR was evaluated using the Naranjo scale. We recorded 72 ADRs in the Clinical Divisions and six in the ED, and these were more frequent in women. Using the Naranjo score, we showed a probable association in 92% of these reactions and a possible association in 8%. The most vulnerable age group involved in ADRs was that of the elderly patients. In conclusion, our results indicate that antihypertensive drugs may be able to induce the development of ADRs, particularly in elderly women receiving multiple drug treatment. Therefore, it is important to motivate the healthcare providers to understand their role and responsibility in the detection, management, documentation, and reporting of ADRs, as also all the essential activities for optimizing patient safety.

Pharmacovigilance and drug safety in Calabria (Italy): 2012 adverse events analysis

Introduction: Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010. Materials and Methods: We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs. Results: A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar®), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups “41-65” (39.07%) and “over 65” (27.9%) were the most affected. Conclusions: Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed.

Capecitabine-induced, rapid decrease of renal function due to drug dispensing error in a hospital pharmacy.

117 2011 51 117-119 M errors are preventable incidents occurring at any point in a chain of events beginning with prescription writing and continuing to both drug dispensation and administration. It has been well reported that medication errors can decrease patient health status and increase health care costs at every stage of the drug delivery process: prescribing, transcribing, dispensing and administering. The hospital pharmacy’s medication dispensing process represents a source of potential adverse drug events (ADEs). In this article, we report a case of acute renal failure likely induced by capecitabine administration due to a dispensing error in a territorial pharmacy.

The safety of ketoprofen in different ages.

Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID), which acts by blocking cyclooxygenase (COX 1 and 2), an enzyme involved in the production of prostaglandins, messengers in the development of inflammation. All NSAIDs reduce signs of inflammation by blocking this enzyme and therefore prostaglandin production. In Calabria, 3.69% of adverse drug reactions (ADRs) reported in the National Network of Pharmacovigilance concerns the use of ketoprofen; only in one case in which the patient was under the age of 12 years, hospitalization was required for severe episode of pancreatitis. In Italy, Ketoprofen is the 6th drug for ADRs incidence (560 ADRs in the year 2012, of which, 31% are severe). Despite the high rate of spontaneous reporting, it must be considered that ketoprofen is one of the most used NSAIDs; therefore, as it happens for other commonly used drugs (eg, amoxicillin), the total number of ADRs should be related to the therapeutic use. However, it remains the problem of fragile patients (eg, children) and the safety of the drug in different ages. This paper presents a retrospective study on 2012 ADRs reviewing literature on the safety of ketoprofen in the elderly, children, and during pregnancy.

Recurrence of atrial fibrillation after switching from brand to generic atenolol

Beta blockers are the initial treatment for rate control of supraventricular tachyarrhythmia in patients without a history of myocardial infarction or left ventricular dysfunction. In this article we report the recurrence of atrial fibrillation after switching to the generic formulation of atenolol.

An uncommon case of arterial aneurysms association with high plasma levels of Matrix Metalloproteinase-9 and Neutrophil Gelatinase-Associated Lipocalin

Abstract The association of an axillary artery aneurysm and an abdominal aortic aneurysm is extremely rare. In this study, we describe this association in a 69 year-old-man. We measured this patient’s metalloproteinases (MMPs) and Neutrophil Gelatinase - Associated Lipocalin (NGAL) levels over a three years period before the abdominal aortic aneurysm rupture. We speculate that high serium levels of MMPs and NGAL may have a prognostic role and may predict aneurysm rupture in patients with an uncommon association of arterial aneurysms.

The Role of Quetiapinein the Treatment of Alzheimer's Disease

Behavioral and psychological symptoms in dementia (BPSD) include an array of neuropsychiatric symptoms, such as delusions, hallucinations, aggression, and agitation. In recent years, the use of antipsychotics, both conventional and atypical, has been widely debated because of concerns about their safety in treating behavioral disturbances in elderly patients affected with dementia, and the possible risks for stroke and sudden death. In this review we described the pharmacokinetic of quetiapine, its correlation in patients with Alzheimer’s disease and its possible role in BPSD. Quetiapine has a bioavailability of 5-13%, about 83% is bound to plasma protein and is largely metabolized in the liver through CYP3A4, the mean plasma half-life is about 6 hand clearance is reduced by 40% in the elderly. Usually CYP3A4 inhibitors are able to increase the plasma levels of quetiapine, while CP3A4 inducers accelerating the drug clearance reduce the quetiapine plasma levels. Quetiapine does not affect metabolism of other compounds known to be metabolized by CYP system. Studies showing its effectiveness for treating BPSD and the authors’clinical experience are reported too. In conclusion, quetiapine appears to be effective for treating BPSD