Expert Opinion on Drug Safety

Description

  • Impact factor
    2.62
  • 5-year impact
    2.43
  • Cited half-life
    4.10
  • Immediacy index
    0.66
  • Eigenfactor
    0.00
  • Article influence
    0.74
  • ISSN
    1744-764X

Publications in this journal

  • Mauro D'Amico, Mauro Pagano, Ambra Pasa, Matteo Puntoni, Matteo Clavarezza, Alessandra Gennari, Alberto Gozza, Silvia Zanardi, Carlotta Defferrari, Nicoletta Provinciali, Eleonora Campazzi, Sara Campora, Laura Paleari, Domenico Marra, Marilena Petrera, Andrea de Censi
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    ABSTRACT: Background: The nasal cavity is a vulnerable zone which may be damaged by vascular disorders. We systematically assessed the frequency and severity of nasal cavity alterations during bevacizumab treatment, to determine its clinical relevance and factors contributing to its onset. Patients and methods: We conducted a hospital-based cohort study in 47 consecutive patients with advanced cancers who were on treatment with chemotherapy and bevacizumab at different doses. All patients underwent otolaryngology (ENT) examination at the time of study initiation. Results: The mean number of cycles at first ENT examination was 16 (standard deviation = 14). A total of 45 patients (96%) showed nose mucosal lesions, of whom 30% had erosions and 62% had grade 1 - 2 epistaxis. One patient had septal perforation. Grades 1 - 4 sinus disorders were noted in 60%. There was a significant trend to a higher risk of grade ≥ 2 nasal events for bevacizumab doses > 7.5 mg/kg, concomitant taxane use and digital nasal self-manipulation. Conclusions: We found a high incidence of nasal cavity lesions in patients receiving bevacizumab, with evidence for a dose-related effect. Most cases were low grade and manageable without drug interruption, but severe toxicity may rarely occur. Oncologists should be aware of this unusual event.
    Expert Opinion on Drug Safety 09/2014;
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    ABSTRACT: Introduction: 5-Hydroxytryptamine3-receptor antagonists (5-HT3-RA) are the most widely used antiemetics in oncology, and although tolerability is high, QTC prolongation has been observed in some patients.Areas covered: The purpose of this article is to outline the risk of cardiac adverse events (AEs) from 5-HT3-RAs, with focus on the three most commonly used, ondansetron, granisetron and palonosetron.Expert opinion: Most of the studies analyze electrocardiogram (ECG) changes after 5-HT3-RA administrations in healthy, young adults, or in noncancer patients to treat postoperative nausea and vomiting (PONV). Only a few studies have addressed ECG changes in cancer patients treated for chemotherapy-induced nausea and vomiting (CINV). Investigations in cancer patients are essential, because these patients are older and have a higher incidence of comorbidity, than those usually included in clinical trials. Furthermore, polypharmacy is frequent and drug–drug interactions between chemotherapy and other QTc-prolonging drugs may influence the pharmacokinetics and pharmacodynamics of the 5-HT3-RAs. During the next 10 – 15 years a huge increase in the number of cancer patients is expected, primarily in the group of 65-plus-year old. Therefore it will be crucial to address the incidence of cardiac AEs in cancer patients with known heart disease receiving chemotherapy and a 5-HT3 RA for the prophylaxis of CINV.
    Expert Opinion on Drug Safety 09/2014;
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    ABSTRACT: Introduction: Sleep and awake bruxism is defined as ‘a parafunctional activity including clenching, bracing, gnashing, and grinding of the teeth’. Some evidence suggests that bruxism may be caused by, or associated with, alterations in the CNS neurotransmission. Several classes of psychotropic drugs interfering with CNS activity may potentially contribute to bruxism. Thus, the purpose of this study was to examine relevant peer-reviewed papers to identify and describe the various classes of psychotropic substances that may cause, exacerbate or reduce bruxism as the result of their pharmacological action in CNS neurons.Areas covered: A literature search from 1980 to the present was performed using PubMed database. The term ‘bruxism’ was used in association with ‘psychotropic’, ‘dopamine (DA)’, ‘serotonin’, ‘histamine’, ‘antipsychotics’, ‘antidepressants’, ‘antihistaminergics’ and ‘stimulants’.Expert opinion: Studies on the effects of DA agonists (Levo-DOPA, psychostimulants) and antagonists (antipsychotics) identified a central role of DA in the pathogenesis of pharmacologically induced bruxism. Important information from studies on drugs acting on serotonin neurotransmission (antidepressants) was recognized. Other mechanisms involving different neurotransmitters are emerging. This is the case of antihistaminergic drugs which may induce bruxism as a consequence of their disinhibitory effect on the serotonergic system.
    Expert Opinion on Drug Safety 09/2014;
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    ABSTRACT: Introduction: Assessment of the metabolic safety of second-generation antipsychotics (SGAs) is mandatory in pregnant women, where the occurrence of metabolic complications and, especially, gestational diabetes mellitus (GDM) may severely impact on pregnancy and fetal outcomes. Areas covered: The aim of this article is to review published data reporting the occurrence of GDM during SGA treatment, and to establish whether or not this iatrogenic complication is a relevant concern in clinical practice. Medical literature information published in any language since 1996 was identified using MEDLINE/PubMed, EMBASE, Scopus, and The Cochrane Library. All articles reporting metabolic complications in pregnancies exposed to single, specific SGAs were acquired, without methodological or language limitations. Expert opinion: Among studies assessing the metabolic safety of specific SGAs, we have 18 cases of GDM overall: 5 cases involve clozapine (CLO), 9 olanzapine (OLA) - the SGA agent that shows the highest number of reported cases of pregnancy exposure - and 2 each for quetiapine and risperidone. Four of these cases, 2 involving CLO and 2 OLA, were complicated by serious fetal and/or neonatal consequences. Such reports of SGA-associated GDM, together with preliminary data coming from retrospective and prospective studies, may represent signals of a potential safety issue.
    Expert Opinion on Drug Safety 09/2014;
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    ABSTRACT: Introduction: In the past two decades, the number of women with autoimmune and inflammatory diseases experiencing a pregnancy has significantly increased in parallel with the enormous advances in the diagnosis and management of these disorders. However, information regarding the safety of immunosuppressive agents comes from case reports and case series and no controlled trials are available.Areas covered: We performed a review of the literature using MEDLINE. The term ‘pregnancy’ was searched in combination with all the principal immunomodulant/immunosuppressive drugs used in rheumatic diseases.Expert opinion: A large number of reports suggest that azathioprine, cyclosporine, hydroxychloroquine and steroids are relatively safe during pregnancy, whereas methotrexate, cyclophosphamide, mycophenolate mofetil and leflunomide are contraindicated. Data about the safety of biological agents are scant, but a growing number of publications suggest that at least TNF inhibitors could be prescribed when benefits outweigh the potential risks. Nevertheless, we cannot draw definite conclusions, as this information has not been confirmed in controlled trials. Prospective registries, some of which are already in place, are invaluable resources to answer many questions, especially on the incidence of fetal malformations. Finally, outcome studies on the offspring especially in regard to immune system and psychomotor development will shed light on long-term safety.
    Expert Opinion on Drug Safety 09/2014;
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    ABSTRACT: Objective: To describe the characteristics of pediatric adverse drug reactions (ADRs) reported in Italian spontaneous reporting database. Methods: Reports of suspected ADRs related to children and adolescents were extracted from 2001 - 2012. After exclusion of duplicates, vaccines and reports containing missing age data, the report characteristics were investigated in terms of implicated drug and adverse drug event across different age-categories. Results: Among 123,129 selected reports, 8338 (6.8%) concerned pediatrics. Of these, 52.2% involved male patients compared to 47.5% female up to the age of 11. After the age of 11 this statistic reversed. 39.4% of pediatric reports were serious and of these, 75.2% required hospitalization mainly in very young children. Most of reports were issued by hospital physicians (61.9%), followed by pharmacists (10.1%), while reports from family pediatricians accounted for 8.1%. The most frequently implicated drug categories were anti-infectives for systemic use (44.9%), drugs for the nervous system (15.6%), and anti-inflammatory drugs (10.2%). The most frequently suspected compounds differed between children and adults and reports for the same drug were likely to be more serious in adults than in children. Conclusions: This ADR reporting system reflects real safety concerns for drugs used in children and emphasizes the need for stratifying analyses by age-subgroup to increase the sensitivity of signal detection procedure.
    Expert Opinion on Drug Safety 09/2014; 13(S1):9-20.
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    ABSTRACT: Introduction: Multiple sclerosis (MS) is a disease that mainly affects young adults who are of reproductive age. MS can lead to severe disability and is associated with worse prognosis in untreated patients. Although MS is not negatively affected by pregnancy itself, it may be a high-risk decision to leave a woman without treatment because she may get pregnant. Areas covered: This paper reviews the literature on pregnancies where the mother was exposed to glatiramer acetate . Few data are available on paternal exposure, but this does not seem to pose a problem due to the pharmacological characteristics of the drug. Only a limited amount of data from individual groups in the world is available in the literature. Expert opinion: TEVA Pharmaceuticals would need to open the database on pregnancy exposure to glatiramer acetate to allow for proper conclusions. Glatiramer acetate is a drug of low risk in pregnancy (category B in the FDA classification) and may be a safe option for the treatment of women of fertile age with MS.
    Expert Opinion on Drug Safety 09/2014;
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    ABSTRACT: Introduction: Recently, incretin-based therapy was introduced for the treatment of type 2 diabetes (T2D). In particular, dipeptidyl peptidase-4 inhibitors (DPP-4i) (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin) play an increasing role in the management of T2D.Areas covered: An extensive literature search was performed to analyze the pharmacological characteristics of DPP-4i and their clinical implications.Expert opinion: DPP-4i present significant pharmacokinetic differences. They also differ in chemical structure, in the interaction with distinct subsites of the enzyme and in different levels of selectivity and potency of enzyme inhibition. Moreover, disparities in the effects on glycated hemoglobin, glucagon-like peptide-1 and glucagon levels and on glucose variability have been observed. However, indirect comparisons indicate that all DPP-4i have a similar safety and efficacy profiles. DPP-4i are preferred in overweight/obese and elderly patients because of the advantages of minimal or no influence on weight gain and low risk of hypoglycemia. For the same reasons, DPP-4i can be safely combined with insulin. However, currently cardiovascular outcomes related to DPP-4i are widely debated and the available evidence is controversial. Today, long-term studies are still in progress and upcoming results will allow us to better define the strengths and limits of this therapeutic class.
    Expert Opinion on Drug Safety 08/2014; 13(S1).
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    ABSTRACT: Objective: Adverse drug reaction (ADR) reporting by patients has a fundamental role in pharmacovigilance. The main objectives of the present study were to assess the impact of a pharmacist-based intervention in promoting direct patient reporting, to evaluate patient ability to identify and report ADRs and to determine their pattern.Research design and methods: The study involved 96 pharmacists in the Campania region of Italy, who interviewed their customers and asked them whether they had experienced an ADR. Patients who had experienced an ADR were invited to complete an ADR reporting form. The quality of completed ADR reporting forms was evaluated before their entry into the Italian Spontaneous Reporting System (Rete Nazionale di Farmacovigilanza [RNF]) and, once entered, their pattern was determined.Results: A total of 18,677 patients were interviewed, and 10.88% had experienced an ADR. After quality control, 54.32% of all reporting forms were entered into the RNF so that patient contribution to spontaneous reporting, null over the years, reached ∼7%. Patients reported mainly non-serious (91.28%) and expected (94.62%) ADRs, and NSAIDs or antibiotics were the most frequently reported drugs.Conclusions: The study shows that pharmacists can have an important role in promoting patient reporting and adds new information on how a patient reporting form should be structured.
    Expert Opinion on Drug Safety 08/2014; 13(S1).
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    ABSTRACT: Objective: Although bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) is well recognized, little is known about it in terms of pathophysiology, epidemiology or management. We analyzed all suspected BRONJ reports sent to the Italian Pharmacovigilance Adverse Event Spontaneous Reporting System (Rete Nazionale Farmacovigilanza [RNF]) to determine their pattern and add new information about this relevant issue.Research design and methods: All suspected BRONJ sent to the RNF between 2003 and 2011 were retrieved. After a case-by-case assessment procedure, we analyzed BP type, BP exposure time and time since last use.Results: Between 2003 and 2011, 555 reports of osteonecrosis of the jaw (ONJ) after BP administration were recorded in the RNF. These events occurred mostly in patients affected by cancer (77.84%) in which zoledronate was the most frequently suspected BP. Most patients experienced ONJ after long-term use of the drug (median time of BP exposure being between 1.3 and 8.8 years). Interestingly, 139 (25.05%) cases of ONJ occurred between 2 and 121 months after BP withdrawal.Conclusion: This study shows that BRONJ can occur much earlier than hitherto reported, adds new data on BRONJ onset following ibandronate treatment and reveals that patients who cease BP-based therapy develop ONJ, raising the question of post-treatment monitoring strategies.
    Expert Opinion on Drug Safety 08/2014; 13(S1).
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    ABSTRACT: Objective: To gain information on safety of drugs used in pediatrics through a 4-year post-marketing active pharmacovigilance program. The program sampled the Italian population and was termed ‘Monitoring of the Adverse Effects in Pediatric population’ (MEAP).Research design and methods: Adverse drug reactions (ADRs) were collected for individuals aged 0 – 17 years treated in hospitals and territorial health services in Lombardy, Tuscany, Apulia and Campania; located to gain an appropriate sampling of the population. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analyzed with respect to time, age, sex, category of ADR, seriousness, suspected medicines, type of reporter and off-label use.Results: We collected and analyzed reports from 3539 ADRs. Vaccines, antineoplastic and psychotropic drugs were the most frequently pharmacotherapeutic subgroups involved. Seventeen percent of reported ADRs were serious; of them fever, vomiting and angioedema were the most frequently reported. Eight percent of ADRs were associated with off-label use, and 10% were unknown ADRs. Analysis of these revealed possible strategies of therapy optimization.Conclusions: The MEAP project demonstrated that active post-marketing pharmacovigilance programs are a valid strategy to increase awareness on pediatric pharmacology, reduce underreporting and provide information on drug actions in pediatrics. This information enhances drug therapy optimization in the pediatric patients.
    Expert Opinion on Drug Safety 08/2014; 13(S1).
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    ABSTRACT: Introduction: Intravitreal injection (IVT) is one of the most common vitreoretinal procedures, a large majority are performed with local anesthesia. The purpose of this study was to investigate the safety to the cornea and anesthetic efficacy of five concentrations of lidocaine gel.Methods: A prospective clinical trial was conducted testing lidocaine gel in five preparations: 2, 3.5, 5, 8 and 12%. Patients with macular degeneration, diabetic edema or retina vein occlusion were scheduled for intravitreal treatment received topical anesthesia with lidocaine gel 5 and 10 min before the procedure. Patients answered the visual analog scale for pain during the procedure. Corneal and conjunctival was evaluated using the Oxford scale.Results: In total, 260 patients were randomized into five groups. The mean pain scores (± standard deviation) were 2.63 (± 1.68) in the 2% group, 2.08 (± 1.35) in the 3.5%; 2.00 (± 1.65) in the 5%, 1.93 (± 1.40) in the 8% and 1.83 (± 1.35) in the 12% group. Mean pain score among all groups was similar (p = 0.077). There was no significant difference between groups in regard to keratitis mean score (p = 0.897).Conclusions: Lidocaine gel at concentrations from 2 to 12% induced similar anesthetic effect for IVTs, without adverse effects on cornea and conjunctiva.
    Expert Opinion on Drug Safety 08/2014;
  • Expert Opinion on Drug Safety 08/2014;
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    ABSTRACT: Introduction: Propylthiouracil (PTU) has been used for the treatment of hyperthyroidism since the 1940s, but over the years reports of significant hepatotoxicity have come forth, particularly in children. This led to a black box warning being issued by the US FDA in 2009, followed by a similar warning by the European Medicines Agency and the United Kingdom Medicines and Healthcare Regulatory Agency later that year. Areas covered: This article provides a concise review of the data on hepatotoxicity associated with the currently available antithyroid drugs: PTU, methimazole (MMI) and carbimazole. The differences in mechanism are examined in detail, as well as clinical presentation, management and monitoring. Use in special populations and trends in use of antithyroid medication are also discussed. Expert opinion: PTU is known to cause severe hepatic failure, particularly in children. Its use in children should be avoided. In adults, it is beneficial to use in the first trimester of pregnancy and thyroid storm. In the rest of the adult population, it should be used with caution. Carbimazole and MMI are associated with less severe hepatic injury and should be preferred when choosing thionamides as a treatment option.
    Expert Opinion on Drug Safety 08/2014;
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    ABSTRACT: There is a well-established relationship between sexual functioning and quality of life. Depression can cause sexual dysfunction (SD) and its treatment can often lead to restoration of sexual functioning. Use of antidepressants has also been associated with SD, with implications for treatment compliance and creation of further distress for the patient. This review evaluates available information regarding SD related to both depression and antidepressant treatment, including literature up to June 2014. It includes eligible published studies that investigated antidepressant-associated SD (AASD). Expert opinion: Depression and SD have a bidirectional association. When screening for depression, baseline sexual functioning should be assessed with validated rating scales. If sexual side effects develop with antidepressant treatment, management options include waiting for spontaneous remission, decreasing the medication dose, switching to an alternative drug or adding an augmentation agent or antidote. Research suggests that bupropion and newer antidepressants exhibit a more favorable SD profile compared with other antidepressants, especially selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors. Bupropion, mirtazapine and buspirone have been studied as augmentation agents/antidotes or substitution agents in management of AASD. Future studies validating genetic factors could enable personal genotyping to guide individualized treatment and also facilitate the development of enhanced therapeutic guidelines to avoid or manage AASD.
    Expert Opinion on Drug Safety 08/2014;
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    ABSTRACT: Introduction: Oral contraceptive pills (OCPs) are the most frequently used form of effective, reversible contraception among women of childbearing potential. In the average risk population, OCPs may offer a protective benefit against ovarian, endometrial and colorectal malignancies. In women at high risk for breast, ovarian, endometrial or colorectal malignancies, the risk–benefit profile is less well studied.Areas covered: In this article, we review pertinent literature on the use of OCPs in patients with genetic susceptibilities due to mutations in BRCA1, BRCA2 or mismatch repair genes implicated in hereditary nonpolyposis colorectal cancer as well as those with a strong family history of malignancies associated with these syndromes.Expert opinion: For women at high risk for ovarian, endometrial and/or colorectal malignancies due to genetic susceptibilities or a strong family history, the possibility of chemoprevention with OCPs may be an attractive option; however, the potential increase in breast cancer, although small, must be considered in clinical decision-making. The ultimate decision to use OCPs in a high-risk woman should be based on a consideration of her specific genetic risk, her age, her reproductive plans and her willingness to consider surgical prophylaxis options.
    Expert Opinion on Drug Safety 08/2014;
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    ABSTRACT: Introduction: ACE inhibitors are first-line therapy in patients with chronic kidney disease (CKD). The main adverse effects of ACE inhibitors are hypotension, renal function impairment and hyperkalemia. Areas covered: This paper reviews evidence from clinical studies regarding adverse effects of ACE inhibitors in patients with CKD. The safety aspects of ACE inhibitors are discussed in relation to their pharmacological action, drug-drug interactions, drug-diet interaction, precautions needed in certain clinical conditions and other adverse effects. Expert opinion: The main adverse effects of ACE inhibitors follow from their interaction with renin-angiotensin-aldosterone system (RAAS)-activity and volume depletion. This interaction can be turned into clinical benefit and increase efficacy of ACE inhibitors by reduction in dietary sodium or adding diuretics. Dual RAAS-blockade is no longer advocated in patients with CKD because of the safety issues, and combination of ACE inhibitors with moderate reduction in dietary sodium intake is a better alternative. The intensified treatment regimens based on ACE inhibitors can potentially improve renoprotection, but increase the risk of adverse effects. Better strategies to address safety concerns are needed. Introduction of clinical rules and safety indicators may help clinicians to identify hazardous co-prescriptions and adverse dietary habits and can decrease the frequency of adverse effects.
    Expert Opinion on Drug Safety 08/2014;
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    ABSTRACT: Introduction: Aripiprazole (ARI) is a second-generation antipsychotic acting as a dopamine-serotonin system stabilizer and partial agonist at D2 receptors. The drug is indicated in several and severe psychiatric disorders which are particularly frequent in women during the childbearing age.Area covered: A systematic review of studies investigating the reproductive safety of ARI.Expert opinion: For first trimester use, reviewed data provide no clear evidence about the safety of the drug for the developing fetus. However, a decline of plasma levels (PLs) throughout the pregnancy compared with PLs before pregnancy was observed. This finding suggests the need to increase the dosage during pregnancy in order to maintain stable PLs. If used during late pregnancy, some signals exist suggesting that ARI may worse neonatal outcomes. Hence, clinicians should consider withdrawing the drug before the last month of pregnancy to reduce the risks of neonatal complications. However, such risks must be weighed against the risks of woman’s symptom deterioration. In any case, parturition should happen in hospitals equipped with well-organized neonatal intensive care units. No information is available on the impact of antenatal exposure to ARI on the main neurodevelopmental milestones. Infant exposure to the drug through maternal milk may increase the risk of insufficient milk production and neonatal somnolence.
    Expert Opinion on Drug Safety 08/2014;

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