Current Drug Safety - Volume 6, Issue 4, 2011

Zopiclone (7.5 mg) is frequently used as a positive control in studies that examine the residual effects of hypnotic drugs on driving ability and related skills. This review summarizes studies examining the effects of zopiclone, and discusses its usefulness as a comparator drug for investigations of residual effects of novel sleep medication. A literature review (Pubmed and Embase) was conducted searching for studies that tested zopiclone on driving. Cross references were checked for additional papers. Eight studies utilizing the standardized on-the-road driving test consistently showed that in the morning following bedtime administration zopiclone (7.5 mg) significantly impaired driving performance. A total of 191 healthy volunteers were tested after placebo and zopiclone (7.5 mg). Meta analyses showed no significant differences in driving performance after zopiclone (7.5 mg) between adult and elderly healthy volunteers. The combined effect size (ES) and 95% confidence interval (95%CI) for healthy volunteers was 0.782 (0.620, 0.944). Relative to placebo, an average increment of 3.0 cm in Standard Deviation of Lateral Position (SDLP) was observed when treated with zopiclone (7.5 mg). This deviation was higher than the increment in SDLP reported for drivers with a blood alcohol concentration of 0.05% (+2.4 cm). Results from driving simulators and psychometric tests are consistent with the on-road driving test results. In conclusion, zopiclone (7.5 mg) is a reliable positive control, that consistently shows significant and meaningful impairment on the on-the-road driving test.

Erectile dysfunction (ED) is often associated with cardiovascular disease (CVD) and the risk of sildenafilinduced orthostatic hypotension (OH) in subjects with CVD is a matter of concern. We describe our experience in using the tilt test (TT) with continuous plethysmography to evaluate the occurrence of OH in patients with CVD and ED after a test dose of sildenafil. When sildenafil was added on top of their usual pharmacological treatment two patients out of 32 (6.2%) developed asymptomatic OH, with a maximum blood pressure fall of 40/20 mm Hg. The low prevalence and modest clinical relevance of OH in our high-risk population coupled with the known high sensitivity and reproducibility of the TT seem to suggest that sildenafil is haemodynamically safer than is generally believed even when added on top of vasoactive treatment. These findings should be put into perspective against the growing wealth of evidence that PDE5 inhibitors may have therapeutic potential for a number of CV conditions.

Purpose: The objective of the present study was to quantify the reported cardiovascular adverse reactions and adverse reactions to cardiovascular drugs to help to design and implement monitoring and prevention strategies. Methods: The pharmacovigilance unit (PU) is a peripheral effector of National Pharmacovigilance Center and receives adverse drug reactions notifications from 10 teaching hospitals. Data on adverse reactions beginning in 2004 and notified to the PU were extracted from the database. Cardiovascular adverse drug reactions and adverse reactions to cardiovascular drugs were identified using Medical Dictionary for Regulatory Activities (MedDRA), and the Anatomical Therapeutic Chemical (ATC) Classification System respectively. The reports of adverse reactions were classified according to their seriousness. Results: From 2004 to 2010, 2516 notifications were received (2383 adverse reactions, 106 lack of efficacy, 26 quality failures). These notifications included 151 cardiovascular adverse reactions and 594 adverse reactions caused by cardiovascular drugs. In the first group, of the 151 cardiovascular adverse reactions through MedDRA SOC classification caused by all ATC group classes, 118 (78.2%) were caused by non cardiovascular drugs. Among them antimicrobials (27,2%) and neurologic drugs (21,2%) were the most frequent. 22 (14.6%) adverse reactions were serious. Long QT syndrome, peripheral edema, hypotension, tachycardia, and bradycardia, were the most frequent. In the second group, of the 594 reports identifying adverse reactions involving all MedDRA SOCs but caused only by cardiovascular drugs, 559 reports (94.1%) were non cardiovascular adverse reactions. Enalapril and furosemide accounted for 65.2% there were 33 (5.6%) serious adverse reactions. The most frequent adverse reactions were hyponatremia, impaired renal function, hypokalemia, metabolic alkalosis, asymptomatic elevation of liver enzymes, hyperkalemia, hyperglycemia, edema, and cough. Conclusion: Non-cardiovascular adverse reactions were the most frequent manifestation of adverse drug reactions caused by cardiovascular drugs and cardiovascular adverse reactions were most often caused by non cardiovascular drugs. This report highlights the importance of systematic evaluation of adverse drug reactions.

Introduction: Monitoring and reporting of adverse drug reactions (ADRs) in specialized hospitals provide an important measure to identify and quantify the risks associated with the use of specific drugs. Aims: This study aimed to determine the incidence, pattern, seriousness, and preventability of hospital-acquired ADRs, in medical wards of a pulmonary teaching hospital in Iran. Methods: The study was conducted based on the ADRs reported by clinicians, nurses, and clinical pharmacists between March 2009 and February 2011 to the ADR reporting unit of the hospital. The incidence, pattern, seriousness, and preventability of the reported ADRs were analyzed. Results: During the period of 24 months, for 11975 patients, 306 ADR reports were received. The most frequently reported reactions were due to anti-infective agents (34.08%). Rifampin accounted for the highest number of the reported ADRs among anti-infective agents. The gastro-intestinal system was the most frequently affected system (21.90% of all reactions). Seventy two (23.53%) of the ADRs were reported as serious reactions and twenty-five (8.17%) of the ADRs were classified as preventable. Conclusions: Our study shows that ADRs pattern in our hospital is different from the other studies. Preventive measures have decreased the preventable ADRs and ensured safer drug use. Education and clinical pharmacist interventions have increased the quality and quantity of reported ADRs.

Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were “cannabinoids”, “cannabidiol” and “side effects”. Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects.

Over the past decades, the use of ovulation inducing drugs has been increasing. A possible causal link between fertility treatments (especially clomiphene citrate and gonadotrophins) and various types of malignancies, including cancers of female reproductive system, thyroid cancer and melanoma, has been postulated. The majority of the available studies on this subject suffers from methodological limitations, including the small number of outcomes, short and incomplete follow-up, and inability to control for potential confounders. Concerning ovarian cancer, while early studies led to the suggestion of an association between ovulation inducing agents and increased risk of malignancies, the majority of data do not support a causal link. An increased risk was recently observed in women giving birth after in vitro fertilization (IVF), but it appeared to be consequential to the infertile status rather than the effect of fertility drugs. More controversial are the results concerning breast cancer with some investigations suggesting an increased risk after exposure to ovulation inducing agents, especially clomiphene citrate, whereas others not supporting this concept. A possible trend towards an increased risk has been reported by some authors for endometrial cancer. Altogether, current data should be thus regarded as a signal for the need of further studies rather than being definitive in them.

Data regarding the use of propranolol in pediatrics are limited despite its widespread use in adults. Since 1984, Propranolol has been used for the prevention of portal hypertensive hemorrhage in pediatric patients. Recently it has been also used for the managemnet of hemangiomas in addition to other indications. The purpose of this review is to evaluate safety and efficacy of propranolol use in the pediatric population, highlighting the most important reported side effects, warnings and precautions.

Albumin constitutes approximately one half of the proteins in the plasma and plays a pivotal role in modulating the distribution of fluid between body compartments. Hence it is commonly employed in cirrhotic patients in association with diuretics for the treatment of ascites. Nevertheless, its usefulness is controversial in this condition and well-stated only in some circumstances. The item of safety of the drug appears to be convincing due to the accurate cautions in the course of its preparation. Side effects are described in literature only as sporadic events. Indeed, albumin administration is effective to prevent the circulatory dysfunctions after large-volume paracentesis and renal failure and after Spontaneous Bacterial Peritonitis (SBP). Finally albumin represents, associated with vasoconstrictors, the therapeutic gold standard for the hepatorenal-syndrome (HRS). Physiopathological bases of the therapeutic use of albumin in hepatic cirrhosis consist in both hypoalbuminemia and portal hypertension consequences. In fact, cirrhotic patient with ascites, in spite of hydrosaline retention, shows an effective hypovolemia with peripheral arterial vasodilatation and increase in heart rate. Therefore the effectiveness of albumin administration in the treatment of ascites is due to its plasma volume expander property as well as its efficacy in restoring plasmatic oncotic pressure. Trials are in progress in order to define the effectiveness of the prolonged home-administration of human albumin in the treatment and prevention of ascites. Finally, it has been recently demonstrated that the binding, transport and detoxification capacities of human albumin are severely reduced in cirrhotics and this impairment correlates with the degree of liver failure. Therefore, the next challenge will be to determine whether the alterations of non-oncotic properties of albumin are able to forecast mortality in cirrhotics with ascites and exogenous albumin chronic administration will be effective in predicting and preventing such alterations.

Introduction: The risk of cancer with the use of biologic agents in rheumatic diseases is still a matter of debate. Published data suggest that the extent of cancer risk might differ according to the type of cancer, and there is recent clinical evidence for a significant increased risk for skin cancer, including melanoma. In contrast with the extensive literature on cancer risk in rheumatoid arthritis, little has been reported on the development of malignancies in spondyloarthroparthies. Case Presentation: We report the case of an otherwise healthy 31-year-old Italian woman with psoriasic arthritis who developed a melanoma of left third toe with metastatic involvement of regional lymphnodes after a 3-year treatment with the TNF-alpha inhibitor adalimumab. Conclusion: This case illustrates the possibility of a causal relationship between TNF-alpha inhibitors and melanoma. We believe that vigilance should continue in patients treated with TNF-alpha blocking agents, until the question on the increased incidence of cancers, including skin cancers, associated with these drugs will be defined.