Adverse Drug Reactions Related to Drug Administration in Hospitalized Patients.

INTRODUCTION: Drug treatment may be related to the development of adverse drug reactions (ADRs). AIM: In this paper, we evaluated the ADRs in patients admitted to Catanzaro Hospital. METHODS: After we obtained the approval by local Ethical Committee, we performed a retrospective study on clinical records from March 01, 2013 to April 30, 2015. The association between drug and ADR or between drug and drug-drug-interactions (DDIs) was evaluated using the Naranjo's probability scale and Drug Interaction Probability Scale (DIPS), respectively. RESULTS: During the study period, we analyzed 2870 clinical records containing a total of 11,138 prescriptions, and we documented the development of 770 ADRs. The time of hospitalization was significantly higher (P<0.05) in women with ADRs (12.6 ± 1.2 days) with respect to men (11.8± 0.83 days). Using the Naranjo score, we documented a probable association in 78% of these reactions, while DIPS revealed that about 22% of ADRs were related to DDIs. Patients with ADRs received 3052 prescriptions on 11,138 (27.4%) having a mean of 6.1±0.29 drugs that was significantly higher (P<0.01) with respect to patients not experiencing ADRs (mean of 3.4±0.13 drugs). About 19% of ADRs were not diagnosed and were treated as new diseases. CONCLUSION: Our results indicate that drug administration induces the development of ADRs also during the hospitalization, particularly in elderly women. Moreover, we also documented that ADRs in some patients are under-diagnosed, therefore, it is important to motivate healthcare to report the ADRs in order to optimize the patients' safety.

Reactivation of chronic hepatitis B during treatment with tenofovir disoproxil fumarate: drug interactions or low adherence?

We describe a case of a 61-year-old man with chronic hepatitis B, hepatitis B e antibody (HBeAb) positive, treated with tenofovir disoproxil fumarate (TDF), who developed virological and biochemical viremic reactivation with an increase in transaminase plasma levels. The patient's history revealed that he had discontinued TDF about 5 days before admission and, from December 2013, had been taking venlafaxine, paroxetine and zolpidem for some episodes of depression. Clinical evaluation and laboratory findings excluded the presence of systemic diseases that might have been able to explain the drug inefficacy, while pharmacological evaluation suggested a possible drug-drug interaction. In order to assess the possible occurrence of resistance, mutational analysis of hepatitis B virus (HBV) was performed and excluded the presence of resistance for TDF. TDF was prescribed, and venlafaxine, paroxetine and zolpidem were discontinued. The follow-up at 3, 6 and 12 months documented a good response to TDF with a time-related decrease of HBV-DNA and alanine aminotransferase.

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.

Drug-drug interactions: antiretroviral drugs and recreational drugs.

With the advances in antiretroviral (ARV) therapy, patients with Human Immunodeficiency Virus (HIV) infection are living longer, however, some patients encounter co- morbidities which sometimes require treatment. Therefore, during the treatment with ARV drugs these patients could take several recreational drugs (e.g. amphetamines, hallucinogenes, opiates, or alcohol) with a possible development of drug-drug interactions (DDIs). In particular, Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) are mainly excreted through the kidney and are not substrates of the cytochrome P450 or P-glycoprotein, therefore the DDIs during this treatment are minimal. In contrast, the other ARV drugs (i.e. non-nucleoside reversetranscriptase inhibitors, Protease inhibitors, Integrase inhibitors, chemokine receptor 5 antagonists and HIV-fusion inhibitors) are an important class of antiretroviral medications that are frequent components of HAART regimens but show several DDIs related to interaction with the cytochrome P450 or P-glycoprotein. In this paper we will review data concerning the possibility of DDI in HIV patients treated with ARV and taking recreational drugs.

Chronic HCV infection increases cardiac left ventricular mass index in normotensive patients.

BACKGROUND & AIMS: Left ventricular hypertrophy (LVH), is an independent predictor for cardiovascular events. We investigated if chronic hepatitis C virus (HCV) infection and the related insulin resistance (IR)/hyperinsulinemia could influence the increase of left ventricular mass (LVM). METHODS: We enrolled 260 outpatients matched for age, body mass index, gender, ethnicity: 52 with never-treated uncomplicated chronic HCV infection (HCV(+)), 104 never-treated hypertensives (HT) and 104 healthy subjects (NT). LVM was calculated according to the Devereux formula and indexed for body surface area. The following laboratory parameters were measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, e-GFR-EPI, HOMA. Quantitative HCV-RNA was assessed by PCR. RESULTS: HCV(+) patients with respect to healthy normotensive subjects had an increased LVMI (100 ± 23 vs. 83 ± 15 g/m(2); p < 0.0001), similar to that observed in HT group (103 ± 25 g/m(2)). Regarding biochemical variables, HCV(+) patients, in comparison with normotensive healthy subjects, had higher triglyceride, creatinine, fasting insulin and HOMA (3.2 ± 1.3 vs. 2.5 ± 1.0; p < 0.0001). At linear regression analysis, the correlation between LVMI and HOMA was similar in HT (r = 0.528, p < 0.0001) and HCV(+) (r = 0.489, p < 0.0001) groups. At multiple regression analysis, HOMA resulted the major determinant of LMVI in all groups, explaining respectively 21.8%, 27.8%, and 23.9% of its variation in NT, HT and HCV(+). At correlational analysis HCV-RNA and HOMA demonstrated a strong and linear relationship between them, explaining the 72.4% of their variation (p = 0.022). CONCLUSIONS: We demonstrated a significant and direct correlation between HOMA and LVMI in patients with chronic HCV infection, similar to that observed in hypertensives.

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.

Annual report on adverse events related with vaccines use in Calabria (Italy): 2012.

Vaccines are administered to large population of healthy individuals, particularly to millions of infants every year, through national immunization programs. Although vaccines represent a good defense against some infectious diseases, their administration may be related with the development of adverse vaccine events (AVEs); therefore their use is continually monitored to detect these side effects. In the presents work, we reported the suspected AVEs recorded in 2012 in Calabria, Italy. We performed a retrospective study on report forms of patients that developed AVEs in Calabria from January 1, 2012 to December 31, 2012. Naranjo score was used to evaluate the association between AVEs and vaccines and only suspected AVEs definable as certain, probable, or possible were included in this analysis. During the study period, we evaluated 461 records of adverse drug reactions (ADRs) and 18 (3.9%) were probably induced by vaccination. AVEs were common in females (almost 77.7%) and in children aged 0-3 years. The largest number of non-serious AVEs involved "skin and subcutaneous tissue disorders" and "general disorders and administration site conditions." In conclusion, we documented that in Calabria the total number of AVEs is very low and it may be useful to increase the pharmacovigilance culture in order to evaluate the safety of these products in large populations.

Limitations and obstacles of the spontaneous adverse drugs reactions reporting: Two "challenging" case reports.

INTRODUCTION: Nowadays, based on several epidemiological data, iatrogenic disease is an emerging public health problem, especially in industrialized countries. Adverse drugs reactions (ADRs) are extremely common and, therefore, clinically, socially, and economically worthy of attention. Spontaneous reporting system for suspected ADRs represents the cornerstone of the pharmacovigilance, because it allows rapid detection of potential alarm signals related to drugs use. However, spontaneous reporting system shows several limitations, which are mainly related to under-reporting. In this paper, we describe two particular case reports, which emphasize some reasons of under-reporting and other common criticisms of spontaneous reporting systems. MATERIALS AND METHODS: We performed a computer-aided search of Medline, PubMed, Embase, Cochrane library databases, national and international databases of suspected ADRs reports in order to identify previous published case reports and spontaneous reports about the ADRs reviewed in this paper, and to examine the role of suspected drugs in the pathogenesis of the described adverse reactions. RESULTS: First, we reported a case of tizanidine-induced hemorrhagic cystitis. In the second case report, we presented an episode of asthma exacerbation after taking bimatoprost. Through the review of these two cases, we highlighted some common criticisms of spontaneous reporting systems: under-reporting and false causality attribution. DISCUSSION AND CONCLUSION: Healthcare workers sometimes do not report ADRs because it is challenging to establish with certainty the causal relationship between drug and adverse reaction; however, according to a key principle of pharmacovigilance, it is always better to report even a suspicion to generate an alarm in the interest of protecting public health.

Nexavar(®)-related adverse reactions: Calabrian (Italy) experience for sorafenib exposition in 2012.

Hepatocellular carcinoma (HCC) remains a major global health problem and Calabria in the south of Italy is not an exception. Sorafenib is the first and only Food and Drug Administration approved drug for the treatment of advanced HCC and it is currently under intensive monitoring by the Health Authorities in Italy Agenzia Italiana del Farmaco. This general report has been developed with the aim of briefly reviewing the data found in the reports of adverse reactions (ADRs) collected in Calabria in 2012 for sorafenib treated patients. Extrapolated data have highlighted some differences between the adverse drug reactions reported in patients younger or older than 70 years and other important differences with the current approved leaflet. Several limitations might be present in data analysis form spontaneous reporting, however, the relevance of reporting ADRs (dermatitis, asthenia, vomiting, etc.) for the early identification of drug related signals has to be underlined.

Diagnosis and follow-up of Bartonella henselae infection in the spleen of an immunocompetent patient by real-time quantitative PCR.

Systemic Bartonella henselae infections are unusual in immunocompetent adults. However, here we report one such case of bartonellosis in a 34-year-old patient, who presented with fever and multinodular splenomegaly. We also describe a novel method of identifying Bartonella henselae by real-time quantitative polymerase chain reaction and sequencing of amplified products. This could prevent splenic bartonellosis being mistaken for lymphoma and thereby avert unnecessary splenectomy.

Hepatitis C virus infection in an endemic area of Southern Italy 14 years later: evidence for a vanishing infection.

BACKGROUND: In a 1996 survey, prevalence of hepatitis C virus antibodies (anti-HCV) in a southern Italian town was 12.6%. AIMS: To identify changes in the epidemiology of hepatitis C virus (HCV) infection. METHODS: Anti-HCV, HCV-RNA (PCR, detection limit 15 IU/mL), HCV genotype (Innolipa). Were performed in a random 1:4 systematic sample of the general population. Multiple logistic regression analysis was used to estimate factors independently associated with the likelihood of anti-HCV positivity. RESULTS: Of 1012 subjects, 58 (5.7%) were anti-HCV-positive, compared to 12.6% 14 years earlier. Prevalence was 0.4% in individuals <30 years old and 31.8% in those ≥ 70 years old. Among 139 HCV-negative in 1996 re-sampled in 2010, only one had seroconverted (incidence: 0.05 × 100 persons/year). Alanine transaminase levels were elevated in 8 (13.8%). HCV-RNA was detected by PCR in 46.5% anti-HCV-positive subjects. In 2010 59% were genotype 2-infected, in 1996 50.7% genotype 1-infected. Previous use of non-disposable glass syringes was a strong independent predictor (OR 3.2; CI 95%=1.4-7.3). CONCLUSION: Epidemiology of HCV infection in an endemic area of south Italy has changed over 14 years, now largely confined to the oldest age group; this seems to be due to the disappearance of its past main mode of transmission, namely the use of glass syringes.

The impact of a vaccination campaign against hepatitis B on the further decrease of hepatitis B virus infection in a southern Italian town over 14 years.

BACKGROUND: Hepatitis B virus infection has decreased in Italy. The aims of this study were to identify changes, if any, in the epidemiological pattern of HBV infection in a southern Italian town first surveyed in 1996 and to assess the effectiveness of vaccination campaign against hepatitis B. METHODS: In 2010, subjects were selected from the census by a systematic 1:4 random sampling procedure. Hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B core antigen (anti-HBc) were detected by ELISA. Associations (odds ratios) linking exposure to hepatitis B virus infection to potential risk factors were estimated by univariate and multivariate analyses. RESULTS: Of the 1100 eligible subjects, 1020 (92.0%) agreed to participate. The prevalences of HBsAg (0.6%) and anti-HBc (15.2%) were significantly lower than in 1996 (0.8% and 21.5%) (p<0.01). No subject below 30 years of age (those that had been targeted for compulsory immunization) had been exposed to HBV infection. At multiple logistic regression analysis, age>45 years (OR=9.8; 95% CI=5.1-18.7) and past use of glass syringes (OR=1.9; 95% CI=1.2-3.1) independently predicted the likelihood of anti-HBc positivity. CONCLUSIONS: These results, albeit obtained in a small town and thus not generalizable, confirm the continuous decreasing trend of HBV infection and demonstrate the effectiveness of the Italian hepatitis B vaccination program.

Pharmacovigilance and drug safety 2011 in Calabria (Italy): Adverse events analysis.

BACKGROUND: Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs). The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco) is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. MATERIALS AND METHODS: We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. RESULTS: Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100) in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %). Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%). There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it), and there is a strong interest in participating to training courses in the field (95% are interested). CONCLUSIONS: Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.

Muscular damage during telbivudine treatment in a chronic hepatitis B patient.

Muscle tissue damage might be related to metabolic and mechanical factors. Certain drugs have been associated with increased blood levels of creatin phospho kinase (CPK) and myoglobin that are biochemical markers of musculoskeletal damage. An increase of CPK plasma levels might suggest severe rhabdomyolysis with possible resulting renal failure. Telbivudine is an antiviral drug indicated for the treatment of chronic hepatitis B (CHB) in adult patients. An increase in CPK plasma levels has been recently described in some telbivudine-treated CHB patients without muscle-skeletal symptoms. In this paper we report a CHB patient that developed a severe increase of CPK plasma levels during telbivudine-treatment. Pharmacological evaluation, using the Naranjo probability scale, indicated a probable relationship between telbivudine and CPK increase, so telbivudine was discontinued and replaced with entecavir with a complete resolution of laboratory findings. In conclusion, telbivudine treatment can induce muscular damage in the absence of skeletal injury, therefore we suggest to closely monitor the muscular function of the patients treated with this drug in order to prevent possible major complications.

Hepatotoxicity induced by methimazole in a previously healthy patient.

We report a case of hepatotoxicity induced by methimazole treatment in a patient affected by hyperthyroidism. A 54-year-old man, presented to our observation for palpitations, excessive sweating, weakness, heat intolerance and weight loss. On physical examination, his blood pressure was 140/90 mmHg and heart beat was 100/min regular. He had mild tremors and left exophthalmos. Laboratory test revealed a significant increase in serum thyroid hormone levels with a decrease in thyroid stimulating hormone levels. A diagnosis of hyperthyroidism was made and he began treatment with methimazole (30 mg/day). Fourteen days later, he returned for the development of scleral icterus, followed by dark urine, and abdominal pain in the right upper quadrant. Laboratory examinations and liver biopsy performed a diagnosis of cholestatic hepatitis, secondary to methimazole usage. Methimazole was promptly withdrawn and cholestyramine, ursodeoxycholic acid, and chlorpheniramine were given. After five days, abdominal pain resolved and laboratory parameters returned to normal. Naranjo probability scale indicated a probable relationship between hepatotoxicity and methimazole therapy. In conclusion physicians should be aware the risk of hepatotoxicity related with methimazole.