Deepti Chopra

Physician's guide to pharmacovigilance: Terminology and causality assessment

Adverse drug events can range from mild to life threatening reactions resulting in inconvenience or serious morbidity and mortality besides being a financial burden on the society. However clinicians often do not recognize this drug related harm. The terms used to describe these events with medication use cause much confusion. Moreover manifestations of adverse drug reactions can be non-specific making it difficult to differentiate from current illness. To determine the likelihood of relationship between the drug and the event assessment of causality is done. The purpose of this article is to review and clarify the terms encompassing the discipline of pharmacovigilance and also to outline the steps in causality assessment with the help of an actual case report.

A randomized, double-blind, placebo-controlled study comparing the efficacy and safety of paracetamol, serratiopeptidase, ibuprofen and betamethasone using the dental impaction pain model

Assessment of postoperative sequelae following the removal of an impacted third molar has been used in clinical pharmacology to evaluate the relative efficacy of various analgesic, anti-inflammatory drugs. This study included 150 patients with impacted lower third molars. They were randomly sorted to receive ibuprofen, paracetamol, betamethasone, serratiopeptidase or placebo. Evaluation of efficacy was made using tape measurement (for swelling), visual analogue scale (for pain evaluation), mouth opening ability and oral temperature. The effect of treatment on hematological parameters, bleeding, wound healing and requirement for rescue medication was also studied. Peak pain scores were observed approximately 5-6 hours after the operation. Betamethasone showed significant analgesic activity from day 1. Ibuprofen and betamethasone were significantly more effective than placebo in reducing swelling. Trismus was least with betamethasone. A significant rise in temperature on the operated side occurred only on day 1 in all the groups. Serratiopeptidase did not showed significant analgesic and anti-inflammatory action. Mild-to-moderate adverse effects were reported.

Comparison of knowledge, attitude and practices of resident doctors and nurses on adverse drug reaction monitoring and reporting in a tertiary care hospital

Background: Lack of knowledge of pharmacovigilance (PhV) and adverse event (AE) reporting culture among the healthcare providers have been identified as major factors for under reporting of AE in developing countries. Hence, this study was planned to assess and compare the knowledge, attitude, and practices (KAP) of resident doctors and nurses about PhV and AE reporting. Material and Methods: This cross-sectional, questionnaire-based study was conducted to compare KAP of 100 doctors and 100 nurses on PhV and AE reporting. Results: All the respondents felt that AE reporting is necessary and two-thirds were aware of the existing PhV Program of India. Significantly, higher proportion of doctors had correct understanding regarding PhV (P<0.05) and knew what should be reported (P<0.05) but nurses (75%) knew better about where to report (P<0.001). Significantly (P<0.001), more doctors (98%) felt that the patients are benefited by reporting AE. Nurses (96%) felt the need for information on drugs causing AE and their management strategy (P<0.001). Around 60% of all the respondents were in favor of mandatory PhV and feedback on the submitted AE. Doctors (67%) (P<0.05) had a practice of inquiring patients for any untoward outcome of therapy. Higher proportion (P<0.05) of nurses (55%) mentioned that observed AE are recorded in patients case record, but random screening of 1000 patients’ record did not reveal it. Nurses mentioned that they never reported any AE (P<0.05) and witnessed discussions on ADRs during the ward rounds (P<0.001). All the respondents preferred phone as the convenient method for reporting AE followed by drop box kept in the ward/OPD and felt the need of frequent workshops and continuing medical education. Conclusion: Resident doctors and nurses had good knowledge and awareness on AE reporting and PhV but their practices need to be improved.

Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: a pilot study.

OBJECTIVE This study compared the efficacy and safety of oxcarbazepine and divalproex sodium in acute mania patients. SUBJECTS AND METHODS In this 12 week, randomized, double-blind pilot study, 60 patients diagnosed with acute mania (DSM-IV) and a baseline Young Mania Rating Scale (YMRS) score of 20 or more received flexibly dosed oxcarbazepine (1,000-2,400 mg/day) or divalproex (750-2,000 mg/day). The mean decrease in the YMRS score from baseline was used as the main outcome measure of response to treatment. A priori protocol-defined threshold scores were <or=12 for remission and >or=15 for relapse. Number of patients showing adequate response and the time taken to achieve improvement was compared. Adverse events were systematically recorded throughout the study. RESULTS Over 12 weeks, mean improvement in YMRS scores was comparable for both the groups including the mean total scores as well as percentage fall from baseline. There were no significant differences between treatments in the rates of symptomatic mania remission (90% in divalproex and 80% in oxcarbazepine group) and subsequent relapse. Median time taken to symptomatic remission was 56 days in divalproex group while it was 70 days in the oxcarbazepine group (p=0.123). A significantly greater number of patients in divalproex group experienced one or more adverse drug events as compared to patients in the oxcarbazepine group (66.7% versus 30%, p<0.01). CONCLUSION Oxcarbazepine demonstrated comparable efficacy to divalproex sodium in the management of acute mania. Also the overall adverse event profile was found to be superior for oxcarbazepine.

Knowledge, attitude and practices associated with adverse drug reaction reporting amongst doctors in a teaching hospital.

AIM This study was aimed at investigating the knowledge, attitude and practices associated with adverse drug reaction (ADR) reporting among doctors in a teaching hospital. METHODS A total of 100 doctors working in a teaching hospital were evaluated with a questionnaire for their knowledge, attitude and practices related to ADR reporting and pharmacovigilance programmes. RESULTS Nearly two third (66%) of the doctors knew the definition of ADR. Only one third (38%, 40%) could correctly define pharmacovigilance and adverse drug event (ADE) respectively. Although 100% of the doctors felt the need for a National Pharmacovigilance Programme (NPP) only approximately three fourth (73%) were aware of the existing programme in India and nearly half of the them (47%) actually knew the current status of the NPP at their institute. Surprisingly only one tenth of the doctors (10%) knew what should be reported. The majority (74.4%) felt that reactions to new drug should be reported and also those reactions that are serious and unusual. Only one third (30%) knew whom to report to and less than half (30%) had actually ever reported an ADR. CONCLUSION The knowledge of ADRs and how to report them is inadequate among doctors. More awareness should be created regarding the purpose and usefulness of ADR reporting through Continuous Medical Education, training and integration of ADR reporting into the clinical activities of the doctors.

Ciclesonide - A Novel Corticosteroid for the Management of Asthma.

Ciclesonide (CIC) is a novel inhaled corticosteroid (ICS) approved by US Food and Drug Administration for the treatment of persistent asthma, available as a pressurized metered-dose inhaler in two strengths, 80 mcg/activation and 160 mcg/activation. Ciclesonide is a corticosteroid with unique pharmacological profile including a high degree of serum protein binding, a low oral bioavailability and rapid systemic elimination. Ciclesonide is a prodrug metabolized by esterases to desisobutyryl ciclesonide (des-CIC), an active metabolite with a 100-fold greater affinity for the glucocorticoid receptor. It has shown to improve pulmonary functions, reduce the need for oral corticosteroids (OCSs) and cause lesser suppression of the hypothalamic-pituitary-adrenal axis in asthmatic patients. Clinical efficacy studies suggest that Ciclesonide is superior to placebo and is at least as effective as several active comparators with an improved therapeutic margin thereby improving the therapeutic outcome in patients of asthma.

Diversity of genotype and mode of spread of Hepatitis C virus in Northern India.

Background/Aim: Hepatitis C is caused by hepatitis C virus (HCV), which is classified into 6 genotypes. It leads to chronic hepatitis in 80% of the cases. Genotype of the virus helps in predicting response to antiviral therapy and also the duration of treatment. Therefore, it is important to know the prevalence of each genotype. Knowledge regarding the route of entry of HCV in the blood is also necessary to formulate a strategy to prevent its spread. Patients and Methods: One hundred and two newly diagnosed patients with chronic hepatitis C, having anti-HCV antibody-positive were included in the study. Their HCV RNA viral load and genotype were determined by Reverse Transcriptase PCR assay on Roche Cobas Ampliprep analyzer. Results: Genotype 3 was commonly detected in 58.8% patients followed by genotype 1 in 20.6%. Twelve patients had genotype 4 (11.8%) and 9 had mixed infection with genotypes 3 and 4. Among these patients, 43.1% of patients had a history of multiple injection exposure. Blood transfusion received by 6.9% and 2.9% had donated blood. Only 1 patient had a history of drug abuse. Conclusion: The distribution of genotypes varies in different regions and therefore its knowledge is important, as it determines the response of the patient to the treatment. The use of autodisabled syringes, their proper disposal, following biomedical waste management guidelines, and organizing continued medical education and workshops will help in preventing the spread of HCV infection.

Adverse Drug Reactions: Trends in a Tertiary Care Hospital

BACKGROUND Pharmacovigilance (PV) System is an integral part of drug therapy which helps in detection, monitoring and designing strategies to minimize the occurrence of adverse drug reaction (ADRs). Present study was planned to study the patterns of ADRs in a tertiary care government hospital. METHODS The present study was carried out for a period of one year. Suspected adverse drug reaction reports due to medications submitted to the Department of Pharmacology under the Pharmacovigilance Programme of India were included. The reports were analyzed for their type, severity, organ system involvement, and the causality assessment was performed using Naranjo Probability Scale. RESULTS A total of 520 ADRs were received. The highest percentage (66.2%) of ADRs was seen in adult patients. Female patients experienced more (57.5%) ADRs. 95% of ADRs occurred in patients receiving 5 or more drugs. Medicine department reported the maximum number (38.46%) of ADRs. Antimicrobial agents (AMA) (35.7%) were the commonest group of drugs causing ADRs. Amongst the organ systems affected, skin constituted a major component (40.4%). Causality assessment revealed that 55% of the ADRs were possible. Majority of the ADRs were non-serious and only 7 cases were serious and required hospitalization. CONCLUSION The results suggest that healthcare professionals (HCP) at this institution are cognizant of PV. However a closer liaison between the HCPs and the hospital PV centre, periodic reinforcement of the HCPs regarding the need for PV can further improve spontaneous reporting. The data will also help in designing strategies for framing policies towards safer use of drugs in future.

The effect of glipizide, metformin and rosiglitazone on nontraditional cardiovascular risk factors in newly diagnosed patients with type 2 diabetes mellitus

Background: Diabetes mellitus (DM) is recognized as a major risk factor for cardiovascular disease (CVD). Traditional cardiovascular risk factors (CVRFs) alone cannot explain excess risk for CVD associated with DM; nontraditional CVRFs also may play an important role. Aim: To study the effects of glipizide, metformin and rosiglitazone on traditional [lipid profile, lipoprotein Lp(a)] and nontraditional CVRFs [homocysteine (Hcy), soluble Vascular Cell Adhesion Molecule (sVCAM-1), malonyldialdehyde (MDA) and nitric oxide (NO) levels]. Setting and Design: An open-label, randomized, parallel group study was conducted in the departments of pharmacology, internal medicine and biochemistry of Lady Hardinge Medical College. Materials and Methods: Ninety newly diagnosed type 2 DM patients were randomly assigned to glipizide, metformin or rosiglitazone treatment daily for a duration of 12 weeks. If needed, the dosages were titrated upward to achieve fasting plasma glucose <126 mg /dL. Plasma glucose, glycosylated hemoglobin (HbA1c), lipid profile, body mass index (BMI), Lp(a), Hcy, sVCAM-1, MDA and NO were estimated both before and after treatment. Statistical Analysis: Data were analyzed using paired Student’s t-test within each group. Results and Conclusion: All the three drugs led to significant decrease in HbA1c, fasting and postprandial plasma glucose levels. Glipizide lowered body weight, BMI, total cholesterol (P < 0.05), low density lipoprotein cholesterol (LDL-C) (P < 0.01) and MDA levels (P < 0.05). Metformin reduced body weight (P < 0.01), BMI (P < 0.01), LDL-C, very low density lipoprotein cholesterol (VLDL-C) and improved high density lipoprotein cholesterol (HDL-C); however, it raised Hcy levels (P < 0.01). Rosiglitazone treatment increased

An observational study to compare the contents and quality of information furnished in CDSCO ADR reporting form, yellow card, medwatch and blue form by the healthcare professionals

BACKGROUND Spontaneous adverse drug reaction (ADR) reporting form is a vital tool for collecting information about ADRs, which helps in establishing the causal assessment and generating a signal. This is feasible if quality information is translated into the reporting form by health care professional (HCPs). Hence, present study was carried out to compare efficiency of HCPs in translating suspected ADR information in the spontaneous reporting forms and to compare the ADR reporting forms of different countries and their duration of training in pharmacovigilance. METHODS In a cross-sectional study, 50 doctors, 50 Nurses and 50 Pharmacists were asked to fill different reporting forms (CDSCO form, Medwatch, Yellow card and the Blue form) using different simulated ADR case reports. Filled forms were analysed for their contents, information captured and time taken to fill these forms. They were also asked about their training and exposure to pharmacovigilance related activities. RESULTS All the spontaneous ADR reporting forms had 24-26 data elements to furnish information. Information regarding dechallenge was lacking in the Yellow card and Blue form. Blue form also lacked the information on rechallenge. Overall nurses took longer time to fill all the ADR reporting forms as compared to the doctors and pharmacists. Majority of HCPs missed to fill reporters information in all the forms. CONCLUSION Study suggested that the quality of information translated by the HCPs needs improvement for which they should be sensitized periodically on the basic elements of pharmacovigilance.