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Ijopp__arp-jun__vol.6_iss.pdfIndian Journal of Pharmacy Practice
Association of Pharmaceutical Teachers of India
A Prospective Study on Adverse Drug Reactions in a Tertiary Care South Indian
Palanisamy S*, ArulKumaran KSG, Rajasekaran A
Department of Pharmacy Practice, KMCH College of Pharmacy, Coimbatore-48
A B S T R A C T
Background: ADRs have a major impact on public health, reducing patients' quality of life and imposing a considerable financial burden on the health care
systems. Objectives: The main objectives were to analyze the pattern and extent of occurrence of ADRs in the hospital, identify co-morbidities, past and present
illness, assess causality and identify the offending drugs, assess the severity and preventability of adverse drug reactions. Methods: Prospective, observational,
spontaneous, reporting study with both active and passive methods. Results: A prospective observational spontaneous reporting study was carried out from
January 2009 to August 2012. A total of 950 ADRs were accepted from the reported total of 1227 ADRs. Female patients experienced more number of ADRs when compared to male patients. Fever was the most commonly observed reason for admission. Maculopapular skin rashes were the commonly observed ADR in the study population. Amoxicillin and Clavulanic acid combination implicated more number of ADRs in the antibiotic category than others. Sixty one percent of the ADRs were moderate in severity followed by minor and severe ADRs. Most of reactions in the study population were managed by withdrawing the offending drug and rechallenge was performed in few subjects. Most of ADRs in the study were definitely preventable (40%) and were predictable in nature. Eighty percent of the reactions were probably related to the offending drugs, 758 reactions in the likely to cause ADRs. Twenty five percent of the ADRs were treated symptomatically in the study population.
Keywords: Adverse drug reactions, Pharmacovigilance, Spontaneous reporting, Allergic reactions, Observational study
prevalent even in developed countries with a long history of Adverse drug reactions (ADRs) cause considerable morbidity functional ADRs reporting system. This may be due to and mortality worldwide and in many cases are avoidable. several reasons like increase in workload, perception that ADRs have a major impact on public health; reducing reporting will not result in any improvement and lack of knowledge that an adverse event has occurred and fear of patients' quality of life and imposing a considerable financial exposing oneself to litigation. A method that could be burden on the health care systems at a time when many health employed to tackle this problem in a hospital set-up is to care systems are under considerable financial strain. ADRs increase awareness about an existing system and the are a recognized hazard of drug therapy. Although some ADRs are minor and resolve without sequelae, others can cause permanent disability or death, and contribute to the Therefore, it is important to motivate health care incidence of adverse drug reactions, resulting in increasing professionals to understand their role and responsibility in the detection, management, documentation, reporting of ADRs and all essential activities for optimizing patient safety. ADRs monitoring and reporting activity is in its infancy in Thus, the program may contribute to decrease morbidity, India. ADRs reporting programs in an institutional basis can mortality, and length of stay, health care costs and liability support the settings up of a sound pharmacovigilance system associated with ADRs. The main objectives of the current in the country. Further, hospital based ADRs programs can prospective observational spontaneous reporting study was to provide valuable information about potential problems in analyze the pattern and extent of occurrence of ADRs in the drug usage in an institution. Throughout the world, most of hospital, to identify the co-morbidities, past and present the ADRs monitoring programs rely on physician initiated illness, to assess causality and to identify the offending drugs (voluntary reporting) and have been partially successful. and to assess the severity and preventability of adverse drug Under-reporting has been the biggest challenge in voluntary reporting method/ spontaneous ADRs reporting and it is METHODOLOGY
Address for Correspondence:
Study site: The study was carried out at 800 beds Kovai
S.Palanisamy, Assistant Professor, KMCH College of Pharmacy, Kovai Estate,
Medical Center and Hospital, where all facilities under one Kalapatti Road, Coimbatore-48. Tamilnadu, India.
roof were available with wide range of specialties. E-mail: firstname.lastname@example.org
Study design: Prospective, observational, spontaneous,
Indian Journal of Pharmacy Practice Volume 6 Issue 2 Apr - Jun, 2013 Palanisamy S - A Prospective Study on Adverse Drug Reactions in a Tertiary Care South Indian Hospital reporting study with both active and passive methods: a)
reaction was established by using the Naranjo's causality Active method: Pharmacist actively looking for suspected
assessment scale , further the causal relation were classified ADRs; b) Passive method: Stimulating prescriber to report
into Definite, probable, possible, and unlikely. Assessment of Severity: Severity of the reaction was
Study period: The study was carried out for a period of three
assessed by using the Modified Hartwig and Siegel Severity year and eight months between January 2009 and August assessment scale and the severity is broadly categorized in to 2012. Ethical committee clearance was obtained from the “mild”, “moderate” and “severe” for each ADR. KMCH Ethics Committee to carry out the study in the Assessment of Preventability: All the reported ADRs were
hospital patients (Ref. No: EC/AP/103/09-2009). assessed for their preventability using the modified criteria of Inclusion criteria: Inpatients, those who were exposed to
Schumock and Thornton's by Lau, et al. and were categorized any adverse drug reactions in the hospital and those who were into “Definitely preventable”, 'probably preventable” and admitted for the treatment of adverse drug reaction (i.e. reason for admission was ADRs) were included in the study.
Preparation and Issue of Alert card: All the patients who
Exclusion criteria: Patients who develop an ADR due to
were admitted to the hospital due to an ADR were provided, accidental or intentional poisoning, ADR due to fresh blood where applicable with an ALERT CARD, so as to prevent the or blood products, ADR due to over dose, patients with drugs future occurrence of similar ADRs in the patient. All the abuse and intoxication were excluded from the study. reported and evaluated suspected ADRs were documented in ADRs notification and documentation form: Separate
a suitably designed form and a feedback to each reporter was ADRs notification and documentation form was designed given using a THANK YOU note. The total cost of treatment which consists of all relevant data including patient's was calculated by using cost of therapy, bed and room charge, demographic details, all drugs the patients received prior to extra number of days in hospital, prescriber fee, monitoring onset of reaction, their route of administration, respective and laboratory studies, emergency department charge if any, dosage, frequency, date of onset of reaction and the patient's allergy status to drugs and foods, ADRs management, details Data Analysis, Interpretation and results
of reporter, etc. This form was made available in all nursing The collected data were analyzed for its appropriateness and stations of the hospital and the out-patient areas for easy suitability and interpretation was made for the collected data. access to all healthcare professionals. It has two fold Statistical analysis was performed with SPSS software, advantages; primarily to serve as an official medium of version17.0. P-values <0.05 were considered to be reporting back to the healthcare professional with necessary statistically significant. From the data analysis, results were information pertaining to the suspected ADRs reported. Secondly, it acts as a method to encourage their continuous Data collection and assessment of causality, severity and
In the current prospective observational spontaneous preventability
reporting study, 1227 Adverse Drug Reactions (ADRs) were reported but only 950 ADRs were accepted. About 277 ADRs When a suspected drug was reported and met the inclusion were not accepted due of lack of information and some and exclusion criteria, data on that particular suspected drug reactions were not categorized as ADRs. The gender and reaction was collected and documented in a suitably distribution shown that 408 (33.25%) ADRs cases were male designed ADR documentation form. Data for the study were and 819 (66.75%) cases were female patients in the reported collected from patient's case sheet, treatment chart, ADRs population. 313 (32.95%) were male patients and 637 investigation reports, and personal interview with (67.05%) were female patients in the accepted ADRs patient/patient's attendant, personal interview with reporting persons / clinicians. The collected data were transferred to the Among the 1227 reported ADRs, 1196 (97.47%) were specially designed ADRs documentation form for evaluation. reported from In-patients and 31 (2.53%) were from out- Assessment of Causality: The extent of relationship between
patients. Among the 950 accepted ADRs cases, 928 (97.68%) suspected ADR and the drug therapy was assessed using the were from In-patients and 22 (2.32%) were from out-patients. WHO Probability assessment scale. It was further classified Allergic status of the accepted ADRs study population shown into Certain, Probable/likely, Possible, Unlikely, 13.68 (n=130) percent female and 8.84 (n=84) percent male Conditional/unclassified and Un-assessable/unclassifiable. were known case of allergic patients; about 53.37 (n=507) The causality relationship between a drug and suspected percent female and 24.11 (n=229) percent male were not Indian Journal of Pharmacy Practice Volume 6 Issue 2 Apr - Jun, 2013 Palanisamy S - A Prospective Study on Adverse Drug Reactions in a Tertiary Care South Indian Hospital having any type of allergic history. In the overall accepted (2.63%) of the study population. 24 (2.53%) patients each ADRs study population, only 22.53 (n=214) percent were had appendicitis, viral pyrexia and diabetes with found to be known allergic patients, majority of patients (77.47%; n=736) were found to be not a known allergic cases. Therapy or medications used for the management of previous Suspected ADRs were observed in all department of the or past illness called as past medication history. In our study, hospital but mostly in dermatology (28.63%; n=272) and the most commonly found drug as past medication was General medicine (24.32%; n=231), followed by Neurology Paracetamol in around 58 (6.11%) patients, Amlodipine in 39 (7.89%; n=75), pulmonology (5.05%; n=48), diabetology (4.11%) patients, Pantoprazole in 37 (3.89%), Zolpidem in 35 (4.74%; n=45), gastroenterology (4.42%; n=42), nephrology (3.68%), Atenolol in 34 (3.58%) patients. Glibenclamide and (3.79%; n=36), gynecology (3.79%; n=36) and slim clinic Metformin combination was given for 34 (3.58%) patients, (3.37%; n=32), etc. The department wise distributions of Insulin with Metformin in 32 (3.37%), Ramipril and ADRs were described in table 1. Fever was the major and Ibuprofen each in 30 (3.16%) patients. Atorvastatin along most commonly observed reason for admission in suspected with Ezetimibe used in 29 (3.05%) patients, Alprazolam in ADRs population, which is observed in around 6.42 (n=61) 27(2.84%), Atenolol with Amlodipine combination in percent of patients, which is followed by cough (n=42; 27(2.84%), Rabeprazole in 24(2.53%), Atorvastatin in 4.42%), general weakness (n=41, 4.32%), rashes (n=39; 23(2.42%), Aspirin in 22(2.32%) and Aspirin with 4.11%), itching (n=39; 4.11%), allergic rhinitis (n=37; 3.89%), abdominal pain and giddiness were commonly found Insulin, Rosuvastatin and Ciprofloxacin were prescribed for in each of 33 (3.47%) patients, followed by others. 19 (2.0%) patients each; Methotrexate and Chloroquine in Study on past medical history of study population was carried 18 (1.89%) patient each, Clopidogrel in 16 (1.68%) patients, out, which revealed that diabetes mellitus was the major Streptokinase in 15 (1.58%), Tenofibrate in 13 (1.37%) of the medical problem in around 61 (6.42%) patients and fever in study population. Ten (1.05%) of the study population around 47 (4.95%), hypertension in 46 (4.84%), received Heparin, Probenecid, Thyroxin sodium and atherosclerosis in 42 (4.42%), breathlessness in 39 (4.11%) Cisplatin as past medication. 8 (0.84%) Vincristine and patients. Stroke was past medical status in 38 (4.0%) patients 7 (0.74%) patient received Digoxin. Glipizide, Phenytoin followed by gastritis in 37 (3.89), fracture in 31 (3.26%), sodium, Sodium valproate, Isoniazid, Piroxicam, Ischemic Heart Disease (IHD), sinusitis and Chronic Renal Haloperidol, and Azathioprine were prescribed as past Failure (CRF) in around each 28 (2.95%) patients, Acute medication in each of 6 (0.63%) patients in the study Renal Failure (ARF) in 26 (2.74%), respiratory failure in 25 Table 1: Department wise distribution of ADRs (n=950)
Name of the Department Female
Indian Journal of Pharmacy Practice Volume 6 Issue 2 Apr - Jun, 2013 Palanisamy S - A Prospective Study on Adverse Drug Reactions in a Tertiary Care South Indian Hospital Diagnosis of disease in the accepted ADRs study population respiratory system (n=25; %) and skeletal system in 5 (0.53) indicates medical condition or the health of patients. In this patients. The detailed system wise ADRs were included in the study, diabetes was major disease condition diagnosed in around 10 (n=95) percent of the study subjects, followed by Each and every patient reported only one ADR (n=950) and fever (n=59; 6.21%), portal hypertension (n=57; 6.00%), none of the patients reported more than one ADR. peptic ulcer (n=50; 5.26%), asthma (n=44; 4.63%), acute Classification of suspected / accepted ADRs revealed that renal failure (n=39; 4.11%) and hypertension (n=35; 3.68%). majority of ADRs in the study population were fall in the Chronic obstructive pulmonary disorder (COPD) and category of Type-A (Augmented and predictable) and it was epilepsy were diagnosed in each of 34 (3.58%) patients, around 548 (57.68%) ADRs, in this 357 (37.58%) ADRs were chronic renal failure in 32 patients (3.37%); myocardial in female and 191 (20.11%) ADRs were in male patients. infarction and tuberculosis were in each of 31 (3.26%) Type-B (Bizarre and unpredictable) ADRs were around patients; migraine, sleep apnea and carcinoma were observed 268 (30.11%), among this 206 (21.68) ADRs were in female in 30 (3.16%) patients each; acute pharyngitis in 29 (3.05%) and 80 (8.42%) ADRs were in male patients. In Type-C patients; Diabetes with atherosclerosis found in 29 (3.05%) ADRs, 15 (1.58%) were found in female and 11 (1.16%) patients; diabetes+hypertension+atherosclerosis was ADRs in male patients with a total of 26 (2.74%) ADRs. observed in 27 (2.84%) patients; diabetes along with Among 20 (2.11%) Type-D ADRs, 11 (1.16%) ADRs were hypertension was diagnosed in around 25 (2.63%) patients, observed in female and 9 (0.95%) were in male patients, followed by atherosclerosis, angina pectoris, followed by Type-E ADRs, Type- F ADRs and others. The gastro-esophageal reflux disease (GERD) etc. types of ADRs were included in table 3.
Status of admission in to the hospital shown that around Maculopapular skin rashes was the most commonly reported 168 (17.68%) patient was admitted for treatment of ADRs and accepted Adverse Drug Reactions (ADRs), it was seen in which includes 103 (10.84%) female and 65 (6.84%) male 93 (9.79%) patients, followed by Severe gastric irritation patients, but a total of 782 (82.32%) patients experienced (n=67; 7.05%), Exfoliative dermatitis (n=59; 6.21%), Acute ADRs during their hospital stay when they were in the urticaria (n=46; 4.84%), Hyper-pigmentation (n=38; treatment of their clinical or diseased condition, which 4.00%), Oral ulcer (n=35; 3.68%), Fixed drug eruption includes 534 (56.21%) female and 248 (26.11%) male (n=33; 3.47%), Nausea and Vomiting (n=32; 3.37%), and Toxic epidermal necrolysis (TEN) (n=30; 3.16%). Study on organ or system affected by the suspected ADRs Abdominal pain and Elevation of liver enzyme were seen in revealed that a total of 9 systems were affected, among these each of 26 (2.74%) patients; Diarrhoea and Anemia also skin and appendages was most badly affected in around observed in each of 23 (2.42%) patients. Hypoglycemia and 373 (39.26%) patients, gastrointestinal system in 304 (32.0%) dysuria were reported by 22 (2.32%) each of the study patients. The other systems affected were endocrine system population. Twenty one (2.21%) patients were found with (n=71; 7.47%), central nervous system (n= 50; 5.26%), morbiliform skin eruption, 20 (2.11%) patients with Steven cardiovascular system (n=48; 5.05%), excretory system Johnson syndrome, 20 (2.11%) patients with dyspepsia, (n=33; 3.47%), hematological system (n=30; 3.16%), 19 (2.0%) with erythroderma and 19 (2.0%) with acute Table 2: Report of organ / system affected by the ADRs (n=950)
Name of the Organ/System Female
Indian Journal of Pharmacy Practice Volume 6 Issue 2 Apr - Jun, 2013 Palanisamy S - A Prospective Study on Adverse Drug Reactions in a Tertiary Care South Indian Hospital hepatitis, 18 (1.89%) with drowsiness, 17 (1.79%) with implicated by antineoplastic drugs; Vincristine 19, dyspnoea, and 16 (1.68%) patients with head ache. Vinblastine 13, Methotrexate 11, 6-Mercaptopurine 10, Constipation, sore throat and hyperglycemia were observed Carboplatin 7, Doxorubicin 6 and Paclitaxel 6 ADRs. in each of 15 (1.58%) patients, followed by dry mouth and 53(5.58%) ADRs were implicated by antidiabetic agents; hyperuricemia in each of 14 (1.47%) patients, glossitis and Insulin 22, Metformin 14, Glipizide 9 and Gliclazide 8 ADRs. arterial hypertension were in each of 12 (1.26%) patients. In the lipid lowering agents, Atorvastatin implicated 10 (1.05%) patients were found with orthostatic hypotension 23 ADRs, Fenofibrate 14, Rosuvastatin 8, and Ezetimibe 4, and 9 (0.95%) each with systemic lupus erythematosus, with a total of 49 (5.16%) ADRs by lipid lowering agents. arterial hypotension and hypokalemia. 8 (0.84%) reported Anticonvulsants produced 45 (4.74%) ADRs; with orthopnoea, 7 (0.74) each reported with extra-pyramidal Carbamazepine 24, Phenytoin 16, Oxcarbazepine 4 and symptoms and urinary retention, etc. The details of reactions Topiramate produced one ADRs. Ranitidine, Omeprazole and Rabeprazole were the antiulcer or antisecretory agents which implicated 15, 11 and 8 ADRs respectively and a total of The drugs implicated in producing Adverse Drug Reactions 34 (3.58%) ADRs were produced by these drugs. Dapsone, (ADRs) were studied extensively and described that a total of Sulphonamides and Sulfamethoxazole with Trimethoprim 81 different drugs implicated 950 ADRs. Among the implicated 15, 7 and 4 ADRs respectively with a total of implicated drugs antibiotics produced more number of ADRs 26 (2.74%) ADRs. Local anesthetics like Xylocaine and it was around 212 (22.32%), in this antibiotics category Gesicaine produced 15 and 8 ADRs respectively with a total Amoxicillin and Clavulanic acid combination produced 23 (2.42%) ADRs. Antiemetics implicated 19 (2.0%) ADRs 46 ADRs followed by Ciprofloxacin 32, Moxifloxacin 26, in which Ondansetron implicated 11 and Phenergan Cloxacillin 18, Levofloxacin 11, Cefuroxime 9, implicated 8 ADRs, etc. The drugs which implicated ADRs Cefoperazone 8, Ceftriaxone 7, Cephalexin 7, Ampicillin 7, Penicillin 6, Doxycyline 5, Erythromycin 5, Vancomycin 3, and Bleomycin 3. Gentamycin, Imipenem, Metronidazole, Severity of suspected ADRs were assessed with modified and Piperacillin with Tazobactam each produced one ADR.
Hartwig and Siegel Severity assessment scale, revealed that majority of suspected ADRs were moderate (n=583; One hundred and thirty one (13.79%) ADRs were produced 61.37%), in which 440 (46.32%) were observed in female by Non-steroidal Anti-Inflammatory Drugs (NSAIDs), in this Aspirin produced majority of ADRs (n=35), followed by patients and 143 (15.05%) in male patients. Mild ADRs were Paracetamol 27, Diclofenac sodium 21, Naproxen 18, found to be 308 (32.42%), in this 158 (16.63%) were detected Indomethacin 12, Celecoxib 7, Ibuprofen 7 and Nimesulide from female patients and 150 (15.79%) from male patients, 4 ADRs. Cardiovascular drugs implicated 9.47 (n=90) followed by severe ADRs, it was around 55 (5.79%), among percent of ADRs, in this category Carvedilol produced 31 this 36 (3.79%) were from female and 19 (2.0%) were from ADRs followed by Amlodipine 27, Nifedipine 16, Verapamil male patients. 4 (0.42%) lethal effects were observed in the 10, and Diltiazem 6 ADRs. Corticosteroids implicated 86 study patients, among this 3 (0.32%) from female and (9.05%) ADRs, in which Dexamethazone produced 30 ADRs, Hydrocortisone 27, Prednisolone 14, Fluticasone 12 and Causality assessment was used to describe the causal Solumedrol 3 ADRs. A total of 72 suspected ADRs were relationship between offending drugs and the reaction and it Table 3: Classification of suspected/ accepted ADRs in the study population (n=950)
Type of ADR’s Female
Indian Journal of Pharmacy Practice Volume 6 Issue 2 Apr - Jun, 2013 Palanisamy S - A Prospective Study on Adverse Drug Reactions in a Tertiary Care South Indian Hospital Table 4: List of Suspected /Accepted ADRs in the study population (n=950)
Description of ADRs Female
Indian Journal of Pharmacy Practice Volume 6 Issue 2 Apr - Jun, 2013 Palanisamy S - A Prospective Study on Adverse Drug Reactions in a Tertiary Care South Indian Hospital Table 5: List of drugs implicated in ADRs and frequency of
Antidiabetic agents (53; 5.58%)
Class of drug(s) Name of the drug
Antibiotics (212; 22.32%)
Lipid lowering agents (49; 5.16%)
Anticonvulsants (45; 4.74%)
Antiulcer or antisecretory agents (34; 3.58%)
Antileprotic and sulpha drugs (26; 2.74%)
Local anaesthetics (23; 2.42%)
NSAIDs (131; 13.79%)
Antiemetics (19; 2.0%)
Opioid analgesics (19; 2.0%)
Cardiovascular drugs (90; 9.47%)
Antitubercular drugs (19; 2.0%)
Antidiarrhoeal (18; 1.89%)
Corticosteroids (86; 9.05%)
Antiplatelet aggregating agents (17; 1.79%)
Antiparkinsonian agents (5; 0.53%)
Antineoplastic drugs (72; 7.58%)
Antimalarial (4; 0.42%)
Antihistamines (4; 0.42%)
Miscellaneous (15; 1.58%)
Indian Journal of Pharmacy Practice Volume 6 Issue 2 Apr - Jun, 2013 Palanisamy S - A Prospective Study on Adverse Drug Reactions in a Tertiary Care South Indian Hospital was done with Naranjo's causality assessment scale and outcome of rechallenge was carried out in 23 (2.42%) patients shown that 20 (2.11%) ADRs were definitely related to drugs, and revealed that 20 (2.11%) patients were completely 759 (79.89%) ADRs were probably related to drugs, recovered and the suspected reaction did not reappear after 165 (17.37%) ADRs were possibility related to drugs and administering the offending drug(s). But in 3 (0.32%) patients 6(0.63%) ADRs were unlikely related to drugs. with rechallenge, the reaction reappeared and they were Probability of the suspected ADRs were assessed with WHO probability assessment scale and revealed that 22 ADRs were Pathophysiological conditions were found as predisposing certain, 758 ADRs were probable or likely, 160 ADRs were factor in 255 (26.84%) patients, amount of drug administered possible, 5 ADRs were unlikely, 5 ADRs were un-assessable in 215 (22.63%) patients, previous history of allergy in or unclassifiable and none of the ADRs was conditional or 197(20.74%), diseased circumstances in 107 (11.26%) patients, race or genetics in 25 (2.63%), Pregnancy in Preventability of the suspected ADRs were assessed with 24(2.53%) patients. Polypharmacy was the important factor Schmock and Thornton criterion modified by Lau, et al. and to cause ADRs in many of the study population, the same was showed that 384 (40.42%) ADRs were definitely preventable, observed in our study also in predisposing factors of ADRs. among this 256 (26.95%) ADRs were present in female and The study on number of drugs per prescription revealed that 128 (13.47) in male patients; probably preventable ADRs only one (0.11%) patient received single medications and were 294 (30.95%) in which 198 (20.84%) ADRs were most of the patients received more than one medication. identified in female and 96 (10.11%) ADRs in male patients; 21(2.21%) patients received 2 drugs, 102 (10.74%) patients 272 (28.63) ADRs were identified as not-preventable and it received 3 drugs, and 76 (8.0%)patients received 4 drugs. was observed in 183 (19.26) female and 89 (9.37) male Majority of patients (n=184; 19.37%) received 5 drugs, 155(16.32%) patients received 6 drugs, 127 (13.37%) Management of ADRs in the study population shown that, in patients received 7 drugs and 82 (8.63%) patients received 89.89 (n=854) percent patients the offending drug was 8 drugs. 9 drugs were found in 18 (1.89%) of the prescription, withdrawn it includes 60.21 (n=572) percent female and 10 drugs in 24 (2.53%) prescriptions, 11 drugs in 63 (6.63%) 29.68 (n=282) percent male patients; dose was altered in prescription, 12 drugs in 34 (3.58%) prescriptions and 10.11 (n=96) percent of the patients including of 6.84 (n=65) 13 drugs in 24 (2.53%) prescriptions. Fourteen drugs were percent female and 3.26 (n=31) percent male patients. prescribed in 14 (1.47%) patients, 15 drugs were prescribed in 16 (1.68%) patients and 9 (0.95%) patients were prescribed Regarding the treatment given for patients after experiencing with more than 15 drugs. The average drug prescribed per an ADR; a total of 264 patients received treatment in this 150 patient was found to be 6.80±0.63 drugs, and shown a (15.79%) were female and 114 (12.0%) were male patients. Symptomatic treatment was given in 236 (24.84%) patients including 138 (14.53%) female and 98 (10.32%) male DISCUSSION
patients; specific treatment was given to 28 (2.95%) patients, A total of 950 ADRs were accepted from the 1227 reported it includes 12 (1.26%) female and 16 (1.68%) male patients. ADRs, 97.68 percent of ADRs were reported from In-patient The outcome ADRs management was studied and shown that department and 2.32 percent ADRs were reported from 948 (99.79%) patients were recovered, among this out-patient department. This finding was similar to an Indian 637(67.05) patients were female and 311 (32.74) were male study population showed that 73(76.04%) ADRs were patients; 2 (0.21%) patients experienced a fatal reaction and reported from inpatient department and 23 (23.96%) ADRs Dechallenge and Rechallenge was observed in the study A total of 219 (23.05%) patient with suspected ADRs found population; in around 927 (97.58%) patients dechallenge was between the age group of 41 and 50 years. Hundred and sixty done, which includes 620 (65.26%) female and 307 (32.32%) eight (17.68%) patient with ADRs observed in the age male patients; rechallenge was performed in only 23 (2.42%) between 51 and 60 years; in the age group of 61 to 70 years, a patients which includes 17 (1.79%) female and 6 (0.63%) total of 204 (21.47%) patients were found to have any one male patients. Assessment on outcome of dechallenge was suspected ADRs. This observations were consistent with carried out and revealed that from 927 (97.58%) dechallenged many studies, patients admitted with ADRs were significantly patients, 925 (97.37%) patients were completely recovered older than patients without ADRs (65-83 years). An Indian with an recovery percentage of 99.78 and 2 (0.21%) male study found adult predominance (70%) over the pediatric patients experienced fatal reaction. The suspected reaction (16%) and geriatric (14%) population. Geriatric patients has not reappeared in the study population. Assessment on reported more number (24; 56%) of ADRs than others. This Indian Journal of Pharmacy Practice Volume 6 Issue 2 Apr - Jun, 2013 Palanisamy S - A Prospective Study on Adverse Drug Reactions in a Tertiary Care South Indian Hospital may be due to the fact that most adult patients who were Around 168 (17.68%) patient were admitted for the treatment receiving multiple drugs therapy and also presented with of ADRs and a total of 782 (82.32%) patients were other co-morbidities such as diabetes, hypertension and experienced ADRs during their hospital stay when they were in the treatment of their clinical or diseased condition. In this study, female patients were more prone to have allergic This observation was similar to the findings of a study in that history ((n=130; 13.68%) when compared to male ((n=84; ADRs leading to hospital admission were recorded in 47 8.84%). This may be due to the poor immune status and less (7.8%) out of 600 patients. This may be due to the utilization tolerability against disease(s) in female patients. Suspected of any over the counter medications or polypharmacy or self ADRs were observed in all department of the hospital but medications of the patients for their simple ailments leads to mostly in dermatology (28.63%; n=272) and General medicine (24.32%; n=231), followed by neurology (7.89%; In this current study, skin and appendages was most badly n=75), pulmonology (5.05%; n=48), diabetology (4.74%; affected in around 373 (39.26%) patients, gastrointestinal n=45) etc. This is the facts due to all cutaneous reactions were system in 304 (32.0%) patients. This observation was similar admitted in the dermatology department and wide use of to many other studies the system most commonly affected by medications in the general medicine department. This findings were similar to a study with maximum number gastrointestinal (12%) system. Most common system of ADRs were reported from the skin 35.13% followed by associated with ADRs were skin, GIT and CNS. The most GIT 29.72% and then from CNS 18.91%. Medicine commonly affected organ system associated with ADRs in department had reported the highest percentage of ADRs our study was the skin (52,5%). Reactions affecting the skin, (42%) followed by the dermatology department (39%). But gastrointestinal tract and central nervous system were the in another study maximum number of ADRs reported from most often reported and together accounted for 62.8% of all general medicine department (19; 42.22%) followed by reactions. Skin and appendage are the main parts of body to cardiology (11; 24.4%) and other departments. have cutaneous drug reactions, photo sensitivity reactions, Fever was the major and most commonly observed reason for fixed drug eruption, etc. Mostly drugs were disintegrated, admission in 61 patients, followed by cough (n=42; 4.42%), distributed, metabolized and absorbed through general weakness (n=41, 4.32%), and others. Diabetes gastrointestinal system, so the system is frequently exposed to mellitus was the major medical problem as past medical all chemicals and drugs, leads to the development of history in around 61 (6.42%) patients, hypertension in 46 (4.84%), etc. Past medical history of patients plays a major Majority of ADRs in the study population were fall in the role in the development of adverse drug reactions, since they category of Type-A (Augmented and predictable) and it was were using many medications for management of diseases around 548 (57.68%) ADRs and Type-B (Bizarre and and all the diseases were inter-related with one another. unpredictable) ADRs were around 268 (30.11%). Polypharmacy for the management of disease(s) prone to These findings were consistent with many other studies most initiate the development of suspected ADRs in the study of the ADRs in the study were classified as Type A (n-1161, population. We observed the polypharmacy in many cases 95%). The majority (91%) of ADRs can be assigned to type A and most of them were developed with any one adverse drug ADRs which are preventable. All the ADRs observed were Type-B, and were unrelated to dosage. Of the reported ADRs Diabetes was the major disease condition diagnosed in around Type A reactions (34; 75.55%) were common compared to 10 (n=95) percent of subjects, followed by fever (n=59; Type B reactions (11; 24.44%). Type A reactions were more 6.21%), portal hypertension (n=57; 6.00%), peptic ulcer common in the study because they were dose related, (n=50; 5.26%), asthma (n=44; 4.63%), acute renal failure predictable, high morbidity, low mortality and respond to (n=39; 4.11%) and hypertension (n=35; 3.68%). This may be due to the changes in life style of the study population and Maculopapular skin rashes (n=93; 9.79%) was the most changes in food behavior; most of the study population likes commonly reported and accepted ADRs in the study to have carbohydrate food frequently than other food items. population, followed by Severe gastric irritation (n=67; This also may be one of reason for developing diabetes and 7.05%), Exfoliative dermatitis (n=59; 6.21%), etc. These their associated complications. Our findings were contrast to findings were consistent with a many other studies in that the a study showed that the most common principal diagnoses most commonly reported reactions were rashes (32%) among inpatients admission was agranulocytosis (9.44%) followed by itching or pruritis (11%), edema (6%) and urticaria (5%). 11.3% (n=21) were cutaneous eruptions, Indian Journal of Pharmacy Practice Volume 6 Issue 2 Apr - Jun, 2013 Palanisamy S - A Prospective Study on Adverse Drug Reactions in a Tertiary Care South Indian Hospital 11.3% (n=21) were hyperglycemia and gastrointestinal hospital admission was related to administration of abnormalities in 25.3% (n=47) patients in another study. angiotensin converting enzyme inhibitors or potassium Most common morphologic varieties of the reactions were sparing diuretics or their combination. Diuretics produced urticaria (27.19%), fixed drug rashes (25.16%) and macular more number ADRs (10; 22.22%) followed by antibiotics and morbiliform eruptions (25.16%). Most common ADRs (8: 17.77%). Anticonvulsants produced 45 (4.74%) ADRs; were gastrointestinal in nature (52.5%); abdominal Carbamazepine 24, Phenytoin 16, Oxcarbazepine 4 and discomfort (37.7%), vomiting (1%), nausea (9.8%); alopecia Topiramate produced one ADRs. These observations were 4.9%. In one study 48 hospitalized patients reported nausea, similar to a study, the most common offending drugs were diarrhea and head ache during the anticancer therapy.
Carbamazepine (16.23%), Phenytoin (15.15%) and Cotrimoxazole (13.53%). Bleeding related to Warfarin A total of 81 different drugs implicated 950 ADRs in the study overdosing as an ADR causing hospitalization was reported population. But in one study they reported a total of 194 ADRs only in seven patients. Similar findings were noted in our resulted from the use of 70 different drugs. Among the study also that antiplatelet aggregating agents like implicated drugs antibiotics produced more number of ADRs, Clopidogrel produced 17 (1.79%) ADRs, anticoagulants like in this Amoxicillin and Clavulanic acid combination produced 46 ADRs followed by Ciprofloxacin 32, Moxifloxacin 26, Cloxacillin 18, etc. The offending drugs and In the current study, majority of the suspected ADRs were the reactions were similar to various other studies, a retrospective study reported Urticaria developed in two 32.42%) and severe (n=55; 5.79%). These observations were patients, one who received Piperacillin/Tazobactam and one consistent with other studies, the severity of ADRs was either who was treated with Imipenem. Asymptomatic liver moderate (urticaria, abnormal LFT) or severe (neutropenia). function disturbances were seen in one patient who received Most of the ADRs (96.5%) were moderately severe while Cefepime therapy. Two out of four who received 3 cases were severe in nature and were preventable. At least Piperacillin/Tazobactam developed severe neutropenia one in five patients was admitted to the hospital due to the during their 2-4 weeks therapy. The drug most commonly severe ADRs and a small portion (0.07%) of patients died in implicated with ADRs was antibiotics (24%) followed by Emergency department. We observed some distinct findings from some other studies in that a higher percentage of patients with severe ADRs were male (44%) compared with patients Antibiotics were the most frequent cause of ADRs with 219 with mild ADRs (38% male). The degree of severity was (38.8%) patients experiencing an ADR associated with this minor in 72.9% of the reports, moderate in 22.4%, severe in drug class. The therapeutic group most frequently suspected of causing ADR comprised anti-infective drugs and vaccines. Amoxicillin and Clavulanic acid association was Four (0.42%) lethal effects were observed in the study most frequently reported, and among the reactions reported patients, among this 3 (0.32%) from female and 1 (0.11%) for this antibiotics. Among antimicrobials, the most common from male patients, which is contrast to an study showed drugs were Cotrimoxazole (15%) and Fluoroquinolones 28(2.3%) patients died as a direct result of the index ADRs (15%) while Phenytoin (67%) and Carbamazepine (20%) and gastrointestinal bleeding was responsible for 15 (54%) were the commonest antiepileptics. Antibiotics were the deaths, while aspirin in isolation or in combination with other treatment group that precipitated the most ADRs (16.3%), drugs was implicated in 17 (61%) deaths. opiates (18; 9.1%), corticosteroids (11; 5.6%). One hundred Causality assessment revealed, twenty (2.11%) ADRs were and thirty one (13.79%) ADRs were produced by related to drugs, 759 (79.89%) ADRs were Non-steroidal Anti-Inflammatory Drugs (NSAIDs), in this probably related to drugs, 165 (17.37%) ADRs were Aspirin produced majority of ADRs (n=35), followed by possibility related to drugs and 6 (0.63%) ADRs were Paracetamol 27, Diclofenac sodium 21, Naproxen 18, unlikely related to drugs. Similar findings were noted from Indomethacin 12, Celecoxib 7, Ibuprofen 7 and Nimesulide 4 other studies also, most of the reported ADRs belonged to the ADRs. This observation was consistent with a study, Non category of probable (70%) followed by possible in 30% of steroidal anti-inflammatory drugs and diuretics were most the cases. All ADRs were found to be probably related to the commonly implicated, Aspirin was the most common drug antibiotic administration. Causality assessment revealed that no reactions were certain or definite, 9 were probable and In the cardiovascular drugs, Carvedilol produced 31 ADRs followed by Amlodipine 27, Nifedipine 16, Verapamil 10, and Probability assessed revealed that 22 ADRs were certain, Diltiazem 6 ADRs. Hyperkalemia as one of the reasons for 758 ADRs were probable or likely, 160 ADRs were possible, Indian Journal of Pharmacy Practice Volume 6 Issue 2 Apr - Jun, 2013 Palanisamy S - A Prospective Study on Adverse Drug Reactions in a Tertiary Care South Indian Hospital 5 ADRs were unlikely, 5 ADRs were un-assessable or events, resulting in increased healthcare costs. It is important unclassifiable and none of the ADRs was conditional or to motivate health care professionals to understand their role unclassified. This is contrast to a study in that causality and responsibility in the detection, management and reporting assessment showed 46% possible, 23% probable and 29% of suspected ADRs and all essential activities for optimizing were un-assessable because the drug was unknown. Three patient safety. The reporting of ADRs needs continuous hundred and eighty four (40.42%) ADRs were definitely stimulation. It is important to achieve the development of a preventable, 294 (30.95%) ADRs were probably preventable positive attitude towards pharmacovigilance among health and 272 (28.63) ADRs were identified as not-preventable. care professionals, including pharmacist, so that ADRs These findings were similar to a study, of the 316 reported reporting becomes an accepted and understood routine. ADRs, majorities (56%) of the reaction were predictable and A limitation of the study was that the rate of ADR related 33 % of the reactions were preventable. The findings were different from other studies in that a majority of ADRs were hospitalization was probably an underestimate due to underreporting or misclassification, because all ADRs not preventable (n=57; 79%). None of the ADRs were possibly were not identified. The actual number of ADRs in definitely probable, 84 ADRs were probable preventable and our patients might also have been higher than the number of ADRs detected and reported during hospitalization because In 89.89 (n=854) percent patients, the reactions were of relatively short length of stay in our hospital (mean managed by withdrawing the offending drug and dose was altered in 10.11 (n=96) percent of patients. Similar findings were observed in another study; In 90% of the cases, the REFERENCES
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Indian Journal of Pharmacy Practice Volume 6 Issue 2 Apr - Jun, 2013
Studienübersicht Onkologie Dezember 2012Preoperative chemoradiotherapy versus chemotherapy alone in NSCLC patients with mediastinal lymph node Bevacicumab, pemetrexed and cisplatin, or erlotinib and bevacizumab, non-squamous NSCLC stratified by EGFR-mutation status. phase II including biopsy at A Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab versus Docetaxel and Pla