“SENSITIVE, SELECTIVE AND RAPID HIGH PERFORMANCE …



A STUDY ON

ASSESSMENT OF ADVERSE DRUG REACTIONS IN TUBERCULOSIS PATIENTS

SYNOPSIS FOR

M PHARM DISSERTATION

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SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BY

RAMESH. S

B. Pharm

UNDER THE GUIDANCE OF

K.V. RAMANATH

M.Pharm, MBA (HRM & HSM), PhD

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DEPARTMENT OF PHARMACY PRACTICE

SAC COLLEGE OF PHARMACY

BG NAGARA

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

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|1 |Name of the candidate & Address |Mr. RAMESH. S |

| | |DEPARTMENT OF PHARMACY PRACTICE, |

| | |SAC COLLEGE OF PHARMACY, |

| | |BG NAGARA, NAGAMANGALA-TALUK, |

| | |MANDYA-DISTRICT, |

| | |KARNATAKA-571448. |

| | | |

| | |PERMANENT ADDRESS: |

| | |S/O SRINIVASULU. M, |

| | |NO 7, 1ST CROSS, NES COLONY, |

| | |MALAVALLI-TALUK, |

| | |MANDYA -DISTRICT, |

| | |KARNATAKA-571430. |

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|2 |Name of the institute |SAC COLLEGE OF PHARMACY |

| | |BG NAGARA, |

| | |NAGAMANGALA -TALUK, |

| | |MANDYA- DISTRICT, |

| | |KARNATAKA -571448. |

| | | |

|3 |Course of the study |MASTER OF PHARMACY IN PHARMACY PRACTICE |

| | | |

| | | 07/07/2010 |

|4 |Date of admission | |

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| 5 |Title of the topic | |

| | |A STUDY ON ASSESSMENT OF ADVERSE DRUG REACTIONS IN TUBERCULOSIS PATIENTS |

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|6 |Need for the study: |

| |According to WHO, Adverse Drug Reaction (ADR) is “Any response to a drug which is noxious and unintended and which occurs at |

| |doses normally used in man for prophylaxis, diagnosis or therapy of disease or for the modification of physiological function”. |

| |It is responsible for a significant number of hospital admissions with reported rates ranging from 0.3% to as high as 11%. Thus, |

| |this definition excludes overdose (either accidental or intentional), drug abuse, and treatment failure and drug distribution |

| |errors. |

| |Long duration of treatment for Tuberculosis patients with drugs like Isoniazid, Pyrazinamide, Rifampin, Ethambutol and |

| |Streptomycin – the drugs used above are potential to cause adverse drug reactions like hepatotoxicity, visual disturbance, |

| |arthralgia, headache, skin rashes etc. Patients with multiple drug therapy are prone to develop an adverse drug reaction due to |

| |alteration of drug or by synergistic effect. Multiple / intercurrent disease and multiple drug therapy are responsible for |

| |increased risk of developing an ADR.1 |

| |Tuberculosis is a contagious infection caused by an airborne bacterium, Mycobacterium tuberculosis.2 Early days physicians |

| |referred to Tuberculosis as phthisis, derived from the Greek term for wasting, because its clinical presentation consisting of |

| |weight loss, cough, fever and hemoptysis.3 |

| |Based on the surveillance and survey data WHO estimates that 9.27 million new cases of TB were found in 2007 (139 per 100000 |

| |population). India, China, Indonesia, Nigeria and South Africa rank 1st to 5th in terms of total number of incident cases. Asia |

| |(South East Asia and Western Pacific regions) accounts for 55% of global cases and the African region for 31% and other three |

| |regions (America, Europe and Eastern Mediterranean regions) accounts for small fractions of global cases. |

| |India ranks first in the estimated number of Tuberculosis cases and approximately to 1962 cases per 11,69016 population at the |

| |rate of 168 cases per 10,00000 population.4 |

| |Hence the government of India in collaboration with WHO and WORLD BANK launched RNTCP(Revised National Tuberculosis Control |

| |Programme) to ensure complete treatment and control of Tuberculosis as well as to reduce its social burden, but the anti-TB drugs|

| |cause higher incidence of Adverse Drug Reactions.5 |

| |Clinical Pharmacist plays a role in assessment and to identify the frequency of incidence among patients who are at greater risk |

| |of developing ADRs. |

| |In this context the present study is carried out with an objective of assessment of adverse drug reactions in tuberculosis |

| |patients. |

| |6.2 Review of literatures: |

| |A study was conducted by Rao MK, Gupta PP, Chaudhary HN et al. on “Study of adverse drug reactions in various regimens under |

| |RNTCP-DOTS strategy- preliminary results”. Its main objective was to assess the adverse drug reactions of various RNTCP (Revised |

| |National Tuberculosis Control Programme) regimens under DOTS (Direct Observed Treatment, Short-Course) strategy. The study was |

| |conducted on the tuberculosis patients of Nehru Hospital of BRD Medical College Gorakhpur (UP). In the initial 71 patients were |

| |included in the study, 54 were males and 17 females were between the ages of 5-80 years. ADRs were found more in category 1st |

| |treatment regimens followed by category 2nd and 3rd. Mean age of the patients who had maximum ADRs belonged to the age group of |

| |20-35 years. Mean age of males developing ADR was 34.7 ± 13.49 and of females 23.75 ± 9.92. This study concluded that 1st regimen|

| |treated patients had maximum ADRs who belonged to 20-35 age group. Maximum patients showed ADRs in first and second month of |

| |therapy.5 |

| |Gholami K, Kamali E, Hajiabdolbaghi M et al. conducted a study on “Evaluation of anti-tuberculosis induced adverse reactions in |

| |hospitalized patients”. The main objective of the study was to assess the rate of adverse drug reactions induced by anti-TB drugs|

| |which was conducted for a period of one year in the infectious disease department, at Imam tertiary teaching hospital in Iran. |

| |The casualty and severity of the reaction were determined using Naranjo algorithm and Hartwig questionnaire. Total no of 81 ADRs |

| |was detected in this study and recognized as major cause of hospital admission in 11 patients where liver and biliary system were|

| |affected frequently. Hepatitis was observed in 21 patients leading to death in 2 patients. This study concluded that anti-TB |

| |drugs could cause significant adverse effects both in quantity and severity leading to hospitalization and even death.6 |

| |A study was conducted by Chhetri AK, Saha A, Verma SC et al. on “A study of adverse drug reactions caused by first line anti |

| |tuberculosis drugs used in DOTS therapy in Western Nepal, Pokhara”. Its main objective was to study the adverse drug reactions |

| |occurring during DOTS therapy and to assess their casualty, severity and predisposing factors. Patients undergoing DOTS treatment|

| |during the 5 month study period at the Regional Tuberculosis Center (RTC) in Pokhara, Western Nepal were studied. Casualty and |

| |severity assessment was carried out as per the Naranjo scale and modified Hartwig and Siegels scale. Statistical analysis was |

| |done to determine the predisposing factors. Totally 137 patients were studied among whom 54.74% reported ADRs, Isoniazid |

| |accounted for 49.3%. The most commonly reported ADR was tingling and burning sensation in hands and feet experienced by 32 |

| |patients. This study demonstrated that occurrence of ADRs from anti-TB drugs was high in population of Western Nepal.7 |

| |Kishore PV, Palaian S, Ojha P et al. conducted the study on “Pattern of adverse drug reactions experienced by Tuberculosis |

| |patients in a tertiary care teaching hospital in Western Nepal”. Its main objective was to study the pattern of ADRs caused by |

| |the antitubercular drugs and study the demographic and ethnic details of the patients experiencing ADRs. This study was done for |

| |the period of 5years on TB patients who received treatment at the Manipal Teaching Hospital, Pokhara, Nepal. Altogether 326 |

| |patients were identified among which 40 experienced atleast one ADR, hepatobiliary system was the most common system affected. |

| |Isoniazid and Pyrazinamide were the suspected drugs responsible for 32.32% of total ADRs. Majority of ADRs were due to multiple |

| |drug therapy and were mild. This study concluded that ADRs due to anti-TB drugs are common.8 |

| |A study was conducted by Ghosh S, Malik SKr, Gupta A et al. on “A prospective, observational cohort study to elicit adverse |

| |effects of anti-TB drugs among patient treated for active Tuberculosis”. Its main objective was to elicit adverse effects of |

| |anti-tubercular drugs among patients treated for active tuberculosis of Mathura Hospital (UP) for 1 year. Total 212 newly |

| |diagnosed pulmonary and extra pulmonary tuberculosis patients were included. Out of the 212 patients treated for TB, 66.04% were |

| |male and 33.96% were female, 43 patients had major side effects - 15 patients experienced jaundice, 21 patients experienced the |

| |syndrome and 7 patients experienced skin rash. This study concluded that male patients above 35 years of age were more prone to |

| |major adverse effect than female.9 |

| | |

| |Khalili H, Dashti-Khavidaki S, Rasoolinejad M et al. conducted the study on “Antituberculosis drugs related hepatotoxicity; |

| |incidence, risk factors, pattern of changes in liver enzymes and outcome”. Its main objective was to evaluate the rate and the |

| |time of incidence pattern of alterations in liver enzyme, risk factors and outcome of antituberculosis drugs induced |

| |hepatotoxicity in Iranian TB patients. In a prospective cohort study, 102 patients (68 male, 34 female) with TB diagnosis were |

| |followed during antituberculosis drug treatment course. Drug induced hepatotoxicity was detected in 32 patients where as HIV and |

| |Hepatitis C virus infections, concomitant use of hepatotoxic drugs and abnormal baseline serum alanine aminotransferase and |

| |aspartate aminotransferase level were risk factors for antituberculosis drugs. The study concluded that in anti-TB drugs |

| |hepatotoxicity was a major problem in Iranian tuberculosis patients and cause treatment interruption in 31.37% of patients.10 |

| |Suzuki Y, Miwa S, Shirai M et al. conducted a study on “Drug Lymphocyte Stimulation Test (DLST) in the diagnosis of adverse |

| |reactions to antituberculosis drugs”. Its objective was to evaluate the usefulness of the DLST to determine anti TB drugs causing|

| |side effects. A prospective study was conducted on 436 Tuberculosis patients without HIV infection who were admitted to Tenryu |

| |Hospital, National Hospital Organization for TB treatment for 5 years. Out of 436 patients, 69 had certain adverse drug |

| |reactions. Of the 261 agents that underwent DLST & Drug Provocation Test (DPT), 28 agents in 20 patients were shown positive by |

| |DLST and 67 agents in 46 patients were identified as causative drug by DPT. The sensitivity of DLST was only 14.9% for the given |

| |anti tubercular drugs (Isoniazid, Rifampicin, Ethambutol and Pyrazinamide). The study concluded that DLST offers little |

| |contribution to the detection of causative agents in patients with adverse anti TB drug reactions.11 |

| |6.3 OBJECTIVES OF THE STUDY: |

| |Primary objective: |

| | |

| |To assess the adverse drug reactions in Tuberculosis patients. |

| |Secondary objectives: |

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| |To identify the frequency of incidence of ADRs. |

| |To detect and document the anti tubercular drug resistance. |

| |To develop ADRs brochures for doctors and providing alert cards for the patients. |

| |To carry out the casualty and severity assessments of ADRs. |

| | |

| |MATERIALS AND METHODS: |

| |7.1 Study design: The study is a prospective observational study. |

| |7.2 Sources of data / Materials: |

| |Source of data: |

| |Patient TB card |

| |Study Materials: |

| |Patient profile form, Adverse drug reaction documentation and evaluation form, suspected adverse drug reaction notification form,|

| |adverse drug reaction alert card, Naranjo scale, WHO probability scale, Hartwig and Siegel’s scale. |

| |Patient profile form: |

| |It will be used to record all the information such as name, age, sex, location, literacy, ethnic group, socioeconomic status, |

| |life style factors and dietary factors, pregnancy status (for female patients) and outcomes of delivery and birth in case of |

| |pregnant patients, any concurrent diseases and medications other than Anti-TB agents that the patient may be taking. |

| |Adverse drug reaction(ADR) documentation and evaluation form: |

| |It will be used to record all the information such as name, age, sex, reason for admission, brief description of reaction, |

| |relevant investigations with dates, relevant past history, the onset and severity of the ADR experienced, the impact of ADR on |

| |the treatment and work capacity of the patient, drug involved, dose of the drug, route and frequency time. |

| |Suspected adverse drug reaction notification form: |

| |This will be used to record the suspected drug, route, dose, frequency, date of starting the suspected drugs and the date of |

| |onset of suspected ADR, brief description of the suspected ADR. |

| |Adverse drug reaction alert card: |

| |It will be used to record the patient name, age, sex, address, suspected drug, description of reaction, date of reaction. This |

| |card will be produced to the doctor by the patient at the time of consultation. |

| |Naranjo scale: |

| |This scale is used to categorize ADRs as definite, probable, possible and unlikely due to a certain drug. It is based on the |

| |score calculated on the basis of points given for each of ten questions that comprises the scale. |

| |WHO probability scale: |

| |It is used to categorize ADRs as certain, probable, possible, unlikely and conditional. |

| |Hartwig and Siegels scale: |

| |It is used to categorize ADRs as mild, moderate and severe. |

| |7.3 Study criteria: |

| |All the patients who are under the treatment of Anti-TB drugs will be screened for ADRs and assessment will be done by using |

| |Naranjo, WHO, Hartwig and Siegels scale. |

| |7.4 Study procedure: |

| |All the patients who will be under the treatment for TB as per the criteria, guidelines, various regimens and other comorbid |

| |treatment cases will be screened for the study. These patients will be observed for various ADRs and relevant findings will be |

| |recorded during clinical visit of the patients and their responses will be documented. The documented findings will be analyzed |

| |by using suitable statistical method. |

| |7.5. Does the study require any investigation or interventions to be conducted on patients? |

| |Yes |

| |7.6. Has Ethical Clearance been obtained from your Institution in case of above? |

| |The Ethical Committee Clearance will be obtained from the Institutional Ethical Committee of Adichunchanagiri Institute of |

| |Medical Sciences (AIMS) / RNTCP centers/ other centers where the study will be conducted. |

| |7.7. Duration of the study: |

| |The study will be conducted for a period of 9 months. |

| |7.8. Study Site: |

| |In the following centers, study will be conducted depending on the availability of |

| |patients and Ethical Committee Clearance. |

| |Adichunchanagiri Hospital and Research Center (AHRC), BG Nagara, Nagamangala Taluk, Mandya District and/or |

| |RNTCP centers at Mysore and/or |

| |BGS Global Hospital, Bengalur. |

| |List of references: |

| | |

| |Parthasarathi G, Olsson S. Adverse Drug Reactions. In: Parthasarathi G, Nyfort-Hansen K, Nahata MC. A Textbook of Clinical |

| |Pharmacy Practice. Chennai: Orient Longman Private Limited; 2004. p. 84-102. |

| |Tuberculosis. In: Beers MH, Fletcher AJ, Porter R, Berkwits M. The Merck Manual of Medical Information. 2nd ed. White house |

| |station: Merck Research Laboratories; 2003. p. 1125-30. |

| |Michael BK. Tuberculosis. In: Kimble MAK, Young LY, Alldredge BK, Corelli RL, Guglielmo BJ, Kradjan WA et al. Applied |

| |Therapeutics. 9th ed. Maryland: Lipincott Williams & Wilkins; 2009. p. 1-26. |

| |Bauquerez R, Blanc L, Bierrenbachi A, Brands A, Ciceri K, Falzan D et al. Global Tuberculosis Control 2009 Epidemiology, Strategy|

| |and Financing. Switzerland: Publications of World Health Organisation; 2009. p. 6-32. |

| |Rao MK, Gupta PP, Chaudhary HN, Shiv Prakash, Pandey. Study of adverse drug reactions in various regimens under RNTCP-DOTS |

|7 |strategy-preliminary results. Indian Journal of Pharmacology 2008;40(2):S148-50. |

| |Gholami K, Kamali E, Hajiabdolbaghi M, Shalviri G. Evaluation of antituberculosis induced adverse reactions in hospitalized |

| |patients. Pharmacy Practice 2006;4(3):134-8. |

| |Chhetri AK, Saha A, Verma SC, Palaian S, Mishra P, Shankar PR. A study of adverse drug reactions caused by first line anti |

| |tubercular drugs used in DOTS therapy in Western Nepal, Pokhara. Journal Pakistan Medical Association 2008;58(10):531-6. |

| | |

| |Kishore PV, Palaian S, Ojha P, Shankar PR. Pattern of Adverse Drug Reactions experienced by Tuberculosis patients in a tertiary |

| |care teaching hospital in Western Nepal. Pakistan Journal of Pharmaceutical Sciences 2008;21(1):51-6. |

| |Ghosh S, Malik SKr, Gupta A, Chaudhary R. A prospective, observational cohort study to elicit adverse effects of |

| |anti-Tuberculosis drugs among patients treated for active Tuberculosis. The Pharma Research 2010;3:10-6. |

| |Khalili H, Dashti-Khavidaki S, Rascolinejad M, Rezaie L, Etminani M. Anti-tuberculosis drugs related hepatotoxicity; incidence, |

| |risk factors, pattern of changes in liver enzymes and outcome. DARU Journal of Pharmaceutical Sciences 2009;17(3):163-7. |

| |Suzuki Y, Miwa S, Shirai M, Ohba H, Murakami M, Fujita K et al. Drug Lymphocyte Stimulation Test in the diagnosis of Adverse Drug|

| |Reactions to anti Tuberculosis drugs. CHEST 2008;1-23. |

| |Rafei UM. Stopping Tuberculosis. New Delhi: WHO South East Asia Regional Office; 2002. |

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| 9 |Signature of the candidate |RAMESH. S |

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|10 |Remarks of the guide |The proposed research work is original and designed on |

| | |rational basis. It would be a good contribution. |

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|11 |11.1 Name and Designation of Guide |K.V. RAMANATH |

| | |M. Pharm, MBA (HRM &HSM), PhD. |

| |ACA/CDC/PGT-M.Ph/SACP/36/2008-09 |Associate Professor, |

| | |Department of Pharmacy Practice, |

| | |SAC College of Pharmacy, |

| | |BG Nagara, Karnataka -571448. |

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| |11.2 Signature | |

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| |11.3 Co-Guide |NOT APPLICABLE |

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| |11.4 Signature |NOT APPLICABLE |

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| |11.5 Head of the Department |Dr. BJ MAHENDRA KUMAR |

| | |M. Pharm, PhD. |

| | |Prof. & H.O.D of Pharmacy Practice, |

| | |SAC College of Pharmacy, |

| | |BG Nagara -571448. |

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| |11.6 Signature | |

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|12 |12.1 Remarks of the Principal | |

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| |12.2 Signature | |

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