SAFETY EVALUATION OF ANTITUBERCULAR THERAPY

UNDER REVISED NATIONAL TB CONTROL PROGRAMME

Mrs Leelavathi D Acharya

Selection Grade Lecturer

Dept. of Pharmacy Practice

MCOPS, Manipal

CONTENTS

Introduction

Objectives

Methodology

Results and discussion

Conclusion

INTRODUCTION

The WHO declared tuberculosis a The WHO declared tuberculosis a

global emergency in 1993.global emergency in 1993.

To intensify efforts to control TB, To intensify efforts to control TB,

Government of India gradually replaced Government of India gradually replaced

NTP by the Directly Observed NTP by the Directly Observed

Treatment Short course (DOTS) Treatment Short course (DOTS)

programmeprogramme

Revised National TB Control Programme Revised National TB Control Programme (RNTCP)(RNTCP)

Various studies on DOTS / daily regimen conducted till date evaluated the efficacy of dosage regimen

There are studies evaluating the safety in regular regimen however few studies have been done till date to evaluate the same in patients on DOTS regimen

There is a need to study the safety of patients on DOTS through monitoring of

ADRs in a hospital set-up

OBJECTIVES

To evaluate the safety of Antitubercular Therapy in patients on DOTS by monitoring adverse drug reaction

To determine the incidence and pattern of ATT induced ADRs in the patients on DOTS

To analyze the various parameters like causality and severity of reported ADRs

METHODOLOGY

Definition

WHO definition of ADRs

Study Sites

1.Department of Tuberculosis and Respiratory Diseases, KasturbaHospital, Manipal

2.DOTS centre Kasturba Hospital, Manipal

3.DOTS centre Government Hospital, Udupi.

Ethical Clearance

Ethical committee of Kasturba Hospital, Manipal, approved the study.

Study Duration and Design

Study Duration

1st October 2005 to 31st May 2006.

Study Design

Prospective study carried out on In-patients

Identification of ADRsIdentification of ADRs

Participation in ward roundsParticipation in ward rounds Review of patient case filesReview of patient case files Interviewing patientsInterviewing patients

DocumentationDocumentation

Follow-upFollow-up

Demographic of the patientDemographic of the patient Type of TB Patient, type of TB, Type of Type of TB Patient, type of TB, Type of

DOTS treatmentDOTS treatment

Incidence of ADRIncidence of ADR

Most common ADRsMost common ADRs

Predisposing factorsPredisposing factors

Type of ADRsType of ADRs

Time of onsetTime of onset

Management and outcomeManagement and outcome

Causality and severityCausality and severity

RESULTS AND DISCUSSION

Total Number of patients → 94Total Number of patients → 94

DOTS centre, Kasturba Hospital, DOTS centre, Kasturba Hospital,

Manipal → 7Manipal → 7

Govt. Hospital, Udupi → 87Govt. Hospital, Udupi → 87

Total number of ADRs → 21Total number of ADRs → 21

28 (30%)

66 (70%)

Female Male

Age group (years)

No. of patients

(%)

18-40 49 52

41-60 33 35

61 and above

12 13

1 b) Age-group wise distribution of patients

1 (a) Gender wise distribution of patients

1. Demographic Characteristics of TB Patients

RESULTS AND DISCUSSION

2. Type of TB patients

Type of patients No. of patients (%)

New 41 43.61

Relapse 30 31.91

Transfer in 0 0

Failure 10 10.63

Treatment after default

12 12.76

Other 1 1.06

3. Type of Tuberculosis

92,( 96%)

4, (4%)

Pulmonary Extra-pulmonary

4. Type of DOTS treatment

4, (4%)38,

( 40%)

52,( 56%)

Category-I Category-II Category-III

5. Incidence of Adverse Drug Reactions

5,( 31%)

11,( 69%)

Patients with more than two ADRs

Patients with one ADR

The study showed high incidence of 17.02% of ADRs

6. Most Common ADRs

S.No SymptomNumber of reactions

(%)

1 Gastritis 7 33.332 Skin reactions 3 14.28

3 Hepatitis 2 9.52

4 Anorexia 1 4.76

5 Dizziness 1 4.76

6 Insomnia 1 4.76

7 Ototoxicity 1 4.76

8 Peripheral neuropathy 1 4.76

9 Psychosis 1 4.76

10 Vertigo 1 4.76

11 Weakness 1 4.76

12 Arthralgia 1 4.76

7. Predisposing Factors

38.09%

14.28%

38.09%

4.76% 4.76%

0

1

2

3

4

5

6

7

8

Nu

mb

er

of A

DR

s

Multipledrug

therapy

Age Nil Alcoholic Dose

8. Type of ADRs

Type No. of ADRs (%)

Type A 6 28.57

Type B 15 71.43

S.No.Suspected ATT

drug/drugsDOTS

CategoryType of ADR

Onset of ADR(Within)

1. HREP I Gastritis a day

2. HR III Skin rash a week

3. S II Skin rash a week

4. HREP II Gastritis a day

5. RH II Dizziness a week

6. S II Ototoxicity Sixth week

7. HREP II Gastritis Second week

8. HREPS II Insomnia Third week

9. HREP I Gastritis Second week

10. RH I Weakness Second week

H: Isoniazid, R: Rifampicin, P: Pyrazinamide, S: Streptomycin.

9. Time of Onset of ADRs

S.NO

Suspected ATT

drug/drugsDOTS Category Type of ADR Onset of ADR

11. HREP I Anorexia a week

12. HREP I Hepatitis Second week

13. P III Hepatitis Second week

14. H IIPeripheral

neuropathyFifth week

15. HREP I Skin rash a week

16. H II Psychosis a week

17. S II Vertigo Fourth week

18. HREP II Gastritis Third week

19. HREP I Gastritis Third week

20. HREP I Gastritis a week

21. HEP I Arthralgia Second week

H: Isoniazid, R: Rifampicin, P: Pyrazinamide, S: Streptomycin.

Time of onset -continued

10. Management of ADRs

S.N0

Management

Treatment Given

Specific

Symptomatic

Nil

1.1.Drug Drug withdrawnwithdrawnn=3n=3

11 22 00

2.2.Dosage Dosage reducedreducedn=0n=0

00 00 00

3.3.No No changechangen=18n=18

00 99 99

11. Outcome of ADRs

OutcomeNumber of

cases(%)

RecoveryRecovery 1313 61.9061.90

ContinuingContinuing 66 28.5728.57

UnknownUnknown 22 9.529.52

FatalFatal 00 00

12. Causality AssessmentWHO Probability

Scalen =61

Naranjo’s algorithmn =61

Certain / DefiniteCertain / Definite 55 00

ProbableProbable 22 22

PossiblePossible 4747 5454

Unassessable / Unassessable / UnclassifiableUnclassifiable 77 NANA

UnlikelyUnlikely 00 55

Conditional / Conditional / UnclassifiedUnclassified 00 NANA

13. Severity Assessment of ADRs by Hartwig et. al . Severity Scale

0,( 0%) 30,

( 49%)

31,( 51%)

Mild Moderate Severe

CONCLUSION

Although incidences of ADRs were

high as 17.02%, most of them were

mild and moderate, which shows that

DOTS therapy is safer as compare to

daily regimen. However monitoring of

ADRs is needed for drug safety and

patient compliance in DOTS.

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