Preventive therapy problems in clinical practice
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PREVENTIVE THERAPY PROBLEMS IN CLINICAL PRACTICE. Uz. Dr. Asiye İNAN SÜER Altındağ , Ankara TB Control Dispensary No. 3 05.04.2013. I have no conflicts of interest to declare. Preventive therapy (PT). *An essential component of national tuberculosis (TB) control programme

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Preventive therapy problems in clinical practice


Uz. Dr. Asiye İNAN SÜER

Altındağ, Ankara TB Control Dispensary No.3


Preventive therapy pt
Preventive therapy (PT)

*An essential component of national tuberculosis (TB) control programme

*One of the most important duty of tuberculosis control dispensary (TCD):

Preventive therapy at persons with increased risk of TB

Decision to pt
Decision to PT

  • Hospital or TCD

  • Exclusion of active TB disease’

  • Not examined for active TB : propability of isoniazid (H) resistance

Application at tcd

To fill “Preventive Chemotherapy Form”

Chest X-ray


Symptoms and medical history

Hepatic enzyme measurement (>35 years or having risk factors)

Application at TCD

Application at tcd training
Application at TCD-Training

İnformation about preventive therapy

  • Treatment duration

  • Close follow up

  • Regular use of drug

  • Side effects

  • Discontinue treatment at symptom onset, then contact TCD

Application at tcd medication
Application at TCD-Medication

  • Planning treatment regimen and dosage

  • Monitoring plan in medical record

  • Free of charge

  • Periodically (usually monthly) given drug (at first meeting 15 days, then 30 days)

  • Pyridoxine (B6 vit)10 mg/day (at risk of peripheral neuropathy)

  • Give appointment and TCD’s telephone number

Conditions that is necessary alternative regimens
Conditions that is necessary alternative regimens

-Serious side effect with H/or history

-Not suitable 6-9 months treatment

-Contacts of H resistance TB case

-Contacts of MDR TB case

Alternative regimens
Alternative regimens

4 months Rifampin (4R)

(better completion, less toxicity than 9H)

3/4 months Isoniazid+Rifampin (3/4HR)

(equivalent effectiveness, completion of therapy and toxicity has been the same as with H)

3 months İsoniazid+ Rifapentin (3H+RPT)

(>12 years, alternative for 9 H)

Efficacy of 3 months of rifampin for the prevention of tb patients with silicosis

Efficacy of 3 months of Rifampin for the Prevention of TBPatients with Silicosis

Hong Kong Chest Service. Am Rev Respir Dis 1992;145:36-41

Treatment of mdr tb contacts
Treatment of MDR-TB contacts

*Q/QE may be safer, better tolerated .

*Recommendations are based on expert opinion.

Lobue P, Menzies D. Respirology 2010,15:603-622

Follow up treatment
Follow up treatment

  • Periodic control (monthly)

  • Ask: Symptoms- side effects and compliance

  • Train and support

  • Chest X-ray control (three months)

  • Compliance problems: DOT

  • Other hepatotoxic medications

Decision of treatment completion
Decision of treatment completion

According to pause period:

6 months PT--- 9 months

9 months PT--- 12 months

4 months R-PT---6 months

completion is acceptable

*Am J Respir Crit Care Med 2000;161:S221-S247

Problems of application
Problems of application

A-In the beginning of PT

B-At follow up period

Pt in turkey 2013 questionnaire
PT in Turkey-2013(Questionnaire )

  • Aim: PT application and problems faced with/recognized during PT

  • Method: Send to 81 province TB coordinators also all TCDs in İstanbul and Ankara by mail

  • Answer : 69 Questionnaire forms collected

    (41 TB coordinators, İst-23 TCDs, Ank-5 TCDs)


Provinces those answered the Questionnaire (yellow)

A problems faced with in the beginning of pt
A-Problems faced with in the beginning of PT

1-Over indication

2-Wrong medication

3-PT neglicance

4-Age related problems

5-PT without TCD follow up

6-Convincement of person/family

Over indication
Over indication

1-Active TB case

2-History of TB

3-Acut liver disease PT contrindicated

Wrong medication
Wrong medication

PT for H resistance/MDR TB case contacts

Questionnaire :Treatment of MDR LTBI

No------45 , No answer---1 Yes-----23

3 drug?

12 H,

5 H/R/HR

3 different regimen (ZQ/PAS-Q/ PROT-Q/PROT-Z)

Pt negligence
PT negligence

-Physicians knowledge about PT

-Physicians belief about PT

-Lack of HCWs at TCDs

- Lack of experience

Physician s opinions about preventive therapy
Physician’s opinions about Preventive Therapy*

  • A questionnaire was applied to 130 physicians from different specifications

Soysal F. Solunum 3;27-30, 2001

Age related problems
Age related problems

  • National TB diagnosis and treatment guideline: Preventive therapy for contacts of TB <35 age

  • The decision to treat LTBI at over 35 years should be made after careful consideration of risks and benefits.

  • Preventive therapy at immunesupressed patients: most of over 35 years, no common side effects

Age related risk of hepatotoxicity
Age-related risk of hepatotoxicity

  • A systematic review, 18.610 participants, 7 relevant studies

  • The median rate of hepatotoxicity;

    aged<35 %0,2

    aged ≥35 %1,7

    “The use of H for the treatment of LTBI is safe in older patients with clinical or biochemical monitoring.”

    Kunst H. Int J Tuberc Lung Dis 2010

Preventive therapy without tcd follow up
Preventive therapy without TCD follow up

-Decision of preventive therapy at hospital

-Not registered TCD

-H at drugstore


(Adherence to treatment? Clinical monitoring? Treatment completion?

Convincement of person family
Convincement of person/family

Parent/family training




B follow up problems
B- Follow up- problems

1- Side effects

2- Compliance to PT

3- Default

Side effects
Side effects

- Peripheral neuropathy

-Hypersensitivity (within days to weeks)

-Hepatic adaptation: asymptomatic, transient elevations of transaminase, %10-20

-Hepatotoxicity (within weeks to months)

nausea, vomiting, abdominal pain, jaundice

or unexplained fatigue


Treatment should be interrupted:

  • Transaminase elevation more than three times the upper limit of normal (ULN) in the presence of hepatitis symptoms and/or jaundice

  • Five times the ULN in the absence of symptoms

  • Bilirubin > 1.5 mg/dl

Isoniazid hepatotoxicity
Isoniazid Hepatotoxicity

  • H hepatotoxicity is age related

    3377 patients, 19 hepatotoxicity (5.6 per 1000)

    25-34 years 4.40

    35-49 years 8.54

    ≥50 years 20.83

  • H hepatotoxicity frequently occurs within the first 3 months

    After 1 month 2.75 per 1000

    After 3 month 7.20

    After 6 month 4.10

    Fountain FF. Chest 2005;128:116-23

Conditions that high risk of side effects
Conditions that high risk of side effects

  • Chronic ethanol consumption

  • Pregnant/ 3 months post-partum

  • Viral hepatitis/ pre-existing liver disease

  • Other hepatotoxic medications

  • ALT/AST or bilirubin abnormal

  • Over 35 years

    Baseline and follow-up serum ALT and bilirubin are recommended for patients with risk factors.

    ATS . Am J Respir Crit Care Med 2006;174:935-52

Suboptimal compliance
Suboptimal compliance

1-Duration of therapy (6-9 months)

2-Logistical issues

3-Adequate communication between health department staff and the patient

4-Negative attidutes towards PT

5- Change of the first indication

6-Difficulties in drug intake

Pt default
PT Default *

E.Kibaroğlu, 4nolu VSD/Ankara, 2012 Toraks kongre sunumu



Adherence to treatment in contacts real conditions alberta 1990 91
Adherence to treatment in contactsReal conditions: Alberta 1990-91

2007 Toraks kongresi, D.Emarson’ın sunumundan