Operational Guide for National Tuberculosis Control Programmes on the Introduction and Use of Fixed-Dose Combination Drugs
(2002; 81 pages) View the PDF document
Table of Contents
View the documentACKNOWLEDGEMENTS
View the documentLIST OF ACRONYMS AND ABBREVIATIONS
View the documentPREFACE
View the documentKEY POINTS
Open this folder and view contents1. INTRODUCTION
Close this folder2. PROGRAMMATIC AND MANAGERIAL REQUIREMENTS FOR FDCS
Open this folder and view contents2.1 DOTS strategy
View the document2.2 FDC formulations in the WHO Model List of Essential Medicines
View the document2.3 Treatment regimens using FDCs
View the document2.4 Justification for dosage forms and dosage schedules
Open this folder and view contents3. FDC DRUG MANAGEMENT
Open this folder and view contents4. ENSURING THE QUALITY OF FDC DRUGS
Open this folder and view contents5. HOW TO INTRODUCE AND CHANGE OVER TO A REGIMEN WITH 4-DRUG FDCS/2-DRUG FDCS: PLANNING AND IMPLEMENTING A "SCENARIO"
View the documentAnnex 1. Glossary and use of terms
View the documentAnnex 2. WHO Certification Scheme - Model Certificate of a Pharmaceutical Product1
View the documentAnnex 3. WHO Certification Scheme - Model Batch Certificate of a Pharmaceutical Product
View the documentAnnex 4. Example of an order form for anti-TB drugs for treatment facilities
View the documentAnnex 5. Steps in the quantification of anti-TB drugs using consumption-based information
View the documentAnnex 6. Suggested reading
View the documentRequest for feedback on the guide
 

2.3 Treatment regimens using FDCs

The standardized treatment regimens for the different categories of TB cases, and dosage schedules (number of tablets) in relation to body weight, are presented in Tables 3, 4 and 5.

Table 1: The recommended dosage of essential first-line anti-TB drugs

Drug
(abbreviation)

Mode of action

Recommended dose (dose range) in mg/kg body weight

   

Daily

Intermittent 3 times per week

rifampicin (R)

bactericidal

10 (8-12)

10 (8-12)

isoniazid (H)

bactericidal

5 (4-6)

10 (8-12)

pyrazinamide (Z)

bactericidal

25 (20-30)

35 (30-40)

streptomycin (S)

bactericidal

15 (12-18)

15 (12-18)

ethambutol (E)

bacteriostatic

15 (15-20)

30 (25-35)

Although used in some programmes, WHO does not recommend the use of thioacetazone (T) because of the risk of severe toxicity, particularly in HIV infected individuals. In general, thioacetazone should be replaced by ethambutol.

Table 2:Fixed-dose combinations from the WHO Model List of Essential Medicines (revised April 2002)

Drug

Dose form

Strength for Daily use

Strength for intermittent use 3 times per week

rifampicin + isoniazid [RH]

Tablet

150 mg + 75 mg
300 mg + 150 mg

150 mg + 150 mg

 

Tablet or pack of granules*

60 mg + 30 mg

60 mg + 60 mg

ethambutol + isoniazid [EH]

Tablet

400 mg + 150 mg

-

isoniazid + thioacetazone [HT]**

Tablet

100 mg + 50 mg
300 mg + 150 mg

-
-

rifampicin + isoniazid + pyrazinamide [RHZ]

Tablet
Tablet or pack of granules*

150 mg + 75 mg + 400 mg
60 mg + 30 mg + 150 mg

150 mg + 150 mg + 500 mg -

rifampicin + isoniazid + pyrazinamide + ethambutol [RHZE]

Tablet

150 mg + 75 mg
+ 400 mg + 275 mg

-
-

* For paediatric use

** Although used in some programmes, WHO does not recommend the use of thioacetazone (T) because of the risk of severe toxicity, particularly in HIV infected individuals. In general, thioacetazone should be replaced by ethambutol.

Table 3: Recommended treatment regimens for each treatment category

Tuberculosis diagnostic category

Tuberculosis patients

Tuberculosis treatment regimens

   

Initial phase (daily or 3 times per week*)

Continuation phase (daily or 3 times per week*)

I

New smear-positive patients; new smear-negative PTB with extensive parenchymal involvement; severe concomitant HIV disease or severe forms of extrapulmonary TB

2 RHZE**

4 RH***

II

Previously treated sputum smear-positive PTB:
- relapse;
- treatment after interruption;
- treatment failure†

2 RHZES/1 RHZE

5 RHE

III

New smear-negative PTB (other than in Category 1) and less severe forms of extrapulmonary TB.

2 RHZE††

4 RH***

* Direct observation of treatment intake is required for the initial phase in smear positive cases, and always when treatment includes rifampicin.

** Streptomycin may be used instead of ethambutol.

*** 4RH may be replaced by 6 EH daily when supervision of treatment is not possible. However, preliminary data from a recent clinical trial have shown that 6EH is much less effective than 4RH in terms of cure, with higher failure and relapse rates.

In meningitis: 2 RHZS/4 RH or 2 RHZS/4 (RH)3, replacing ethambutol with streptomycin.

† Whenever possible, drug sensitivity testing is recommended before prescribing category II treatment in failure cases. In patients with proven MDR-TB, it is recommended to use category IV regimens which are not described in this Guide (please refer to guidelines for management of failure and chronic cases in MDR-TB).

†† Ethambutol may be omitted for patients with non-cavitary, smear-negative pulmonary TB who are known to be HIV-negative, patients who are known to be infected with fully drug-susceptible bacilli. Young children with primary TB should be given 3 drugs combination only (without ethambutol).

R - rifampicin; H - isoniazid; Z - pyrazinamide; E - ethambutol; S - streptomycin; PTB - pulmonary tuberculosis.

Note: Standard code for TB treatment regimens. Each anti-TB drug has an abbreviation (shown in the Tables above). Aregimen consists of 2 phases. The number before a phase is the duration of that phase in months. Anumber in subscript (e.g. 3) after a letter is the number of doses of that drug per week. If there is no number in subscript after a letter, then treatment with that drug is daily. For example: 2 RHZE/4 (RH)3. The duration of the initial phase is 2 months and drug treatment is daily, with rifampicin (R), isoniazid (H), pyrazinamide (Z) and ethambutol (E). The continuation phase is 4 (RH)3. The duration is 4 months, with rifampicin (R) and isoniazid (H) three times per week.

Table 4: Dosage schedules for adults: number of 4-, 3- and 2-drug FDC tablets

Patient body weight (kg)

Initial phase

Continuation phase

 

2 months

4 months

or 6 months*

 

Daily

or Daily

or 3 times per week

Daily

or 3 times per week

Daily

 

RHZE**
150 mg+75 mg+400 mg+275 mg

RHZ
150 mg + 75 mg + 400 mg

RHZ
150 mg +150 mg + 500 mg

RH
150 mg + 75 mg +

RH
150 mg + 150 mg

EH
400 mg +150 mg

30-39

2

2

2

2

2

1.5

40-54

3

3

3

3

3

2

55-70

4

4

4

4

4

3

71 and more

5

5

5

5

5

3

R - rifampicin; H - isoniazid; Z - pyrazinamide; E - ethambutol

* 4RH may be replaced by 6 EH daily when supervision of treatment is not possible. However, preliminary data from a recent clinical trial have shown that 6EH is much less effective than 4RH in terms of cure, with higher failure and relapse rates.

** Maximum recommended daily dose of rifampicin in FDCs is 750 mg.

Table 5:Dosage schedules for smear-negative children: number of 3- and 2-drug FDC tablets

Patient body weight (kg)

Initial phase

Continuation phase

 

2 months

4 months

 

Daily

or Daily

or 3 times per week

 

RHZ
60 mg+30 mg+150 mg

RH
60 mg+30 mg

RH
60 mg+60 mg

<7

1

1

1

8-9

1.5

1.5

1.5

10-14

2

2

2

15-19

3

3

3

20-24

4

4

4

25-29

5

5

5

R - rifampicin; H - isoniazid; Z - pyrazinamide

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