This document provides information on tuberculosis (TB) treatment guidelines according to the Revised National Tuberculosis Control Program (RNTCP) in India. It discusses the classification of anti-TB drugs into 5 groups and the classification of TB cases. It also summarizes the management principles and treatment regimens for multi-drug resistant TB, rifampin-resistant TB, mono-drug resistant TB, poly-drug resistant TB, extensive drug resistant TB, and INH-resistant TB as defined by the RNTCP. Standard intensive and continuation phase regimens are provided for each TB classification.

1. PRESENTED TO: DR. SASWATI SINHA
PRESENTED BY:
VISHNU.R.NAIR,
PHARM.D INTERN(AMRI HOSPITAL ACADEMIC TRAINEE),
NATIONAL COLLEGE OF PHARMACY.

2. GENERAL INTRODUCTION

3. Full form: “Revised National Tuberculosis Control Program”
State-run TB control initiative of the Indian Government
Main objective of RNTCP : “To implement WHO guidelines for TB &
DOTS therapy strategy in Indian scenario”

4. CLASSIFICATION OF ANTI-TB DRUGS(RNTCP
CONCEPT)

5.  According to RNTCP guidelines  ATDs(Anti-tubercular drugs) have been classified into 5
groups, to facilitate proper management of the disease
 Groups include:
A. GROUP I(1st line oral drugs):
- Most potent
- Best tolerated oral drugs
- Used routinely
- Drugs include isoniazid(H), rifampin(R), pyrazinamide(Z) & ethambutol (E)
- Use code “RIPE” to remember drug names in this category!

6. B. GROUP II(Injectable drugs):
- Potent
- Bactericidal
- Injectables in nature
- Chiefly include aminoglycosides like Streptomycin(S), Amikacin(Am), Kanamycin(Km) &
(Capreomycin)
- Use code “SACK” to remember names of drugs in this category!

7. C. GROUP III (FLUOROQUINOLONES):
- Well-tolerated
- Bactericidal
- Oral drugs
- According to RNTCP guidelines  for all patients with drug-resistant TB  SHOULD RECEIVE
ONE FLUOROQUINOLONE!
- Drugs include Ofloxacin, Levofloxacin, Ciprofloxacin and Moxifloxacin
- Use code “CLOM” to remember names of drugs under this category!

8. D. GROUP IV(2nd line oral drugs):
- Less-effective
- Bacteriostatic
- More toxic than 1st line oral agents!
- Drugs include ethionamide, prothionamide, cycloserine, terizidone, PAS, rifabutin and
rifapentine.
- Use code “PP-RR-ECT” to remember name of drugs in this category!
E. GROUP V(Unclear efficacy drugs):
- Drugs with unclear efficacy(Use code “CCC-LIB” to remember name of drugs in this category!)
- Not recommended for MDR-TB!
- May be used as RESERVE DRUGS (in XDR-TB)!
- Drugs include bedaquiline, clarithromycin, clofazimine, clofazimine, linezolid, co-amoxiclav
and imipenem-cilastatin.

9. CLASSIFICATION OF TB CASES(RNTCP
CONCEPT)

10.  For selection of appropriate ATT(Anti-tubercular therapy)  RNTCP(2016) has classified TB
cases into:
A. DRUG-SENSITIVE TB:
- In this case  patient’s bacilli  susceptible to all 1st line drugs
- Such patients  may include:
i. Newly-diagnosed patients
ii. Patients, pre-treated with TB in past
B. MULTI-DRUG RESISTANT TB(MDR-TB):
- In this case  patient’s bacilli  resistant to BOTH RIFAMPIN & INH!
- May/may not be resistant to other 1st line ATDs

11. C. RIFAMPIN-RESISTANT TB(RR-TB):
- In this case  patient’s bacilli  resistant to ONLY RIFAMPIN & NOT INH!
- May/may not be resistant to other ATDs.
D. MONO-DRUG RESISTANT TB:
- In this case  patient’s bacilli  resistant to ANY ONE 1st line ATD(Except rifampin)
E. POLYDRUG-RESISTANT TB(PDR-TB):
- In this case  patient’s bacilli  resistant to MORE THAN ONE 1ST LINE ATD(except rifampin
& INH)
F. EXTENSIVE DRUG RESISTANT TB(XDR-TB):
- In this case  patient’s bacilli  resistant to a FQ & a 2nd line injectable ATD!

12. MANAGEMENT OF MDR-TB(PRINCIPLES
INVOLVED)

13.  MDR-TB has a rapid course, with worse outcomes
 Treatment involves complex multiple 2nd line drug regimens, which confer the following
demerits:
a. Longer treatment duration
b. Expensive
c. High risk of toxicity
 In India  MDR-TB constitutes:
a. 3% of all new TB-cases
b. 17% of retreatment cases
 According to WHO global report(2015)  India has the HIGHEST NUMBER of MDR-TB
cases!(Approx. 71,000 cases annually)

14.  General principles of MDR-TB management include:
a. Include 4 effective drugs in regimen(6 drugs can also be included, provided efficacy
regarding any of them is uncertain; back-up!)
b. Avoid usage of cross-resistance drugs, chiefly:
- 2 FQs
- Kanamycin with Amikacin
- Ethionamide with prothionamide
- Cycloserine with terizidone
- Ethionamide with INH(low-level resistance)
c. When selecting drugs for treatment  select in a hierarchical order, for example:
2 Group I drugs( Z, E) + one injectable drug(Group II) + One FQ(Group III) + 2 Group IV drugs.

15. d. Standard RNTCP regimen for MDR-TB consists of :
- 6 drugs in “intensive phase”(for 6-9 months)
- 4 drugs in “continuation phase”(for 18 months)
e. Minimal 6 month of intensive phase  can be extended by 1 month each time(to a total
maximum of 9 months)  provided, sputum culture at 4th , 5th & 6th months of intensive phase
turns out to be positive
f. Pyridoxine (at dose of 100 mg/day)  should be given to all patients during therapy to avoid
precipitation of neurotoxicity(attributed to ATDs)!

16. INTENSIVE PHASE(6-9 MONTHS) CONTINUATION PHASE(18 MONTHS)
Kanamycin(Km) Levofloxacin (Lfx)
Levofloxacin (Lfx) Ethionamide(Eto)
Ethionamide(Eto) Cycloserine(Cs)
Cycloserine(Cs) Ethambutol(E)
Pyrazinamide(Z)
Ethambutol(E)
STANDARD RNTCP REGIMEN FOR MDR-TB
N.B: Pyridoxine (100 mg/day) should also be added to above regimen

17. MANAGEMENT OF RIFAMPIN-RESISTANT
TB(RR-TB):

18.  According to both WHO & RNTCP(2016)  RR-TB is treated as MDR-TB
 Since patients with RR-TB are sensitive to INH  INH is also added to “intensive phase”
 Thus, RNTCP regimen for RR-TB includes(Add pyridoxine 100 mg/day):
INTENSIVE PHASE(6-9 MONTHS) CONTINUOUS PHASE(18 MONTHS)
Kanamycin(Km) Levofloxacin(Lfx)
Levofloxacin(Lfx) Ethionamide(Eto)
Ethionamide(Eto) Cycloserine(Cs)
Cycloserine(Cs) Ethambutol(E)
Pyrazinamide(Z) INH
Ethambutol(E)
INH

19. MANAGEMENT OF MONODRUG RESISTANT
TB:

20. Management strategy explained in the following table(Add
pyridoxine 100mg/day):
INTENSIVE PHASE(3-6 MONTHS) CONTINUATION PHASE(6 MONTHS)
Rifampin + two of 1st line drugs(sensitive to bacilli) + one
injectable 2nd line drug + 1 fluoroquinolone
Total of 5 drugs, to be given in intensive phase.
- Stop injectable drug
- Continue with remaining 4 drugs for 6 months.

21. MANAGEMENT OF POLYDRUG RESISTANT
TB(PDR-TB)

22.  Management strategy includes(add pyridoxine 100mg/day to the below treatment regimen:
INTENSIVE PHASE(3-6 MONTHS) CONTINUATION PHASE(6 MONTHS)
Rifampin + one injectable 2nd line drug + one
fluoroquinolone + any 1st line drug (to which bacilli is
sensitive) + one of the oral 2nd line drugs(Ethionamide/
Cycloserine/ PAS)
Total of 5 drugs to be used in continuation phase.
- Stop injectable drug
- Continue remaining 4 drugs.

23. MANAGEMENT OF INH-RESISTANT TB:

24.  In order to strategize treatment for INH-resistant TB  firstly an insight into mechanisms of
INH-resistance is important
 INH resistance can occur in 2 ways:
A. LOW-LEVEL INH RESISTANCE:
- inhA gene  plays role in activity of NAD-dependent enoyl-acyl carrier protein reductase
- In low-level INH resistance  mutation occurs in the inhA gene
- In such situations:
i. Focus on using HIGH DOSE OF INH (900 mg/day, for average body weight of 46-70 kg)
ii. Add pyridoxine to treatment regimen
iii. Monitor for potential neurotoxicity
iv. Avoid concurrent usage of Ethionamide(since it won’t be effective in low-level INH
resistance)!

25. B. HIGH-LEVEL INH RESISTANCE:
- KatG gene  encodes for enzyme catalase peroxidase  helps in conversion of INH to its
active metabolite  shows antitubercular activity
- In high-level INH resistance  mutation in KatG gene occurs  conversion doesn’t occur 
drug is rendered ineffective!
- In such situations:
i. Avoid usage of INH!
ii. Ethionamide may be used(Since Ethionamide is effective in patients with high-level INH
resistance)!

26. MANAGEMENT OF EXTENSIVE DRUG-
RESISTANT TB(XDR-TB)

27.  Extremely difficult to treat
 High chances of mortality!
 To prevent further progression of resistance  stop standard MDR-regimen immediately!
 Since Group-V drugs are both costly & toxic  an expert clinical panel may decide on
appropriate drug selection!
 According to RNTCP(2016) guidelines:
- 7 drugs should be used in intensive phase(6-12 months)
- 6 drugs should be used in continuous phase(18 months)

28. STANDARD RNTCP GUIDELINES FOR XDR-TB MANAGEMENT:
INTENSIVE PHASE(6-12 MONTHS) CONTINUOUS PHASE(18 MONTHS)
Capreomycin (1000 mg) Moxifloxacin (400 mg)
Moxifloxacin (400 mg) INH high dose (900 mg)
INH high dose (900 mg) PAS (12 g)
PAS (12 g) Clofazimine(200 mg)
Clofazimine(200 mg) Linezolid (600 mg)
Linezolid (600 mg) Amoxicillin/clavulanate (875+125 mg); 2 tablets in
morning & 1 tablet in evening.
Amoxicillin/clavulanate (875+125 mg); 2 tablets in
morning & 1 tablet in evening.

29. BODY WEIGHT CATEGORY(in kg) INTENSIVE PHASE CONTINUATION PHASE
HRZE HRE
25-39 2 2
40-54 3 3
55-69 4 4
70 and above 5 5
• For intensive phase  each tablet contains INH(75 mg), Rifampin(150 mg),
Pyrazinamide(400 mg) & Ethambutol(275 mg)
• For continuation phase  each tablet contains INH(75 mg), Rifampin(150 mg)&
Ethambutol(275 mg)

30. DRUG DAILY DOSE(in mg/kg)
INH 5 (4-6)
RIFAMPIN 10 (8-12)
PYRAZINAMIDE 25 (20-30)
ETHAMBUTOL 15 (15-20)
STREPTOMYCIN 15 (12-18)
PLEASE NOTE: If patient’s age > 50 years  maximum dose of streptomycin will be 0.75 g/day!

31. THANK YOU!!