1. Gina S. de los Reyes, M.D., FPCP, FPCCP
TB Treatment Regimen
Gina S. de los Reyes, M.D., FPCP, FPCCP

2. Outline Short Course Treatment; Fixed Dose Combination
Classification of TB Cases
Treatment Regimens
Treatment of TB in Special Situations
Symptom-based approach to adverse effects of TB drugs

3. Who requires treatment for PTB?
1. Active PTB (Class 3)
2. Inactive PTB (Class 4) but with no previous
adequate/completed treatment
3. TB suspect (Class 5) when the probability of
TB is high, while awaiting confirmation

4. Aims of Treatment 1. To cure patients with the least
interference with their lives.
2. To prevent death in seriously ill patients.
3. To prevent extensive damage to the lungs
with the consequent complications.
4. To avoid relapse of the disease.
5. To prevent the dev’t of drug-resistant T.B (acquired resistance).
6. To protect his/her family and the
community from infection.

5. Anti-TB drugs : Actions & Adverse Effects First line drugs
Gastro’nal
Cutaneous rxn
Hepatitis
Bactericidal
Rifampicin
Peripheral Neuropathy
Isoniazid
Adverse Effects
Action
Drug

6. Anti-TB drugs Ototoxicity Cutaneous Hypersen- sitivity Bactericidal
Streptomycin
Hepatotoxicity
Arthralgia
Pyrazinamide
Retrobulbar neuritis
Bacteriostatic
Ethambutol

7. Second-line drugs Capreomycin Ethionamide Kanamycin Prothionamide
Viomycin
Amikacin
Co-amoxiclav
Clarithromycin
Rifamycin derivatives- Rifabutin, Rifapentene
Ethionamide
Prothionamide
Sodium para- aminosalicylate (PAS)
Cycloserine
Ofloxacin
Ciprofloxacin

8. Drug Doses Dosage in mg/kg (range) Drug Daily Thrice/week
Isoniazid
(4-6) (8-12)
Rifampicin
(8-12) (8-12)

9. Drug Doses Pyrazinamide 25 35 (28-30) (30-40) Ethambutol 15 30
(28-30) (30-40)
Ethambutol
(15-20) (25-35)
Streptomycin
(12-18) (12-18)

10. FIXED- DOSE COMBINATION (FDC) ANTI-TB DRUGS
Formulation where two or more anti-TB drugs are present in fixed proportions
Advocated by WHO & the International Union Against Tuberculosis & Lung Diseases (IUATLD) to replace single-drug preparations as treatment for TB
FDC anti-TB combinations (1)
The other key strategy is the use of fixed dose combinations or FDCs.
FDC are formulations where 2 or more anti-TB drugs are present in fixed proportion in a single tablet.
FDCs have been recommended by the WHO and the IUATLD as the preferred mode of TB treatment, to replace single drug preparations.

11. FDCs For the patient: simplified drug intake Fewer pills to swallow
Pills are identical
Correct regimen is followed
FDCs (2)
For the patient, the ritual of taking the pills is very much simplified
For one, the patient, in most cases, will be taking a fewer numbers of pills,
Second, all the pills are identical and therefore, there is no confusion what to take first
Third, he is assured that he is taking the correct regimen.
All in all, these factors should result in better adherence to the treatment.

12. FIXED DOSE COMBINATION: SIMPLER DOSE COMPUTATION
Body Weight (kg)
4-FDC (HRZE)
37 to 54
3 tablets
55 to 70
4 tablets
> 70
5 tablets
FDC: simple dose computation
Using FDC, the number of tablets to take is never more than 5, and only depends on the actual body weight.
To make it even simpler, for most Filipinos, the magic number is 55 kgs. 55 kg or more requires 4 tablets while those less than 55 kgs take only 3 tablets.
Practical dosing:
< 55 kg: 3 tablets daily > 55 kg: 4 tablets daily

13. Short Course Chemotherapy
6 months regimen which includes Rifampicin and Pyrazinamide
Standard Treatment- at least 12 months (w/o Rifampicin)

14. 2 Phases of SCC
Intensive phase months
Continuation phase- 4 months

15. Short Course Chemotherapy Advantages
Easy to take
Pt feels better quickly
Sputum becomes (-) quickly
Relapse rate lower
If relapse occurs, TB remains sensitive
Much cheaper than standard tx

16. Objectives of SCC
To achieve better bactericidal and sterilizing activities
To prevent emergence of resistance

17. Resistant Mutants Small number which are naturally resistant
More will occur in TB cavity
If only one drug is given the sensitive TB are destroyed but the resistant ones multiply
NEVER GIVE A SINGLE DRUG (MONOTHERAPY)
In any population of TB there will be a small number which are naturally resistant. More of them will occur among the millions of TB in any TB cavity. If only one drug is given the sensitive TB are destroyed but the resistant ones multiply. NEVER GIVE A SINGLE DRUG (MONOTHERAPY).

18. Classification of TB Cases
Pulmonary TB
Smear (+)
Smear (-)
Extrapulmonary TB

19. PTB-Smear Positive +/- X-ray abnormalities consistent with active TB
At least 2 sputum specimens (+) for AFB
+/- X-ray abnormalities consistent with active TB
1 sputum specimen (+) for AFB
and with X-ray abnormalities consistent with active TB
with sputum culture (+) for M. tuberculosis
Normal cxr but with dse-15-20%
18% firbocalcific has smear positive

20. PTB – Smear Negative At least 3 sputum specimens (-) for AFB
X-ray abnormalities consistent with active TB
No response to a course of antibiotics and/or symptomatic medications
Decision by a medical officer to treat with anti-TB drugs
Acceptable to start tx based on cxr findings with a compatible clinical presn even if smear negative

21. Extrapulmonary TB
At least 1 mycobacterial smear/culture (+) from an extrapulmonary site
(organs other than the lungs: pleura, lymph nodes, gut, skin, joints, bones, meninges, intestines, peritoneum, pericardium, etc)
Histological and/ or clinical evidence consistent with active TB & there is decision by a Medical Officer to treat pt with anti-TB drugs

22. Types of TB Cases New Relapse Failure Return after default (RAD)
Transfer-in
Other

23. Types of TB Cases
New- pt who has never had tx for TB or who has taken anti-TB drugs for < 1month
Relapse - pt. previously treated for TB, has been declared cured or tx completed, and is diagnosed with ( + ) smear or culture for TB
Failure- pt while on tx is sputum smear ( + ) at 5 months or later during the course of tx

24. Types of TB Cases
Return after default A patient who returns to treatment with positive bacteriology (smear or culture), following interruption of treatment for months or more.
Transfer-in- pt who has been transferred from another facility with proper referral slip to continue

25. Types of TB Cases
Other
1. Pt starting treatment again after interrupting treatment for >2 mos. and has remained smear (-)
2. Pt who was initially registered as new smear-negative case, turned out to be smear (+) during the tx.
3. Chronic case: pt who is sputum(+) at the end of a re-treatment regimen.

26. Treatment Regimens
Each standard drug is indicated by a capital letter. H- Isoniazid R- Rifampicin Z- Pyrazinamide E- Ethambutol S- Streptomycin

27. Treatment Regimens Regimen TB Patient Regimen I 2HRZE/4HRE
New pulmonary smear (+ ) cases
New seriously ill pulmonary smear (-) cases with extensive parenchymal involvement
New severely ill extra- pulmonary TB cases

28. Treatment Regimens Regimen TB Patient Regimen II: 2HRZES/ 1HRZE/5HRE
Failure cases
Relapse cases
RAD (smear +)
Other (smear +)

29. Treatment Regimens Regimen TB Patient Regimen III: 2HRZ/4HR
New smear (-) but with minimal PTB on x-ray as confirmed by Medical Officer
New extra-pulmonary TB (not serious)
High resis if inh resis is > 4%; in phil-14.9% to 16.9% inh reis

30. Treatment of TB in Special Situations
TB in pregnancy/lactation
TB in pts with hepatic disease
TB in pts with renal disease
TB in the elderly
TB in HIV/AIDS

31. Tuberculosis in Pregnancy
INH, Ethambutol & Rifampicin can be used
Not recommended: Pyrazinamide, Streptomycin, Kanamycin, Capreomycin
Strep hazardous throughout- ototoxixity and fetal malformation
Consensus Statement ( Phil. Practice guidelines Group on Infectious Diseases)

32. TB treatment in Pregnancy
Non-cavitary Disease -9HRE
Cavitary Disease- 12HRE
Treat if symptomatic; If resistant to HR, may use Z after 1st trim; inadeq data on teratogenicity
TB prophy - <35 yo, N cxr, (+)ppd, asx-delay until 3-6months postpartum except ppd>15 and no prev tx, >10 with high prev, with cxr inactive ptb; >5 mm in immunocomp; HIV+, recent converters, close contacts
>35, ppd<15 – no tx unless immunocomp or close contacts; H hepatitis higher esp >35yo
Consensus Statement ( Phil. Practice guidelines Group on Infectious Diseases)

33. TB and Lactation Breast feeding not discouraged
Anti-TB drug concentration - low, non-toxic & non-therapeutic in breast milk
Supplemental pyridoxine to baby; if mother and baby both taking antiTB meds- do not breastfeed; 25MG/D VIT B6
Consensus Statement ( Phil. Practice guidelines Group on Infectious Diseases)

34. TB treatment & Liver Disease
Hepatitis virus carriage or a past hx of acute hepatitis w/o clinical evidence of chronic liver disease
Rx- Usual short course chemotherapy
established chronic liver disease
2SHRE/6HR
2SHE/10 HE

35. TB treatment & Liver Disease
Hepatic failure
Streptomycin & Ethambutol can be given.
If a third drug is needed, Isoniazid or Rifampicin can be given cautiously in lowered doses
Acute Hepatitis – defer until hepatitis resolved or
3SE/6HR

36. TB treatment & renal insufficiency/ renal failure
Isoniazid, Rifampicin & Pyrazinamide can be given in normal dosages
2HRZ/6HR
Etham 5-23mkd; pza mkd

37. Others TB in the Elderly TB in HIV + with susceptibility testing
9HR
TB in HIV +
with susceptibility testing
2HRZE/4-7HR
w/o susceptibility testing
Non-cavitary- 9HRZE
Cavitary -12HRZE
Tb in elderly- harbor few bacilli that are resistant

38. Symptom-based approach to adverse effects of TB drugs
Reassure the patient
Rifampicin
3. Orange/red
Colored urine
Give anti- histamine
Any kind of drugs
2. Mild skin reactions
Give medication at bedtime
1. Gastro- intestinal intolerance
Management
Drugs responsible
Side-effects
(Minor)

39. Pyridoxine (Vit B6) 100-200 mg for tx;
10mg for prevention
Isoniazid
5. Burning sensation of the feet
Warm compress;
Rotate sites of injection
Streptomycin
4. Pain at injection site
Management
Drug(s) responsible
Side effects

40. Antipyretics
Rifampicin
7. Flu-like symptoms
(fever, inflammation of the resp. tract)
Aspirin or NSAID
Allopurinol
Pyrazinamide
6. Arthralgia
Management
Drug(s) responsible
Side effects

41. Discontinue Anti-TB drugs
Any kind of drugs (esp Strep)
1. Severe skin rash due to hypersensitivity
D/C anti-TB drugs
If sx subside, resume tx and monitor
Any kind of drugs (esp Isoniazid, Rifampicin and Pyrazinamide
2. Jaundice due to hepatitis
Management
Drug(s) responsible
Major side effects

42. Discontinue Ethambutol & refer to an opthalmologist
3. Impairment of visual acuity & color vision (optic neuritis)
Discontinue Streptomycin
Streptomycin
4. Hearing impairment, tinnitus, vertigo
Management
Drug(s) responsible
Major side effects

43. Major side effects
Drug(s) responsible
Management
5. Oliguria or albuminuria due to renal disorder
Streptomycin
Rifampicin
Discontinue
Strep, Rifampicin
6. Psychosis & convulsion
Isoniazid
Discontinue Isoniazid
7.Thrombo-
cytopenia, anemia, shock
Discontinue Rifampicin

44. Thank You for your kind attention!

45. 2HRZE/4HR 2H3R3Z3E3/4H3R3

46. Challenge doses for detecting cutaneous or hypersensitivity to anti-TB drugs
Day Day 2
Challenge Doses
Isoniazid mg mg
Rifampicin mg mg
Pyrazinamide mg g
Ethambutol mg mg
Streptomycin mg mg
Drug