Key Updates To DRTB Regimens 2023

Key Updates to the Current Treatment Guidelines for
the Programmatic Management of Drug-Resistant

Tuberculosis (PMDT)
November-December 2023
Background and Key Updates
BACKGROUND
▪ In 2019, the global TSR was 60% - an improvement in recent years from 50% in 2012 - and the same year the
novel, shorter all oral regimens were recommended by the WHO, which replaced injectable-containing regimens
with all-oral regimens
▪ To amplify the efforts towards ending TB in the country, the Department of Health through the Disease
Prevention and Control Bureau (DPCB) unceasingly works to ensure access to the more preferred all-oral
regimens to sustain the increasing treatment success rates for DR-TB treatment. In the Omnibus Health
Guidelines (OHG) released last June 2022, these novel regimens for DR-TB were already included.
▪ On December 15, 2022 , the WHO issued the “WHO Consolidated Guidelines on Tuberculosis Module 4: Drug
Resistant Tuberculosis Treatment, 2022 Update,” which included the updated and detailed recommendations on
the preferred use of a 6-month treatment regimen composed of bedaquiline, pretomanid, linezolid and
moxifloxacin (BPALM), 9-month short regimen and 18-months longer regimen for eligible RR/MDR-TB patients.
On the same date WHO operational Handbook on Tuberculosis Module 4: Treatment of DRTB was also issued
with practical guidance for implementation
Department of Health – Disease Prevention and Control Bureau

Trend of PMDT Treatment Outcome 1999- 2021
All Oral
Long regimens with SLIs for 6-8 months regimens

BASIS
Treatment
TRIAL AIM DRUGS DURATION
success rate
Safety,
NIX Trial efficacy, BPaL 26-39 weeks 90%
tolerability
BPaLM (Mfx) 88.3 %
TB
Safety, efficacy BPaL 24 weeks 86.5 %
PRACTECAL
BPaLC (Cfz) 76.5 %
Optimize Lzd
Zenix dosing and BPaL 26-39 weeks 89.3%
duration

KEY UPDATES
1. New DRTB Regimens included in the OHG
2. Revisions in regimen nomenclature
3. Use of Bdq and Dlm in children of all ages
4. Use of Bdq-containing regimens in pregnant women
5. Revision in definitions
6. Revised abbreviations of some TB medications/terms

1. New DRTB Regimens included in the OHG

2. Revisions in DRTB regimen nomenclature
Previous DRTB regimens Key updates to DRTB regimens
Regimen 3 SSOR (9-11 mos.) BPaLM/BPaL
4-6 Bdq(6) LfxCfzPtoHdHEZ/ 5 LfxCfxEZ BPaLM for FQs (26 weeks)
BPaL for FQr (6 or 9 months)
Regimen 4 SLOR FQs (18-20 mos.) SSOR (9-11 months)
6 BdqLfxLzdCfz/ 12-14 LzdCfzCs (18-20 mos.)
BdqLfxCfzLzd(2)HhEZ
BdqLfxCfzPtoHhEZ
Regimen 5 SLOR FQr (18-20 mos.)
6 BdqLzdDlmCfzCs/12-14 LzdCfzCs CTR FQ-s (Child Treatment Regimen)
Bdq - Lfx - Lzd - Cfz (Cs/Dlm)
REVISIONS
Regimen 6 FQs (pedia) (9-18 mos)
a. <3 y.o LfxLzdCfzCs (Pas/Pto) Duration: 9-12 months nonsevere TB disease
b. 3-6 y.o. LfxLzdCfzCs(Dlm/Pas) 15-18 months for severe TB disease
c. > 6 y.o BdqLfxLzdCfz (Cs/Dlm)
CTR FQ-r (Child Treatment Regimen)
Regimen 7 FQr (pedia) (9-18 mos)
Bdq - Lzd - Cfz - Cs (Dlm/PAS)
a. LzdCfzCsPas (Pto/Dlm)
b. LzdCfzCsDlm (Pas/Pto) Duration: 9-12 months nonsevere TB disease
c. BdqLzdCfzCs (Dlm/Pas) 15-18 months for severe TB disease
Hr-TB (mono Hr-TB Regimen)
ITR (18-20 mos.) 6-month (H)RZELfx
ITR (18-20 months)

3. Use of Bdq and Dlm in children of all ages
Delamanid is now
recommended by WHO
for the treatment of
MDR RR-TB in adults
and children of all ages
Bedaquiline is now
recommended by WHO
for the treatment of
MDR/RR-TB in adults
and children of ALL
ages

4. Use of Bdq containing regimen in pregnant women
The use of bedaquiline in pregnancy has

been associated with infants born with a
lower mean birth weight than infants whose
mothers did not take bedaquiline. However,
when infants were followed up over time, no
evidence of late adverse impacts were
found.

5. Definition of Terms
TERMS OLD DEFINITION NEW DEFINITIONS
2 negative cultures taken at least 30 BCTB with at least 2 consecutive

Bacteriologic conversion days apart (usually in the intensive negative cultures taken on different
phase) occasions at least 7 days apart
At least 2 positive consecutive

cultures taken on different
2 positive cultures taken at least 30
occasions at least 7 days apart after
Bacteriologic reversion days apart (usually in the
bacteriologic conversion or in
continuation phase)
patients without bacteriologic
confirmation of TB

TERMS OLD DEFINITIONS NEW DEFINITIONS
A patient who died for any

A patient who dies for any reason reason before starting
DIED
during the course of treatment treatment or during the
course of treatment
A patient whose treatment was

interrupted for > 2 consecutive months A patient who did not start
treatment or whose treatment
Lost to follow-up
A patient diagnosed with active TB but was interrupted for 2
was not started on treatment (Initial consecutive months or more
LTFU)

TERMS OLD DEFINITION NEW DEFINITION
•Large cavitary lesions involving more

than one lobe of the lungs
•Even without cavitation if there is Presence of bilateral cavitary

involvement of a significant portion disease or extensive
Extensive TB parenchymal damage on
of the lung parenchyma chest x-ray
•Bilateral cavitary disease or extensive

parenchymal damage on chest
radiography

6. Revised abbreviations of some TB drugs (as used in BPAL/M regimens)
DRUGS OLD ABBREVIATION NEW ABBREVIATION
Bedaquiline Bdq B or Bdq
Linezolid Lzd L or Lzd
Pretomanid Pa
Moxifloxacin Mfx M or Mfx
High Dose Isoniazid Hdh Hh
Clofazimine Cfz C or Cfz
OLD – Maximum Dose New – Maximum Dose

Pyridoxine
200 mg /day (4 tabs) 100 mg/day (2 tabs)

6. Revised abbreviations of some terms/others
TERM OLD NEW
CTR Conventional Treatment Regimen Child Treatment Regimen
IP Intensive Phase Initial Phase (IP)
CP Continuation Phase Maintenance phase (MP)

Assigning Appropriate Treatment Regimen
General Considerations
1. BPaLM shall be the preferred standardized regimen for eligible FQ-
susceptible RR/MDR-TB patients.
2. Eligible patients with pre-XDR TB shall be given BPaL.
3. FQ-susceptible patients not eligible for BPaLM should be checked with

eligibility to SSOR
4. Patient’s not eligible to all the standard regimens shall be referred to

TBMAC for ITR design

5. Individuals less than 14 years (<14 y.o.) shall be given the standard
regimen for children
6. Pregnant or breastfeeding patients shall be referred to TBMAC for

evaluation of eligibility to Lzd–containing SSOR or ITR
7. In cases of possible Fq resistance, (history of > 4 weeks of Fq use, or

contact of a person with FQ-r strain) best to use BPaLM until DST of
Fq is available. If results show FQ-r, omit Mfx and continue the
regimen as BPaL. No dose recount is needed.**
Assignment of DR-TB Regimens
Collect 3 sputum specimens for
Patient diagnosed as RR/MDR-TB
LPA/Xpert XDR, SM, TBC and DST
Check exclusion criteria to BPaLM
NO to all YES to any
Check general exclusion criteria for SSOR

Start BPaLM
NO to all YES to any

Confirmed Fq No Fq resistance
resistance
Start SSOR Consult with
Continue as BPaL TBMAC for ITR
Continue BPaLM
( Pregnant/breastfeeding) With
without Hgb <8; severe
Hgb <8; severe peripheral peripheral neuropathy
neuropathy and any sign of and any sign of optic
optic neuritis on baseline neuritis on baseline
Start SSOR with Lzd Start SSOR with Pto

Check results of Xpert- XDR, first-line and second-line LPA and phenotypic DST
1. TB involving CNS, osteoarticular and disseminated (miliary) TB
2. Known allergy to any of the component drugs.
3. More than one month exposure to bedaquiline, linezolid, pretomanid or

delamanid , unless resistance is ruled out through DST; or less than 1
BPaLM/BPaL month exposure but with confirmed resistance to bedaquiline, linezolid,
pretomanid or delamanid.
4. Contact of a patient who had failed treatment with MDR-TB treatment

If YES to any of the regimen containing bedaquiline, linezolid, pretomanid/delamanid
exclusion criteria, 5. Risk of toxicity or intolerance to any drugs in BPaLM/BPaL as manifested
by:
DO NOT GIVE
BPaLM/BPaL ⮚ Presence of severe to life-threatening anemia (hemoglobin level of
less than 8 g/dl)
⮚ Pre-existing severe to life-threatening peripheral neuropathy (Grade

If NO to all of the 3-4)
exclusion criteria, ⮚ History of chronic active hepatitis or with AST/ALT >5 times ULN1
GIVE BPaLM/BPaL ⮚ History of heart disease (heart failure, myocardial infarction, cardiac
conduction abnormality, arrhythmia)
⮚ QTcF > 500 ms2
if eligible, give BPaLM/BPaL. If not, 6. Pregnant, breastfeeding or women of reproductive age not willing to use
check eligibility to SSOR contraception during the course of BPaLM/BPaL regimen

General Exclusions:
1. Extensive3 or disseminated TB (miliary) or severe/intractable

extrapulmonary TB (e.g. TB meningitis, bone/joint TB, pericardial
TB)
SSOR
2. Confirmed resistance to Bdq, Lfx/Mfx, Cfz, Pto or Lzd
3. Previous exposure to Mfx/Lfx, Bdq, Cfz, Pto or Lzd for >1 month
If YES to any of the (unless proven susceptible)
exclusion criteria,
4. Close contact of a patient who had failed treatment with MDR-TB
DO NOT GIVE SSOR treatment regimen containing Lfx/Mfx, Bdq, Cfz, Pto or Lzd
5. Risk of toxicity or intolerance to any drugs in the regimen as

manifested by:
If NO to all of the ⮚ History of heart disease (heart failure, myocardial infarction,

cardiac conduction abnormality, arrhythmia)
exclusion criteria,
GIVE SSOR ⮚ QTcF > 500ms
⮚ History of chronic active hepatitis or AST/ALT >5 times

elevated)
If no to all the general exclusions ⮚ History of chronic renal insufficiency (Creatinine clearance
- decide if SSOR Lzd or Pto <20 ml/min)
variation
SSOR (Lzd)
If YES to any of the

⮚Hemoglobin < 8g/dL
exclusion criteria,
DO NOT GIVE SSOR ⮚Evidence of severe peripheral
with Lzd neuropathy, or
If NO to all of the ⮚any sign or suspicion of optic neuritis

general exclusions and at baseline
specific exclusions
GIVE SSOR with Lzd

SSOR (Pto)
If YES to any of the

exclusion criteria,
DO NOT GIVE SSOR DST results with mutations conferring both
Pto/Eto resistance (low level H-resistance or inHA
mutation) and high level H-resistance/katG
mutation
If NO to all of the
exclusion criteria,
GIVE SSOR

Old DRTB Regimens Nomenclature

Regimens Nomenclature:
● BPaLM
● BPaL
● SSOR Lzd
● SSOR Pto
● CTR FQ-s
● CTR FQ-r
● Hr-TB
● ITR

Old DRTB Regimens Nomenclature

Regimens Nomenclature:
● BPaLM
● BPaL
● SSOR Lzd
● SSOR Pto
● CTR FQ-s
● CTR FQ-r
● Hr-TB
● ITR

Initiation Of Treatment
1. Perform pretreatment evaluation and baseline tests
2. Check for possible drug-drug interactions that may potentially

occur to any of the first-line and second line drugs
3. Assign the appropriate treatment regimen based on exclusion

criteria (refer to algorithm above)
4. Check for weight based dosing of component drugs (for

BPaLM/BPaL regimen dosages are fixed)
Annex D. Recommended Schedule of Baseline, Routine and Post-treatment Monitoring Examinations
for DR-TB Patients
2nd week from
start of treatment End of 6 and 12 months
Examination Baseline Monthly
(for Lzd-containing Treatment post-treatment
regimens)
Clinical evaluation by physician including weight ✓ ✓ ✓ ✓ ✓
Bacteriologic tests
Smear microscopy ✓ ✓ ✓ ✓
TB culture ✓ ✓ ✓ ✓
Drug susceptibility testing If culture remains positive at month 4 of treatment,

First- and second-line Xpert XDR or LPA ✓ in case of culture reversion, or culture positivity
Phenotypic DST ✓ during post-treatment ff-up
Diagnostic tests
Chest X-ray (Conduct every 6 months while on treatment) ✓ ✓ ✓
Electrocardiogram (12 leads for adults; 15 leads for children)
✓ ✓ ✓ ✓
(Regimen contains Cfz, Bdq, Mfx, Dlm, Pa, and/or Lfx)
Visual acuity and color vision
✓ ✓ ✓ ✓
(Regimen contains Lzd and/or E)
Brief peripheral neuropathy screening
✓ ✓ ✓ ✓
(Regimen contains Lzd, H, Cs, Trd, Lfx, Mfx, and/or Am)
✓
Mental health screening (PHQ-9)
✓ (If Cs or Hh- ✓
(Regimen contains Cs and/or H)
containing)

Annex D. Recommended Schedule of Baseline, Routine and Post-treatment Monitoring Examinations
for DR-TB Patients
2nd week from
start of treatment End of 6 and 12 months
Examination Baseline Monthly
(for Lzd-containing Treatment post-treatment
regimens)
Bacteriologic tests
Collect 3 Sputum Specimens:
Drug1.susceptibility
FL and SL LPA testing
or Xpert MTB/XDR If culture remains positive at month 4 of treatment,
2. Two specimens forXpert
First- and second-line XDR or
SM, TBC LPA
, pDST ✓ in case of culture reversion, or culture positivity
Phenotypic DST ✓ during post-treatment ff-up
Diagnostic tests
Chest X-ray (Conduct every 6 months while on treatment) ✓ ✓ ✓
Electrocardiogram (12 leads for adults; 15 leads for children)
✓ ✓ ✓ ✓
(Regimen contains Cfz, Bdq, Mfx, Dlm, Pa, and/or Lfx)
✓ ✓ ✓ ✓
(Regimen contains Lzd and/or E)
✓ ✓ ✓ ✓
(Regimen contains Lzd, H, Cs, Trd, Lfx, Mfx, and/or Am)
✓
(Regimen contains Cs and/or H)
containing)

2nd week
from start of
6 and 12
treatment (for End of
Examination Baseline Monthly months post-
Lzd- Treatment
treatment
containing
regimens)
Blood chemistry/ Hematology/ Immunologic tests
ALT and AST
(Regimen contains Z, H, Pa, Bdq, Eto/Pto, Cs/Trd, and ✓ ✓ ✓ ✓
PAS)
CBC
✓ ✓ ✓ ✓
(Regimen contains Lzd, Mpm, H, and Pa)
FBS or HbA1C ✓
Serum K^ ✓
✓
Creatinine ✓ (If Am or S-
containing)
TSH ✓
(if Pto/Pas-containing)
Albumin ✓
(Dlm containing regimen)
Pregnancy test (for women of reproductive age) ✓
HIV screening ✓
HBV and HCV+ test ✓

2nd week
from start of
6 and 12
treatment (for End of
Examination Baseline Monthly months post-
Lzd- Treatment
treatment
containing
regimens)
ALT and AST
(Regimen contains Z, H, Pa, Bdq, Eto/Pto, Cs/Trd, and ✓ ✓ ✓ ✓
PAS)
CBC
✓ ✓ ✓ ✓
FBS or HbA1C ✓
Serum K^ ✓
✓
containing)
TSH ✓
(if Pto/Pas-containing)
Albumin ✓
HIV screening ✓

BPaL/BPaLM Regimen
Dosage/
Drug Strength Duration
Duration
4 tabs daily for 2 weeks; then
2 tabs 3x/week for the
remaining 24 weeks
Bedaquiline
100 mg /tablet or
(Bdq) B
200 mg daily x 8 weeks then
100 mg daily
26 weeks
Pretomanid (Pa) 1 tablet daily

200 mg /tablet
Pa
Linezolid
600 mg/tablet 1 tablet daily
(Lzd) L
Moxifloxacin (Mfx)
400 mg/tablet 1 tablet daily
M

BPaL/BPaLM Regimen
▪ Dose modifications for Bdq, Mfx, and Pa are not allowed.
▪ Mfx cannot be substituted with Lfx.
▪ Fluoroquinolone-susceptible patients can be started on the BPaLM regimen for

6 months (26 weeks).
▪ In case of fluoroquinolone resistance identified after treatment initiation, Mfx

may be discontinued and the regimen continued as BPaL for 6 or 9 months
• In case of intolerance to Mfx (e.g. cardiotoxicity) during the course of treatment,

Mfx may be omitted and the regimen may be continued as BPaL for 6 or 9
months
BPaL/BPaLM Regimen
• BPaLM shall be given for a maximum duration of 6 months. BPaL may be
extended only to 9 months (39 weeks from start of therapy) if TBC remains
positive at month 4 OR there is lack of clinical response (based on clinical
judgment of the treating physician) between months 4 and 6. Physician’s
judgement may be used if clinical assessment and other monitoring
parameters like SM and comparative chest x-ray , if TBC result is not available
at 6 months
▪ Temporary cessation of the full regimen is allowed for suspected drug-related

toxicity. Reintroduction of the full regimen can be considered after a cessation
of no more than 14 days of consecutive interruption or up to a cumulative 4
weeks of non-consecutive treatment interruption.

BPaL/BPaLM Regimen
▪ Missed doses of >7 days of the whole BPaL/BPaLM shall be compensated by extending the
treatment duration for the number of missed doses. Individuals who switch from BPaLM to
BPaL shall consider their treatment start date the same as the date BPaLM was initiated,
because the treatment continued with three effective drugs during the entire treatment
period.
▪ Considerations on Lzd dosing:
⮚ Modification not allowed in the first 9 weeks of treatment. However, if the patient manifests
toxicity or intolerance to Lzd, reassess pt. for eligibility to continue treatment or shift to a new
regimen upon the advice of the TBMAC.
⮚ If permanently discontinued during the 1st 9 weeks, discontinue entire regimen and refer to
TBMAC for switching to SSOR or ITR. Dose recount must be done when switching to a new
regimen.
⮚ Dose reduction (to 300 mg) after the first 9 weeks may be done in the presence of adverse
events
⮚ If either Bdq or Pa needs to be permanently discontinued, the entire BPaL-M/BPaL regimen
should be discontinued
Timing of dose reduction and modification of Lzd
( Lzd 600 mg is preferred for the whole duration of treatment; however, with significant toxicity the
following modifications are possible.)
1-9 weeks of >9-18 weeks of >18-26 weeks of
Regimen >27-39 weeks
treatment treatment treatment
If necessary, Lzd Regimen cannot
BPaLM
If not tolerated, may be omitted be extended
Lzd may be until the end of
reduced to 300 treatment with
mg daily until Bdq, Pa +/-Mfx
600 mg daily, Regimen may
the end of remaining to
ideally be extended, if
treatment, or complete the
continued necessary. Lzd
resumed regimen; or Lzd
BPaL throughout the may continue at
anytime to 600 may be
regimen the tolerated
mg daily, as restarted
duration dose, or stopped
tolerated, but anytime at
if not tolerated.
ideally not either 600 mg or
omitted. 300 mg daily, as
tolerated.
⮚ If either Bdq or Pa needs to be permanently discontinued, the entire BPaL-M/BPaL regimen should be
discontinued
▪ For Fq-susceptible patients whom BPaL-M
cannot be given but who are eligible for
SSOR, and whose baseline assessment shows
no evidence of severe myelosuppression
(<8g/dl), severe peripheral neuropathy and no
sign or suspicion of optic neuritis - SSOR with
Lzd should be given.
▪ Women who are pregnant or breastfeeding

should be assessed for eligibility to SSOR with
Lzd. If not eligible, refer to TBMAC for ITR.

⮚Bdq is given for 6 months, but may be extended to 9
months if the initial phase of the regimen is extended
SSOR from 4 to 6 months because of positive sputum
smears at month 4 of treatment.
Lzd Variation
⮚Bdq shall be given with initial loading dose of 400 mg
4-6 Bdq(6) - Lzd(2) - Lfx - Cfz - Z - for the first 2 weeks, followed by 200 mg 3 times a
E -Hh / 5 Lfx - Cfz - Z – E week (with at least 48 hours between doses)
thereafter.
IP: 4-6 Bdq(6) - Lzd(2) - Lfx - Cfz - Z
o If one dose of Bdq is missed in the 2-week
- E – Hh
loading phase, the missed dose does not need to
MP: 5 Lfx - Cfz - Z - E be made up and the daily dosing schedule can
be continued.
o If one dose of Bdq is missed in the maintenance
Dosages of the different anti- phase but is remembered within the 48-hour
TB drugs in the 9-month all- dosing period, the dose should be administered
oral regimen shall be as soon as possible, and the next dose adjusted
determined based on the latest to be taken 48 hours later. Resume usual thrice a
WHO recommended dosage by week dose schedule thereafter.
weight band for medicines
used in the MDR-TB regimens
SSOR Lzd Variation
Scenario Action
● If one dose of Bdq is missed in the 2-week

the missed dose does not need to be made up and the
loading phase,
daily dosing schedule can be continued.
● If one dose of Bdq is missed in the the dose should be administered as soon as possible,
maintenance phase but is remembered within and the next dose adjusted to be taken 48 hours later.
the 48-hour dosing period, Resume usual thrice a week dose schedule thereafter.
● If Bdq is interrupted for >2 weeks (but <8 the drug should be reloaded at the higher daily dose for
weeks) during the maintenance phase of 7 days before resuming the thrice-weekly dosing
dosing, schedule.
● If Bdq is interrupted for <2 consecutive weeks

no reloading is required.
during the maintenance phase,
the patient and treatment plan should be reassessed

● If Bdq is interrupted for >8 consecutive weeks because the patient will no longer be eligible to continue
or restart the 9-month all-oral regimen.

⮚ Lzd is only given for 2 months. If Fq-
resistance is not yet ruled-out, missed
doses can be added on to the end of the
2-month period if Lzd is well tolerated. For
cases where Fq susceptibility has been
confirmed, no need to make up for the
missed doses of Lzd.
SSOR
⮚ Lzd dose (600 mg) should not be reduced
Lzd Variation to less than the recommended dose to
reduce severity of adverse effects. If full
dose is not tolerated during the first 2
months of treatment, then the patient
may be switched to Pto variation
(provided Fq susceptible and not
pregnant) or refer to TB MAC for ITR
without Lzd.

⮚ If either Z or E (only one) is
discontinued due to intolerance ,
SSOR adverse event or confirmed resistance,
the regimen may continue without
Lzd Variation necessitating to switch to a longer
regimen.
⮚ If both Z and E are discontinued due

to intolerance, adverse event or
confirmed resistance, shift to ITR.

⮚ If resistance to Pto or Hh (only one) is
confirmed, the regimen may continue
without necessitating to switch to a
SSOR longer regimen
Lzd Variation ⮚ If resistance to both Pto and Hh is

confirmed, continue with the regimen
⮚ If any other drugs of the SSOR

regimen (Bdq/Lfx/Cfz) are
discontinued due to intolerance or
adverse events, shift to ITR.

Transition From Initial To Maintenance Phase For Patients On SSOR Lzd
Month 2 D/C Lzd
Refer to TB MAC
Department of Health - Disease Prevention and Control Bureau
Transition From Initial To Maintenance Phase For Patients On SSOR Lzd
Smear result at
NEGATIVE D/c Hh
Month 4
POSITIVE
Extend Hh 1 month, extend D/c Bdq after 24 weeks
BDQ to 9 months
Smear result of NEGATIVE

D/c Hh
Month 5
POSITIVE
Extend Hh 1 month, extend BDQ to
9 months
NEGATIVE
Smear result of
D/c Hh
Month 6
POSITIVE
Refer to TB MAC
Department of Health - Disease Prevention and Control Bureau
• All seven drugs are given for 4 months,
with the possibility of extending to 6 SSOR
months if the patient’s sputum smear
remains bacteriologically positive at the Pto variation
end of 4th or 5th month. 4-6 Bdq(6) - Lfx - Cfz - Z - E - Hh -
Pto / 5 Lfx - Cfz - Z – E
• Pto and Hh are dropped between 4 to 6
months (depending on smear status at IP: 4-6 Bdq(6) - Lfx - Cfz - Z - E - Hh
– Pto
month 4).
MP: 5 Lfx - Cfz - Z - E
• Bdq is given for 6 months, but may be Dosages of the different anti-
extended to 9 months if the initial TB drugs in the 9-month all-
phase of the regimen is extended from oral regimen shall be
determined based on the latest
4 to 6 months because of positive WHO recommended dosage by
sputum smears at months 4 or 5 of weight band for medicines
treatment. used in the MDR-TB regimens

• If Pto is not tolerated, then the patient
may be switched to Lzd variation or
refer to TBMAC for ITR without Pto. If
both Lzd and Pto after being used
alternatively are not tolerated, shift to
ITR. SSOR
• How to give Pto:
o Start Pto in two divided doses Pto variation
(morning and evening) if total daily
dose is >250 mg for the first 2 weeks
of treatment.
o Once tolerance to Pto has improved,
change Pto dosing to once daily
after 2 weeks.
o Advise patients to take Pto only after
light meals

⮚ If resistance to both Pto and Hh is
confirmed, shift to ITR
⮚ If resistance to Pto or Hh (only one) is

confirmed, the regimen may continue
without necessitating to switch to a
longer regimen SSOR
⮚ If either Z or E (only one) is
discontinued due to intolerance ,
Pto variation
adverse event or confirmed resistance,
the regimen may continue without
necessitating to switch to a longer
regimen.
⮚ If both Z and E are discontinued due

to intolerance, adverse event or
confirmed resistance, shift to ITR.
Transition From Initial To Maintenance Phase For Patients On SSOR Pto
Smear result at
NEGATIVE
Month 4 D/c Hh, Pto
POSITIVE
Extend Hh & Pto 1 month,
extend BDQ to 9 months
Smear result of NEGATIVE

D/c Hh, Pto
Month 5
POSITIVE
Extend Hh & Pto 1 month, extend
BDQ to 9 months
NEGATIVE
Smear result of
D/c Hh, Pto
Month 6
POSITIVE
Refer to TB MAC
• ITR should be offered when the BPaLM
or 9-month all oral regimen cannot be
used, or if the patient presents with
ITR
drug intolerance, adverse reactions,
additional resistance to, or lack of
response to the shorter regimens..
• The stepwise approach, following the

priority order based on the revised
classification of regimen components,
is preferred, and must be composed of
at least four likely effective drugs.
And at least 3 drugs are included for the
rest of treatment if Bdq is stopped

If dispersible tablets are not
available, adult formulations
can be diluted in 10mL of
water

Renal dosing is applicable to other
regimens except BPaLM/BPaL

Available Pediatric Formulations as of October 2023
Bedaquilline 20mg (Dispersible Tablet)
Delamanid 25mg (Dispersible Tablet)
Linezolid 150mg (Dispersible Tablet)
Cycloserine 125mg (Capsule)
Clofazimine 50mg (Capsule)
Levofloxacin 100mg (Dispersible Tablet)

Guide On Deciding Appropriate Treatment Regimen Based On baseline LPA/XPERT DST Results
High Level H (Hh)

FQ Resistance Pto/Eto Resistance
Initial Regimen Resistance Detected Clinical and Programmatic Action
detected Detected (InhA )
(katG)
- +/- +/- Continue BPaLM
BPaLM / BPaL Drop Mfx, continue as BPaL; continue
+ +/- +/- dose count. Reclassify as pre-XDR-TB
- +/- +/- Continue SSOR Lzd

SSOR Lzd
+ +/- +/- Shift to ITR. Restart dose count
- - - Continue SSOR Pto
- + - Continue SSOR Pto
- - + Continue SSOR Pto

SSOR Pto Shift to ITR, Continue dose count if
within 1 month of treatment initiation,
- + + Restart dose count if more than 1 month
of treatment initiation
+ +/- +/- Shift to ITR. Restart dose count
*Note: The patient’s initial regimen was based on the eligibility criteria
Guide On Deciding Appropriate Treatment Regimen Based On baseline LPA/XPERT DST Results
High Level H (Hh) Pto/Eto Resistance

FQ Resistance Clinical and Programmatic Action
Initial Regimen Resistance Detected Detected
detected
katG InhA
CTR FQ S
- +/- +/- Continue CTR FQ S
+ +/- +/- Shift to CTR FQ R. Restart dose count
Review initial regimen and revise if
ITR +/- +/- +/- needed in consultation with TB MAC

Monitoring Response To Treatment
Recommended Schedule of Baseline, Routine and Post –Treatment Monitoring Examinations for DR-TB Patients
2nd week from

start of
End of 6 and 12 months post-
Examination Baseline treatment (for Monthly
Treatment treatment
Lzd containing
regimens)
Bacteriologic tests
Drug susceptibility testing If culture remains positive at month 4 of treatment, in
First- and second-line Xpert XDR or LPA ✓ case of culture reversion, or culture positivity during
Phenotypic DST ✓ post-treatment ff-up
Diagnostic tests
Chest X-ray (Conduct every 6 months while on
✓ ✓ ✓
treatment)
Electrocardiogram
✓ ✓ ✓ ✓
(Regimen contains Cfz, Bdq, Mfx, Dlm, Pa, and Lfx)
✓ ✓ ✓ ✓
(Regimen contains Lzd and E)
✓ ✓ ✓ ✓
(Regimen contains Lzd, H, Cs, Trd, Lfx, Mfx, and Am)
✓
(Regimen contains Cs and H)
containing)
2nd week from

start of
End of 6 and 12 months post-
Treatment treatment
Lzd containing
regimens)
Bacteriologic tests
Drug susceptibility testing If culture remains positive at month 4 of treatment, in
First- and second-line Xpert XDR or LPA ✓ case of culture reversion, or culture positivity during
Phenotypic DST ✓ post-treatment ff-up
Diagnostic tests
Chest X-ray (Conduct every 6 months while on For
✓ ITR ✓ ✓
treatment)
Electrocardiogram
(Regimen contains Cfz, Bdq, Mfx, Dlm, Pa, and Lfx) TB✓ Culture will
✓ be done ✓every other
✓ month after 6
Visual acuity and color vision months of treatment

✓ ✓ ✓ ✓
(Regimen contains Lzd and E)
✓ ✓ ✓ ✓
(Regimen contains Lzd, H, Cs, Trd, Lfx, Mfx, and Am)
✓
(Regimen contains Cs and H)
containing)
2nd week from

start of
6 and 12 months
Examination Baseline treatment (for Monthly End of Treatment
post-treatment
Lzd containing
regimens)

ALT and AST
✓ ✓ ✓ ✓
(Regimen contains Z, H, Pa, Bdq, Eto/Pto, Cs/Trd, and PAS)
CBC
✓ ✓ ✓ ✓
FBS or HbA1C ✓
Serum K^ ✓
✓
containing)
✓
TSH (If Pto/Pas-
containing)
Albumin
HIV screening ✓

MONITORING OF TREATMENT
Monitoring treatment response Monitoring for drug safety

(effectiveness)
1. Response to treatment should be 1. Lzd-containing regimens shall include

monitored on the basis of monthly monitoring of the following
sputum smear microscopy and culture, a. (For BPaLM/BPaL note that Lzd
collected at the same frequency, and modification is only allowed after 9
monthly regular clinical assessment, and weeks of the BPaLM/BPaL regimen,
as needed, of signs and symptoms of TB b. For 9-month SSOR no Lzd
disease. modification is allowed
2. ECG monitoring for any signs of QT

2. Appropriate action shall be taken in cases prolongation should be done at monthly
of adverse drug reactions, poor intervals (or more frequently, if warranted)
bacteriological or clinical response to for the duration of the treatment,
treatment, or acquired resistance to including cases of treatment
drugs in the regimens. prolongation.

Monitoring treatment response Monitoring for drug safety

(effectiveness)
3. All patients receiving shorter regimens 3. Blood tests monitoring for myelosupression,
should be followed up for clinical reassessment hepatotoxicity
6 months and 12 months post-treatment, to (CBC, AST/ALT, creatinine, potassium
monitor for potential relapse.
4. Other diagnostic tests like BPNS for
peripheral neuropathy,
Snellens/Ishihara tests for optic neuritis

Monitoring treatment response (effectiveness) Monitoring for drug safety
● More frequent monitoring based on the physician’s clinical judgement may be advisable in specific situations; such as,
but not limited to, the following cases:
a. Elderly
b. PLHIV
c. Diagnosed with hepatitis (caused by Hepatitis B virus or Hepatitis C virus)
d. Diabetes mellitus
e. Moderate to severe hepatic or renal impairment
f. Anemia at any grade
g. Baseline visual disturbances (e.g. glaucoma, cataract, or color blindness)
● All patients receiving shorter regimens should be followed up for clinical reassessment 6 months and 12 months post-
treatment, to monitor for potential relapse.
● Schedule of baseline and follow-up clinical, laboratory and bacteriologic examinations for patients on individualized
treatment regimens shall follow MOP6 guidelines. Except for Lzd containing regimens where monitoring should be
done 2 weeks after treatment.

Treatment Outcome
Outcome Definition
A patient whose treatment regimen needed to be terminated or permanently changed to a new
regimen or treatment strategy, due to any of the following:
● No clinical and/or bacteriological response to appropriate treatment regimen. Examples:
○ Bacteriologic reversion or lack of bacteriologic conversion by month 4 (BPaLM);
○ Lack of smear conversion or presence of culture reversion during the extended months 7-
9 of BPaL correlated clinically;
○ Lack of evidence of at least two negative cultures by the end of an extended initial phase
(six months) of the SSOR
○ [SSOR] persistent positive sputum smear at 6th month during the extension of initial
Treatment
phase;
failed
○ [ITR] Bacteriologic reversiona anytime after 6 months of treatment
● Toxicity or intolerance to a drug in the regimen (pharmacologic failure)
○ More than 2 weeks consecutive treatment interruption of all medicines in the BPaLM
regimen
○ More than 4 weeks cumulative nonconsecutive treatment interruption of all medicines in
the BPaLM/BPaL regimen
○ Permanent discontinuation of any of the other drugs of the SSOR (Bdq/Lfx/Cfz) or to both
Z and E
● Evidence of acquired resistance to key medicines in the regimen

Outcome Definition
New Definitions !!!!A patient whose treatment regimen needed to be terminated or permanently changed to a new
aBacteriologic regimen
reversion:orattreatment strategy,positive
least 2 consecutive due tocultures
any of the following:
taken at least 7 days apart
● No clinical
either after bacteriologic and/ororbacteriological
conversion response
in patients without to appropriate
bacteriologic confirmationtreatment
of TB regimen. Examples:
○ Bacteriologic reversion or lack of bacteriologic conversion by month 4 (BPaLM);
bBacteriologic conversion: BCTB with at least 2 consecutive negative cultures taken at least 7
days apart
○ Lack of smear conversion or presence of culture reversion during the extended months 7-
9 of BPaL correlated clinically;
○ Lack of evidence of at least two negative cultures by the end of an extended initial phase
(six months) of the SSOR
○ [SSOR] persistent positive sputum smear at 6th month during the extension of initial
Treatment
phase;
failed
○ [ITR] Bacteriologic reversiona anytime after 6 months of treatment
● Toxicity or intolerance to a drug in the regimen (pharmacologic failure)
○ More than 2 weeks consecutive treatment interruption of all medicines in the BPaLM
regimen
○ More than 4 weeks cumulative nonconsecutive treatment interruption of all medicines in
the BPaLM/BPaL regimen
○ Permanent discontinuation of any of the other drugs of the SSOR (Bdq/Lfx/Cfz) or to both
Z and E
● Evidence of acquired resistance to key medicines in the regimen

A patient with bacteriologically confirmed MDR/RR-TB at the beginning of
treatment who has completed treatment, with evidence of bacteriological
Cured
conversionb (two or more consecutive negative cultures taken at least 7
days apart) and no evidence of failure.
A patient who completed treatment with clinical improvement whose

Treatment
outcome does not meet the definition for CURED, and without evidence
completed
of failure.
A patient who died for any reason before starting treatment or during the
Died
course of treatment.
A patient who did not start treatment or whose treatment was interrupted
Lost to follow-up
for 2 consecutive months or more.
Not evaluated A patient for whom no treatment outcome was assigned.

A patient with bacteriologically confirmed MDR/RR-TB at the beginning of
treatment who has completed treatment, with evidence of bacteriological
Cured
conversionb (two or more consecutive negative cultures taken at least 7
Remember days apart) and no evidence of failure.
Record the treatment outcome and update patient record on ITIS
A ofpatient
Issue the certificate who
completion completed
of treatment treatment
and advise patientswith clinical
on post improvement
treatment follow- whose
Treatment
ups outcome does not meet the definition for CURED, and without evidence
completed
of failure.
A patient who died for any reason before starting treatment or during the
Died
course of treatment.
A patient who did not start treatment or whose treatment was interrupted
Lost to follow-up
for 2 consecutive months or more.
Not evaluated A patient for whom no treatment outcome was assigned.

Post Treatment Follow-Up
POST-TREATMENT FOLLOW-UP
When? 6th and 12th month post treatment
What to do?
⮚ Comparative chest x-ray
⮚ Record results in treatment card
⮚ Collect 2 specimens per visit for SM, TBC and pDST
2nd week from

start of
End of 6 and 12 months
Treatment post-treatment
Lzd containing
regimens)
Bacteriologic tests
Drug susceptibility testing If culture remains positive at month 4 of
First- and second-line Xpert XDR or LPA ✓ treatment, in case of culture reversion, or culture
Phenotypic DST ✓ positivity during post-treatment ff-up
Diagnostic tests
Chest X-ray ✓ ✓ ✓
Active Drug Safety Monitoring and
Management (aDSM)
General Strategies for Managing Adverse Events (AEs)
Check for other potential
Conduct a thorough causes of the AE. Follow the recommended
clinical history and Request/perform additional actions based on the severity
physical examination laboratory and other grade of the AE
diagnostic tests, as needed
Adjust drug dosages as

long as it will not
Modify the regimen to ensure Provide relevant information
compromise the
effectiveness and safety and counsel the patient
effectiveness of the
regimen
Refer to TBMAC for Refer to specialist for

difficult and challenging concomitant
Provide psychosocial support
cases uncontrolled/unmanageable
co morbidities and AEs

Severity Grading of AE
Asymptomatic or mild symptoms; clinical or diagnostic

1 MILD
observations only; intervention not indicated
Minimal, local or non-invasive intervention indicated; limiting

2 MODERATE
age-appropriate instrumental ADL*
Medically significant but not immediately life-threatening;

3 SEVERE hospitalization or prolongation of hospitalization indicated;
disabling; limiting self care ADL**
4 LIFE-THREATENING Urgent intervention indicated

5 DEATH
*Instrumental Activities of Daily Living (ADL) refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.
**Self-care Activities of Daily Living (ADL) refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden
GRADE 1/MILD AEs to be managed by nurses

GRADE 2 and above/Moderate and above AEs to be managed by physicians
Peripheral Neuropathy
POSSIBLE ANTI-TB DRUG CAUSES:

Lzd, H, Cs/Trd, Lfx, Mfx, Am

Peripheral Neuropathy
Lzd, H, Cs/Trd, Lfx, Mfx, Am
Paresthesia: a disorder characterized by functional disturbances of sensory neurons resulting in

abnormal cutaneous sensations of tingling, numbness pressure, cold, and/or warmth
Grade 1 Grade 2 Grade 3

Adverse event Grade 4
BPNS = 1-3 BPNS = 4-6 BPNS = 7-10
Severe
discomfort; or Incapacitating;
Moderate
Mild discomfort; narcotic or not
discomfort; non-
Paresthesia no treatment analgesia responsive to
narcotic analgesia **
required **required with narcotic
required;
symptomatic analgesia
improvement;

Peripheral Neuropathy (2)
BPNS = 1-3 BPNS = 4-6 BPNS = 7-10
Regimen Actions to be taken
Reduce dose of Lzd to
300 mg/day and monitor
weekly. If symptoms Permanently stop Lzd.
Consider drug holiday
improve, may resume to
for 1-2 weeks; if
600 mg/day as tolerated OR
symptoms improve,
restart Lzd at a lower
OR Drug holiday for 1-2 weeks. If there is
BPaLM/BPaL* dose of 300 mg/day,
reversion to baseline, may restart Lzd at 300
or 600 mg/day as
Consider drug holiday for mg/day provided it does not revert back to
tolerated. If symptoms
1-2 weeks, and if Grade 3 or 4.
worsen, stop Lzd
symptoms improve,
permanently
restart Lzd at a lower Otherwise, permanently stop Lzd
dose of 300 mg/day or at
600 mg/day, as tolerated

Adverse Event Grade 4
BPNS = 1-3 BPNS = 4-6 BPNS = 7-10

of Lzd up to 3
cumulative doses
Consider drug holiday of
and/or Hh for 1-2
Lzd up to 3 cumulative
weeks. If symptoms
doses and/or Hh for 1-2
improve, restart Lzd Stop Lzd and/or Hh permanently then shift
SSOR with Lzd,Hh weeks. If symptoms
and/or Hh at the to ITR
improve, restart Lzd
same dose.
and/or Hh at the same
If symptoms worsen,
dose.
stop Lzd and/or Hh
permanently then
shift to ITR

BPNS = 1-3 BPNS = 4-6 BPNS = 7-10

Permanently stop Lzd, Hh and/or Cs
of the suspected
Consider drug holiday of agent for 1-2 weeks; if
the suspected agent for symptoms improve, OR
1-2 weeks; if symptoms restart Hh and/or Cs
improve, restart Hh at the same dose, and Drug holiday of the suspected agent for
ITR with Lzd, Hh, Cs and/or Cs at the same Lzd at a lower dose of 1-2 weeks. If there is reversion to
dose, and Lzd at a lower 300 mg/day or at 600 baseline, may restart Hh and/or Cs at
dose of 300 mg/day or mg/day, as tolerated. the same dose, and/or Lzd at 300
at 600 mg/day as
mg/day provided it does not revert
tolerated If symptoms worsen,
back to Grade 3 or 4. Otherwise,
stop the drug(s)
permanently. permanently stop the drugs.

Myelosuppression
POSSIBLE ANTI-TB DRUG CAUSE:

Lzd, Mpm, H, Pa

Myelosuppression
POSSIBLE ANTI-TB DRUG CAUSE: Lzd/Mpm/H/Pa
GRADING
4
1 2 3
LIFE-
MILD MODERATE SEVERE
THREATENING
Hemoglobin 9.5 – 10.5 g/dL 8.0 – 9.4 g/dL 6.5 – 7.9 g/dL <6.5 g/dL
75,0000 – 50,000 – 74,999 / 20,000 – 49,999 /
Platelet <20,000 / mm³
99,999 / mm³ mm³ mm³
Absolute
1,000 – 1,500 /
Neutrophil 750 – 999 / mm³ 500 – 749 / mm³ <500 / mm³
Count mm³

1 2 3 4
MILD MODERATE SEVERE LIFE-THREATENING
Drug holiday for Lzd for Drug holiday for Lzd for 1-
Monitor carefully, do 1-2 weeks, consider 2 weeks. Hospitalize the
weekly CBC and consider erythropoietin therapy if patient and consider
Monitor carefully, reduction of Lzd dose to 300 available. blood transfusion or
do weekly CBC and mg daily. Restart at a reduced erythropoietin therapy if
BPaLM/BPaL*
consider reduction dose of Lzd 300 mg/day, available.
of Lzd dose to 300 For Grade 2 neutropenia, once toxicity has Restart at a reduced dose
ITR with Lzd
mg daily stop Lzd. Restart at lower decreased1 or consider of Lzd, 300 mg/day once
dose once toxicity has stopping Lzd toxicity has decreased to
reduced to baseline. permanently. Grade 1 or consider
stopping Lzd
permanently.
Drug holiday for Lzd for
Monitor carefully, do weekly Drug holiday for Lzd for up to 3 cumulative doses.
CBC up to 3 cumulative doses Hospitalize the patient
Monitor carefully, do
SSOR with Lzd** and consider and consider blood
weekly CBC
For Grade 2 neutropenia, erythropoietin therapy if transfusion or
stop Lzd available erythropoietin therapy if
available
All Lzd containing regimens
Note: A decrease in haemoglobin level of 10% or more after 4 weeks of
treatment may help to identify those at high risk for severe anaemia
1 2 3 4
Drug holiday for Lzd for 1-
For BPaL/M 1-2 weeks, consider
Monitor carefully, do 2 weeks. Hospitalize the
*Dose reduction of Lzd is allowed only after 9
weekly CBC and consider weeks of Lzd 600
erythropoietin mg/day.
therapy if patient and consider
TemporaryMonitor
or permanent
carefully, discontinuation of Lzd
reduction of Lzd dose is allowed
to 300 available.only when there blood transfusion or
are only 8 weeks remaining
do weekly CBC and mg in the Restart at a reduced
daily.treatment course (or after 18 weeks of 600 erythropoietin therapy if
BPaLM/BPaL*
dose of Lzd 300 mg/day, available.
mg/day or consider reduction
300 mg/day).
of Lzd dose to 300 For Grade 2 neutropenia, once toxicity has Restart at a reduced dose
ITR with Lzd
mg daily stop Lzd. Restart at lower decreased1 or consider of Lzd, 300 mg/day once
dose once toxicity has stopping Lzd toxicity has decreased to
For SSOR with Lzd variationreduced to baseline. permanently. Grade 1 or consider
stopping Lzd
**May allow up to 3 accumulated missed doses of Lzd but resume at 600 permanently.
mg/day and add the missed doses at the end of the 2-month period. No
dose reduction of Lzd is allowed. Shift to another
Monitor carefully, do weeklyregimen, if not tolerated.
Drug holiday for Lzd for up to 3 cumulative doses.
CBC up to 3 cumulative doses Hospitalize the patient
Monitor carefully, do
SSOR with Lzd** and consider and consider blood
weekly CBC
For Grade 2 neutropenia, erythropoietin therapy if transfusion or
stop Lzd available erythropoietin therapy if
available
All Lzd containing regimens
Note: A decrease in haemoglobin level of 10% or more after 4 weeks of
treatment may help to identify those at high risk for severe anaemia
OPTIC NEURITIS
Lzd/E
A disorder characterized by involvement of the optic nerve (2nd cranial nerve)
Adverse event Grade 1 Grade 2 Grade 3 Grade 4
Symptomatic; Limiting vision in the

Asymptomatic (or moderate decrease in affected eye; VA
mild symptoms); visual acuity (VA) worse than 20/40
clinical or diagnostic [20/40 (6/12) or better] (6/12) but better than Blindness [20/200
observations only or or drop of 2 lines on 20/200 (6/60) or drop (6/60) or worse] in the
unable to read 4 or VA (Snellen) chart or of 2 lines on VA affected eye
more plates in the unable to read 4 or (Snellen) chart or
color vision test more plates in color unable to read 4 or
vision test. more plates in color
vision test.
Regimen Action to be taken
BPaLM/BPaL
Discontinue Lzd and/or E immediately regardless of severity grade for optic neuritis and
ITR with Lzd and E must refer patient to an ophthalmologist as soon as possible. Do not restart if optic neuritis is
confirmed or unless there is an alternative diagnosis.
SSOR with Lzd (& E)

Hepatitis
POSSIBLE ANTI-TB DRUG CAUSES:
Z, H, Pa, Bdq, Pto/Eto, Cs,/Trd, PAS

Hepatitis
POSSIBLE ANTI-TB GRADING
DRUG CAUSES:
Z,H,Pa,Bdq,Eto/Pto, 1 2 3 4
Cs/Trd, Pas MILD MODERATE SEVERE LIFE-THREATENING
ALT / AST level >ULN-3X ULN >3X-5X ULN >5X-20X ULN >20 X ULN
If without signs and
symptoms, continue
treatment regimen, and
Regardless of
monitor ALT/AST every two
regimen
weeks until reversion to Grade
1
Continue treatment If with signs and symptoms,

regimen with interrupt the entire regimen,
routine monitoring (interruption allowed for
Regardless of signs and symptoms, interrupt entire
schedule <2consecutive weeks or < 4 regimen (interruption allowed for <2 consecutive weeks
non-consecutive weeks or < 4 non-consecutive weeks cumulative).
BPaL-M
cumulative)
BPaL
Treatment may be Treatment may be reintroduced after toxicity is resolved
reintroduced after toxicity is or ALT/AST returned to Grade 1 with close ALT/AST
resolved or Alt/AST returned to
Grade 1 With close ALT/AST
monitoring
monitoring

Hepatitis
POSSIBLE ANTI-TB GRADING

DRUG CAUSES:
Z,H,Pa,Bdq,Eto/Pto, 1 2 3 4
Cs/Trd, Pas
ALT / ALT level >ULN-3X ULN >3X-5X ULN >5X-20X ULN >20 X ULN
If with signs and
symptoms, stop all TB
and non-TB drugs.
Continue
Monitor ALT/AST weekly. Regardless of symptoms, stop all TB and non-TB
treatment
Treatment may be drugs. Monitor ALT/AST weekly.
regimen with
SSOR reintroduced after Treatment may be reintroduced after toxicity is
routine
toxicity is resolved for resolved or ALT/AST returned to Grade 1,
monitoring
ITR ALT/AST returned to following drug reintroduction/rechallenge
schedule
Grade1, following drug guidelines.
reintroduction/rechallen
ge*
as per guidelines

QT Prolongation
POSSIBLE
ANTI-TB GRADING
DRUG
CAUSES: 1 2 3 4
Cfz,Bdq,Mfx, MILD MODERATE SEVERE LIFE-THREATENING
Dlm,Pa,Lfx
>500 ms or >60 ms change from
>500 ms on at least two (2) separate
baseline and Torsade de Pointes or
ECGs at least 30 minutes apart
QTcF 450 – 480 ms 481 – 500 ms polymorphic ventricular
without signs/symptoms of serious
tachycardia or signs/symptoms of
arrhythmia*
serious arrhythmia
Consider hospitalization and replete Hospitalize as soon as possible and

Monitor more closely (at least weekly electrolytes as necessary; address replete electrolytes as necessary;
Regardless of ECG) until QTcF has returned to less other identified cause(s). Address other identified cause(s).
regimen than grade 1.
Repeat ECG in 24-48 hours until Repeat ECG in 24-48 hours until
QTcF is <500 ms QTcF is <500 ms.

QT Prolongation
POSSIBLE
ANTI-TB DRUG GRADING
CAUSES:
Cfz,Bdq,Mfx,Dl 1 2 3 4
m,Pa,Lfx MILD MODERATE SEVERE LIFE-THREATENING
May interrupt the entire regimen Interrupt the entire regimen for <
(allowed for < 2 consecutive weeks or 2 consecutive weeks or < 4 non-
< 4 non-consecutive weeks consecutive weeks cumulative.
BPaLM/
BPaL cumulative). Reintroduce the regimen when
Reintroduce the regimen when QTcF QTcF is <500 ms with close ECG
is <500 ms with close ECG monitoring monitoring,
Monitor more closely (at least weekly Stop the suspected /causative
May stop the suspected/causative
ECG) until QTcF has returned to less drug(s) and shift to another
drug(s) and shift to another regimen
than grade 1. regimen
SSOR
Stop the suspected /causative

May stop the suspected/causative
drug(s) . Reintroduce crucial
drug(s) . Reintroduce crucial drugs(s)
drugs(s) when QTcF is back to
when QTcF is back to baseline or
ITR baseline or change to other
change to other agent(s)
agent(s)

Active Drug Safety and Monitoring and Management
1. For breastfeeding patients, exercise caution and monitor infants due to breast milk deposition of
Bdq (e.g., cardiotoxicity, hepatotoxicity). This applies to all Bdq-containing regimens.
2. Brief Peripheral Neuropathy Screening (BPNS) and Visual Acuity (Snellen) & Color Vision Test
(Ishihara) must be done every 2 weeks during the first month of treatment and then monthly for
all Lzd-containing regimens.
3. ECG monitoring for any signs of QT prolongation should be done at monthly intervals (or more
frequently, if warranted) for the duration of the treatment, including cases of treatment
prolongation.
4. AST and ALT should be monitored monthly (or more frequently, if warranted) to check for possible
hepatotoxicity.
5. Appropriate action shall be taken in cases of adverse drug reactions, poor bacteriological or
clinical response to treatment, or acquired resistance to drugs in the regimens.

Active Drug Safety and Monitoring and Management
6. Report all serious adverse events (SAEs) or adverse events of special interest (AESIs)
through the Pharmacovigilance Monitoring System (PViMS).
7. In case PViMS is not accessible, complete the FDA Suspected Adverse Reaction Form
(aDSM reporting form). The paper report shall be submitted (refer to AO 2020-0025) to
the Center for Health Development (CHD) NTP Coordinator and National Drug Policy
Compliance Officer (NDPCO). This shall be later entered into PViMS by NDPCO.
8. Through PViMS or paper format, submit the report within two working days or 48 hours
from the occurrence of the event or immediately upon receipt of information.
9. Manage all adverse events accordingly and promptly regardless of severity and
seriousness.

Serious Adverse Events Adverse Events of Special
(SAE) Interest (AESI)
Any untoward medical occurrence that at
any dose: • Acute kidney injury
• Results in death • Hepatitis
• Is life threatening • Hypokalemia
• Requires inpatient hospitalization • Myelosuppression
or results in prolongation of
existing hospitalization • Optic Nerve Disorder
• Results in persistent • Ototoxicity
disability/incapacity • Pancreatitis
• Is a congenital anomaly/birth • Peripheral Neuropathy
defect
• Prolonged QT interval (using
• AEs that do not immediately result
in one of these outcomes, but
Fridericia Formula)
which require an intervention to • Psychiatric Disorders and CNS
prevent a serious outcome are toxicity
included

Reporting of
SAE and
AESI

Temporary DOH PD E-mail for ADSM Reporting
[email protected]

Rifampicin-resistant/Multidrug-resistant Tuberculosis
(RR/MDR-TB) In RR/MDR-TB In Individuals Below 14 Years Old
1. TB MAC shall be consulted. Initiation of treatment shall be in accordance with the regimen and dosage advised by TB
MAC.
2. A regimen consisting of four to five drugs shall be given for the entire treatment duration.
3. In children without microbiological confirmation of TB disease or rifampicin resistance, the choice of regimen should
consider the following:
• Drug resistance pattern of the isolate obtained from the most likely index case.
• Age-appropriateness of prescribed medication
• Drug tolerance and adverse drug reactions
• Availability of pediatric formulations
4. Treatment monitoring for children shall compose of the following:
a) Bacteriological monitoring (culture, SM) of sputum for pulmonary TB or specimen of affected extrapulmonary site if
feasible
b) Clinical monitoring
• Resolution of TB signs and symptoms,
• Monthly weight gain and growth
• Baseline chest x-ray and follow up chest x-ray at six months to check for resolution of lesions in case of
pulmonary TB
• Follow-up scans (CT scan/MRI scan/UTZ) at six months for intrathoracic or EPTB diagnosed by imaging, and
• Healing of other EPTB lesions (e.g. cold abscess)

MDR-TB regimen for Children
FQ - susceptible FQ - resistant
Bdq - Lfx - Lzd - Cfz (Cs/Dlm) Bdq - Lzd - Cfz - Cs (Dlm/PAS)
Determine severity or extensiveness of disease.

Severe or extensive disease in children is usually defined by the presence of any of the following:
• Extrapulmonary TB other than lymphadenopathy (peripheral nodes or intrathoracic lymph node TB
without airway obstruction)
• Complicated TB pleural effusion (with empyema or pneumothorax)
• Positive TB bacteriology (smear, Xpert MTB/RIF or other WHO recommended RDT, or culture)
• Cavitary, bilateral disease, or miliary pattern as evaluated on chest x-ray
• Presence of comorbid conditions or disease such as severe malnutrition
• Presence of oedema of both feet regardless of the grade or severe wasting (weight-for-height) Z score
below negative 3 or mid-upper arm circumference below 115 mm] or advanced immunosuppression.
Determine treatment duration:

o 9-12 months for non-severe/non-extensive disease depending on clinical progress as assessed by physician
o 15-18 months for severe or extensive disease.
Appropriate dosing, precaution, and strict monitoring must be observed on the use of Lzd. In cases where BPNS and
visual tests are difficult to perform and hematological side effects are likely, replacing Lzd with an alternative likely
effective drug (e.g., drugs in parentheses) may be considered.

Rifampicin-susceptible and Isoniazid-
resistant TB (Hr-TB)
Rifampicin-susceptible and Isoniazid-resistant TB (Hr-TB)
1. In patients with confirmed rifampicin-susceptible, isoniazid-resistant tuberculosis (Hr-TB), treatment with

rifampicin, ethambutol, pyrazinamide and levofloxacin is recommended for a duration of 6 months
Hr-TB Regimen Composition and Duration
6 (H) RZE - Lfx
• Lfx must be given for 6 months and is the preferred quinolone. When Hr-TB is diagnosed after the start of the
regimen for DS-TB, the companion medicines (HRZE) would end up being given for more than 6 months.
• Prolongation of treatment in patients with cavitary disease and with persistent positivity on sputum smear and
culture not satisfying the criteria for treatment failure should be referred to TB MAC and may be considered on a
case-by-case basis.
2. Do not give Lfx in the following circumstances:

a. Rifampicin resistance cannot be tested,
b. Documented resistance or known intolerance to fluoroquinolones,
c. Pre-existing QT prolongation, or
3. Clinical and bacteriologic monitoring shall generally follow the same schedule as DS-TB.
4. Culture with smear microscopy is recommended to check for any emergent resistance, especially to
rifampicin.
5. Non-response to treatment should be investigated with rapid molecular test and DST.

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Key Updates To DRTB Regimens 2023

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Key Updates To DRTB Regimens 2023

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Key Updates to the Current Treatment Guidelines for

the Programmatic Management of Drug-Resistant

Department of Health – Disease Prevention and Control Bureau

Department of Health – Disease Prevention and Control Bureau

Department of Health – Disease Prevention and Control Bureau

1. New DRTB Regimens included in the OHG

2. Revisions in regimen nomenclature

3. Use of Bdq and Dlm in children of all ages

4. Use of Bdq-containing regimens in pregnant women

6. Revised abbreviations of some TB medications/terms

Department of Health – Disease Prevention and Control Bureau

Department of Health – Disease Prevention and Control Bureau

Department of Health – Disease Prevention and Control Bureau

Department of Health – Disease Prevention and Control Bureau

The use of bedaquiline in pregnancy has

Department of Health – Disease Prevention and Control Bureau

2 negative cultures taken at least 30 BCTB with at least 2 consecutive

At least 2 positive consecutive

Department of Health – Disease Prevention and Control Bureau

TERMS OLD DEFINITIONS NEW DEFINITIONS

A patient who died for any

A patient whose treatment was

Department of Health – Disease Prevention and Control Bureau

•Large cavitary lesions involving more

•Even without cavitation if there is Presence of bilateral cavitary

•Bilateral cavitary disease or extensive

Department of Health – Disease Prevention and Control Bureau

DRUGS OLD ABBREVIATION NEW ABBREVIATION

Bedaquiline Bdq B or Bdq

Linezolid Lzd L or Lzd

Moxifloxacin Mfx M or Mfx

High Dose Isoniazid Hdh Hh

Clofazimine Cfz C or Cfz

OLD – Maximum Dose New – Maximum Dose

Department of Health – Disease Prevention and Control Bureau

TERM OLD NEW

CTR Conventional Treatment Regimen Child Treatment Regimen

IP Intensive Phase Initial Phase (IP)

CP Continuation Phase Maintenance phase (MP)

Department of Health – Disease Prevention and Control Bureau

2. Eligible patients with pre-XDR TB shall be given BPaL.

3. FQ-susceptible patients not eligible for BPaLM should be checked with

4. Patient’s not eligible to all the standard regimens shall be referred to

Department of Health – Disease Prevention and Control Bureau

6. Pregnant or breastfeeding patients shall be referred to TBMAC for

7. In cases of possible Fq resistance, (history of > 4 weeks of Fq use, or

Check exclusion criteria to BPaLM

NO to all YES to any

Check general exclusion criteria for SSOR

NO to all YES to any

Start SSOR with Lzd Start SSOR with Pto

2. Known allergy to any of the component drugs.

3. More than one month exposure to bedaquiline, linezolid, pretomanid or

4. Contact of a patient who had failed treatment with MDR-TB treatment

⮚ Pre-existing severe to life-threatening peripheral neuropathy (Grade

⮚ QTcF > 500 ms2

Department of Health – Disease Prevention and Control Bureau

1. Extensive3 or disseminated TB (miliary) or severe/intractable

5. Risk of toxicity or intolerance to any drugs in the regimen as