UPDATE

PEDOMAN PMDT WHO 2019

Workshop Sosialisasi Update Pengobatan TB Resistan Obat di

Indonesia
Makassar, 9 Oktober 2019

• Setiawan Jati Laksono│ NPO TUB │ WCO Indonesia • www.searo.who.int/indonesia

Evolusi
Pengobatan
TB RO
Pedoman WHO untuk Pengobatan dan Manajemen TB
RO, 1996 +

2019

2016

2016

2017 2018
Pedoman PMDT WHO 2008
Pedoman PMDT WHO 2011
Pedoman PMDT WHO 2014
Pedoman PMDT WHO 2016
Update Pedoman PMDT WHO 2019
Mengapa
Pengobatan TB RO
Berubah Terus?
Bagaimana Pengobatan TB RO Yang Ideal?
• Efikasi yang baik
• Durasi 3-6 bulan
• Kombinasi 3-4 OAT
• Tanpa Injeksi
• FDC
• Efek Samping lebih sedikit
• Toksisitas lebih rendah
• Paduan OAT yang sama untuk TB RR/MDR/XDR
• ………..
Inovasi dan studi menuju Pengobatan TB RO yang
ideal masih berlangsung
 Evidence Based Decision
• Anonymized individual data yang diperoleh dari clinical trial,
kohort/ studi observasi dan data program (STR dan LTR)
dikumpulkan dalam sebuah individual MDR/RR-TB patient
data base (IPD) yang dikelola oleh McGill University, Canada,
yang dikontrak oleh WHO.
• Metode Cochrane untuk meta-analysis digunakan untuk
menilai kontribusi relatif masing-masing obat pada hasil
pengobatan, desain paduan, lama pengobatan yang paling
efektif dan dampak profil resistensi terhadap hasil
pengobatan.
• WHO membentuk suatu Guideline Development Group yang
melakukan review terhadap hasil serangkaian analisis di atas
menggunakan system GRADE untuk mendapatkan scientific
evidence yang digunakan untuk menyusun suatu pedoman
dan rekomendasi yang evidence-based.
 2016: 269 Reports until 2014; 54% supportive, 33% contradictory, & 13%
inconclusive on association of salt reduction with reduction in Cardio-
cerebrovascular disease.

Trinquart L, et al. Int J. Epid, 2016;45;1

Implikasi terkait Kekuatan Rekomendasi
 Kepastian untuk memperkirakan dampak

Certainty Definition
High Further research is very unlikely to change our confidence in
the estimate of effect.
Moderate Further research is likely to have an important impact on our
confidence in the effect and may change the estimate.
Low Further research is very likely to have an important impact on
our confidence in the estimate of effect and is likely to
change the estimate.
Very low Any estimate of effect is very uncertain.

Adapted from Guyatt GH et al. BMJ. 2008 Apr 26,336(7650):924-6

Consolidated WHO DR-TB treatment guidelines, 2019

• Dikeluarkan WHO pada bulan Maret 2019 In March 2019, untuk

menggabungkan beberapa policy update menjadi satu dokumen,
dengan penjelasan mengenai evidence yang terkait dengan
pengambilan keputusan tersebut.
• Berisi rekomendasi mengenai:
• TB resistan INH (Hr-TB)
• longer dan shorter regimen untuk TB RO
• Penggunaan tindakan bedah pada pasien TB RO
• Waktu pemberian ART pada TB RO dengan HIV
• Monitoring pengobatan dengan Biakan
• Model layanan
Apa Yang
Berubah?
• TB resistan INH (Hr-TB)
• Longer dan shorter regimen untuk TB RO
• Penggunaan tindakan bedah pada pasien TB RO
• Waktu pemberian ART pada TB RO dengan HIV
• Monitoring pengobatan dengan Biakan
• Model layanan
Pertanyaan Utama: Hr-TB
Pada pasien yang resistan terhadap INH (tetapi bukan
TB MDR):
• Apa paduan terbaik?
• Berapa lama durasi pengobatan yang terbaik?
• Panduan mana yang Kemungkinan keberhasilan lebih
besar dan Efek samping lebih sedikit?
 Isoniazid-resistant TB (Hr-TB)
Evidence summary (1)

• Individual patient data meta analysis (IPD-MA) from

33 observational studies with an analysable
population of 5418 Hr-TB patients
• 26% in Asia; 33% in Europe; 31% in the Americas; and
6% in Africa
• Regimens analysed composed of R, H, E, Z, FQ and S
 6-month (H)REZ regimen had a higher
likelihood of treatment success and less
amplification of resistance than >6 months

(H)REZ+Lfx regimens had higher success and

Isoniazid- lower deaths and amplification of resistance
than (H)REZ
resistant
TB (Hr-TB) <4 months of Z with FQ in regimen was
associated with better treatment success

Evidence <3 months of Z with S in regimen was

summary associated with lower treatment success and
higher mortality

Analysis for adverse events not possible

owing to dissimilar methods of data
collection
 Isoniazid-resistant TB (Hr-TB)
Main recommendations (1)
In patients with confirmed rifampicin-susceptible and
isoniazid-resistant tuberculosis, treatment with
rifampicin, ethambutol, pyrazinamide and levofloxacin is
recommended for a duration of 6 months.

[conditional recommendation;
very low certainty in the evidence]
 Isoniazid-resistant TB (Hr-TB)
Main recommendations (2)
In patients with confirmed rifampicin-susceptible and
isoniazid-resistant tuberculosis, it is not recommended to
add streptomycin or other injectable agents to the
treatment regimen

[conditional recommendation; very low certainty in the

evidence]
 Isoniazid-resistant TB (Hr-TB)
Main remarks (1)
• Any deviations from the main recommendation to
give 6 months of REZ has to balance benefits to
harms.
• H may be added for convenience (to use 4-drug
FDC) and may increase regimen effectiveness if only
low-level H resistance is present
• Very few children (0-14 years) were included in the
IPD but the GDG recommended that the treatment
policy applies equally to children. Can also be used
in extrapulmonary Hr-TB
 Isoniazid-resistant TB (Hr-TB)
Main remarks (2)
Some of the reasons which may determine changes to
the main recommendation are:
• HR-TB with additional resistance - suspected or
confirmed - to E or Z
• previous treatment for TB
• Drug intolerance or DDI (e.g. FQ with R)
• extensive disease
• HIV infection on antiretroviral therapy
• absence of the katG mutation
 Isoniazid-resistant TB (Hr-TB)
Implementation considerations
Hr-TB treatment is given in one of two situations:
1. Hr-TB is confirmed before TB treatment is started:
6(H)REZ-Lfx is started immediately.
2. Hr-TB is discovered after the start of treatment with
2HREZ/4HR regimen: i.e. patient with undiagnosed
Hr-TB at start or who developed Hr-TB while on
first-line treatment. Rapid testing for RR-TB is done
and if excluded 6(H)REZ-Lfx is given.
• TB resistan INH (Hr-TB)
• Longer dan shorter regimen untuk TB RO
• Penggunaan tindakan bedah pada pasien TB RO
• Waktu pemberian ART pada TB RO dengan HIV
• Monitoring pengobatan dengan Biakan
• Model layanan
 Pada pasien TB RR/ MDR , OAT apa
saja yang bisa memperbaiki hasil
pengobatan ketika diberikan sebagai
Paduan Pengobatan Jangka Panjang?

Pada pasien TB RR/ MDR yang diobati

PERTANYAAN dengan Paduan sesuai Pedoman
UTAMA: LTR WHO:

• OAT yang diberikan kurang atau lebih dari 5

jenis OAT pada tahap awal pengobatan?
• Total durasi terbaik <20 bulan atau > 20 bulan?
• Berapa durasi pengobatan minimum setelah
konversi biakan?
• Berapa durasi tahap awal yang terbaik? <8
bulan atau > 8 bulan
 Longer MDR-TB regimens
Evidence summary (1)
• The main 2018 IPD-MA included 13,104 records from 53 studies in 40
countries. It contained recent datasets from several countries, including a
large dataset from South Africa with many patients treated with
bedaquiline-containing longer regimens

• For adverse events (AEs) resulting in permanent discontinuation of

medicines in longer regimens, a subset of 5,450 IPD records from 17 studies
was used, supplemented with additional information from 10 other studies
that only reported AEs for either Bdq (N=130), Lzd (N=508) or carbapenems
(N=139).
 Longer MDR-TB regimens
Evidence summary (2)

• In addition the GDG considered

– Final results from Phase III Trial 213 of delamanid
– Safety and pharmacologic exposure data from unpublished
paediatric studies of bedaquiline and delamanid
– Review of studies reporting outcomes of patients treated with
perchlozone, interferon gamma and sutezolid.
 Longer MDR-TB regimens
Relative risk for (i) treatment failure or relapse and (ii) death (versus treatment success)
2018 IPD-MA for longer MDR-TB regimens

Treatment failure or relapse vs. Death

Group A treatment success vs. treatment success
Number Adjusted OR Number Adjusted OR
treated (95% CI) treated (95% CI)
Levofloxacin OR
3,143 0.3 (0.1-0.5) 3,551 0.2 (0.1-0.3)
moxifloxacin
Bedaquiline 1,391 0.3 (0.2-0.4) 1,480 0.2 (0.2-0.3)
Linezolid 1,216 0.3 (0.2-0.5) 1,286 0.3 (0.2-0.3)
 Longer MDR-TB regimens
Relative risk for (i) treatment failure or relapse and (ii) death (versus treatment success),
2018 IPD-MA for longer MDR-TB regimens

Treatment failure or relapse Death

Group B vs. treatment success vs. treatment success
Number Adjusted OR Number Adjusted OR
treated (95% CI) treated (95% CI)
Clofazimine 991 0.3 (0.2-0.5) 1,096 0.4 (0.3-0.6)
Cycloserine OR
5,483 0.6 (0.4-0.9) 6,160 0.6 (0.5-0.8)
terizidone
 Longer MDR-TB regimens
Relative risk for (i) treatment failure or relapse and (ii) death (versus treatment success),
2018 IPD-MA for longer MDR-TB regimens and delamanid Trial 213 (intent-to-treat population)

Treatment failure or Death

Group C relapse vs. treatment vs. treatment success
success
Number Adjusted OR Number Adjusted OR
treated (95% CI) treated (95% CI)
Ethambutol 1,163 0.4 (0.1-1.0) 1,245 0.5 (0.1-1.7)
Delamanid 289 1.1 (0.4-2.8)* 290 1.2 (0.5-3.0)*
Pyrazinamide 1,248 2.7 (0.7-10.9) 1,272 1.2 (0.1-15.7)
Imp-cln OR meropenem 206 0.4 (0.2-0.7) 204 0.2 (0.1-0.5)
Amikacin 635 0.3 (0.1-0.8) 727 0.7 (0.4-1.2)
Streptomycin 226 0.5 (0.1-2.1) 238 0.1 (0.0-0.4)
Ethionamide OR
2,582 1.6 (0.5-5.5) 2,750 2.0 (0.8-5.3)
prothionamide
p-aminosalicylic acid 1,564 3.1 (1.1-8.9) 1,609 1.0 (0.6-1.6)
* unadjusted risk ratios as defined by the study investigators of Trial 213 by month 24
 Longer MDR-TB regimens
Relative risk for (i) treatment failure or relapse and (ii) death (versus treatment success),
2018 IPD-MA for longer MDR-TB regimens

Treatment failure or Death

Other medicines relapse vs. treatment vs. treatment success
success
Number Adjusted OR Number Adjusted OR
treated (95% CI) treated (95% CI)
Kanamycin 2,946 1.9 (1.0-3.4) 3,269 1.1 (0.5-2.1)
Capreomycin 777 2.0 (1.1-3.5) 826 1.4 (0.7-2.8)
Amoxicillin-clavulanic acid 492 1.7 (1.0-3.0) 534 2.2 (1.3-3.6)
 Serious adverse events (SAEs)
Medicine Absolute risk of AE
Median % 95% credible interval
Bedaquiline 2.4% [0.7, 7.6]
Moxifloxacin 2.9% [1.4, 5.6]
Amoxycillin-Clavulanic acid 3.0% [1.5, 5.8]
Clofazimine 3.6% [1.3, 8.6]
Ethambutol 4.0% [2.4, 6.8]
Levofloxacin 4.1% [1.9, 8.8]
Streptomycin 4.5% [2.3, 8.8]
Cycloserine / terizidone 7.8% [5.8, 10.9]
Capreomycin 8.4% [5.7, 12.2]
Pyrazinamide 8.8% [5.6, 13.2]
Ethionamide / prothionamide 9.5% [6.5, 14.5]
Amikacin 10.3% [6.6, 17.0]
Kanamycin 10.8% [7.2, 16.1]
p-aminosalicylic acid 14.3% [10.1, 20.7]
Thioacetazone 14.6% [4.9, 37.6]
Linezolid 17.2% [10.1, 27.0]
 Longer MDR-TB regimens
Number of agents
Number of likely effective Treatment failure or Death
relapse vs. treatment success vs. treatment success
agents* Adjusted OR (95% CI) Adjusted OR (95% CI)
4 vs 5 1.0 (0.7-1.3) 1.1 (0.9-1.5)
6 vs 5 1.0 (0.6-1.7) 0.9 (0.6-1.3)
IP

2 vs 1 highly effective agent* 0.9 (0.5-1.6) 0.6 (0.3-0.96)

>2 vs 1 highly effective agent* 0.6 (0.2-1.8) 0.4 (0.2-1.01)
2 vs 3 1.3 (0.8-2.1) 1.3 (0.8-2.0)
CP

4 vs 3 1.2 (0.9-1.5) 1.0 (0.8-1.3)

>1 vs 1 highly effective agent* 0.5 (0.1-1.7) 0.8 (0.2-2.5)

* Highly effective agent = Lfx, Mfx, Gfx (if DST=susceptible) and Lzd, Bdq,
Imp-Cln, Mpm (unless resistance documented)
 Longer MDR-TB regimens
Revised classification of component medicines
GROUP MEDICINES
Group A Levofloxacin OR Moxifloxacin Lfx / Mfx
Bedaquiline Bdq
Linezolid Lzd
Group B Clofazimine Cfz
Cycloserine OR Terizidone Cs/ Trd
Group C Ethambutol E
Delamanid Dlm
Pyrazinamide Z
Imipenem-cilastatin OR Meropenem Ipm-Cln / Mpm
Amikacin (OR Streptomycin) Am (S)
Ethionamide OR Prothionamide Eto / Pto
p-aminosalicylic acid PAS
 Longer MDR-TB regimens
Recommendations for regimen design

• In MDR/RR-TB patients on longer regimens, all three Group A agents and at

least one Group B agent should be included to ensure that treatment starts
with at least four TB agents likely to be effective, and that at least three
agents are included for the rest of treatment after bedaquiline is stopped.
• If only one or two Group A agents are used, both Group B agents are to be
included.
• If the regimen cannot be composed with agents from Groups A and B
alone, Group C agents are added to complete it

[conditional recommendation, very low certainty in the estimates of effect]

 Longer MDR-TB regimens
Regimen composition
Choice of medicines depends upon the
• expected balance of effectiveness and harms
• preference for oral over injectable agents
• the results of drug-susceptibility testing (DST)
• reliability of DST methods
• population drug resistance levels
• history of previous use of medicine in a patient
• drug tolerability
• potential drug-drug interactions
 Longer MDR-TB regimens
Implementation considerations (1)

• Three most effective agents grouped together and strongly

recommended
• Most patients may start treatment with at least 4 agents likely to be
effective and continue with 3 after 6 months
• An all-oral regimen is possible in most patients
• Amikacin and streptomycin placed lower in the priority ranking (if DST
is negative and audiometry possible) (S resistance not detectable with
2nd line HAIN)
• Kanamycin and capreomycin linked to poorer outcomes in IPD meta-
analysis and no longer recommended
 Longer MDR-TB regimens
Implementation considerations (2)
• The optimal duration of Bdq, Dlm and Lzd is not known. Use of Bdq &
Dlm beyond 6 months still considered “off label”
• Amx-Clv to be used only with Imp-Cln or Mpm and do not count as a
separate effective agent
• Z is only counted as an effective agent when DST results confirm
susceptibility.
• Eto/Pto and PAS only proposed for regimens which do not contain
Bdq, Lzd, Cfz or Dlm (or very last resort)
• No patients on thioacetazone, very few on high-dose isoniazid and
gatifloxacin – not in Groups A-C
 Longer MDR-TB regimens
Duration – evidence summaries
• IPD-MA done on subsets of the 13,104 cases in the main dataset; main reasons for
record exclusion being LFU, death, or because variables needed for analysis or
adjustment were missing
• Total duration – IPD-MA on a subset of 6,356 patients from 51 observational
studies. Of 6,356 patients, 5,352 were treated with an individualized MDR-TB
regimen and 1,004 were treated with a standardized MDR-TB regimen.
• Duration after culture conversion – IPD-MA on subset of 4,175 patients from 39
observational studies. All but 3 of the 4,175 patients were on individualized
regimens.
• Duration of injectable phase – records from 3,750 patients for the primary
analyses, from 42 observational studies; 2,720 were treated with an individualized
MDR-TB regimen and 1,030 with standardized MDR-TB regimens
 Longer MDR-TB regimens
Failure or relapse vs. success by different durations of treatment

Relative risk
Duration Comparator Intervention
(95% CI)
IP: 5-6 mo vs 7-8.5 mo 38/623 145/730 aOR 0.9
(6.1%) (19.9%) (0.4 to 2.3)
IP: 6-7 mo vs 7-8.5 mo 38/623 24/554 aOR 0.2
(6.1%) (4.3%) (0.0 to 1.1)
Total: 18-20 mo vs. 20-22 31/1376 87/1407 aOR 2.1
mo (2.3%) (6.2%) (0.7 to 6.1)
After culture conversion: aOR 5.5
12-15 mo vs 15-17 mo 9/537 23/278
(0.9 to
(1.7%) (8.3%)
33.7)
After culture conversion: 9/537 20/1118 aOR 1.2
17-19 mo vs 15-17 mo (1.7%) (1.8%) (0.4 to 3.7)
 Longer MDR-TB regimens
Duration – conditional upon patient response

• Total length = 18-20 months

• Time after conversion = 15-17 months
• Injectable phase (if applicable) = 6-7 months
 Contoh Penerapan
• Untuk sebagian besar kasus TB RO bisa dimulai dengan pemberian 4
macam obat dan dilanjutkan dengan 3 macam obat (setelah BDQ
dihentikan) dipandang sudah memadai. (Conditional Recommendation)
• Bisa juga dipilih opsi untuk memberikan 5 obat pada awal pengobatan
dengan pertimbangan:
• Keharusan menambahkan obat baru bila BDQ dihentikan pada akhir bulan ke
enam dan LNZ sudah dihentikan lebih awal karena terjadi tosisitas.
• Hasil DST yang reliabel tidak diketahui untuk salah satu obat, sementara
diketahui angka resistan untuk obat tersebut tinggi.
• Bila paduan obat yang diberikan kemungkinan besar kurang kuat untuk
menyembuhkan pasien (Misalnya hanya ada 2 obat dari grup A dan Grup B yang
masuk dalam paduan).
• Paduan dengan BDQ
• 6 Bdq Lfx Cfz Cs // 14 Lfx Cfz Cs
• Or 6 Bdq Lfx Lzd Cs// 14 Lfx Lzd Cs
• Paduan tanpa BDQ
• 6 Lfx Lzd Cfz Cs// 14 Lfx Lzd Cs
South Africa All Oral LTR
Basic
Kelompok Umur Tahap Awal Tahap Lanjutan
Dewasa, Remaja, Anak >12 tahun 6-8 LZD-BDQ-LFX-CFZ-TRD 12 LFX-CFZ-TRD
(>30kg)
Anak < 12 tahun (<30kg) 6-8 LZD-(DLM/BDQ/PAS)-LFX-CFZ- 12 (PAS)-LFX-CFZ-TRD-(Hhd/ETO)
TRD-(Hhd/ETO)

FQ Resistant
Kelompok Umur Tahap Awal Tahap Lanjutan
Dewasa, Remaja, Anak >12 tahun 6-8 LZD*-BDQ-(DLM/PAS)-CFZ- 12 LZD*-CFZ-TRD-(Hhd/ETO)-Z
(>30kg) TRD-(Hhd/ETO)-Z
Anak < 12 tahun (<30kg) 6-8 PAS-(DLM/BDQ)-LZD-CFZ- 12 PAS-LZD-CFZ-TRD-(Hhd/ETO)-Z
TRD-(Hhd/ETO)-Z
PERTANYAAN
UTAMA: STR
• Pada pasien TB RR/ MDR, apakah STR 9-
12 bulan akan meningkatkan
keberhasilan pengobatan dibandingkan
dengan Paduan Pengobatan Jangka
Panjang?
 Shorter MDR-TB regimen
Study results
• STREAM Stage 1 trial showed that in patients eligible for the shorter MDR-TB
regimen, the likelihood of treatment success was close to 80% in both arms

• Observational studies of shorter MDR-TB regimens also showed a comparable

likelihood of treatment success with longer regimens overall. No data from Bdq-
containing 9-month regimens were made available.

• Higher risk of failure or relapse in the shorter regimen when compared with
longer ones, especially when resistance was present or when Group A agents
were included in longer regimens. The shorter regimen had a lower risk of
treatment interruption.
 Shorter MDR-TB regimen
STREAM Stage 1 trial – final results
favourable outcome (follow up: mean 132 weeks)

Study Control Relative risk

Population
regimen regimen (95% CI)
mITT population 193/245 99/124 RR 0.99*
(78.8%) (79.8%) (0.88 to 1.01)
per protocol 186/227 67/83 RR 1.02**
(81.9%) (80.7%) (0.90 to 1.15)
* The difference in proportions (1.1% (-7.7%, 9.8%)) becomes
smaller after adjustment for HIV status (1.0% (-7.5%, 9.5%)) but the
upper confidence limit is <10%, the maximal value allowed by the
trial protocol to consider non-inferiority.
** The difference in proportions (-1.2% (-11.1%, 8.6%)) becomes
smaller after adjustment for HIV status (-0.7% (-10.5%, 9.1%))
 Shorter MDR-TB regimen
STREAM Stage 1 trial – final results
Lack of conversion, reversion or relapse (follow up: mean 132 weeks)

Relative risk
Population Study regimen Control regimen
(95% CI)
mITT RR 1.88*
26/245 (10.6%) 7/124 (5.6%)
population (0.84 to 4.21)

* Unadjusted RR for lack of conversion, reversion or relapse in

patients with baseline resistance to pyrazinamide was 5.95 (95%
CL: 0.80, 44.15) and baseline resistance to ethionamide was 3.41
(95% CL: 0.20, 58.32)
 Shorter MDR-TB regimen (1)
Recommendation
In MDR/RR-TB patients who have not been previously treated for more
than 1 month with second-line medicines used in the shorter MDR-TB
regimen or in whom resistance to fluoroquinolones and second-line
injectable agents has been excluded, a shorter MDR-TB regimen of 9–12
months may be used instead of the longer regimens.

[conditional recommendation, low certainty in the estimates of effect]

4-6 Am-Mfx-Pto-Cfz-Z-Hhigh-dose-E / 5 Mfx-Cfz-Z-E

 Shorter MDR-TB regimen (2)
Tighter criteria, different landscape
• Preference by the clinician and patient for a longer MDR-TB regimen
• Confirmed resistance or suspected ineffectiveness to a medicine in the shorter MDR-TB
regimen (except isoniazid resistance)
• Exposure to one or more 2nd line medicines in the shorter MDR-TB regimen for >1 month
(unless susceptibility to these 2nd line medicines is confirmed)
• Intolerance to medicines in the shorter MDR-TB regimen or risk of toxicity (e.g. drug-drug
interactions)
• Pregnancy
• Disseminated, meningeal or central nervous system TB
• Any extrapulmonary disease in PLHIV
• One or more medicines in the shorter MDR-TB regimen not available
FAILING SHORTER REGIMEN or NON-RESPONSE,
YES DRUG INTOLERANCE, EMERGENCE OF ANY OTHER NO
EXCLUSION CRITERION
Standardized, shorter
New, individualized MDR-TB regimen
longer MDR-TB regimens may be offered
(conditional recommendation)
 Shorter MDR-TB regimen (3)
Implications for future use
• Programmes already implementing the shorter MDR-TB regimen with good
results and capacity to monitor for ototoxicity
• switch from Km to Am
• while Km is used close follow-up for non-response to treatment or early
relapse
• lower the threshold to switch non responders to a new longer regimen
• Programmes planning to offer the shorter regimen to newly-diagnosed patients
to continue only if they have DST capacity to exclude at least FQ and SLI
resistance
• Programmes considering modified shorter regimens (e.g. replacing injectable with
BDQ) can do so as operational research
South Africa All Oral STR
Kelompok Umur Tahap Awal Tahap Lanjutan
Dewasa, Remaja, Anak >12 tahun 4-6 LZD*-BDQ-LFX-CFZ-Hhd-Z-E 5 LFX-CFZ-Z-E
(>30kg)
Anak 6-12 tahun (15-30kg) 4-6 LZD*-DLM-LFX-CFZ-Hhd-Z-E 5 LFX-CFZ-Z-E

Anak < 6 tahun (<15kg) 4-6 LZD*-PAS-LFX-CFZ-Hhd-Z-E 5 LFX-CFZ-Z-E

 Terima kasih
WHO Country Office for Indonesia
Gama Tower 5th
Jl HR Rasuna Said Kav. C-22, Jakarta 12940
Indonesia

• Setiawan Jati Laksono/ TUB WCO INO • www.searo.who.int/indonesia