AntiTB PDF

Outline
General information of first-line anti-TB drugs

Antituberculosis drug-induced adverse reactions
(hepatotoxicity, cutaneous)
Clinical significant drug interactions
24 2555
Antituberculosis drugs
First-line drugs
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol
Streptomycin
Rifapentin
Rifabutin
Second line drugs

Cycloserine
Ethionamide
Para-aminosalicylic acid
Capreomycin
Levofloxacin*
Moxifloxacin*
Gatifloxacin*
Amikin/kanamycin*
* Not approved by FDA-US
Isoniazid (IsoNicotinic acid Hydrazide)

(since year 2495)

()

3-5 mg/kg (max= 300 mg/day)

cerebrospinal, ascitic, pleural fluids, placenta
barrier, milk
Metabolized: acetylation (determine by acetylator
status), dehydrazination
Excreted in the urine
Isoniazid (IsoNicotinic acid Hydrazide)

(since year 2495)
Pyridoxine deficiency due to its

competition with pyridoxal phosphate
for enzyme apotryptophanase
Pregnancy category C
Small concentration of INH in breast milk do not
produce toxicity in nursing newborn
Rifampicin: warning/precaution
Rifampicin
RNA -subunit
RNA polymerase

Metabolized by deacetylation
Elimination mainly through the bile, to a much lesser
extent, the urine (dosage adjustment is not necessary)
Excreted in breast milk

Transient hyperbilirubinemia rifampicin

bilirubin
bilirubin

Hepatitis (see next)

ADRs associated with intermittent regimen or higher
dose and are caused by rifampicin antibodies
- Flu-like syndrome (0.4-0.7%)
- Thrombocytopenia , acute hemolytic anemia (0.1%)
- Acute renal failure
Pyrazinamide

The pyrazine analog of nicotinamide

PZA is a prodrug that convert to active form
(pyrazinoic acid) by mycobacterial enzyme
pyrazinamidase
MOA: target an enzyme involved in fatty acid
synthesis
Well absorbed from GI tract
Widely distributed in body tissues and fluids
70% of an oral dose is excreted in urine
Ethambutol
MOA: inhibition of
arabinosyl transferase
(enzyme that polymerizes arabinose into
arabinan and then arabinogalactan, a
mycobacterial cell wall constituent )
Approximately 20%
of ethambutol is metabolized
by liver
Pyrazinamide

Lactation: found in small amounts in breast milk.
Hyperuricemia: PZA inhibits renal excretion of
urates, frequently resulting in hyperuricemia
(usually asymptomatic)
Ethambutol
Excretion:
- unchanged drug is excreted
approximately 50% in the urine,
20-22% in the feces
Marked accumulation may occur with renal
insufficiency
Patients with decreased renal
function require reduced dosage
Ethambutol
Streptomycin
Pregnancy category B
Visual effects
(especially in higher dose; 18% with dose > 30
mg/kg/day ) generally reversible when the drug is
discontinued
Adverse Drug Reactions of anti-TB drugs

Major ADRs

Hepatotoxicity
Cutaneous ADRs (skin
rash with or without
itching)
Ototoxicity
Visual impairment
Minor ADRs

Anorexia
Nausea/vomiting
Abdominal pain
Joint pains
Peripheral neuropathy
(burning, numbness or
tingling sensation in
hands or feet)
Drowsiness
Streptomycin is a protein
synthesis inhibitor
Excrete unchanged by the kidney
Main ADRs
- hypersensitivity reaction
- ototoxicity (especially baby, patients age more
than 40 years)
- nephrotoxicty
Adverse Drug Reaction of anti-TB drugs (n=500)

ADR
()
Skin
77 (15.4)
23.3
Hepatitis
N/V
Dizziness
46 (9.2)
42 (8.4)
25 (5.0)
36.9
4.8
4.0
Abdominal pain
Joint pain
18 (3.6)
16 (3.2)
0.0
12.5
Peripheral neuropathy
13 (2.6)
0.0
Visual impairment
10 (2.0)
60.0
Fever
9 (1.8)
0.0
Ototoxicity
8 (1.6)
25.0
Thongraung W, et al. Thai Pharm Health Sciences Journal 2009;4(1):46-51
ADRs of anti-TB drugs: symptom-based approach

Major ADRs
Skin rash
Drug (s) probably

responsible
H, R, Z, S
Stop anti-TB drugs
H, R, Z
S
Stop anti-TB drugs

Stop streptomycin
Stop streptomycin
Most anti-TB
drugs
Stop anti-TB drugs
Ethambutol
Stop Ethambutol
Jaundice, hepatitis
Deafness
Dizziness (vertigo,
nystagmus)
Confusion (suspect
drug-induced acute
liver failure jaundice)
Visual impairment
ADRs of anti-TB drugs: symptom-based approach

Minor ADRs
Management
World Health Organization (2009) Treatment of tuberculosis:

Guidelines-4th ed. WHO/ HTM/TB/2009.420. Geneva: WHO Press.
Anorexia, nausea,
abdominal pain
Joint pains
Numbness/tingling
Drowsiness
Orange/red urine
Flu syndrome (fever,
chills, malaise,
headache, bone pain)
Anti-TB induced hyperuricemia
10
.. 2528
baseline serum uric acid serum uric acid
2
Patients
New case
(n=88)
Relapse
(n=44)
H
Give before bedtime
R
Tell before start
Intermittent Change to daily dose
dosing of R
Anti-TB induced hyperuricemia
2532; 10(3): 14-148
Drug
Management
responsible
H, R, Z
Give with small meals or
before bedtime
If persist, protracted
vomiting, sign of
bleeding, refer urgently
Z
ASA, NSAIDs or paracet.
H
Pyridoxine 50-75 mg/day
No. (%) with

increase
uric acid
Baseline
End of 2
month
84 (95.5)
5.5
10.40
42 (95.)
4.77
10.26
Mean serum uric acid
2532; 10(3): 14-148

30 (30/88 = 34.0%)
13 (13/44 = 29.5%)
10-60
ASA NSAIDs
Anti-TB induced hepatotoxicity

Definitions
Institute
Definitions
WHO 2009 No detail
ATS 2006
ALT > 3X ULN with jaundice and/or
hepatitis symptoms (abdominal pain,
nausea, vomiting, fatigue) or
ALT > 5 X ULN
Thai-NTP
AST > 3 XULN
208,

CDC 2003 AST > 5 X ULN
Hong-Kong Same but include bilirubin > 2 x ULN
2002

Incidence & Prevalence
1 2 ADR
Thailand: ~ 4.0-9.0 %, Other countries: ~ 3-15 %
INH alone: 0.1-0.6 %
RMP alone: 0.0-1.6 %
PZA alone: no data

Mechanism: INH

isoniazid isoniazid

hydrazine
(hepatocellular
damage)
slow acetylator
isoniazid fast acetylators (adjusted odds
ratio, 3.66; 95% CI, 1.58-8.49; P =.003)

Mechanism: INH
Mechanism: Rifampicin
Isoniazid
(Isonicotinic Acid Hydrazide)
Acetylation
Hydrolysis
Acetylisoniazid
Isonicotinic acid
Hydrolysis
Hydrolysis
Acetyhydrazine
Acetylation
Rifampicin
hepatocellular injury cholestatic
jaundice
rifampicin 2
- rifampicin

- rifampicin
isoniazid
Hydrazine
(Toxic metabolite)
Acetylation
Diacetylhydrazine
(Non-toxic metabolite)
Thongraung W, et al. J Eval Clin Pract. 2011. doi: 10.1111/j.1365-2753.2011.01706.x.

Rifampicin transient hyperbilirubinemia

rifampicin bilirubin
bilirubin
bilirubin
Capelle et al rifampicin 600 mg
single dose serum bilirubin
3
McColl et al rifampicin 600 mg 1
7 4
total bilirubin
1 (10
)

bilirubin 7


rifampicin isoniazid
rifampicin enzyme inducer

isoniazid
toxic metabolite isoniazid

Mechanism: Pyrazinamide

pyrazinamide
pyrazinamide
isoniazid
pyrazinoic acid
21
pyrazinamide rifampicin

3 isoniazid

Causative agents
If rechallenge
Among 34 patients who were rechallenged with
anti-TB, 8 patients increased their liver enzymes
2 patient increased liver enzyme after PZA
6 patients increased liver enzyme after RMP (5
patients took INH before RMP)
Thongraung W, et al. J Eval Clin Pract. 2011. doi: 10.1111/j.1365-2753.2011.01706.x.
Causative agents
Causative agents
If rechallenge
pyrazinamide
0.52 100 person-month
isoniazid
0.18 100 person-month
If rechallenge
Among 32 patients who were rechallenged with
anti-TB
20 patient increased liver enzyme after PZA
3 patients increased liver enzyme after RMP
Yee D, et al. Am J Respir Crit Care Med. 2003;167(11):1472-1477
. 2010;20(3):221-231.
Causative agents
Risk factors
If rechallenge
rifampicin ( 1.41)
pyrazinamide ( 1.25)
isoniazid ( 0.30)
Factors
Age > 35 years
Age > 60 years
Female
Abnormal pretreatment ALT/AST
Pre-treatment bilirubin > 2mg/dl
Adjusted OR (95% CI)

1.61 (1.14 - 3.40)
1.97 (1.24 - 2.08)
1.90 (1.07 - 4.40)
2.5 (1.1 - 5.5)
9.4 (1.0 85.5)
HIV
HBsAg positive
3.54 (1.25 10.05)

5.5 (2.1 14.3)
Ormerod LP, Horsfield N. Tuber Lung Dis. 1996;77(1):37-42

Risk factors
Management
Factors
Albumin < 3.5 mg/dl
Extrapulmonary TB
Adjusted OR (95% CI)

2.3 (1.1 - 4.8)
2.33 (1.16 4.67)
NAT2 slow acetylators
4.697 (3.291- 6.705)
Higher dose of rifampicin

PZA dose > 30-40 mg/kg/day
2.0 (2.1 14.3)**

3.33 (1.30 8.50)
Initial management

isoniazid, rifampicin
pyrazinamide
Management
Management
Alternative regimen

???

2
ethambutol streptomycin fluoroquinilones

(ofloxacin)
Alternative regimen
Saigal et al
ofloxacin

31
2
1 (n=15)
pyrazinamide
2HRE/7HR
2 (n=16)
rifampicin ofloxacin
2HZEO/10HEO
1 26.6% 2
(p=0.043)
Management
Management
Alternative regimen
Szklo et al
INH,
RMP, PZA 3SEO/9EO

40

Alternative regimen
Ho et al
fluoroquinolones
1 (H, R, Z)

H, R, Z
134 3
1 () (n=27) ethambutol
(with/without streptomycin)
levofloxacin (with/without streptomycin)
Management
Management
Alternative regimen
moxifloxacin (with/without streptomycin)

ADR:
(levofloxacin= 4, moxifloxacin = 4)

5

( 1 , levofloxacin 1 , moxifloxacin 3
)
levofloxacin moxifloxacin
Rechallenge

(
transaminase
2 X ULN 1

2
Management
Management
Rechallenge: simultaneous or sequential

Tahaoglu et al prospective randomized trial
2
1 (sequential
rechallenge) H, R
PZA
2 (simultaneous
rechallenge) PZA
1 recurrent hepatitis 2
recurrent hepatitis 24.0 (p< 0.021)
Rechallenge: simultaneous or sequential

Sharma et al prospective randomized trial
(n=237)
3
1
isoniazid rifampicin pyrazinamide
2
R, H, Z
(ATS)
3 H, R, Z

(BTS)
recurrent hepatiits 3


Management
Rechallenge: Which drug should be first?
Lowest incidence of hepatitis
WHO, ATS: rifampicin, then INH
BTS, Thai-NTP: INH, then rifampicin
Anti-TB induced cutaneous ADRs
rifampicin isoniazid
rechallenge PZA ???

Incidence, prevalence
Types of CADR :Case reports (other countries)
Thailand
.. 2536- 2553: 15-45
Setting, year
Other countries
1.8 42.9
Types
Causative agents
Korea, 2010
Cutaneous vasculitis
RMP, PZA
India, 1998,
2009
Exfoliative dermatitis
Anti-TB
Korea, 2008
DRESS
Anti-TB, celecoxib
Tunisia, 2005
TEN
STR
France, 1996
Erythema Multiforme
PZA
Hong Kong,
1995
MP rash
Ethambutol
Types of CADR: Case reports (Thailand)
Types of CADR: prevalence case (Thailand)
Setting, year
Types
, 2009 MP rash
Causative agents
RMP, PZA

,
2008
Exfoliative dermatitis
Ethambutol
Record review in a large hospital

673 CADR 32 ( 19.6)
88.8
61.2
- erythematous papule 22.8
- maculopapular rash 18.9
- urticaria/angioedema 9.5
- erythema multiforme 2.7
-
43.2)
Thongraung W, 2010 (unpublished data)

Types of CADR: prevalence case (Malaysia)

Retrospective study
47 ( 5.7)
- Morbiliform rash 34
- Erythema multiform 4
- Urticaria 4
- Exfoliative dermatitis lichenoid eruption 5 )
97.0 CADR 2
Tan WC, et al. Med J Malaysia 2007; 62(2): 143-6.

Types of CADR: Incidence case (Thailand)

prospective study (n=269)

Cutaneous ADRs 58 ( 21.6)
Mean time since starting treatment 12.7 + 15.8 days,
median 8 days (range 0-88 days)
CADRs
- 47 ( 17.5)
- 11 ( 4.1)
- Maculopapular rash 7 ( 2.6)

- Urticaria 3 ( 1.1)
- Stevens-Johnson syndrome 1 ( 0.4)
Management of Cutaneous ADR
(ATS/CDC/IDSA 2003)
(, )
Guidelines
WHO 2010
Types and Severity
Types and Severity

Itching without
rash
Rash

antihistamines
moisturizer
Closely monitor
Itching without rash

Rash (limited area)
Petechial rash
(check platelet)
Generalized erythematous
rash especially associated
with fever, mucous
membrane involvement
(Thai NTP 2008)

Types and Severity
CPM
CPM calamine
steroid
0.1% TA cream
(generalized
erythematous rash)

prednisolone
2-3

antihistamines
rifampicin
platelet baseline

(Thai pharmacists)
Severity of cutaneous ADR induced by anti-TB

Severity
Clinical presentation
Mild
Moderate
Petichial rash, exfoliative dermatitis, SJS-TEN,

DRESS, AGEP, anaphylaxis,
,
Severe
(Thai pharmacists)

Severity
Mild
Initial management
antihistamine, topical
steroid, moisturizer
Closely monitor
(Thai pharmacists)

Severity
Initial management
Moderate
antihistamine, topical
steroid, moisturizer
Closely monitor

(Thai pharmacists)

Severity
Severe
(Evidence from Thai Patients)

Mild cutaneous ADR:
Itch without rash
(n=47)
Initial management

&
(n = 23, 48.9%)
(n = 20, 42.6%)
(n = 3, 6.4%)
&
(n = 21, 44.7%)
(n = 21, 44.7%)
(n = 0, 0.0%)
&
(n = 3, 6.4%)
(n = 3, 6.4%)
(n = 0, 0.0%)

(Evidence from Thai Patients)
moderate cutaneous ADR:

Itch with rash
(n=10)
&
(n = 1, 10.0%)
&
(n =8, 80.0%)
(n = 8, 80.0%)
(n = 1, 10.0%)
(n = 0, 0.0%)
(n = 0, 0.0%)
&
(n = 1, 10.0%)
(n = 1, 10.0%)
WHO guidelines 2010

(rifampicin
isoniazid)
INH 50 mg
3

(n = 0, 0.0%)
ATS/CDC/IDSA 2003

Petechial rash RIF

2-3
RIF

INH, ETM PZA

3 4

4
Thai-NTP 2008
2-3
E, R, H, Z
(mg)
400
800
300
450
100
300
500
1500
Provocation test, Desensitization, Graded challenge
Patients suitable for

graded challenge or desensitization
Pt with suspected drug allergy
Pt with
good state of health
Pt need immediate
treatment
Provocation test
Desensitization
Desensitization, Graded challenge
Graded
challenge
Patients with HIV infection, cystic fibrosis, or

tuberculosis
Patients whom an immediate re-introduction of
antibiotherapy is required
Patients with cancer or rheumatology who
experienced immediate HSR to their first-line
chemotherapy and no alternative drugs are available
66
Drug desensitization
Drug desensitization
induction of drug tolerance

Drug Tolerance is defined as a
state in which a patient with a drug allergy
will tolerate a drug without an adverse
reaction.
Desensitization induces a temporary state of
tolerance to the drug, which is maintained
only as long as the patient continues to take
the specific drug
It has to be repeated every time the patients
required treatment with the drug or its potentially
cross-reacting drug
67

Starting doses are at 1:1,000,000 to 1:100 of the
target therapeutic dose
Dose escalations are doubled at 15-30 min
intervals for immediate reactions, or at intervals of
up to 24 h for non-immediate reactions.
68
Graded challenge
Graded challenge
should be performed at the time the patients required

immediate treatment with the suspected drug
For patient unlikely to be allergic to drug
Graded challenge should almost never be performed if
the reaction history is consistent with a severe nonIgEmediated reaction, such as SJS, TEN, interstitial
nephritis, hepatitis, or hemolytic anemia.
Rare exceptions: treatment with a life-threatening
illness in which the benefit of treatment outweighs the
risk of a potentially life-threatening reaction
69
The starting dose for a graded challenge is higher than

for induction of drug tolerance
The number of steps in the procedure may be 2 or
several
The interval between dose are dependent on the type
of previous reaction
The entire procedure may take hours or days to
complete
70
Rechallenge for SJS induced by anti-TB drugs

Graded challenge & Desensitization
Graded challenge
Diagnosis or therapeutic
At the time when
patient required
immediate treatment with
suspected drug
No intention to induce
tolerance
Start 1/100 of daily
dose
Interval: any
Desensitization
Therapeutic
At the time when
patient required
immediate treatment with
suspected drug
Intention to induce
tolerance
Start 1/100,000 1/1,000 of daily dose
Interval: 15 min and
double dose
Kura MM, Hira SK. Int J dermatol. 2001;40(7):481-4.
Methods:
8 pulmonary TB-HIV patients with SJS (all had >
75% BSA involved & mucous membrane affected)
Stopped all anti-TB drugs, treated all patients with
dexamethasone 12 mg/day tapered rapidly over 2-3
wks
After complete resolution of the skin lesions,
reintroduction of anti-TB (H, R, Z, E) was started
Drugs were started one after another at weekly
intervals, gradually increasing doses and no others
medications were given during this period
72
Rechallenge for SJS induced by anti-TB drugs
Rechallenge for SJS induced by anti-TB drugs (cont.)

Week
Day
Drug
Dose (mg)
Clinical signs
17
RMP
150
None
19
RMP
300
None
21
RMP
450
None
None
23
RMP
600
None
200
None
25
PZA
250
None
EMB
400
None
27
PZA
500
13
EMB
600
None
15
EMB
800
29
PZA
1000
1 had skin
reaction
Others none
31
PZA
1500
Week
1
Day
1
Drug
INH
Dose (mg)
50
Clinical signs
None
1
1
3
5
INH
INH
100
200
None
None
INH
300
EMB
11
2
2
73
None
Case report:
Oral rapid desensitization to INH & RMF
Case report
A 45 year-old pulmonary TB patient was started with
PZA (1500), RIF (600), INH (300)
After 12 days, she developed a measles-like rash,
arthralgia
All anti-TB were stopped
First rechallenge with PZA (500 mg), no reaction
Then, rechallenge with RIF (150 mg)
After 3 hrs later after RIF, pruritis, urticaria,
angioedema, chest heaviness, shortness of breath
developed
RIF was stopped & treated with EPI, DIP
75
74
None
Case report:
Case report
Several hrs later, she developed a fever to 40oC, chill,
arthralgia
5 days later, INH (300), PZA (1500), ETM (700), STR
(1000) was started, 15 min after the first dose pruritis,
urticaria, angioedema developed, then all drugs were
stopped
INH (100) was restarted, generalized pruritis was
developed
She was referred for evaluation and possible
desensitization
76
Case report:
Case report:
Case report
1st desensitization (INH elixir (50mg/5 ml) diluted with sorbital)
Skin Prick Test (wheal/flare)

0.9 NSS
Histamine 1/1,000
Intradermal test(Wheal/flare)
0.9 NSS 0.05 ml
+ 9/16 Histamine 1/10,000

(0.5 ml)
+15/29
Sorbital 70%
Sorbital 70%
ND
INH 0.1 mg/ml 0.9 NS

(0.05 ml)

(0.05 ml)
RIF 0.1 mg/ml sorbital
RIF
RIF 1.0mg/ml sorbital
RIF
ND
77
ND
Dose, mg
32.0
50
100
150
150
150
Continue
INH
150 mg q 12 hrs
Dose, mg
7.00
7.15
7.30
7.45
INH
INH
INH
INH
0.1
0.5
1.0
2.0
8.00
8.30
9.00
INH
INH
INH
4.0
8.0
16.0
78
Drug
INH
INH
INH
INH
INH
INH
Drug
Case report:
Case report:
Time
9.30
10.30
12.30
14.30
15.00
24.30
Time
Case report
9 hrs into desensitization, a fever of 38.8oC, mild
chest heaviness developed (tx with DIP,
metaproterenol inhalation)
She was able to continue desensitization without
further symptoms except for persistent fever
Prednisolone 40 mg was given, patients defervesced
6 hrs later
Prednisolone was maintained to suppress fever
There was no later development of fever, rash,
athralgias, angioedema or chest complaints
The next day, RIF was restarted
79
80
Case report:
Case report:
Time
7.00
7.15
7.30
7.45
Drug
RMF
RMF
RMF
RMF
Dose, mg
0.1
0.5
1.0
2.0
8.00
8.15
8.30
RMF
RMF
RMF
4.0
8.0
16.0
81
Desensitization Therapy
for allergic reactions to antituberculosis Drug
Time
8.45
9.15
10.15
12.15
16.15
24.15
Drug
RMF
RMF
RMF
RMF
RMF
RMF
Dose, mg
32.0
50
75
100
150
300
Continue
RMF
300 mg q 12 hrs
There was no adverse reaction on RIF desensitization82
Kobashi Y, et al Med. 2010; 49(21): 2297-301
Setting: Japan
Methods: retrospective
Study subjects: All 46 TB patients shown allergic
reactions ( 23 pts with skin eruption, 16 pts with fever, 7
pts with fever & skin reactions)
Causative drugs (based on the clinical course judged by
attending physicians and/or drug lymphocyte stimulation
test (DLST)): RFM 30 cases (15 clinical & DLST, 15
clinical), INH 16 cases (9 clinical & DLST, 7 clinical)
Desensitization protocol: Japanese Society for
tuberculosis (JST) 1997
83
Desensitization protocol
Day
1
2
INH (mg)
25
25
RIF (mg)
25
25
3
4
25
50
25
50
5
6
7
8
50
50
100
100
50
50
100
100
84
Day
9
10
11
INH
100
200
200
RIF
100
200
200
12
200
200
13
300
300
14
15
16
300
300
400
300
300
450
RESULTS
Failed (7/30)
Failed (3/16)
85
Alternative Tuberculosis Regimens

Causative drug
Isoniazid
Rifampicin
Pyrazinamide
Isoniazid & Rifampicin
Alternative TB regimen
6-9 RZE
2HES/10HE
2HRE/7HE
18-24 SEFx
86

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Outline

General information of first-line anti-TB drugs

Second line drugs

* Not approved by FDA-US

Isoniazid (IsoNicotinic acid Hydrazide)

Isoniazid (IsoNicotinic acid Hydrazide)

Pyridoxine deficiency due to its

Transient hyperbilirubinemia rifampicin

Hepatitis (see next)

The pyrazine analog of nicotinamide

Adverse Drug Reactions of anti-TB drugs

Adverse Drug Reaction of anti-TB drugs (n=500)

Thongraung W, et al. Thai Pharm Health Sciences Journal 2009;4(1):46-51

ADRs of anti-TB drugs: symptom-based approach

Drug (s) probably

Stop anti-TB drugs

Stop anti-TB drugs

Stop anti-TB drugs

ADRs of anti-TB drugs: symptom-based approach

World Health Organization (2009) Treatment of tuberculosis:

Anti-TB induced hyperuricemia

Anti-TB induced hyperuricemia

2532; 10(3): 14-148

No. (%) with

Mean serum uric acid

2532; 10(3): 14-148

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity

Thongraung W, et al. J Eval Clin Pract. 2011. doi: 10.1111/j.1365-2753.2011.01706.x.

Anti-TB induced hepatotoxicity

Rifampicin transient hyperbilirubinemia

Anti-TB induced hepatotoxicity

rifampicin enzyme inducer

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity

Thongraung W, et al. J Eval Clin Pract. 2011. doi: 10.1111/j.1365-2753.2011.01706.x.

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity

Yee D, et al. Am J Respir Crit Care Med. 2003;167(11):1472-1477

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity

Adjusted OR (95% CI)

3.54 (1.25 10.05)

Ormerod LP, Horsfield N. Tuber Lung Dis. 1996;77(1):37-42

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity

Adjusted OR (95% CI)

NAT2 slow acetylators

4.697 (3.291- 6.705)

Higher dose of rifampicin

2.0 (2.1 14.3)**

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity

ethambutol streptomycin fluoroquinilones

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity

Anti-TB induced hepatotoxicity