Transcript TB IN CHILDREN - Ministry of Health

TB WITH LIVER &
RENAL IMPAIRMENT
by
Dr. Umadevi A. Muthukumaru
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LEARNING OBJECTIVES
• To understand the management of TB patients
with underlying liver & renal impairment
• To become familiar with various regimens
used in TB patients with liver & renal
impairment
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INTRODUCTION
• Patients with liver & renal impairments may
need regular frequent monitoring while on
antiTB treatment
– They may develop side effects due to treatment or
may end up receiving inadequate therapy
– Expert consultation is advisable when treating
these patients
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LIVER IMPAIRMENT
• Unstable or advanced liver disease - baseline
LFT prior to treatment1
• Regular monitoring at weekly & biweekly
intervals during the initial 2 months2
• Then more widely spaced assessments
throughout the rest of treatment period
1WHO,
2Yew
2010
WW et al., Respirology, 2006
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LIVER IMPAIRMENT
• If baseline LFTs are more than 3X upper limit
of normal before initiation of therapy, a
regimen containing fewer hepatotoxic drugs
can be considered
• The likelihood of drug induced hepatitis is
greater & is potentially life threatening
• Expert consultation is usually needed
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ANTITB REGIMEN IN TB PATIENTS
WITH LIVER DISEASE
• Patients may tolerate standard antiTB therapy
• The more unstable the liver disease, the fewer
hepatotoxic drugs that can be used
• Fluoroquinolones1 & aminoglycosides can be
utilised to make up a less hepatotoxic antiTB
regimen
1Gosling
RD et al., Am J Respir Crit Care Med, 2003
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ANTITB DRUGS IN LIVER IMPAIRMENT
Drugs
Isoniazid & rifampicin, plus
ethambutol
Duration
9 months
Isoniazid, rifampicin,
2 months
streptomycin & ethambutol,
followed by isoniazid &
Progressively rifampicin
6 months
more severe
liver disease Rifampicin, pyrazinamide & 6 - 9 months
ethambuthol
Isoniazid, ethambutol &
2 months
streptomycin,
followed by
isoniazid & ethambutol
10 months
Streptomycin, ethambutol &
18 - 24
fluoroquinolones
months
Ethambutol given
until isoniazid
susceptibility is
documented
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RECOMMENDATION 25
• Regular monitoring of liver enzymes should be
performed in patients on antiTB treatment
with pre-existing liver disease or at risk of
drug-induced hepatitis. (Grade C)
• Expert consultation is advisable in treating TB
patients with advanced or unstable liver
disease. (Grade C)
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RENAL IMPAIRMENT
• Regimen for patients with renal failure
includes 2 months of isoniazid, rifampicin,
pyrazinamide & ethambutol followed by 4
months of isoniazid & rifampicin1
• Significant renal excretion of ethambutol &
metabolites of pyrazinamide occurs, hence
doses must be adjusted to intermittent dosing
1WHO,
2010
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RENAL IMPAIRMENT
• Pyrazinamide should be administered after
hemodialysis to avoid premature drug
removal1
• All 4 antiTB drugs can be administered after
hemodialysis to facilitate DOT
• Avoid streptomycin
1Malone
RS et al., Am J Respir Crit Care Med, 1999
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ANTITB DRUGS IN RENAL IMPAIRMENT
Drug
Change in
frequency?
Recommended dose &
frequency 1
Isoniazid
No change
Max 300 mg PO once daily
Rifampicin
No change
Max 600 mg PO once daily
Yes
25 - 30 mg/kg per dose PO
3 times per week
Yes
15 - 25 mg/kg per dose PO
3 times per week
Pyrazinamide
Ethambutol
1CrCl:
Creatinine clearance by Cockcroft-Gault equation, intermittent dialysis
PO: by mouth
IBW: ideal body weight
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Standard doses are given unless there is intolerance
RECOMMENDATION 26
• Frequency of pyrazinamide & ethambutol
should be adjusted in patients with TB & renal
failure. (Grade C)
• Streptomycin should be avoided if possible in
patients with TB & renal failure. (Grade C)
• Physician with experience in TB management
should be consulted for all TB patients with
renal impairment. (Grade C)
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TAKE HOME MESSAGES
• Monitoring of LFT is essential in the
management of TB patients with liver disease
• Using less hepatotoxic regimen may be
necessary in unstable liver disease
• Dose adjustment is necessary for TB patients
with renal impairment & on hemodialysis
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THANK YOU
[email protected]
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