Al-Dabbagh et al., Pediatric Drug-Resistant TB Guidelines
SDC 3
Table 2. Potential adverse effects and suggested drug monitoring recommendations
Adverse effects
[References]
Incidence
in
children
Potential causative
agents
Monitoring parameters
Recommendations
Hearing loss
7-9 %
All Aminoglycosides
and Tuberactinomycinsa
Baseline audiometric testing
and then monthly. Weekly
trough and peak levels.
3%
All Aminoglycosides
and Tuberactinomycins
Baseline serum urea (BUN)
and creatinine; repeat
monthly while receiving an
injectable agent; repeat
more frequent if the baseline
results were abnormal.
12-50 %
INH, Pyrazinamide,
Ethionamide.
Fluoroquinolones, PAS,
Macrolides, Amoxicillin/
Clavulinate
Clinical observation. c
9%
Pyrazinamide, INH,
rifampin, PAS,
ethionamide,
fluoroquinolones,
macrolides
6-9 %
Ethionamide, PAS
6-11%
Cycloserine,
fluoroquinolones.
thioamides
Monthly clinical
monitoring.
Liver function tests at
baseline and repeat if:
- abnormal baseline tests
- develops symptoms
- pre-existing liver disease
- concomitant use of
hepatotoxic drugs,
- history of ethanol abuse
- prior hepatitis from the
same drug.
Baseline TSH and then
repeat every three months.
Risk of hypothyroidism
increases when both
ethionamide & PAS used.
Clinical observation. c
Once a therapeutic steady state
has been reached, monitor
trough and peak levels of
aminoglycosides once weekly. If
hearing loss develops, consider
stopping the offending agent if
possible.
Adjust doses and/or frequency
with serial monitoring and
consult with a clinical
pharmacist.
Adjust all other medications
according to Creatinine
clearance.
Consider stopping the offending
agent if severe.
When initiating a new drug
which may cause
gastrointestinal symptoms, the
dose should be split into 2-3
doses; then combine in single
dose as tolerated.
Stop therapy if clinical hepatitis
develops (liver tenderness,
hepatomegaly, or jaundice).
Screen for infectious etiologies.
Treatment may be restarted
gradually after normalization of
liver enzymes, under hospital
supervision and frequent
monitoring.
[1-4]
Renal toxicity
[1-3]
Gastrointestinal
symptomsb
[3-7]
Hepatotoxicity
[1, 2, 4, 5]
Hypothyroidism
[1-4, 8]
Psychiatric effects
[1, 3, 4, 8]
Start replacement therapy if
hypothyroidism is present.
Consult an endocrinologist.
If symptoms are mild, clinical
observation and support is
advised, but if symptoms are
severe and psychosis is present,
lower the dose and consider
stopping the suspected agent and
provide appropriate
antipsychotic therapy.
42
Al-Dabbagh et al., Pediatric Drug-Resistant TB Guidelines
SDC 3
Skin
manifestationsd
3-8%
INH, rifampin,
fluoroquinolones,
cycloserine,
ethionamide,
ethambutol, clofazimine,
amoxicillin/clavulanate
Clinical observation. c
0.7-4.5%
Fluoroquinolones,
pyrazinamide
Clinical observation. c
9%
Ethambutol, linezolid
3%
All aminoglycosides
and tuberactinomycins
Baseline then monthly
visual acuity and color
vision testing.
Baseline electrolytes,
magnesium and calcium;
repeat monthly while on
injectable agent (or more
frequent if abnormal at
baseline).
[3-5, 7, 8]
Arthralgia,
arthritis
[1, 4, 6]
Blurring of vision
[1, 2, 4]
Electrolyte
abnormalities
[1-3]
a
If mild rash, consider antihistamines for itchiness, Stop
the most likely causative agents
if severe rash and refer to a
dermatologist. When the rash is
improved the medications can
be restarted one by one.
Obtain platelet count if petechial
rash develops while on rifampin
therapy, and if low, stop it.
Thrombocytopenia is a
contraindication for rifampin.
Check serum uric acid level if
the patient becomes
symptomatic; do not give
allopurinol but lower dose or
stop offending drug (esp.
pyrazinamide).
Stop the causative agent.
Ophthalmology consultation and
follow-up is recommended
Treat according to standard of
care for hypokalemia or other
deficiencies.
: Tuberactinomycins includes Capreomycin and Viomycin.
b
: Symptoms include gastritis, loss of appetite, nausea and/ or vomiting.
c
: All patients should be educated for all possible side effects and be instructed to contact
their primary physicians in case adverse events are noticed.
d
: Symptoms include hypersensitivity reactions, skin rash and/ or itchiness, and skin
discoloration.
Data in this table were derived from pediatric studies; other reports on adverse effects
from second-line antituberculosis medication were reported in both adults and children
[9-11], however, these other studies were not included in this Table, as data relevant to
pediatric care could not readily be extracted from them.
43
Al-Dabbagh et al., Pediatric Drug-Resistant TB Guidelines
SDC 3
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
WHO. Guidelines for the programmatic management of drug-resistant
tuberculosis. 2006 [cited 2010 July 4]; Available from:
http://whqlibdoc.who.int/publications/2006/9241546956_eng.pdf.
Curry, F.J. Drug-Resistant Tuberculosis: A Survival Guide for Clinicians.
2008 [cited 2010 June 25]; Second Edition:[Available from:
http://www.nationaltbcenter.edu/drtb.
Drobac, P.C., et al., Community-based therapy for children with multidrugresistant tuberculosis. Pediatrics, 2006. 117(6): p. 2022-9.
Feja, K., et al., Management of Pediatric Multidrug-Resistant Tuberculosis and
Latent Tuberculosis Infections in New York City From 1995 to 2003. Pediatric
Infectious Disease Journal, 2008. 27(10): p. 907-912.
Blumberg, H.M., et al., American Thoracic Society/Centers for Disease
Control and Prevention/Infectious Diseases Society of America: treatment of
tuberculosis. Am J Respir Crit Care Med, 2003. 167(4): p. 603-62.
Schaaf, H.S., et al., Evaluation of young children in contact with adult
multidrug-resistant pulmonary tuberculosis: a 30-month follow- up. Pediatrics,
2002. 109(5): p. 765-771.
Schaaf, H.S., K. Shean, and P.R. Donald, Culture confirmed multidrug
resistant tuberculosis: diagnostic delay, clinical features, and outcome. Arch
Dis Child, 2003. 88(12): p. 1106-11.
Mukherjee, J.S., et al., Clinical and programmatic considerations in the
treatment of MDR-TB in children: a series of 16 patients from Lima, Peru. Int
J Tuberc Lung Dis, 2003. 7(7): p. 637-44.
Torun, T., et al., Side effects associated with the treatment of multidrugresistant tuberculosis. Int J Tuberc Lung Dis, 2005. 9(12): p. 1373-7.
Geerligs, W.A., et al., Multidrug-resistant tuberculosis: long-term treatment
outcome in the Netherlands. Int J Tuberc Lung Dis, 2000. 4(8): p. 758-64.
Furin, J.J., et al., Occurrence of serious adverse effects in patients receiving
community-based therapy for multidrug-resistant tuberculosis. Int J Tuberc
Lung Dis, 2001. 5(7): p. 648-55.
44