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Choosing a Regimen for Treatment of Latent Tuberculosis
Latent Tuberculosis Infection (LTBI)
Karen Martinek, RN, MPH
Why Treat LTBI?
• Prevents the development of tuberculosis (TB)
• Saves money – less costly to treat LTBI than active TB
How Do I Choose a Regimen?
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Factors to Consider (1)
• Likelihood of completion
• Appropriate for age, exposure, other issues
– <2, 2‐11 years, 12 years +
– Human immunodeficiency virus (HIV)+ and antiretrovirals
– Co‐morbidities, pregnancy, drug interactions
– Social concerns: homelessness, drug and alcohol use, mental health issues, etc.
– Drug resistance
Table 1: LTBI treatment regimens for susceptible disease
Ra ng* Evidence†
Drug
Frequency
Duration
Issues
HIV ‐
HIV+
Isoniazid
Daily
9 months
(6 months)
Long duration, poor adherence
A (II)
B (I)
A (II)
C (I)
Isoniazid
2X wkly
9 months
(6 months)
Long duration, directly observed therapy (DOT)
B (II)
B (II)
B (II)
C (I)
Rifampin
Daily
4 months
Many possible drug interactions
B (II)
B (III)
Isoniazid +
Rifapentine
1X wkly
3 months
DOT
B (I)
Not to be used with ARVs
Rifampin + Pyrazinamide
Daily or 2X 2 months
wkly
Isoniazid +
Rifampin
Daily
Other regimens
Potentially fatal. NOT recommended
3 months** Not recommended in US
4 months
*A = preferred; B = acceptable alternative; C = offer when A and B cannot be given.
† I = randomized clinical trial data; II = data from clinical trials that are not randomized or were conducted in other populations; III = expert opinion
** = But 4 month option used in untreated TB4/abnormal CXR
Factors to Consider (2)
•
•
•
•
Efficacy
Patient preference
Possible side effects
Cost
– Drug (s)
– Directly observed therapy (DOT) costs, if any
– Staff time
– Monitoring
• DOT access / availability 2
Table 2: Factors to consider when selecting an LTBI treatment regimen for susceptible disease
Factor
Regimen
INH daily
9 mos.
INH daily
6 mos.
INH BIW
9 mos.
< 2 yrs. of age*
X
X
2 – 11 yrs. of age
X
X
12 yrs.** – adult
X
Pregnancy****
X
X
HIV + / ARVs
X
X
X
INH/RPT
INH BIW RIF daily 1 X wk.
6 mos.
4 mos.
3 mos./12 wks.
**
X
**
***
X
X
X
X
INH monoresistance
X
Social issues
X
X
DOT
X
X
X
X
* Infants and children under 5 years of age with LTBI have been recently infected and, therefore, are at high risk for progression to disease.
** Not generally recommended unless contact to INH resistant TB case. Use 6 mos. regimen for children < 15 yrs. of age.
*** INH/RPT should only be used on a case-by-case basis in children 2-11 yrs.
**** After TB disease is excluded, consider immediate treatment for LTBI if the woman is HIV-infected or a recent contact, and monitor.
Table 3: Selecting an LTBI treatment regimen for susceptible disease: completion, efficacy, cost, side effects and drug interaction considerations INH daily
9 mos.
INH daily
6 mos.
INH BIW
9 mos.
RIF daily
4 mos.
INH/RPT wkly
X 12 wks.
Completion
Poor adherence
Completion:
53-76%
Completion:
50%
 adherence
Completion: 72-91%
 adherence --Completion: 82%
Efficacy
Standard of
care
93% efficacy
69% efficacy
Acceptable
alternative to
daily INH
Equivalent to 6 mos. INH
Limited data
Same as INH 9
mos
mos.
Cost
effectiveness
Inexpensive
Inexpensive
Inexpensive
 DOT costs
Drug costs higher
Drug and DOT
costs higher
Side effects
Hepatotoxicity
1-2% adults
Hepatotoxicity
1-2% adults
Hepatotoxicity
1-2% adults
-Hepatoxicity
0.3% vs. 1.4% for INH
-Hypersensitivity
syndrome
-orange body fluids
-See INH and
RIF regimens
-Hepatoxicity
same as INH X 9
mos.
Drug
Interactions
Dilantin,
antabuse
Dilantin,
antabuse
Dilantin,
antabuse
Lots – oral contraceptives,
coumadin, antiretrovirals,
sulfonyureas, methadone
See INH and RIF
regimens
Table 4: LTBI regimen costs in Alaska
# Doses /
Duration
Drug
Cost
DOT
Cost
Total
Cost
INH 300 mg
270 daily
9 mos.
$16
$0
$16
-Standard of care
-Poor completion rates
INH 300 mg
180 daily
6 mos.
$11
$0
$11
Rarely used in AK
RIF 600 mg
120 daily
d il
4 mos.
$110
$0
$110
-For
F exposure to
t INH resistant
i t t TB
-Used if problems tolerating INH
-Not for children unless INH resistant case
INH 900 mg
76 (BIW)
9 mos.
$14
$760
$774
-Regimen of choice in AK for high risk or high
priority contacts
-Expensive due to DOT costs
INH 900 mg
52 (BIW)
6 mos.
$9
$520
$529
Rarely used in AK
INH / RPT
12 1Xwkly
3 mos.
$115
$120
$235
-Least costly DOT regimen
-↓ side effects than INH BIW
-Promising completion rates
Regimen
Comments
3
Which regimen?
For a homeless , alcohol‐using contact to 4 (+) acid‐fast bacilli (AFB) smear cavitary TB case, which regimen would you choose?
• INH daily for 9 mos.
• INH daily for 6 mos.
• RIF daily for 4 mos.
• INH BIW for 9 mos.
• INH BIW for 6 mos
• INH / RPT weekly for 3 mos.
Which regimen?
11‐year‐old boy in remote village. Newly infected contact. Failed 9 mos. INH after 2 mos. of self‐administered treatment. Which regimen would you choose?
• INH daily for 9 mos.
INH d il f 9
• INH daily for 6 mos.
• RIF daily for 4 mos.
• INH BIW for 9 mos.
• INH BIW for 6 mos
• INH / RPT weekly for 3 mos.
Which regimen?
For a newly infected, HIV + pregnant female, which regimen would you choose?
• INH daily for 9 mos.
• INH daily for 6 mos.
y
• RIF daily for 4 mos.
• INH BIW for 9 mos.
• INH BIW for 6 mos
• INH / RPT weekly for 3 mos.
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References
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•
•
•
•
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ATS/CDC. Targeted tuberculin testing and treatment of latent TB infection . MMWR
2000;49(No. RR–6). (PDF)
CDC. (2011). Treatment Options for Latent Tuberculosis Infection. Available at: http://www.cdc.gov/tb/publications/factsheets/treatment/LTBItreatmentoptions.
htm
CDC. (2010). Latent Tuberculosis Infection: A Guide for Primary Health Care Providers. Available at: http://www.cdc.gov/tb/publications/ltbi/treatment.htm
CDC. (2011). Recommendations for use of isoniazid‐rifapentine regimen with direct observation to treat latent mycobacterium tuberculosis infection. (MMWR Vol.60 No. 48). Georgia U.S. Department of health and Human Services.
Holland, D. (2012). “Economic considerations of short‐course LTBI treatments”. Presentation. 2012 National Tuberculosis Meeting. Atlanta, Georgia.
Menzies,D., Jahdali, HA & Otaibi, BA.(2011). Recent developments in treatment of latent tuberculosis infection. Indian J Med Res 133, March 2011, pp. 257‐266.
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