|
|
NEWS AND NEW DEVELOPMENTS
|
|
|
|
|
|
Reduced Toxicity with Gradual Initiation of Trimethoprim-Sulfamethoxazole
as Primary Prophylaxis for Pneumocystis Carinii Pneumonia:
AIDS Clinical Trials Group 268 [JAIDS 2000;24:337]:
This is ACTG 268, which examined the relative efficacy of gradual
initiation of TMP-SMX for PCP prophylaxis compared to the standard
method of 1 DS/day. The dosing schedule for those randomized to
the gradual introduction are summarized in the following table:
|
TMP-SMX
Dose Regimen for Gradual Initiation
Using Suspension with 40 mg TMP + 200 mg SMX/mL
|
|
Day
|
Dose
|
|
1
- 3
|
1
mL
|
|
4
- 6
|
2
mL
|
|
7 - 9
|
5
mL
|
|
10
- 12
|
10
mL
|
|
13
- 14
|
20
mL
|
|
15
|
DS
tab
|
All patients received 1 DS tab from week two through week 12 when
results were evaluated. There were 186 participants in each group.
The results showed that a significantly greater number of participants
given standard therapy discontinued this treatment, and the number
of adverse reactions in this group was significantly greater for
rash, fever, and pruritis as summarized below:
|
TMP-SMX
Prophylaxis Results
|
|
|
Gradual
n = 186 |
Routine
n = 186 |
| Terminated
study drug |
32
(16%) |
62*
(33%) |
|
Adverse
events
Rash
Fever
Pruritis
Nausea
|
35
(19%)
26 (19%)
39 (21%)
37 (20%) |
63
(34%)*
57 (31%)*
57 (31%)*
39 (21%)
|
| *p
= < 0.05 |
Comment: The rate of discontinuation of TMP-SMX during the
first 12 weeks of PCP using the standard regimen of 1 DS/day was 33%,
higher than the authors anticipated, but consistent with many studies
of PCP prophylaxis. Although the benefit of gradual introduction has
been known for some time, it appears that relatively few clinicians
use it. The high rate of reactions to this drug in patients with AIDS
is commonly ascribed to toxic metabolites resulting from altered drug
metabolism. The theoretical reason for gradual initiation of TMP-SMX
to work is that it permits time for enzyme induction, presumably through
the cytochrome p450 pathway. The results of this study support the
concept that adverse drug reactions due to TMP-SMX are due to toxic
metabolites rather than an allergic reaction, and this concept is
also supported by resolution of the reaction while continuing the
drug and recurrence of reactions when drug levels are increased through
drug interactions as with many antiretroviral agents. The authors
point out that, although their dosing regimen works, it is not necessarily
the best method for gradual introduction of TMP-SMX. posted 10/6/2000
|
|
|
|
|
|
back
to news table of contents