Crixivan (Indinavir sulfate)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Crixivan, under the provisions of the FDA's accelerated
approval process, was approved as a treatment for HIV infection in
adults when antiretroviral therapy is warranted. This indication is
based on analyses of surrogate endpoints in studies of up to 24
weeks in duration.
Crixivan, a potent inhibitor of the HIV protease enzyme that is
critical to replication of the virus that causes AIDS, can be taken
in combination with other anti-HIV therapies or alone.
In clinical trials, treatment with Crixivan caused improvements
in the surrogate markers for HIV disease--CD4 cell counts and viral
load, the indicators of disease status in people with HIV. Crixivan
was also generally well tolerated. It produced increases in CD4
cell counts, an important measure of immune system function, and
significant reductions in viral load, or levels of HIV in the
bloodstream. However, the clinical relevance of changes in viral
load induced by Crixivan is not a cure for AIDS, and its effect on
the development of opportunistic infections and survival has not
yet been shown, although such studies are under way.
Crixivan has been studied in more than 2,000 people in 14
studies to date, including several ongoing studies. One recent
multicenter trial studied Crixivan alone and in combination with
two other antiviral drugs, zidovudine and lamivudine (Retrovir and
Epivir) in subjects who had previously been treated with
zidovudine. At 24 weeks in this "triple-therapy" trial,
mean decreases observed in viral load were 98% in 22 subjects
taking the triple combination of Crixivan with zidovudine and
lamivudine. The clinical relevance of changes in viral load
effected by Crixivan has not been established.
At 24 weeks, 20 of 22 subjects (91%) taking Crixivan with
zidovudine and lamivudine had HIV levels in their blood below the
limit of detection of the test used. In the same study, seven of 20
subjects (35%) taking Crixivan alone, and zero of 19 (none) of the
subjects taking zidovudine and lamivudine had HIV levels below the
limit of detection of the test used. Subjects receiving the triple
combination and subjects taking Crixivan alone had mean increases
at 24 weeks of 100 cells/mm3, compared to mean increases of 33
cells/mm3 in subjects taking zidovudine and lamivudine.
Crixivan has been generally well tolerated in clinical trials.
Nephrolithiasis (defined as flank pain, blood in the urine or
kidney stones) occurred in approximately 4% of subjects. People who
take Crixivan are encouraged to drink at least 48 ounces of water
every day to maintain hydration and help avoid nephrolithiasis. In
phase II clinical studies, less than 6% of subjects taking Crixivan
alone discontinued therapy due to drug-related adverse experiences.
Among the most common side of moderate or severe intensity reported
in greater than or equal to 2% of subjects on Crixivan alone in
clinical trials are: nausea, abdominal pain, headache, diarrhea,
vomiting, weakness/fatigue, insomnia, flank pain, taste changes,
acid regurgitation, and back pain. Crixivan is contraindicated in
subjects with clinically significant hypersensitivity to any of its
HIV destroys CD4 cells, which orchestrate the body's immune
response--its natural defense against infection and disease. The
number of CD4 cells in the blood, or CD4 cell counts, are an
indicator of the health of the immune system. Viral load is a
measure of the amount of HIV circulating in the bloodstream.
Although not specifically studied, the prescribing information
for Crixivan contains a warning against taking terfenadine,
astemizole, cisapride, triazolam, or midazolam with Crixivan
because their use in combination may create the potential for
serious and/or life threatening events (i.e. cardiac arrhythmias,
prolonged sedation). In drug interaction studies, no clinically
significant interactions were seen with Crixivan and zidovudine,
d4T, lamivudine, fluconazole, clarithromycin,
trimethoprim/sulfamethoxazole, isoniazid, Ortho-Novum 1/35,
cimetidine, and quinidine.