Home » Drug Information » FDA Approved Drugs » 1997
Medical Areas: Immunology | Pediatrics/Neonatology | Family Medicine | Infections and Infectious Diseases
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Abbott Laboratories
Approval Status: Approved March 1996/March 1997
Treatment Area: HIV infection
Norvir has been recommended as a treatment for HIV infection
when used in combination with nucleoside analogues. A protease
inhibitor, Norvir was recommended in combination with nucleoside
analogues or as a monotherapy in subjects where therapy is
In March of 1997, Norvir was approved for the treatment of
children with HIV and AIDS. The recommended dosage of Norvir in
children, in combination with nucleoside analogues, is 400 mg/m2,
twice daily, and should not exceed 600 mg, twice daily. The
starting dose is 250 mg/m2 twice daily, which should be titrated to
400 mg/m2. The evaluation of the antiviral effect of Norvir in
children is ongoing.
In clearing Norvir for the treatment of HIV infection, the FDA
reviewed efficacy and safety data from trials that showed the agent
to have substantial antiviral activity and to reduce the risk of
disease progression and mortality. This marks the fastest drug
approval in the history of the FDA--72 days from the date of the
filing of the new drug application.
A randomized, double-blind, placebo-controlled study involving
1,090 subjects with advanced AIDS and previous antiretroviral
therapy was conducted at 67 investigational sites in the United
States., Canada, Europe, and Australia. Norvir or placebo was added
to baseline therapy, if any. A six-month analysis of this
population showed that the cumulative mortality rate among Norvir
subjects was 5.8%--approximately half of the 10.1% rate among
subjects receiving placebo. This six-month study depicts the first
survival benefit demonstrated by a protease inhibitor. The clinical
benefit of Norvir treatment for periods longer than six months is
In a subset of 211 subjects, statistically significant increases
in the average CD4 count from baseline were observed with Norvir
over the first 16 weeks of the study. The CD4 count was not
significantly changed in the placebo group. In a subset of 159
subjects, Norvir produced statistically significant decreases in
average HIV RNA levels compared to placebo. Measurement of viral
RNA is an indicator of the amount of HIV in a subject's blood.
The clinical significance of HIV RNA is unknown.
A second, ongoing trial is testing Norvir alone, AZT alone, and
the two agents in combination in 356 subjects randomized to one of
the three treatment groups. These subjects had not been treated
with antiretroviral drugs. Norvir and the combination group
produced statistically significant decreases in mean average viral
RNA levels compared with AZT. Furthermore, statistically
significant mean average increases in CD4 count were observed at 16
weeks with both arms compared to AZT.
Additionally, in an open-label, triple combination trial
involving 32 subjects, combination therapy involving Norvir and the
nucleoside analogues AZT and ddC nearly doubled the median CD4 cell
count from baseline. The triple therapy also caused reductions in
the number of HIV RNA particles in the blood by week 20.
The dosing recommendation for Norvir in children (age 2-16) is
based primarily on pharmacokinetic and safety data from an ongoing
Phase I/II study being conducted by a team of scientists at the HIV
and AIDS Malignancy Branch of the National Cancer Institute, in
collaboration with Abbott Laboratories.
Currently, researchers have enrolled 51 HIV-infected children
with either no prior therapy, progressive disease, or toxicity to
another antiretroviral regimen. The use of Norvir was evaluated in
the 44 children who had completed at least four weeks of treatment
as of Sept. 30, 1996. Norvir was given alone for the first 12
weeks, then in combination with zidovudine and /or didanosine.
The most common adverse effects were nausea (23% to 26%),
diarrhea (13% to 18%), vomiting (13% to 15%), muscular weakness (9%
to 14%), taste disturbance (5% to 10%), anorexia (1% to 6%),
abnormal functioning of tissue (3% to 6%), and abdominal pain (3%
In HIV-infected subjects age two to 16 years, the adverse event
profile was similar to that seen during clinical trials and
post-marketing experience in adults. The most common adverse events
in adults include nausea, diarrhea, vomiting, asthenia and taste
disturbance. Safety of Norvir in children below age two has not
been established. Norvir should not be used in combination with
highly metabolized medications known to cause serious or
life-threatening adverse events.
Mechanism of Action
Protease inhibitors are a new class of drug with a mechanism of
action that is different from most of the previously available
antiretroviral treatments for AIDS. Protease inhibitors, such as
Norvir, block the action of protease, an enzyme involved in the
final development of the virus. By blocking protease activity,
protease inhibitors prevent production of infectious viral
Norvir should not be used in combination with many highly
metabolized medications known to produce serious or
life-threatening adverse events.