Treatment Issues Vol. 11, no. 2

w ISSUES
C

I

w

w
E
w

FDA Approves Nelfinavir
On March 14, the U.S. Food and Drug
Administration granted Agouron's protease
inhibitor nelfinavir (brand name: Viracept)
clearance for distribution through the agency's
accelerated approval procedure. Nelfinavir is
the fourth protease inhibitor to be approved for
adults and the first to be approved for children.
The FDA-approved indication gives broad
guidelines for usage, simply stating, "for the
treatment of HIV infection when antiretroviral
therapy is warranted." The adult dosage is 750
mg three times a day. The pediatric formulation is available in an oral powder and doses
are determined by weight for children two to
13 years old. For optimal absorption, it is best
to take nelfinavir with a meal or a light snack.
Nelfinavir has considerable stability in the
body, which allows patients some leeway in
scheduling their doses. Agouron spokeswoman
Joy Schmitt commented, "In all of our clinical
trials as well as our expanded access programs,
we've always simply stated TID dosing [three
times daily]. It's been as loosely structured as
that. There hasn't been a need to put a timing
on it, though obviously there needs to be common sense on how an individual would take
the drug."
The most common reported side effect is
mild to moderate diarrhea, which according to
the package insert can usually be controlled
with non-prescription drugs. Although the
FDA did not require that nelfinavir be used
along with other antiviral therapy, the package
insert recommends combining it with nucleoside analogs.
There has been much speculation on the
utility of using nelfinavir as first-line treatment. This is because HIV that develops nelfinavir resistance may not be cross-resistant to
the other current protease inhibitors, which
could be used as follow-up drugs. But such a
conclusion is based on HIV isolates taken from
just five patients during nelfinavir therapy,
according to the official package insert. The
isolates demonstrated emerging resistance to
nelfinavir but did not exhibit decreased susceptibility to the other protease inhibitors in
lab cultures.
For those people who have become resistant
to other protease inhibitors and need to switch
treatments, nelfinavir could be an option. However, the package insert notes that six of seven
HlV isolates that had developed reduced sensitivity to ritonavir during therapy with that protease inhibitor also showed decreased sensitivity

to nelfinavir. For more information on the nelfinavir resistance question, see Treatment Issues,
February, 1997, pages 6-8.
Nelfinavir is 29% more expensive than
Merck's indinavir (Crixivan), with a wholesale
cost of $5650 for a year's supply. Although the
New York State AIDS Drug Assistance Program
included nelfinavir on its list of covered drugs
even before FDA approval, widespread inclusion
of nelfinavir in Medicaid and ADAP formularies
will further stretch scarce public health
resources. There is a nelfinavir patient assistance
program reachable at 888/777-6637. The program will first attempt to find outside means of
reimbursement but can provide the drug free of
charge if necessary. Agouron will also provide
nelfinavir free of charge to uninsured children in
the U.S..
Ritonavir Approved for Children
The FDA also granted approval for a pediatric ritonavir formulation on March 14. In so
doing, the agency increased the number of protease inhibitors available for children from zero
to two in one day (see above for nelfinavir). Dosing recommendations are based on safety data
collected from ongoing studies of children aged
two to 16. The safety of ritonavir in children
under two has not been established. When taking ritonavir, children unfortunately suffer from
the same long list of side effects and drug-drug
interactions as adults do. The evaluation of ritonavir's antiviral effect in children is still in
progress. An interim report at this winter's
Fourth Conference on Retroviruses and Opportunistic Infections (abstract 722) indicated that
ritonavir's antiviral activity in children was similar to that in adults.
More Pharmacies to Carry Crixivan
Since indinavir (Crixivan) entered the market
in March, 1996, its manufacturer, Merck & Co.,
has given the mail-order Stadtlander's Pharmacy exclusive distribution rights in order to manage the limited supplies available. This was to be
a temporary situation until Merck was able to
bring new production facilities on line later that
year. After many delays, Merck will finally
expand the distribution program to include
other pharmacies as of May 1, 1997. But sales
will still be limited to participating pharmacies,
and people must still enroll in a cumbersome
distribution program. We are not yet at the point
when a person can walk into a pharmacy with a
script for this protease inhibitor and expect to
have it filled immediately.

march 1997

N