Subject: Deadly Norvir warnings!
From: [email-masked]
Date: Sat, 30 Nov 1996 03:45:59 -0500

More dangers reported by Abbott laboratories regarding its protease inhibitor
Norvirx (ritonavir). These adverse events (based on "postmarketing
experience") indicate that had these drugs been sufficiently studied prior to
approval rather than rushed through the process at the behest of bought-off
"AIDS" activists, perhaps the consequent loss of HIV-positive lives could
have been prevented.

Note that the most severe toxicities are "hepatic" in nature meaning that
these compounds are pure poison for the many of us already, and perhaps
unknowingly, suffering from concomitant Hepatitis B or C infection.

Despite the pop-culture hype promoting these agents as "the cure" it is
increasingly apparent that for many, especially those of us in late-stage
AIDS, these products are our final death sentence.

Time to wake up and smell the corpses! There's mass murder in our midst. And
it has a $15,000.00 a year price tag. Bet your bottom dollar the next Abbott
warning concerns protease + ecstacy. Our friends are already dropping over on
the dance floors.

==========

Pharmaceutical Products Division
Abbott Laboratories
200 Abbott Park Road
Abbott Park, IL 60064-3537

November, 1996

IMPORTANT DRUG WARNING

Dear Health Care Provider"

I am writing you with important new safety and prescribing information about
Norvirx (ritonavir), Abbott's HIV protease inhibitor. The Norvir Product
Information has been updated to reflect new information about drug
interactions and adverse effects based on postmarketing experience. New
information on the interaction of Norvir in combination with Invirasex
(saquinavir, Roche) has also been added. And finally, a review of the
importance of dose titration upon the initiation of Norvir therapy is
included.

NEW DRUG INTERACTIONS:

* Ergot alkaloid preparations have been added as contraindications. Based on
postmarketing experience, coadministration of ritonavir with ergotamine or
dihydroergotamine has been associated with acute ergot toxicity characterized
by peripheral vasospasm and ischemia of the extremities. Some of the patients
received treatment with vasodilators.

* Pimozide (Orapx, Gate Pharmaceuticals) has also been added as a
contraindication, based on a predicted interaction between Norvir and
pimozide.

* Cardiac and neurologic events have been reported in postmarketing
experience when ritonavir has been coadministered with disopyramide,
mexiletine, nefazadone, or fluoxetine. The possibility of drug interaction in
these cases cannot be excluded. The list of medications whose plasma level
may be potentially affected when used with Norvir (Table 3) has been updated.

* Two phase I interaction studies evaluated the single-dose and multiple-dose
pharmacokinetic interactions between ritonavir and saquinavir in healthy
non-HIV infected volunteers. Results were consistent with the fact that
ritonavir is a potent CYP 3A4 inhibitor. Saquinavir plasma concentrations
were increased significantly (greater than 20-fold increased in
concentrations) when coadministered with ritonavir. The pharmacokinetics of
ritonavir were not significantly affected with the coadministration of
saquinavir. This information has been added to the Drug Interaction section.

A study to determine antiviral activity, safety, and pharmacokinetics of the
combination of ritonavir and saquinavir in HIV-infected patients is ongoing.
This study enrolled approximately 130 HIV-infected patients and includes four
treatment arms. Preliminary results including safety were presented at the XI
International Conference on AIDS in Vancouver, Canada and the 36th ICAAC
Meeting in New Orleans, LA. However, the appropriate doses for this
combination, with respect to safety and activity, has not been established.

POSTMARKETING ADVERSE EVENTS

* The WARNINGS section of the product information on Norvir has been revised
to include the following information:

To alert the health care provider about the potential for hypersensitivity
reactions with Norvir therapy. This section states that allergic reactions
including urticaria, mild skin eruptions, bronchospasm, angioedema, and
rarely, anaphylaxis and Stevens-Johnson syndrome have been reported.

Hepatic transaminase elevations exceeding 5 times the upper limit of normal,
clinical hepatitis, and jaundice have occurred in patients receiving Norvir
alone or in combination with other antiretroviral drugs (see Table 5). There
may be an increased risk for transaminase elevations in patients with
underlying hepatitis B or C. Therefore, caution should be exercised when
administering Norvir to patients with pre-existing liver diseases, liver
enzyme abnormalities, or hepatitis.

There have been postmarketing reports of hepatic dysfunction, including some
fatalities. These have generally occurred in patients taking multiple
concomitant medications and/or with advanced AIDS. A definitive causal
relationship has not been established.

* The PRECAUTIONS sections has been updated to include the following
statement:

As with other HIV protease inhibitors, there have been reports of increased
bleeding, including spontaneous skin hematomas and hemarthrosis, in patients
with hemophilia type A and B receiving ritonavir. In some patients additional
factor VIII was given. In more than half of the reported cases, treatment
with protease inhibitors was continued or reintroduced. A causal relationship
has not been established.

* The ADVERSE REACTIONS section has been revised as follows:

There have been postmarketing reports of seizure. Hyperglycemia has been
reported in individuals with and without a known history of diabetes. Cause
and effect relationship has not been established. Dehydration, usually
associated with gastrointestinal symptoms, and sometimes resulting in
hypertension, syncope, or renal insufficiency has been reported. Syncope,
orthostatic hypotension, and renal insufficiency have also been reported
without known dehydration.

* The OVERDOSE section has been updated. Renal failure with cosinophilia has
been reported with ritonavir overdose.

DOSE TITRATION

Use of the dose titration schedule may help to reduce treatment-emergent
adverse events while maintaining appropriate plasma levels. Ritonavir should
be started at no less than 300 mg twice daily and increased by 100 mg twice
daily increments up to 600 mg twice daily. Patients should be aware that
frequently observed adverse events, such as mild to moderate gastrointestinal
disturbances and paraesthesias, may diminish as therapy is continued.

There have been reports of difficulty I  distinguishing between the names
ritonavir and Retrovir (zidovudine, Glaxo Wellcome Inc.) on prescription,
resulting inpatients receiving wrong medication. It is recommended that
physicians use the trademark name, Norvir, when prescribing ritonavir.

Norvir is indicated in combination with nucleoside analogues or as
monotherapy for the treatment of HIV-infection when therapy is warranted. For
patients with advanced HIV disease, this indication is based on the results
from a study that showed as reduction in both mortality and AIDS-defining
clinical events for patients who received Norvir. Median duration of
follow-up in this study was 6 months. The clinical benefit from Norvir
therapy for longer periods of treatment is unknown. For patients with less
advanced disease, this indication is based on changes in surrogate markers in
studies evaluating patients who received Norvir alone or in combination with
other antiretroviral agents.

The most common adverse events in the clinical studies included nausea,
diarrhea, weakness, and taste perversion. Many other adverse events, some
potentially serious, have been noted with the use of ritonavir. See the
Norvir Product Information for a more complete list.

Enclosed is a copy of the Norvir Product Information, and updated Health Care
Professional Drug Interaction and Patient Dosing Interaction Cards. If you
would like further medical information please contact Medical Services at
1-800-633-9110. If you would like additional copies of the Patient Dosing
Interaction Card, ask your Abbott HIV Specialist or Medical Center
Representative, or call 1-800-441-4987.

Sincerely,

David Pizzuti, M.D.,
Divisional Vice President
Medical Affairs and Pharmaceutical Ventures

Enclosures:
Norvirx (ritonavir) Product Information, Abbott Laboratories
Health Care Professional Drug Interaction Card
Patient Drug Interaction Pocket Card

c 1996, Abbott Laboratories * Ref. 03-4720-R3 * Nov. 1996 * Printed in U.S.A.