Rezulin News

From: Subject: Rezulin News Date: Mon, 21 Feb 2005 15:39:11 -0000 MIME-Version: 1.0 Content-Type: multipart/related; boundary="----=_NextPart_000_007C_01C5182B.7D68D5D0"; type="text/html" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2800.1441 This is a multi-part message in MIME format. ------=_NextPart_000_007C_01C5182B.7D68D5D0 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://web.archive.org/web/19990823043401/www.rezulin.com/bkgrnder1.html Rezulin News

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Rezulinnews = Home=20

Prescribing Information =

Citizens'=20 Petition Response

Link to=20 Warner-Lambert Site

Link = to ADA=20 Site

Link to FDA = Site=20

WASHINGTON, D.C., March 26, 1999 =

RISK-BENEFIT ASSESSMENT OF = REZULIN=20

No = type 2=20 diabetes treatment is risk-free and each has = been=20 associated with serious adverse events. However, = the=20 risk-benefit of any treatment must be assessed = within=20 the context of the devastating consequences of = the=20 disease itself and the difficulty to achieve and = maintain glycemic control. A risk-benefit = assessment of=20 Rezulin must consider:=20

The risks of uncontrolled diabetes are=20 substantial, and treatment is required when = diet and=20 exercise fail.=20

With 65% of type 2 diabetes patients not = able to=20 achieve the American Diabetes Association = action=20 standard of an HbA_1c of 8, there is = a clear=20 need for therapies that help patients to = achieve and=20 sustain glycemic control.=20

The unique nuclear mechanism of action of = Rezulin=20 and lack of renal effects make it especially = relevant=20 and useful in certain patient populations = (e.g., early=20 diabetes, elderly, patients with renal = impairment).=20

The clinically proven benefits of Rezulin = are=20 important and complementary to certain other = type 2=20 diabetes medications.

The = Risks:=20

Rezulin has been prescribed to approximately = 1.6=20 million patients since it was first marketed in = March=20 1997. Since that time, the FDA has received 35 = reports=20 of liver-related deaths and transplants, which = it has=20 classified as possibly or probably related to = Rezulin=20 use. In addition, 8 patients have been reported = as=20 having experienced encephalopathy. The actions = taken by=20 Parke-Davis and the FDA since October 1997 have=20 dramatically decreased the incidence of serious = adverse=20 liver events. Thus, the incidence of reported = liver=20 failure leading to death or transplant was = approximately=20 1 in 36,000 during 1997 and approximately 1 in = 57,000 in=20 patients initiating Rezulin therapy since = January 1,=20 1998. When evaluating the incidence of serious = adverse=20 events, it is important to consider the = following:=20

Eight of the events occurred prior to = initiation=20 of liver enzyme monitoring=20
Twenty-five of the 27 remaining cases = involved=20 patients who apparently were not monitored = according=20 to the recommendations in the product labeling =
Only one of the 35 death and transplant = cases=20 involved a patient who was monitored = substantially in=20 accordance with the product labeling as it = exists=20 today.

It is important to understand = that many=20 cases are extremely complex and confounding = factors may=20 make interpretation of the data difficult. In = those=20 patients who experienced liver-related problems = while=20 using Rezulin:=20

12 of those patients had pre-existing = diseases of=20 the liver, gallbladder, or biliary tract=20
4 had a history of alcohol abuse, which is = associated with liver disease=20
10 suffered from viral hepatitis or=20 cytometgalovirus infection, which are = associated with=20 liver disease=20
12 had a history of cardiac disease=20
30 of the patients were using other = medications=20 that are possibly implicated in their = liver-related=20 problems=20
1 suffered from hypotension/shocked liver=20
8 suffered from sepsis=20
10 had autoimmune diseases.

As = with any=20 other drug, an estimate of the incidence of = adverse=20 liver events associated with Rezulin is complex = and=20 somewhat inexact. In the context of diabetes, it = is=20 important to note that pharmacologic treatment = is not=20 optional after diet and exercise have failed. = Moreover,=20 each of the available therapies for treatment of = the=20 disease is associated with its own risks and = benefits.=20 Given the need for pharmacotherapy, a physician = must=20 decide, based on comparative risks and benefits, = which=20 therapy is appropriate for each individual = patient.=20

The Benefits:=20

Rezulin is an important addition to the = limited=20 armamentarium of therapies available to treat = type 2=20 diabetes. In particular, the drug addresses an = unmet=20 medical need in the many patients who either = cannot=20 achieve or sustain long-term glycemic control on = other=20 therapies. It has a unique nuclear mechanism of = action=20 which is highly relevant to the disease process: = the=20 reduction in insulin resistance produced by = Rezulin=20 leads to a decrease in plasma insulin and=20 HbA_1c.=20

Particularly when used in combination with = other=20 agents, Rezulin use has resulted in significant=20 decreases in HbA_1c levels, enabling = many type=20 2 diabetes patients to meet American Diabetes=20 Association treatment goals for the first time = and, in=20 some patients, reducing or eliminating the need = for=20 exogenous insulin.=20

In four clinical trials, Rezulin was shown to = improve=20 glycemic control in patients with type 2 = diabetes, when=20 used either as a monotherapy - by itself - or = when used=20 in combination with certain other agents.=20

Safety must not be considered in a vacuum. = When=20 considering therapies for a disease as serious = as=20 diabetes, each drug must be considered in light = of its=20 risks and benefits; the FDA has determined that = the=20 benefits of each of the available diabetes = therapies=20 outweigh the associated risks.=20

Rezulin may be used concomitantly with a = sulfonylurea=20 or insulin to improve glycemic control in type 2 = diabetes patients. Rezulin, as monotherapy, is = indicated=20 as an adjunct to diet and exercise to lower = blood=20 glucose in patients with type 2 diabetes. = Rezulin should=20 not be used as monotherapy in patients = previously well=20 controlled on sulfonylurea therapy. For patients = inadequately controlled with a sulfonylurea = alone,=20 Rezulin should be added to, not substituted for, = the=20 sulfonylurea.=20

Management of type 2 diabetes should also = include=20 diet control, weight loss and exercise. Rezulin = should=20 not be used in type 1 diabetes or for the = treatment of=20 diabetic ketoacidosis.=20

Rare cases of severe idiosyncratic adverse=20 hepatocellular events have been reported during = marketed=20 use (see Hepatic boxed WARNING in the full = prescribing=20 information).=20

The hepatic event is usually reversible, but = very=20 rare cases of hepatic failure, leading to death = or liver=20 transplant, have been reported. Adverse liver = events=20 have occurred after both short- and long-term = treatment.=20

Although liver enzyme monitoring cannot = completely=20 eliminate the potential for serious liver = problems, it=20 should help reduce the risk.=20

Rezulin patients should have their liver = enzymes=20 monitored. Serum transaminase levels should be = checked=20 at the start of therapy, monthly for the first = eight=20 months of therapy, every two months for the = remainder of=20 the first year of Rezulin therapy, and = periodically=20 thereafter.=20

In clinical studies, Rezulin was generally=20 well-tolerated. The incidence of withdrawals = during=20 clinical trials was similar for patients treated = with=20 placebo or Rezulin (4%). The most common adverse = events=20 included infection (22% placebo vs. 18% = Rezulin),=20 headache (11% placebo vs. 11% Rezulin), and pain = (14%=20 placebo vs. 10% Rezulin).=20

In premenopausal anovulatory patients with = insulin=20 resistance, Rezulin treatment may result in = resumption=20 of ovulation. These patients may be at risk for=20 pregnancy. Rezulin should not be used during = pregnancy=20 unless the potential benefits exceed the = potential=20 risks.=20

Although an increase in plasma volume of 6% = to 8%=20 compared with placebo was observed in a 6-week = study of=20 troglitazone treatment in 24 normal volunteers, = there=20 was no increased incidence of adverse events = potentially=20 related to volume expansion (e.g. congestive = heart=20 failure) in controlled clinical trials for = Rezulin.=20 Patients with New York Heart Association (NYHA) = Class=20 III and IV cardiac status were not studied = during=20 clinical trials; therefore, Rezulin is not = indicated in=20 patients with NYHA Class III or IV cardiac = status unless=20 the expected benefit is believed to outweigh the = potential risk.=20

Rezulin may be used concomitantly with a = sulfonylurea=20 or insulin to improve glycemic control. Rezulin, = as=20 monotherapy, is indicated as an adjunct to diet = and=20 exercise to lower blood glucose in patients with = type 2=20 diabetes. Rezulin should not be used as = monotherapy in=20 patients previously well controlled on = sulfonylurea=20 therapy. For patients inadequately controlled = with a=20 sulfonylurea alone, Rezulin should be added to, = not=20 substituted for, the sulfonylurea.=20

Please see accompanying full prescribing = information=20 for Rezulin.=20 =

=A91999 = Warner-Lambert=20 Company. All rights reserved. Use of and access to the information on = this site=20
are subject to the terms and conditions set out in the Agreement to = use the=20 Warner-Lambert Company Web sites.
Please review this Privacy Statement = before=20 proceeding.
Created by Nethod, = LLC. on=20 behalf of the Warner-Lambert Company.
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