Amid lawsuits, scrutiny, U.S. drug maker adds safety warnings on Tylenol caps

WASHINGTON, Sept. 4, 2013 — Bottles of Tylenol sold in the U.S. will soon bear red warnings alerting users to the potentially fatal risks of taking too much of the popular pain reliever. The unusual step, disclosed by the company that makes Tylenol, comes amid a growing number of lawsuits and pressure from the U.S. federal government that could have widespread ramifications for a medicine taken by millions of people every day.

Johnson & Johnson says the warning will appear on the cap of new
bottles of Extra Strength Tylenol sold in the U.S. starting in October
and on most other Tylenol bottles in coming months. The warning will
make it explicitly clear that the over-the-counter drug contains
acetaminophen, a pain-relieving ingredient that's the nation's leading
cause of sudden liver failure.

“We're always looking for ways to
better communicate information to patients and consumers,” says Dr.
Edwin Kuffner, vice-president of McNeil Consumer the Johnson &
Johnson unit that makes Tylenol.

Overdoses from acetaminophen
send 55,000 to 80,000 people to the emergency room in the U.S. each year
and kill at least 500, according the Centers for Disease Control and
Prevention and the Food and Drug Administration. Acetaminophen can be
found in more than 600 common over-the-counter and prescription products
used by nearly one in four American adults every week, including
household brands like Nyquil cold formula, Excedrin pain tablets and
Sudafed sinus pills.

Tylenol is the first of these products to
include such a warning label on the bottle cap. McNeil says the warning
is a result of research into the misuse of Tylenol by consumers. The new
cap message will read: “CONTAINS ACETAMINOPHEN” and “ALWAYS READ THE
LABEL.”

The move comes at a critical time for the company, which
faces more than 85 personal injury lawsuits in federal court that blame
Tylenol for liver injuries and deaths. At the same time, the Food and
Drug Administration is drafting long-awaited safety proposals that could
curtail the use of Tylenol and other acetaminophen products.

Much
is at stake for McNeil and its parent company. Johnson & Johnson
does not report sales of Tylenol, but total sales of all
over-the-counter medicines containing acetaminophen were more than $1.75
billion last year, according to Information Resources Inc., a retail
data service.

Safety experts are most concerned about
“extra-strength” versions of Tylenol and other pain relievers with
acetaminophen found in drugstores. A typical two-pill dose of Extra
Strength Tylenol contains 1,000 milligrams of acetaminophen, compared
with 650 milligrams for regular strength. Extra Strength Tylenol is so
popular that some pharmacies don't even stock regular strength.

Most
experts agree that acetaminophen is safe when used as directed, which
generally means taking 4,000 milligrams, or eight pills of Extra
Strength Tylenol or less, a day.

Each year, some 100 million Americans use acetaminophen, but liver damage occurs in only a fraction of one per cent of users.

Still,
liver specialists say those cases are preventable. They say that part
of the problem is that there are sometimes hundreds of pills in a
bottle, making it easy for consumers to pop as many as they please. For
example, McNeil sells Extra Strength Tylenol in bottles containing up to
325 tablets

“The argument goes that if you take acetaminophen
correctly you will virtually never get into trouble,” says Dr. William
Lee of the University of Texas Southwestern Medical Center, who has
studied acetaminophen toxicity for four decades. “But it's the very fact
that it's easily accessible over-the-counter in bottles of 300 pills or
more that puts people in harm's way.”

Lee applauded the new
warning, but said McNeil's marketing has contributed to the
“freewheeling” way that Americans take the drug. For decades, McNeil has
advertised Tylenol as “the safest kind of pain reliever” when used as
directed. “That has been their standard ploy in the past, and I would
argue that safest it is
not,” he says.

McNeil's Kuffner stands
by the company's safety claim: “When taken as directed, when people
read and follow the label, I believe that Tylenol and the acetaminophen
ingredient is one of the safest pain relievers on the market.”

McNeil
is the only major drugmaker adopting the bottle cap warning at this
time, according to the Consumer Products Association, a trade group for
over-the-counter medicine companies.

“While this is not an
industry-wide initiative at this time, it fits squarely within the many
ongoing industry-wide educational initiatives to further acetaminophen
safe and responsible use by consumers,” said Emily Skor, a
vice-president with the trade group, which represents McNeil, Bayer,
Procter & Gamble and other non-prescription drugmakers.

In Canada, products
containing acetaminophen must include warning about
liver toxicity, including specific information for people with serious
kidney and liver disease and alcohol users, according to Health Canada’s
Acetaminophen Labelling Standard.

The labeling standard also
requires labels to include warnings against use with other drugs
containing acetaminophen and against taking more than the maximum
recommended dose.

20 years of warning
McNeil has updated the safety warnings on Tylenol periodically since the 1990s.

In
1994, the company added a warning about the risk of liver damage when
combining alcohol with Tylenol following a lawsuit brought by Antonio
Benedi, a former aide to President George H.W. Bush, who fell into a
coma and underwent emergency liver transplant after mixing Tylenol with
wine at dinner.

A jury awarded him $8.8 million in damages after
concluding that McNeil failed to warn consumers about the risk. The FDA
made the alcohol warning mandatory for all manufacturers of
acetaminophen in 1998.

Then, in 2002, an expert panel of FDA
advisers recommended that the government agency require all
acetaminophen products to carry a warning about the risk of “severe
liver damage” when not taken as directed. The group's votes are
non-binding, though the FDA usually follows them. McNeil voluntarily
added the warning to its products in 2004, five years before the FDA
made it mandatory.

Today, McNeil appears to be moving ahead of
regulators again. In 2009, the FDA assembled another expert panel to
consider more sweeping changes to reduce acetaminophen overdoses. The
panel recommended several changes, including lowering the recommended
nonprescription daily dose for adults. McNeil voluntarily adopted that
recommendation, lowering the recommended adult dose of Extra Strength
Tylenol to 3,000 milligrams per day, or six pills of Extra Strength
Tylenol, down from 4,000 milligrams per day, or eight pills. The label
stipulates that patients can still take a higher dose if recommended by a
doctor.

But the company has not embraced a more drastic
recommendation by the FDA's expert panel: eliminating the
over-the-counter “extra strength” formulation altogether, which would
mean lowering the acetaminophen dose from 1,000 milligrams to 650
milligrams, or two tablets of 325 milligrams each. The panel said the
1,000-milligram dose should only be available via prescription.

McNeil
argues that the lower dose is less effective and could drive people to
take anti-inflammatory pain relievers, a different class of drugs that
includes aspirin and ibuprofen. Those medicines can cause stomach ulcers
and dangerous gastrointestinal bleeding.

FDA spokeswoman Erica
Jefferson says the agency is actively working on new rules for both
children and adult acetaminophen products. While the agency won't give a
timeframe for completion, the federal government's website that tracks
new regulations lists December as the target date for publishing the
proposed rules.

As early as 1977, FDA advisers recommended adding
more warnings to the acetaminophen label about liver damage, but the
agency didn't require the language until 2009.

“They are very
slow to respond to these things and it's always a little frustrating,”
says Dr. Lewis Nelson of New York University, who chaired the 2009 FDA
panel.

Anatomy of an overdose
Experts first identified
acetaminophen overdose as a major public health concern in the 1990s,
but it has taken years to form a clearer picture of the problem.

Acetaminophen
overdoses occur when the liver is overwhelmed by too much of the drug,
producing a toxic byproduct that kills liver cells. Liver failure occurs
when most cells are no longer able to function. At that point, a
patient then generally has 24 to 48 hours to live without a transplant.

Of
the roughly 500 acetaminophen deaths reported annually, about half are
accidental, with the rest deemed suicides. About 60 per cent of the
unintentional overdoses involve prescription opioid-acetaminophen
combination drugs such as Percocet and Vicodin, according to a database
of liver failure cases run by Dr. Lee at the Southwestern Medical Center
in Dallas. Those two products alone were prescribed more than 173
million times last year, according to IMS Health.

So how do these accidental acetaminophen deaths occur? Imagine you've had major dental surgery, and your dentist prescribes a
five-day supply of Percocet. You take the recommended two pills every six hours for 2,600 milligrams of acetaminophen, well below the 4,000-milligram-a-day safety threshold.

But you're still experiencing pain, so you decide to add Extra Strength Tylenol, six caplets a day for another 3,000 milligrams. Now you're feeling better but you still have trouble sleeping, so you take Nyquil, for another 650 milligrams. After a few days on this 6,250 milligram regimen, experts say acute liver damage is a real risk.

The labels on all of these products warn against mixing them. But researchers say many consumers either don't read or don't understand such warnings.

Even after
taking into account people who ignore labels, there are still cases of
liver damage that stump researchers. These are the people who have
apparently taken about 4,000 milligrams a day or less, well within the
safety threshold.

“It's still a little bit of a puzzle,” says Dr.
Anne Larson, of the Swedish Medical Center in Seattle. “Is it genetic
predisposition? Are they claiming they took the right amount, but they
really took more? It's difficult to know.”

The question is
critical in the lawsuits piling up against McNeil in the Eastern
District of Pennsylvania, near McNeil's headquarters in Fort Washington,
Pa. Virtually all of the 85 cases claim that the plaintiffs suffered
liver failure despite taking Tylenol as directed.

According to
one of those complaints, Madeline Speal, of Salzburg, Pa., took Tylenol
for three days in November 2009 “at appropriate times and in appropriate
doses.” But on Nov. 28, she was admitted to Latrobe Area Hospital with
catastrophic liver damage. She was then transferred to the University of
Pittsburgh Medical Center where she underwent an emergency liver
transplant.

The cases against McNeil, which share the same legal
wording, allege that the company risked the lives of consumers by making
“conscious decisions not to redesign, re-label, warn or inform the
unsuspecting consuming public.”

The lawsuits have been
consolidated under a single federal judge to streamline the pretrial
process, though they will eventually be returned to judges in their
original districts for trial.

J&J and McNeil continue to
reiterate that Tylenol is safe. “We remain confident in the safety and
efficacy of Tylenol products, which rightfully have been trusted by
doctors, hospitals and consumers for more than 50 years,” McNeil said in
a statement.

But lawyers for the patients suing McNeil say Tylenol can still be dangerous even when used at or just above recommended levels.

“Products
that are available to consumers should have a reasonable margin of
safety,” said Laurence Berman, one of several attorneys representing
Tylenol users.