FDA Approves New Use for Micardis(R) in Cardiovascular Risk Reduction and Twynsta(R) as New Combination Treatment for High Blood Pressure

FDA Approves New Use for Micardis(R) in Cardiovascular Risk Reduction and
Twynsta(R) as New Combination Treatment for High Blood Pressure
MICARDIS is First ARB Indicated to Reduce Risk of Cardiovascular Events in
High-Risk Patients 55+ who are Unable to Take an ACE Inhibitor

RIDGEFIELD, Conn., Oct. 19 /PRNewswire/ -- Boehringer Ingelheim
Pharmaceuticals, Inc. announced today that the U.S. Food and Drug
Administration (FDA) approved the supplemental New Drug Application (sNDA) for
its angiotensin II receptor blocker (ARB) Micardis® (telmisartan) Tablets 80
mg for reduction of the risk of myocardial infarction, stroke, or death from
cardiovascular causes in patients 55 years of age or older at high risk of
developing major cardiovascular events who are unable to take
angiotensin-converting enzyme (ACE) inhibitors.(1) MICARDIS is the most
studied ARB in this high-risk patient population and has been commercially
available to treat hypertension (high blood pressure) since its approval in
1998. The FDA also approved a New Drug Application (NDA) for the combination
agent Twynsta® (telmisartan/amlodipine) Tablets for the treatment of
hypertension alone or in combination with other anti-hypertensive agents, or
as initial therapy for patients who are likely to need multiple drugs to
achieve their blood pressure goals.

"For those at high risk of cardiovascular events, it's important to find a
treatment that helps reduce their risk. Further, two-thirds of people
currently treated for hypertension are not at target blood pressure goals,"
said Dr. James Young, professor of medicine and executive dean of the
Cleveland Clinic Lerner College of Medicine at Case Western Reserve
University. "The newly approved use of telmisartan for cardiovascular risk
reduction in high-risk patients who are unable to take an ACE inhibitor, and
the availability of a telmisartan-amlodipine combination for hypertension,
give patients and physicians much needed new treatment options for these
chronic health problems."

Patients at high cardiovascular risk may have a history of coronary artery
disease, peripheral arterial disease, stroke, transient ischemic attack or
high-risk diabetes with evidence of end-organ damage. Some studies estimate
that up to 20 percent of patients taking an ACE inhibitor experience side
effects, usually cough, suggesting that some patients might be less likely to
take this medication as prescribed.(2,3) The approval of this additional
indication for MICARDIS is based on the largest clinical trial program ever
undertaken with an ARB, involving more than 31,000 high-risk cardiovascular
patients with normal blood pressure or treated high blood pressure with a
history of a broad range of cardiovascular diseases.(2,4) The results of these
studies supported that MICARDIS is more effective than placebo.(1)

TWYNSTA combines the complementary blood pressure lowering effects of
telmisartan, the active ingredient in MICARDIS, with the calcium channel
blocker (CCB) amlodipine. TWYNSTA is not indicated for cardiovascular risk
reduction. The new medicine will be available in pharmacies in November 2009
in the following strengths: 40/5 mg, 40/10 mg, 80/5 mg, 80/10 mg.

The FDA approval of TWYNSTA is based on the results of one placebo-controlled
and two active-controlled trials involving a total of 3,505 patients with
stage 1 or stage 2 hypertension. Results demonstrate that TWYNSTA was
generally well-tolerated and provided significant blood pressure reductions in
a variety of hypertensive patient populations compared with placebo or
monotherapy.(5)

"The approval of MICARDIS for cardiovascular risk reduction and TWYNSTA for
hypertension demonstrates Boehringer Ingelheim's commitment to providing
valuable options for the treatment of cardiovascular disease," said Dr. Thor
Voigt, senior vice president, Medicine and Drug Regulatory Affairs, Boehringer
Ingelheim Pharmaceuticals, Inc. "New options are important for the ultimate
goal of ensuring patients receive appropriate treatment based on their
individual needs."

About Hypertension
According to the American Heart Association, about one in three U.S. adults
-approximately 73 million people - has high blood pressure, or
hypertension.(6) High blood pressure is most common in people over the age of
35, and is particularly prevalent among the following populations: female,
black, middle-aged, elderly, and obese people, heavy drinkers and women taking
birth control pills.(7) However, because there are no symptoms, nearly
one-third of people with high blood pressure are not aware that they have the
condition.(8) Left untreated, high blood pressure can lead to serious
cardiovascular health risks, such as stroke, heart attack, heart failure or
kidney failure.(8)

About Cardiovascular Disease
Cardiovascular disease (CVD) claims the life of one American every 37
seconds.(9) According to the American Heart Association, approximately 80
million Americans have one or more forms of cardiovascular disease.(9)
Thirty-five percent of all deaths in the U.S., or approximately one in three,
are due to cardiovascular diseases.(10) Among those with CVD, 8 million
Americans have experienced a heart attack (myocardial infarction) and 6.5
million have experienced a stroke. Additionally, in 2005, 860,000 Americans
died from cardiovascular diseases.(9) It is estimated that the cost of CVD in
the United States, including health care expenditures and lost productivity
from deaths and disability, will be more than $475 billion in 2009.(10)

About Micardis® (telmisartan) Tablets
Telmisartan is marketed in the U.S. as MICARDIS Tablets by Boehringer
Ingelheim Pharmaceuticals, Inc.

MICARDIS is indicated for the treatment of hypertension. It may be used alone
or in combination with other antihypertensive agents.

MICARDIS is also indicated for reduction of the risk of myocardial infarction,
stroke, or death from cardiovascular causes in patients 55 years or older at
high risk of developing major cardiovascular events who are unable to take ACE
inhibitors. Because studies with telmisartan did not exclude that it may not
preserve a meaningful fraction of the effect of the ACE inhibitor to which it
was compared, consider using the ACE inhibitor first.

WARNING: AVOID USE IN PREGNANCY
When used in pregnancy, drugs that act directly on the renin-angiotensin
system can cause injury and even death to the developing fetus. When
pregnancy is detected, MICARDIS tablets should be discontinued as soon as
possible [see Warnings and Precautions].

In patients with an activated renin-angiotensin system, such as volume- and/or
salt-depleted patients, symptomatic hypotension may occur after initiation of
therapy with MICARDIS Tablets. This condition should be corrected prior to
administration of MICARDIS Tablets, or treatment should start under close
medical supervision.

As the majority of telmisartan is eliminated by biliary excretion, patients
with biliary obstructive disorders or hepatic insufficiency can be expected to
have reduced clearance. MICARDIS Tablets should be used with caution in these
patients.

In patients whose renal function may depend on the activity of the
renin-angiotensin-aldosterone system (e.g., patients with severe CHF),
treatment with angiotensin-converting enzyme inhibitors and angiotensin
receptor antagonists has been associated with oliguria and/or progressive
azotemia and (rarely) with acute renal failure and/or death. Similar results
may be anticipated in patients treated with MICARDIS Tablets.

In studies of ACE-inhibitors in patients with renal artery stenosis, increases
in serum creatinine or blood urea nitrogen were observed. An effect similar to
that seen with ACE inhibitors should be anticipated with MICARDIS Tablets.

Dual blockade of the renin-angiotensin-aldosterone system (e.g., by adding an
ACE-inhibitor to an angiotensin II receptor antagonist) should be used with
caution and should include close monitoring of renal function. Concomitant use
of telmisartan and ramipril is not recommended.

The most common adverse events occurring with MICARDIS Tablets at a rate of
greater than or equal to 1% and greater than placebo, respectively, were:
upper respiratory tract infection (URTI) (7%, 6%), back pain (3%, 1%),
sinusitis (3%, 2%), diarrhea (3%, 2%), and pharyngitis (1%, 0%).

With MICARDIS monotherapy and other angiotensin II receptor blockers and ACE
inhibitors in general, BP response in blacks is noticeably less than in
Caucasians.

No overall differences in effectiveness and safety of MICARDIS were observed
in elderly patients compared to younger patients, but greater sensitivity of
some older individuals cannot be ruled out.

In nursing mothers, nursing or MICARDIS should be discontinued.

For more information about MICARDIS or to receive a package insert please
contact Boehringer Ingelheim Pharmaceuticals Inc. Drug Information Unit at
1-800-542-6257, option #4.

About Twynsta® (telmisartan/amlodipine) Tablets
Telmisartan/amlodipine is marketed in the U.S. as TWYNSTA Tablets by
Boehringer Ingelheim Pharmaceuticals, Inc.

TWYNSTA is indicated for the treatment of hypertension, alone or with other
antihypertensive agents. It may also be used as initial therapy in patients
who are likely to need multiple drugs to achieve their blood pressure goals.

WARNING: AVOID USE IN PREGNANCY
When used in pregnancy, drugs that act directly on the renin-angiotensin
system can cause injury and even death to the developing fetus. When pregnancy
is detected, TWYNSTA should be discontinued as soon as possible [see Warnings
and Precautions].

In patients with an activated renin-angiotensin system, such as volume- and/or
salt-depleted patients, symptomatic hypotension may occur after initiation of
therapy with TWYNSTA Tablets. This condition should be corrected prior to
administration of TWYNSTA Tablets, or treatment should start under close
medical supervision with a reduced dose.

Since the vasodilation induced by amlodipine in TWYNSTA is gradual in onset,
acute hypotension has rarely been reported after oral administration.
Nonetheless, caution, as with any other peripheral vasodilator, should be
exercised when administering amlodipine, particularly in patients with severe
aortic stenosis.

As the majority of telmisartan is eliminated by biliary excretion, patients
with biliary obstructive disorders or hepatic insufficiency can be expected to
have reduced clearance. TWYNSTA should be used with caution in these patients.

Since amlodipine is extensively metabolized by the liver and the plasma
elimination half-life (t1/2) is 56 hours in patients with impaired hepatic
function, caution should be exercised when administering TWYNSTA to patients
with severe hepatic impairment.

In patients whose renal function may depend on the activity of the
renin-angiotensin-aldosterone system (e.g., patients with severe CHF),
treatment with angiotensin-converting enzyme inhibitors and angiotensin
receptor antagonists has been associated with oliguria and/or progressive
azotemia and (rarely) with acute renal failure and/or death. Similar results
may be anticipated in patients treated with TWYNSTA Tablets.

In studies of ACE inhibitors in patients with renal artery stenosis, increases
in serum creatinine or blood urea nitrogen were observed. An effect similar to
that seen with ACE inhibitors should be anticipated with TWYNSTA Tablets.

Dual blockade of the renin-angiotensin-aldosterone system (e.g., by adding an
ACE-inhibitor to an angiotensin II receptor antagonist) should be used with
caution and should include close monitoring of renal function. Concomitant use
of telmisartan and ramipril is not recommended.

Patients, particularly, those with severe obstructive coronary artery disease,
may develop increased frequency, duration or severity of angina or acute
myocardial infarction on starting calcium channel blocker therapy or at the
time of dosage increase.

Closely monitor patients with heart failure.

In the placebo-controlled factorial design study, discontinuation due to side
effects occurred in 2.2% of patients treated with the telmisartan/amlodipine
combination and in 4.3% of the patients in the placebo group. The most common
reasons for discontinuation of therapy with TWYNSTA Tablets were peripheral
edema (0.5%), dizziness (0.4%), and hypotension (0.4%). The most common
adverse reactions that occurred in greater than or equal to 2% of patients and
at a higher incidence than placebo were peripheral edema, dizziness, and back
pain.

In clinical studies, the magnitude of blood pressure lowering with TWYNSTA in
black patients approached that observed in non-black patients, but the number
of black patients was limited.

In patients who are 75 years or hepatically impaired, amlodipine should
usually be started or added at a dose of 2.5mg.

In nursing mothers, nursing or TWYNSTA should be discontinued.

For more information about TWYNSTA or to receive a package insert please
contact Boehringer Ingelheim Pharmaceuticals Inc. Drug Information Unit at
1-800-542-6257, option #4.

Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the
largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT)
and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical
companies. Headquartered in Ingelheim, Germany, it operates globally with 138
affiliates in 47 countries and approximately 41,300 employees. Since it was
founded in 1885, the family-owned company has been committed to researching,
developing, manufacturing and marketing novel products of high therapeutic
value for human and veterinary medicine.

In 2008, Boehringer Ingelheim posted net sales of US $17 billion (11.6 billion
euro) while spending approximately one-fifth of net sales in its largest
business segment, Prescription Medicines, on research and development.

For more information, please visit http://us.boehringer-ingelheim.com.

References
1. MICARDIS PI. Boehringer Ingelheim Pharmaceuticals. Inc. Ridgefield,
Conn.
2. The Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects
with cardiovascular Disease (TRANSCEND) Investigators. Effects of the
angiotensin-receptor blocker telmisartan on cardiovascular events in
high-risk patients intolerant to angiotensin-converting enzyme
inhibitors: a randomised controlled trial. Lancet. 2008;
doi:10.1016/S0140-6736(08)61242-8.
3. Wogen J, Kreilick C, Livornese R, Yokoyama K, Frech F. Patient
adherence
with amlodipine, lisinopril or valsartan therapy in a usual-care
setting.
JMCP. 2003; 9: 424-429.
4. The Ongoing Telmisartan Alone and in Combination with Ramipril Global
Endpoint Trial (ONTARGET) Investigators. Telmisartan, ramipril, or both
in patients at high risk for vascular events. N Engl J Med. 2008; 358:
1547-59.
5. TWYNSTA PI. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield,
Conn.
6. American Heart Association. High Blood Pressure Statistics.
http://www.americanheart.org/presenter.jhtml?identifier=4621. Accessed
Sept. 15, 2009.
7. American Heart Association. What is High Blood Pressure?
http://www.americanheart.org/presenter.jhtml?identifier=2112. Accessed
May 28, 2009.
8. American Heart Association. High Blood Pressure.
http://www.americanheart.org/presenter.jhtml?identifier=2114. Accessed
May 28, 2009.
9. American Heart Association. Heart Disease and Stroke Statistics --
2009
Update.

http://www.americanheart.org/downloadable/heart/1240250946756LS-1982%20He
art%20and%20Stroke%20Update.042009.pdf. Accessed May 28, 2009.

10. U.S. Centers for Disease Control and Prevention. Heart Disease and
Stroke Prevention.
http://www.cdc.gov/NCCDPHP/publications/AAG/dhdsp.htm. Accessed on
September 3, 2009.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.

Ann Wainright, Public Affairs & Communications, Boehringer Ingelheim
Pharmaceuticals, Inc., +1-203-791-6318, usnews@boehringer-ingelheim.com