FDA Approves Twynsta

FDA Approves Twynsta (telmisartan/amlodipine) for Hypertension

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

Ridgefield, CT, October 19, 2009 - 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 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 ≥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%20Heart%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.

Posted: October 2009

Twynsta (telmisartan and amlodipine) FDA Approval History

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