New Warning, Contraindications Announced for Aliskiren-Containing Drugs

Treatment with an antihypertensive that contains aliskiren plus an angiotension-converting enzyme inhibitor or angiotensin receptor blocker is newly contraindicated in patients with diabetes, the Food and Drug Administration announced on April 20.

The contraindication is based on an increased risk of renal impairment, hypotension, and hyperkalemia, as seen in preliminary data from the ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints) trial, according to the FDA statement. It is being added to the labels for all drugs containing aliskiren (Tekturna), a renin inhibitor.

A warning against the use of aliskiren-containing products in patients with moderate renal impairment who are also taking an ACE inhibitor or angiotensin receptor blocker (ARB) is also being added to these drug labels. Moderate renal impairment is defined as a glomerular filtration rate (GFR) less than 60 mL/min for this purpose.

The ALTITUDE trial is a randomized, double-blind, placebo-controlled study of more than 8,500 people with type 2 diabetes and a high risk for cardiovascular and renal events. It evaluated whether aliskiren plus conventional treatment reduced cardiovascular and renal morbidity and mortality.

All patients were on an ARB or ACE inhibitor. The study was terminated early, after a median of about 27 months, because of a lack of efficacy and because the risks of renal impairment, hypotension, and hyperkalemia were increased in patients on aliskiren, compared with those on placebo. Nearly 37% of those in the aliskiren arm had hyperkalemia and almost 19% had hypotension, compared with 27% and almost 15% of those on placebo, respectively. For both side effects, serious adverse events were also higher in the aliskiren arm.

In addition, about 12% of patients on aliskiren had a renal adverse event, compared with about 10% of those on placebo.

The risk of stroke was higher among those on aliskiren, compared with those on placebo (2.7% vs. 2%), as was the risk of death (6.9% vs. 6.4%), but the FDA statement said that, at this time, "the significance of these findings is unknown" and that the agency has not reached a conclusion about a link between aliskiren and these events.

The single-ingredient formulation of aliskiren was approved in March 2007. Other products that contain aliskiren include:

• aliskiren, amlodipine besylate, and hydrochlorothiazide (Amturnide).

• aliskiren and hydrochlorothiazide (Tekturna HCT).

• aliskiren and amlodipine (Tekamlo).

Aliskiren is also available in combination with valsartan, an ARB marketed as Valturna, but after July 2012 this product will no longer be marketed, according to the FDA. Novartis is keeping it available until that time to give health care professionals time to transition patients to other therapy, according to a Dear Healthcare Professional letter from Novartis.

About 2.4 million prescriptions for aliskiren-containing products were dispensed to 451,000 patients from U.S. outpatient retail pharmacies in 2011, the FDA said. About 22% of patients on aliskiren-containing products were also taking an ACE inhibitor or ARB and diabetes medications – and almost 31% of patients on Valturna also were taking diabetes medications.

More information is available from aliskiren manufacturer Novartis at 888-997-5385 or www.pharma.us.novartis.com.

Adverse events associated with the use of aliskiren products should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/MedWatch/report.htm.

Treatment with an antihypertensive that contains aliskiren plus an angiotension-converting enzyme inhibitor or angiotensin receptor blocker is newly contraindicated in patients with diabetes, the Food and Drug Administration announced on April 20.

The contraindication is based on an increased risk of renal impairment, hypotension, and hyperkalemia, as seen in preliminary data from the ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints) trial, according to the FDA statement. It is being added to the labels for all drugs containing aliskiren (Tekturna), a renin inhibitor.

A warning against the use of aliskiren-containing products in patients with moderate renal impairment who are also taking an ACE inhibitor or angiotensin receptor blocker (ARB) is also being added to these drug labels. Moderate renal impairment is defined as a glomerular filtration rate (GFR) less than 60 mL/min for this purpose.

The ALTITUDE trial is a randomized, double-blind, placebo-controlled study of more than 8,500 people with type 2 diabetes and a high risk for cardiovascular and renal events. It evaluated whether aliskiren plus conventional treatment reduced cardiovascular and renal morbidity and mortality.

All patients were on an ARB or ACE inhibitor. The study was terminated early, after a median of about 27 months, because of a lack of efficacy and because the risks of renal impairment, hypotension, and hyperkalemia were increased in patients on aliskiren, compared with those on placebo. Nearly 37% of those in the aliskiren arm had hyperkalemia and almost 19% had hypotension, compared with 27% and almost 15% of those on placebo, respectively. For both side effects, serious adverse events were also higher in the aliskiren arm.

In addition, about 12% of patients on aliskiren had a renal adverse event, compared with about 10% of those on placebo.

The risk of stroke was higher among those on aliskiren, compared with those on placebo (2.7% vs. 2%), as was the risk of death (6.9% vs. 6.4%), but the FDA statement said that, at this time, "the significance of these findings is unknown" and that the agency has not reached a conclusion about a link between aliskiren and these events.

The single-ingredient formulation of aliskiren was approved in March 2007. Other products that contain aliskiren include:

• aliskiren, amlodipine besylate, and hydrochlorothiazide (Amturnide).

• aliskiren and hydrochlorothiazide (Tekturna HCT).

• aliskiren and amlodipine (Tekamlo).

Aliskiren is also available in combination with valsartan, an ARB marketed as Valturna, but after July 2012 this product will no longer be marketed, according to the FDA. Novartis is keeping it available until that time to give health care professionals time to transition patients to other therapy, according to a Dear Healthcare Professional letter from Novartis.

About 2.4 million prescriptions for aliskiren-containing products were dispensed to 451,000 patients from U.S. outpatient retail pharmacies in 2011, the FDA said. About 22% of patients on aliskiren-containing products were also taking an ACE inhibitor or ARB and diabetes medications – and almost 31% of patients on Valturna also were taking diabetes medications.

More information is available from aliskiren manufacturer Novartis at 888-997-5385 or www.pharma.us.novartis.com.

Adverse events associated with the use of aliskiren products should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/MedWatch/report.htm.

Treatment with an antihypertensive that contains aliskiren plus an angiotension-converting enzyme inhibitor or angiotensin receptor blocker is newly contraindicated in patients with diabetes, the Food and Drug Administration announced on April 20.

The contraindication is based on an increased risk of renal impairment, hypotension, and hyperkalemia, as seen in preliminary data from the ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints) trial, according to the FDA statement. It is being added to the labels for all drugs containing aliskiren (Tekturna), a renin inhibitor.

A warning against the use of aliskiren-containing products in patients with moderate renal impairment who are also taking an ACE inhibitor or angiotensin receptor blocker (ARB) is also being added to these drug labels. Moderate renal impairment is defined as a glomerular filtration rate (GFR) less than 60 mL/min for this purpose.

The ALTITUDE trial is a randomized, double-blind, placebo-controlled study of more than 8,500 people with type 2 diabetes and a high risk for cardiovascular and renal events. It evaluated whether aliskiren plus conventional treatment reduced cardiovascular and renal morbidity and mortality.

All patients were on an ARB or ACE inhibitor. The study was terminated early, after a median of about 27 months, because of a lack of efficacy and because the risks of renal impairment, hypotension, and hyperkalemia were increased in patients on aliskiren, compared with those on placebo. Nearly 37% of those in the aliskiren arm had hyperkalemia and almost 19% had hypotension, compared with 27% and almost 15% of those on placebo, respectively. For both side effects, serious adverse events were also higher in the aliskiren arm.

In addition, about 12% of patients on aliskiren had a renal adverse event, compared with about 10% of those on placebo.

The risk of stroke was higher among those on aliskiren, compared with those on placebo (2.7% vs. 2%), as was the risk of death (6.9% vs. 6.4%), but the FDA statement said that, at this time, "the significance of these findings is unknown" and that the agency has not reached a conclusion about a link between aliskiren and these events.

The single-ingredient formulation of aliskiren was approved in March 2007. Other products that contain aliskiren include:

• aliskiren, amlodipine besylate, and hydrochlorothiazide (Amturnide).

• aliskiren and hydrochlorothiazide (Tekturna HCT).

• aliskiren and amlodipine (Tekamlo).

Aliskiren is also available in combination with valsartan, an ARB marketed as Valturna, but after July 2012 this product will no longer be marketed, according to the FDA. Novartis is keeping it available until that time to give health care professionals time to transition patients to other therapy, according to a Dear Healthcare Professional letter from Novartis.

About 2.4 million prescriptions for aliskiren-containing products were dispensed to 451,000 patients from U.S. outpatient retail pharmacies in 2011, the FDA said. About 22% of patients on aliskiren-containing products were also taking an ACE inhibitor or ARB and diabetes medications – and almost 31% of patients on Valturna also were taking diabetes medications.

More information is available from aliskiren manufacturer Novartis at 888-997-5385 or www.pharma.us.novartis.com.

Adverse events associated with the use of aliskiren products should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/MedWatch/report.htm.