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RASILEZ (aliskiren) and RASILEZ HCT (aliskiren/hydrochlorothiazide) - Potential Risks of Cardiovascular and Renal Adverse Events in Patients with Type 2 Diabetes - For Health Professionals
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(PDF Version - 41 K)Contact: Marketed Health Products Directorate
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This is duplicated text of a letter from Novartis Pharmaceuticals Canada Inc. Contact the company for a copy of any references, attachments or enclosures.
Health Canada Endorsed Important Safety Information on RASILEZ (aliskiren) and RASILEZ HCT (aliskiren/hydrochlorothiazide)
January 18, 2012
Dear Health Care Professional,
Subject: Potential risks of cardiovascular and renal adverse events in patients with type 2 diabetes treated with aliskiren (RASILEZ*) or aliskiren/hydrochlorothiazide (RASILEZ HCT*).
Novartis Pharmaceuticals Canada Inc. ("Novartis"), in collaboration with Health Canada, would like to inform you about important new safety information for aliskiren-containing products following interim results review from the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE). Interim results indicated a higher incidence of non-fatal strokes, renal complications (end stage renal disease and renal death), hyperkalemia and hypotension in aliskiren-treated patients.
Aliskiren (RASILEZ*) is currently indicated for the treatment of mild to moderate essential hypertension. It may be used alone or concomitantly with thiazide diuretics, angiotensin converting enzyme inhibitors, angiotensin II AT1 receptor blockers or dihydropyridine calcium channel blockers. Aliskiren and hydrochlorothiazide (RASILEZ HCT*) are indicated for the treatment of mild to moderate essential hypertension in patients for whom combination therapy is appropriate.
Analyses of the ALTITUDE interim results from the ALTITUDE study are ongoing. However, pending further analyses, a contra-indication in patients with diabetes taking an ACE inhibitor or an ARB is now advised. The treatment of diabetic patients taking aliskiren-containing products should therefore be reviewed as early as possible, taking the following advice into consideration:
- Aliskiren or aliskiren-containing fixed combination products should not be used in combination with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) in patients with diabetes, therefore:
- Healthcare professionals should stop aliskiren-containing treatment in patients who are diabetic and also taking an ACE inhibitor or an ARB. Alternative antihypertensive treatment should be considered if necessary.
- Treatment with aliskiren-containing products should not be initiated in diabetic patients who are also taking either an ACE inhibitor or ARB.
- Patients should NOT stop any of these treatments before discussing with a healthcare professional.
Further information on the safety concern
The ALTITUDE study was conducted in type 2 diabetic patients, known to be at risk of fatal and non-fatal cardiovascular and renal events. In this study, Aliskiren 300 mg (or placebo) was given in addition to standard of care, including an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB).
The 4-year multinational randomized, double-blind, placebo-controlled study was designed to evaluate the potential benefits of aliskiren in reducing the risk of cardiovascular and renal events in more than 8606 patients, including 329 Canadian patients.
The primary endpoint of the ALTITUDE study was the first occurrence of one of the following events: cardiovascular death, resuscitated sudden death, non-fatal myocardial infarction, non-fatal stroke, unplanned hospitalization for heart failure, doubling of baseline serum creatinine concentration to above the upper limit of normal (sustained for at least one month), and onset of end stage renal disease or renal death.
The ALTITUDE study was reviewed on a regular basis by a Data Monitoring Committee (DMC), which noted an emergence of imbalance of adverse events only after 18-24 months. The results of that interim analysis are shown in the table below.
| Variable | Aliskiren (N=4283) | Placebo (N=4296) | Total (N=8579) | HR | 95% CI | P-value |
|---|---|---|---|---|---|---|
|
581 (13.6%) | 542 (12.6%) | 1123 (13.1%) | 1.09 | (0.97, 1.22) | 0.1663 |
|
444 (10.4%) | 396 (9.2%) | 840 (9.8%) | 1.14 | (0.99, 1.30) | 0.0664 |
|
166 (3.9%) | 180 (4.2%) | 346 (4.0%) | 0.93 | (0.76, 1.15) | 0.5178 |
| Component event: | ||||||
|
179 (4.2%) | 162 (3.8%) | 341 (4.0%) | 1.12 | (0.90, 1.38) | 0.3110 |
|
13 (0.3%) | 8 (0.2%) | 21 (0.2%) | 1.64 | (0.68, 3.95) | 0.2737 |
|
90 (2.1%) | 88 (2.0%) | 178 (2.1%) | 1.03 | (0.77, 1.39) | 0.8302 |
|
112 (2.6%) | 85 (2.0%) | 197 (2.3%) | 1.34 | (1.01, 1.77) | 0.0439 |
|
150 (3.5%) | 155 (3.6%) | 305 (3.6%) | 0.98 | (0.78, 1.23) | 0.8716 |
|
72 (1.7%) | 60 (1.4%) | 132 (1.5%) | 1.22 | (0.87, 1.72) | 0.2518 |
|
141 (3.3%) | 159 (3.7%) | 300 (3.5%) | 0.90 | (0.71, 1.12) | 0.3431 |
| Death from any cause | 297 (6.9%) | 277 (6.4%) | 574 (6.7%) | 1.08 | (0.92, 1.27) | 0.3661 |
On the basis of preliminary interim analyses, the Data Monitoring Committee concluded that study patients were unlikely to benefit from aliskiren. Furthermore, there was a higher incidence of adverse events related to non-fatal stroke, renal complications (end stage renal disease and renal death), hyperkalemia and hypotension in this high-risk population.
Additional analyses from ALTITUDE are ongoing and the Canadian Product Monograph will be updated in 2012.
Call for Reporting
Healthcare professionals should report any suspected adverse reactions associated with use of aliskiren to Health Canada (See below). Adverse reaction should also be reported to Novartis (See below)
Novartis Pharmaceuticals Canada Inc.
385 Bouchard blvd,
Dorval, Quebec, H9S 1A9
Phone: 1-800-363-8883 (Medical Information)
You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:
- Report online at MedEffectTM Canada
- Call toll-free at 1-866-234-2345
- Complete a Reporting Form and:
- Fax toll-free to 1-866-678-6789, or
- Mail to: Canada Vigilance Program
Health Canada
Postal Locator 0701E
Ottawa, Ontario K1A 0K9
The Reporting Forms, postage paid labels, and Guidelines can be found on the MedEffectTM Canada Web site in the Adverse Reaction Reporting section. The Reporting Form is also in the Canadian Compendium of Pharmaceuticals and Specialties.
For other health product inquiries related to this communication, please contact Health Canada at:
Marketed Health Products Directorate
E-mail: mhpd_dpsc@hc-sc.gc.ca
Telephone: 613-954-6522
Fax: 613-952-7738
To change your mailing address or fax number, contact the Market Authorization Holder (Industry).
Should you have any questions or require additional information regarding the use of RASILEZ* (aliskiren) or RASILEZ HCT* (aliskiren and hydrochlorothiazide), please contact Novartis Pharmaceuticals Canada Inc., Medical Information Department at 1-800-363-8883.
Sincerely,
original signed by
Jean-Marie Leclerc, M.D. FRCP(C)
Chief Scientific Officer and Senior Vice-President Clinical and Regulatory Affairs
*RASILEZ and RASILEZ HCT are registered trademarks
