Concomitant Use Of Tekturna With ACE Inhibitors And ARBs Contraindicated In Patients With Diabetes; Plus An FDA Caution Regarding Renal Impairment
Tekturna (aliskiren) was approved by the FDA for marketing in March 2007 after it was evaluated for safety in 6,460 patients, and only 1250 patients were treated for longer than 1 year. As we have learned too often with many newly marketed drugs, the true incidence of serious adverse events may not be realized until many thousands or millions of exposures have occurred in a patient population less homogeneous than the group participating in the premarketing trials. And that scenario may be the case with Tekturna as well as the other aliskiren related drugs:
- Tekturna HCT (aliskiren hemifumarate and hydrochlorothiazide)
- Tekamlo (aliskiren hemifumarate and amlodipine besylate)
- Amturnide (aliskiren hemifumarate, amlodipine besylate, and hydrochlorothiazide
- Valturna (aliskiren hemifumarate and valsartan). NOTE: Novartis stopped marketing Valturna in July 2012, i.e., withdrawn from the market.
Tekturna is taken orally and prescribed to treat high blood pressure (hypertension). In December 2011 the drug company Novartis announced the termination of its clinical ALTITUDE study of Tekturna after researchers observed an increased number of serious side effects in the study’s participants.
For a concise report of that development and the subsequent FDA action, we look to this April 2012 article by journalist Larry Husten: "Aliskiren (Tekturna) Gets New Warning and Contraindication From FDA":
The FDA has issued new warnings about antihypertensive drugs containing the direct renin inhibitor aliskiren (including Tekturna, Amturnide, Takamio, and Valturna) when used in combination with ACE inhibitors or angiotensin receptor blockers (ARBs). The FDA now states that these drug combinations are contraindicated in patients with diabetes, and it is new warning to avoid the use of this combination in patients with moderate to severe renal impairment (GFR <60 mL/min).
The new warnings are based on preliminary data from the ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints) clinical trial. As previously reported here, ALTITUDE was terminated last December when the independent Data Monitoring Committee (DMC) found an increased risk for non-fatal stroke, renal complications, hyperkalemia, and hypotension in patients taking aliskiren after a median followup of about 27 months. More than 8,500 patients with type 2 diabetes and renal disease were randomized to receive aliskiren or placebo in addition to an ACE inhibitor or an ARB.
Click here to read the FDA Drug Safety Communication.
More recently, in connection with the FDA warning about Tekturna, Amturnide, Takamlo, and Valturna, the consumer advocacy group Public Citizen called for a "Black-Box Warning" for Tekturna and certain other high blood pressure medications -- angiotensin-receptor blockers (ARBs), angiotensin-converting-enzyme (ACE) inhibitors -- so that doctors are alerted to avoid using them in any combination due to the serious side effects which were revealed in the ALTITUDE trial.
From this October 4, 2012 press release, "Widely Used Blood Pressure Drugs Should Include a Strong Warning Against Use of Drugs in Combination, Public Citizen Tells FDA":
The use of ACE inhibitors and ARBs in combination has become commonplace in recent years due to a theoretical belief that such combination use would confer an added benefit over the use of the drugs individually. However, this theory has been unequivocally disproven in two large studies involving tens of thousands of patients with heart disease and diabetes that failed to show any clinical advantage of combination therapy. On the contrary, the studies showed a higher rate of several life-threatening side effects, such as low blood pressure, kidney failure and dangerously high blood potassium levels, in patients taking the drugs together compared with patients on only one of the medications.
A third study [i.e., ALTITUDE] involving the combined use of the new drug [Tekturna (aliskiren)] with ACE inhibitors and ARBs in patients with diabetes and kidney disease was halted early for identical reasons: a higher rate of the same serious side effects with no added benefit with combination use. An aliskiren/ARB combination drug, Valturna, was withdrawn from the market shortly thereafter.
Despite this wealth of data, the FDA has failed to respond by adequately warning doctors and patients of the clear danger of the combined use of ACE inhibitors, ARBs and [Tekturna] ....
If you are interested in learning more, see the Public Citizen document: "Petition to the FDA for Black Box Warnings on ACE Inhibitors, ARBs, and Aliskiren".
Essentially, the FDA should make Novartis add a Black-Box warning to the Tekturna label so as to inform doctors and patients that, as made apparent by the ALTITUDE study, patients with Type-2 diabetes are more likely to experience the following side effects than are patients with Type-2 diabetes who are not taking Tekturna:
• Increased blood potassium levels (hyperkalemia)
• Kidney (renal) damage
• Low blood pressure (hypotension)
We will continue to monitor the safety issues involving Tekturna, and report significant developments here.
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