The EMA ( European Medicines Agency ) has finalised a review of Aliskiren-containing medicines, recommending that these medicines should be contraindicated in patients with diabetes or moderate to severe renal impairment who take angiotensin converting enzyme ( ACE ) inhibitors or angiotensin receptor blockers ( ARBs; sartans ).
In addition, the Agency recommended the inclusion of a warning that the combination of Aliskiren and ACE inhibitor or sartan is not recommended in all other patients because adverse outcomes cannot be excluded.
Aliskiren-containing medicines are approved for the treatment of essential hypertension.
Advice for doctors and patients
Doctors should stop prescribing Aliskiren-containing medicines to patients with diabetes ( type 1 or type 2 ) or with moderate to severe kidney impairment who are also taking an ACE inhibitor or angiotensin receptor blocker, and should consider alternative antihypertensive treatment as necessary.
For all other patients receiving Aliskiren-containing medicines in combination with an ACE inhibitor or an sartan, the balance of benefits and risks of continuing treatment should be considered carefully.
Patients should discuss their treatment with their doctor at their next scheduled ( non-urgent ) appointment. They should not stop any of their treatment before speaking to their doctor, because stopping anti-hypertensive medication without medical supervision can put them at risk.
Patients in clinical trials with Aliskiren should contact their study site for guidance on their medication.
The recommendations follow a review of all available safety data by the Agency’s Committee for Medicinal Products for Human Use ( CHMP ). The review was started in December 2011 after the EMA was informed by the marketing authorisation holder of the decision to terminate the ALTITUDE study early.
This placebo-controlled phase III trial included patients with type 2 diabetes mellitus and renal impairment and/or cardiovascular disease.
In most patients, arterial blood pressure was adequately controlled. The patients included in the trial received Aliskiren in addition to either an ACE inhibitor or a sartan.
Although the information available at the time was limited, the CHMP gave interim recommendations in December 2011, advising doctors that they should not prescribe Aliskiren-containing medicines to diabetic patients in combination with ACE inhibitors or sartans.
Since then further data and analyses from the ALTITUDE study, alongside all data from other studies and spontaneous reports of suspected adverse drug reactions, have become available and were reviewed by the CHMP. The data suggest a risk of adverse outcomes ( hypotension, syncope, stroke, hyperkalaemia and changes in renal function, including acute renal failure ) when Aliskiren is combined with ACE inhibitors or sartans, especially in diabetic patients and those with impaired renal function. Although less evidence is available for other patient groups, adverse outcomes cannot be excluded and therefore the CHMP no longer recommends the use of this combination.
Eight Aliskiren-containing medicines are authorised in the European Union ( EU ) since 2007: Rasilamlo, Rasilez, Rasilez HCT, Rasitrio, Riprazo, Riprazo HCT, Sprimeo and Sprimeo HCT. Some of these medicines ( Rasilamlo, Rasilez HCT, Rasitrio, Riprazo HCT and Sprimeo HCT ) are combinations of Aliskiren with other antihypertensive medicines.
Aliskiren-containing medicines are available as tablets and marketed in all EU Member States, except Estonia, Latvia, Lithuania and Romania. ( Xagena )
Source: European Medicines Agency, 2013