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June 29, 2016

Aliskiren – New contraindications and warnings

Aliskiren – New contraindications and warnings due to the risks of cardiovascular and renal adverse reactions (Brands include Rasilez, Rasilez HCT, Rasilamlo)

Aliskiren is an antihypertensive agent which inhibits the renin-angiotensin-aldosterone system through a direct effect on renin, blocking the conversion of angiotensinogen to angiotensin I and decreasing levels of angiotensin I and angiotensin II. It has been licensed for use across the EU since 2007 either alone, or in combination with other antihypertensive medicines.

A review of aliskiren-containing medicines was initiated by the European Medicines Agency (EMA) in December 2011 after the ALTITUDE study was terminated early on the basis of preliminary interim analyses. The ALTITUDE study (Aliskiren Trial In Type 2 diabetes Using cardiovascular and renal Disease Endpoints) was a 4-year, randomised, placebo-controlled trial that included patients with type II diabetes and renal impairment and/or cardiovascular disease. The study was designed to evaluate the effect of aliskiren on the risk of cardiovascular and renal events in these high-risk patients, and participants received aliskiren or placebo in addition to either an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB).

The interim analysis showed that study patients were unlikely to benefit from aliskiren and there was a higher incidence of non-fatal strokes, renal complications (including acute renal failure), hyperkalaemia and hypotension in patients in the aliskiren group. In December 2011, healthcare professionals were informed of the interim results of the trial and advised that aliskiren use in combination with an ACE inhibitor or an ARB was contraindicated in all diabetic patients. Further review of analyses from the ALTITUDE study, alongside data from other studies and spontaneous reports, confirmed the 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 ARBs, 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 combination is not recommended for any patient.

In addition, the use of aliskiren is no longer recommended in any patient with severe renal impairment (GFR <30ml/min per 1.73m2) irrespective of whether it is used in combination with an ACE inhibitor or an ARB, another antihypertensive, or as monotherapy. This recommendation is based on an analysis of postmarketing surveillance data that showed an increased risk of renal adverse events and hyperkalaemia with aliskiren in this patient group.

This information was recently communicated to healthcare professionals, a copy of which is available on www.imb.ie.

Advice for healthcare professionals

  • Prescribers should review the treatment of all patients taking aliskiren in combination with an ACE inhibitor or an ARB at a routine appointment.
  • Treatment with aliskiren-containing medicines should be discontinued (or not initiated) in diabetic patients, or non-diabetic patients with renal impairment (GFR <60ml/min per 1.73m2) who are taking an ACE inhibitor or an ARB.
  • Aliskiren in combination with ACE inhibitors or ARBs is not recommended in any other patient groups.
  • Use of aliskiren (either as monotherapy or in combination) is no longer recommended in patients with severe renal impairment (GFR <30ml/min per 1.73m2).
  • The benefits and risks of continuing aliskiren treatment should be considered carefully at the individual patient level.
  • Alternative antihypertensive treatment should be considered as necessary.

Key Message

Use of aliskiren in combination with ACE inhibitors or ARBs is contraindicated in:

– diabetic patients (type I or type II); and

– non-diabetic patients with an estimated glomerular filtration rate (GFR) <60ml/min per 1.73m2.

In all other patient groups, the combination is not recommended.

Any use of aliskiren (either as monotherapy or in combination with other medicines) is no longer recommended in any patient with severe renal impairment.