Mechanism of action

  • Renin Inhibitors act by > directly inhibit renin!
  • Renin converts angiotensinogen to angiotensin I
  • Renin inhibitors (Aliskiren) competes with angiotensinogen for the active site of the renin enzyme
  • Reduces plasm renin by approx. 75%
  • Furthermore, causes sustained reduction in angiotensin I and II

Only renin inhibitor which is licensed to be used in hypertension is ALISKIREN

Indication and dose

Essential hypertension which is alone or in combination with other hypertensives.

  • Orally
  • 150mg OD
  • Increase to 300mg OD, if necessary

Contra-Indications

  • Patients who are taking ACE-inhibitors or an ARB alongside aliskiren, with an eGFR < 60ml/min/1.73m2
  • Patients who are taking ACE-inhibitors or an ARB alongside aliskiren, with diabetes mellitus, hereditary angioedema, idiopathic angioedema

Cautions

  • In combination with an ACE-inhibitor and ARB
  • Diuretics
  • Hx of angioedema
  • Mod-severe congestive HF
  • Patients at risk of renal impairment
  • Salt depletion
  • Volume depletion

Concomitant use of drugs which affect the RAAS system is not recommended. Due to an increased risk of hypokalaemia, hypotension + renal impairment.

Patients with diabetic nephropathy are a t higher risk of suffering from hyperkalaemia.

 

Interactions

The interactions listed here are POTENTIALLY SERIOUS which is indicated by a black dot in the BNF. Further details of these interactions can be found in the BNF or Stockleys.

Furthermore, there are other interaction which are not potentially serious, nevertheless they should still be monitored and clinical judgement should be used.

  • ACE Inhibitors
  • Angiotensin II Blockers
  • Antifungals: Itraconazole
  • Ciclosporin
  • Grapefruit Juice

 

Side effects

Common: Arthralgia, dizziness, hyperkalaemia, diarrhoea

If diarrhoea is severe, persistent and distressing the patient. Then the drug should be discontinued

Pregnancy

  • Manufacturers recommend to AVOID
  • Drugs affecting RAAS system shown to cause foetal malformations + neonatal death

Breast feeding

  • Manufacturers recommend to AVOID
  • Animal studies show that it is present in milk

Renal Impairment

  • Avoid if eGFR < 30ml/min/1.73m2
  • Use with caution in renal artery stenosis
  • Monitor plasma K+ concentration in renal impairment

Monitoring requirements

  • Monitor patients with Hx of angioedema

 

References

BNF 70, Joint Formulary Committee (2015) British National Formulary. 70th Ed., London: British Medical Association and Royal Pharmaceutical Society of Great Britain.

 

British Hypertension Society. (2008). Angiotensin Receptor Blockers (ARBs). Available: http://www.bhsoc.org/pdfs/therapeutics/Direct%20Renin%20Inhibitors.pdf. Last accessed 03/02/2016.

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