Aliskiren
Direct renin inhibitors
Direct renin inhibitorsPregnancy: contraindicated
Contraindicated: drugs acting on the renin-angiotensin system injure the fetus, especially in the second and third trimesters; it is stopped as soon as pregnancy is detected.
The only direct renin inhibitor: lowers blood pressure by blocking the first step of the renin-angiotensin system. A second-line antihypertensive.
Also called: aliskiren hemifumarate
Quick facts
- Group
- Direct renin inhibitors
- Target
- Renin
- Used for
- High blood pressure
- Key effects
- Diarrhoea · Abdominal pain and heartburn · Cough
- Monitor
- Blood pressure · Serum potassium · Creatinine and eGFR
- ATC
- C09XA02
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows aliskiren in the active site of human renin.
Renin, released by the kidney when perfusion falls, cleaves angiotensinogen to angiotensin I. Aliskiren binds the active site of renin and blocks this step, so plasma renin activity, angiotensin I, angiotensin II and aldosterone all fall. Loss of feedback raises the amount of renin released, but its activity remains blocked, unlike with ACE inhibitors and ARBs, which raise renin activity.
- Binds the active site of renin
- Angiotensinogen is not cleaved to angiotensin I
- Angiotensin II and aldosterone fall
- Vessels relax, sodium retention falls, pressure drops
Indications
- High blood pressure, alone or with other antihypertensives Arterial hypertension →
Adverse effects
Common
- Diarrhoea (the commonest)
- Abdominal pain and heartburn
- Cough (less often than with ACE inhibitors)
- Dizziness, headache, rash
Contraindications
- Use with an ACE inhibitor or ARB in patients with diabetes
- Pregnancy
- Hypersensitivity to the drug
- Children under 2 years of age
Key interactions
- ACE inhibitors or ARBs
- Dual RAAS blockade: more hyperkalaemia, hypotension and kidney injury; contraindicated in diabetes and generally avoided.
- Ciclosporin or itraconazole
- Strong rise in aliskiren levels through P-glycoprotein and CYP3A4 inhibition; combination avoided.
- NSAIDs
- Reduced antihypertensive effect and risk of kidney injury in older, volume-depleted or kidney patients.
- Potassium supplements, salt substitutes, potassium-sparing diuretics
- Risk of hyperkalaemia.
- Furosemide
- Its effect may be reduced after aliskiren is started.
What is monitored
- Blood pressure
- Serum potassium
- Creatinine and eGFR
- Pregnancy status in people who could become pregnant
Administration and safety
- Oral tablet, once a day, always in the same relation to meals; high-fat meals are avoided around the dose.
- Volume depletion (diuretics, vomiting, diarrhoea) is corrected before starting.
- Stopped as soon as pregnancy is detected.
- Look-alike risk with other RAAS drugs on medication lists: check it is not doubled with an ACE inhibitor or ARB.
Pregnancy and breastfeeding
Contraindicated: drugs acting on the renin-angiotensin system injure the fetus, especially in the second and third trimesters; it is stopped as soon as pregnancy is detected.
Nursing care
- Before: blood pressure, potassium, kidney function, diabetes status, current ACE inhibitor/ARB use, pregnancy status.
- During: blood pressure (standing and lying), potassium and creatinine.
- Teach to report swelling of face, lips or tongue, and fainting.
- Teach to avoid potassium salt substitutes unless advised and to report vomiting or diarrhoea.
Pharmacokinetics
- Absorption
- Oral and poorly absorbed (very low bioavailability); high-fat meals reduce absorption, so it is taken the same way each day relative to meals.
- Metabolism
- Little metabolism; CYP3A4 is the main enzyme; P-glycoprotein limits absorption.
- Elimination
- About a quarter of the absorbed dose appears unchanged in urine; biliary excretion through P-glycoprotein also contributes.
- Half-life
- Accumulation half-life about 24 hours (label).
- Onset and duration
- Most of the effect of a dose is reached in about two weeks.
Test yourself
Think of the answer, then tap the question to see it.
Why is aliskiren contraindicated together with an ACE inhibitor in a patient with diabetes?
Dual RAAS blockade raises the risk of kidney injury, hyperkalaemia and hypotension without extra benefit.
How do ACE inhibitors and aliskiren differ in their effect on plasma renin activity?
ACE inhibitors raise plasma renin activity; aliskiren lowers it because renin itself is blocked.
What is the most common adverse effect of aliskiren?
Diarrhoea.
Which two drugs strongly raise aliskiren levels and are avoided with it?
Ciclosporin and itraconazole.
Connections
← Back to the class: Direct renin inhibitors
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Aliskiren: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2023); DailyMed - ALISKIREN tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); Crystal Structure of Renin with Inhibitor 10 (Aliskiren) (RCSB Protein Data Bank, 2007); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.