Direct renin inhibitor Pregnancy: Contraindicated — fetal renal failure, oligohydramnios, hypotension, skull hypoplasia, death. Discontinue immediately if pregnancy detected.

Aliskiren

Brand names: Rasilez, Tekturna

Adult dose

Dose: 150 mg OD; increase to 300 mg OD after 2–4 weeks if BP not controlled

Route: Oral

Frequency: Once daily

Max: 300 mg/day

Take consistently with or without food (high-fat meals reduce absorption ~70% — keep timing consistent).

Dose adjustments

Renal

Avoid in eGFR <60 if combined with ACEi/ARB (ALTITUDE — increased AKI/hyperkalaemia/stroke). Caution in any renal impairment.

Clinical pearls

NOT first-line — modest BP-lowering effect comparable to ARB but limited mortality data.
ALTITUDE trial (NEJM 2012) stopped early for harm when combined with ACEi/ARB in diabetic CKD — increased AKI, hyperkalaemia, hypotension, non-fatal stroke.
Reserve for ACEi/ARB intolerance (cough, angioedema with ACEi); avoid combination therapy.
Diarrhoea is dose-related and often persistent — counsel before starting and review at 2–4 weeks.
Effect on RAAS biomarkers (plasma renin activity) lasts up to 2 weeks after discontinuation.

Contraindications

Pregnancy (all trimesters — fetal toxicity)
History of angioedema with aliskiren
Combination with ACEi or ARB in patients with diabetes or eGFR <60 (ALTITUDE trial — harm)
Concomitant ciclosporin, itraconazole, quinidine (P-gp inhibitors — markedly increased exposure)
Severe hepatic impairment

Side effects

Hyperkalaemia (especially with ACEi/ARB/spironolactone)
Hypotension, dizziness
Diarrhoea (dose-related, often persists — common cause of discontinuation)
Angioedema (rare — class effect of RAAS modulators)
Acute kidney injury
Cough (less than ACEi)
Rash, urticaria

Interactions

ACEi / ARB in DM or CKD: contraindicated (ALTITUDE — AKI, hyperkalaemia, stroke)
K-sparing diuretics, K supplements: additive hyperkalaemia
NSAIDs: ↓ antihypertensive effect, ↑ AKI risk
Ciclosporin, itraconazole: dramatically ↑ aliskiren levels — contraindicated
Lithium: ↑ levels, toxicity risk
Furosemide: ↓ furosemide AUC by ~50% — may lose diuretic effect

Monitoring

U&Es 1–2 weeks after start, after each dose increase, then 6-monthly
BP at 2 and 4 weeks after start

Reference: BNF 90; ALTITUDE NEJM 2012;367:2204-13; MHRA Drug Safety Update Feb 2012; NICE NG136; ESC Hypertension Guidelines 2018. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways