Aliskiren fumarate

Oral
Essential hypertension

Mild to moderate: No dosage adjustment needed. Severe: Contraindicated.

No dosage adjustment needed.

May be taken with or without food. Take consistently w/ or w/o meals. Avoid taking w/ high fat meals.

History of angioedema; severe renal impairment. Concomitant use w/ ACE inhibitors or angiotensin II receptor antagonists in patients w/ DM and renal impairment (GFR <60 mL/min). Concomitant use w/ ciclosporin, itraconazole and quinidine. Pregnancy.

Serious CHF, sodium or volume depletion. Discontinue if diarrhoea is severe and persistent. Lactation.

Diarrhoea, dyspepsia, GERD, abdominal pain, hypotension, headache, fatigue, dizziness, back pain, cough, rashes, hyperuricaemia, gout, renal calculi, hyperkalaemia, decreases in Hb levels (dose-related), angioedema and seizures.
Potentially Fatal: Anaphylactic reactions.

PO: D

Periodically monitor serum potassium concentration and renal function.

Symptoms: Hypotension. Management: Supportive treatment.

Increased risk of hypotension w/ other antihypertensives. Increased risk of acute renal failure w/ ACE inhibitors, angiotensin II receptor antagonists or NSAIDs. Antihypertensive effect may be reduced w/ NSAIDs. Increased serum levels w/ atorvastatin, itraconazole, ketoconazole, verapamil. Significant decrease in furosemide concentrations w/ aliskiren. Increased risk of hyperkalaemia w/ potassium-sparing diuretics, potassium supplements or any substances that may increase serum potassium levels.
Potentially Fatal: Increased risk of renal impairment, hypotension and hyperkalaemia w/ ACE inhibitors or angiotensin II receptor antagonists. Markedly increased plasma concentration w/ ciclosporin, itraconazole and quinidine.

Avoid concomitant use w/ grapefruit juice. May decrease bioavailability w/ St John's wort.

Description:
Mechanism of Action: Aliskiren is an orally active, potent, non-peptide and selective direct renin inhibitor used in the management of HTN. By inhibiting the enzyme renin, it prevents conversion of angiotensinogen into angiotensin I and therefore inhibits subsequent production of angiotensin II and aldosterone. Unlike ACE inhibitors and angiotensin II receptor antagonists which cause a compensatory rise in plasma renin activity, treatment w/ aliskiren decreases plasma renin activity and concentrations of angiotensin I, angiotensin II and aldosterone.
Pharmacokinetics:
Absorption: Poorly absorbed from GI tract. Absorption is reduced when taken w/ high fat diet. Bioavailability: Approx 2.5%. Time to peak plasma concentration: 1-3 hr.
Distribution: Distributes extensively into extravascular space. Plasma protein binding: Approx 50%.
Metabolism: Minimal metabolism via CYP3A4 isoenzyme.
Excretion: Mainly in the faeces (via the bile) and urine (approx 25% of absorbed dose) as unchanged drug. Elimination half-life: Approx 24-40 hr.

Store between 15-30°C.

ACE Inhibitors/Direct Renin Inhibitors