What it's for (Indications)
- Aliskiren, marketed under brand names such as Rasilez, was historically indicated for the treatment of essential hypertension.
- Its approval encompassed use as monotherapy to lower elevated blood pressure, as well as in combination with other antihypertensive agents.
- These combination therapies often included thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or calcium channel blockers.
- The therapeutic objective was to achieve blood pressure control, which is crucial for reducing the long-term risks of cardiovascular events such as stroke, myocardial infarction, heart failure, and progression of renal disease.
- However, it is critically important to note the significant re-evaluation and subsequent changes in aliskiren's clinical utility and regulatory status.
- Following the publication of key clinical trial data, notably the ALTITUDE study, serious safety concerns emerged.
- This study demonstrated an increased risk of non-fatal stroke, renal complications (including acute renal failure), hyperkalemia, and hypotension when aliskiren was co-administered with ACE inhibitors or ARBs in patients with type 2 diabetes and established renal disease or cardiovascular disease.
- As a direct consequence of these safety concerns, aliskiren's marketing authorization has been withdrawn or significantly restricted in many countries globally.
- Therefore, while its historical indication was essential hypertension, its current clinical use is severely limited, and its prescription, particularly in combination with ACE inhibitors or ARBs, is largely contraindicated due to these serious adverse events.
- Clinicians must consult the most up-to-date regional prescribing information and guidelines regarding its limited and specific applications, if any remain.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | For adults and pediatric patients weighing 50 kg or greater who are at least 6 years of age, the recommended starting dose is 150 mg once daily. If blood pressure remains uncontrolled, the dose may be increased to 300 mg once daily. Doses above 300 mg did not show increased efficacy but led to an increased rate of diarrhea. The antihypertensive effect is largely achieved (85% to 90%) within 2 weeks. Patients should establish a routine pattern for taking aliskiren with regard to meals, as high-fat meals can substantially decrease absorption. |
Safety & Warnings
Common Side Effects
- Common adverse reactions include diarrhea (incidence 2.
- 3%), rash, hypokalemia (low blood potassium levels), and rarely anemia.
- Serious adverse reactions observed in clinical trials include anaphylactic reactions, head and neck angioedema, and hypotension.
- Patients should consult their doctor immediately if symptoms persist or worsen.
Serious Warnings
- Black Box Warning: WARNING: FETAL TOXICITY. When pregnancy is detected, discontinue aliskiren tablets as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
- This medicine should be used with extreme caution in patients taking diuretics, those on a low sodium diet, or individuals prone to dehydration.
- Driving should be avoided as this medicine may affect ability to drive.
- Anaphylactic reactions, head and neck angioedema, and hypotension have been reported and require careful monitoring.
How it Works (Mechanism of Action)
Renin is secreted by the kidney in response to decreases in blood volume and renal perfusion. Renin cleaves angiotensinogen to form the inactive decapeptide angiotensin I (Ang I). Ang I is converted to the active octapeptide angiotensin II (Ang II) by ACE and non-ACE pathways. Ang II is a powerful vasoconstrictor and leads to the release of catecholamines from the adrenal medulla and prejunctional nerve endings. It also promotes aldosterone secretion and sodium reabsorption. Together, these effects increase blood pressure. Ang II also inhibits renin release, thus providing a negative feedback to the system. This cycle, from renin through angiotensin to aldosterone and its associated negative feedback loop, is known as the renin-angiotensin-aldosterone system (RAAS). Aliskiren is a direct renin inhibitor, decreasing plasma renin activity (PRA) and inhibiting the conversion of angiotensinogen to Ang I.
Commercial Brands (Alternatives)
No other brands found for this formula.