Usage
- Aliskiren is prescribed for the treatment of hypertension (high blood pressure) in adults and children 6 years of age and older weighing 50 kg or more.
- Pharmacological classification: Direct Renin Inhibitor.
- Mechanism of Action: Aliskiren directly inhibits renin, an enzyme that plays a crucial role in the renin-angiotensin-aldosterone system (RAAS). By inhibiting renin, aliskiren reduces the production of angiotensin I, which subsequently leads to lower levels of angiotensin II and aldosterone. This results in vasodilation (widening of blood vessels) and decreased sodium and water retention, ultimately lowering blood pressure.
Alternate Names
- International Nonproprietary Name (INN): Aliskiren
- Brand names: Tekturna, Rasilez.
How It Works
- Pharmacodynamics: Aliskiren lowers blood pressure by inhibiting renin, the rate-limiting step in the RAAS pathway. This leads to a decrease in the production of angiotensin I, angiotensin II, and aldosterone. The reduction in angiotensin II causes vasodilation and decreased peripheral vascular resistance. Reduced aldosterone levels lead to decreased sodium and water retention by the kidneys.
- Pharmacokinetics:
- Absorption: Aliskiren is absorbed orally, but the extent of absorption is reduced by high-fat meals.
- Metabolism: Aliskiren undergoes minimal metabolism, primarily by CYP3A4.
- Elimination: Aliskiren is primarily excreted unchanged in the feces and to a lesser extent in urine.
- Mode of Action: Aliskiren binds directly to the active site of renin, preventing it from cleaving angiotensinogen to angiotensin I.
- Receptor binding, enzyme inhibition, or neurotransmitter modulation: Aliskiren acts as a competitive inhibitor of renin.
- Elimination pathways: Primarily fecal excretion and some renal excretion.
Dosage
Standard Dosage
Adults:
- Initial dose: 150 mg orally once daily.
- Maintenance dose: The dosage may be increased to 300 mg daily if blood pressure is not adequately controlled. The maximum recommended dose is 300 mg daily.
Children (6-17 years):
- <20 kg: Not recommended.
- 20 to <50 kg: 75 mg orally once daily, may be increased to 150 mg daily. (Not FDA-approved in the United States due to lack of an appropriate dosage form).
- ≥50 kg: 150 mg orally once daily, may be increased to 300 mg daily.
Special Cases:
- Elderly Patients: Lower initial doses may be considered.
- Patients with Renal Impairment (CrCl <30 mL/min): Use with caution due to increased risk of hyperkalemia and renal dysfunction.
- Patients with Hepatic Dysfunction: No dosage adjustment is required.
- Patients with Comorbid Conditions (Diabetes): Aliskiren is contraindicated in patients with diabetes who are also taking ACE inhibitors or ARBs. Use with caution in other patients with diabetes.
Clinical Use Cases
Aliskiren is specifically indicated for hypertension and doesn’t have a role in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments may be necessary in patients with renal impairment.
Side Effects
Common Side Effects:
- Diarrhea
- Cough
- Rash
- Dizziness
- Headache
- Back pain
Rare but Serious Side Effects:
- Angioedema (swelling of the face, lips, tongue, or throat)
- Hypotension (low blood pressure)
- Hyperkalemia (high potassium levels)
- Renal impairment (worsening kidney function)
Long-Term Effects:
Potential long-term effects of aliskiren are still being studied.
Adverse Drug Reactions (ADR):
Angioedema and anaphylaxis require immediate medical attention.
Contraindications
- Hypersensitivity to aliskiren.
- Concomitant use with ACE inhibitors or ARBs in patients with diabetes.
- Pregnancy (second and third trimesters).
- Breastfeeding.
- Children younger than 2 years of age.
Drug Interactions
- CYP450 interactions: Aliskiren is primarily metabolized by CYP3A4. Avoid concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole).
- Other drug interactions:
- ACE inhibitors and ARBs (contraindicated with diabetes, use with caution otherwise)
- Cyclosporine (avoid concomitant use).
- NSAIDs (may increase risk of renal impairment).
- Furosemide (aliskiren may reduce furosemide exposure).
- Potassium supplements (may increase risk of hyperkalemia).
- Food and lifestyle factors: High-fat meals decrease aliskiren absorption.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated during the second and third trimesters. Avoid in the first trimester.
- Fetal risks: May cause fetal harm, including renal failure, oligohydramnios, fetal lung hypoplasia, skeletal deformations, hypotension, and death.
- Breastfeeding: Breastfeeding is not recommended while taking aliskiren due to potential for serious adverse reactions in infants.
Drug Profile Summary
- Mechanism of Action: Direct renin inhibitor, reduces the production of angiotensin I, angiotensin II, and aldosterone.
- Side Effects: Diarrhea, cough, rash, dizziness, angioedema, hypotension, hyperkalemia.
- Contraindications: Hypersensitivity, concomitant use with ACEi/ARB in diabetes, pregnancy, breastfeeding, children <2 years.
- Drug Interactions: ACE inhibitors, ARBs, cyclosporine, NSAIDs, furosemide, potassium supplements.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: 150-300 mg once daily. Children (≥6 years, ≥50kg): 150-300 mg once daily.
- Monitoring Parameters: Blood pressure, renal function (serum creatinine, potassium), signs of angioedema.
Popular Combinations
Aliskiren can be combined with other antihypertensives such as hydrochlorothiazide or amlodipine, but combining with ACE inhibitors or ARBs is generally avoided or contraindicated. The combination of aliskiren and valsartan (Valturna) is no longer marketed.
Precautions
- General Precautions: Monitor renal function and potassium levels, especially in patients with pre-existing renal impairment.
- Specific Populations: See above sections on dosage and pregnancy/breastfeeding.
- Lifestyle Considerations: High-fat meals reduce absorption.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Aliskiren?
A: Adults: 150 mg once daily, may be increased to 300 mg daily. Children (6-17 years, ≥50kg): 150 mg once daily, may be increased to 300 mg daily. Children <20 kg and < 6 years old: Not recommended.
Q2: How does Aliskiren differ from ACE inhibitors and ARBs?
A: Aliskiren directly inhibits renin, the first step in the RAAS pathway, while ACE inhibitors block the conversion of angiotensin I to angiotensin II, and ARBs block the action of angiotensin II at its receptor.
Q3: Can Aliskiren be used in patients with renal impairment?
A: Use with caution in patients with renal impairment (CrCl <30 mL/min) and monitor closely for hyperkalemia and worsening renal function.
Q4: What are the most serious side effects of Aliskiren?
A: Angioedema (swelling of face, lips, tongue or throat), hypotension, hyperkalemia, and renal impairment.
Q5: Can Aliskiren be used during pregnancy or breastfeeding?
A: No. Aliskiren is contraindicated during pregnancy (second and third trimesters) and breastfeeding.
Q6: What are the common drug interactions with Aliskiren?
A: ACE inhibitors, ARBs, cyclosporine, NSAIDs, furosemide, and potassium supplements can interact with Aliskiren.
Q7: Does food affect Aliskiren absorption?
A: Yes. High-fat meals reduce the absorption of Aliskiren.
Q8: How long does it take for Aliskiren to take effect?
A: The blood pressure-lowering effect of aliskiren is substantially attained within 2 weeks.
Q9: Can Aliskiren be used with other antihypertensive medications?
A: Aliskiren can be used with other antihypertensives such as hydrochlorothiazide and amlodipine. However, concomitant use with ACE inhibitors or ARBs is either avoided, contraindicated, or warrants caution, especially in patients with diabetes or renal impairment.
