Usage
- Medical Conditions: Aliskiren + Hydrochlorothiazide is prescribed for the treatment of hypertension (high blood pressure) in adults. It is used when treatment with either medication alone does not adequately control blood pressure.
- Pharmacological Classification: Antihypertensive, Renin-Angiotensin System Antagonist, Diuretic. It combines a direct renin inhibitor (aliskiren) with a thiazide diuretic (hydrochlorothiazide).
- Mechanism of Action: Aliskiren inhibits renin, an enzyme that plays a key role in the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure. By inhibiting renin, aliskiren reduces the production of angiotensin II, a potent vasoconstrictor. Hydrochlorothiazide increases the excretion of sodium and water by the kidneys, thereby reducing blood volume and lowering blood pressure. The combination of these two mechanisms provides a synergistic effect in lowering blood pressure.
Alternate Names
- International/Regional Variations: No widely recognized international variations exist for this combination drug itself, though individual components have regional variations.
- Brand Names: Tekturna HCT
How It Works
- Pharmacodynamics: Aliskiren + Hydrochlorothiazide lowers blood pressure by a dual mechanism: inhibiting the RAAS and increasing diuresis. Aliskiren binds directly to renin, preventing the conversion of angiotensinogen to angiotensin I. This subsequently reduces angiotensin II levels, leading to vasodilation, decreased aldosterone secretion, and reduced sodium and water retention. Hydrochlorothiazide inhibits sodium reabsorption in the distal convoluted tubule of the nephron, leading to increased excretion of sodium, chloride, and water.
- Pharmacokinetics: Aliskiren is moderately absorbed orally, and high-fat meals can significantly reduce its absorption. It is not extensively metabolized and is primarily excreted unchanged in the bile and feces. Hydrochlorothiazide is well-absorbed orally and is not metabolized. It is excreted primarily unchanged by the kidneys.
- Mode of Action/Receptor Binding: Aliskiren acts by direct competitive binding to renin. Hydrochlorothiazide inhibits the sodium-chloride cotransporter in the distal tubule of the kidney.
- Elimination Pathways: Aliskiren is primarily eliminated through biliary/fecal excretion, while hydrochlorothiazide is primarily eliminated through renal excretion.
Dosage
Standard Dosage
Adults:
- Initial dose: 150 mg aliskiren/12.5 mg hydrochlorothiazide once daily.
- Maximum dose: 300 mg aliskiren/25 mg hydrochlorothiazide once daily. Dosage titration may be done at intervals of 2 weeks as needed to control blood pressure.
Children:
- The safety and efficacy in children under 18 years have not been established. Use is not recommended.
Special Cases:
- Elderly Patients: No specific dosage adjustments are typically required, but caution is advised due to potential age-related decline in renal function. Close monitoring is recommended.
- Patients with Renal Impairment: Not recommended for patients with creatinine clearance (CrCl) less than 30 mL/min. No adjustment necessary for patients with CrCl greater than 30 mL/min.
- Patients with Hepatic Dysfunction: No dosage adjustment is recommended.
- Patients with Comorbid Conditions: Close monitoring is necessary for patients with diabetes, cardiovascular disease, or other conditions that may affect blood pressure or renal function.
Clinical Use Cases
Aliskiren + Hydrochlorothiazide is specifically indicated for hypertension and does not have specific dosage recommendations for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Other medications may be more suitable for managing blood pressure in these settings.
Dosage Adjustments
- Dose adjustments may be needed based on individual patient response and tolerability. Dosage titration should be performed gradually.
- Renal impairment significantly limits the use of this combination.
Side Effects
Common Side Effects
- Dizziness, lightheadedness
- Diarrhea
- Cough
- Fatigue
Rare but Serious Side Effects
- Angioedema (swelling of the face, lips, throat, or tongue)
- Hypotension (low blood pressure)
- Renal impairment (worsening kidney function)
- Hyperkalemia (elevated potassium levels)
- Fetal toxicity (if used during pregnancy)
Long-Term Effects
- Potential long-term effects are primarily related to the underlying condition (hypertension) and not directly attributable to the medication itself when used appropriately.
Adverse Drug Reactions (ADR)
- Angioedema, severe hypotension, acute renal failure, hyperkalemia require immediate medical attention.
Contraindications
- Pregnancy (due to risk of fetal harm)
- Hypersensitivity to aliskiren, hydrochlorothiazide, or sulfonamides
- Anuria (lack of urine production)
- Concurrent use with other direct renin inhibitors or ACE inhibitors/ARBs in patients with diabetes
Drug Interactions
- Other antihypertensive medications (additive effect)
- Potassium-sparing diuretics (increased risk of hyperkalemia)
- Lithium (increased lithium levels)
- Nonsteroidal anti-inflammatory drugs (NSAIDs) (may reduce antihypertensive effect)
- CYP3A4 inhibitors (may increase aliskiren levels)
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (Contraindicated due to potential for fetal harm)
- Fetal Risks: Aliskiren can cause fetal injury and death, particularly during the second and third trimesters.
- Breastfeeding: Hydrochlorothiazide is excreted in breast milk. Aliskiren’s presence in breast milk is unknown. The combination is not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Dual action: renin inhibition (aliskiren) and diuresis (hydrochlorothiazide).
- Side Effects: Dizziness, diarrhea, cough, fatigue; rarely angioedema, hypotension, renal impairment.
- Contraindications: Pregnancy, hypersensitivity, anuria, concurrent use with other RAAS inhibitors in diabetics.
- Drug Interactions: Other antihypertensives, potassium-sparing diuretics, lithium, NSAIDs.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy, not recommended when breastfeeding.
- Dosage: Adults: 150/12.5 mg once daily, up to 300/25 mg once daily. Children: Not recommended.
- Monitoring Parameters: Blood pressure, renal function (serum creatinine, electrolytes), potassium levels.
Popular Combinations
This medication is itself a combination. While it can be used with other antihypertensives if necessary, close monitoring for hypotension is required. Combining this drug with an ACE inhibitor or ARB in patients with diabetes is contraindicated.
Precautions
- General Precautions: Monitor renal function, electrolyte levels (particularly potassium), and blood pressure regularly. Assess for hypersensitivity reactions.
- Specific Populations: See Dosage section for specifics.
- Lifestyle Considerations: Advise patients to avoid excessive alcohol intake and maintain a healthy diet.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Aliskiren + Hydrochlorothiazide?
A: Initial dose for adults is 150 mg aliskiren/12.5 mg hydrochlorothiazide once daily, which can be increased to a maximum of 300 mg/25 mg once daily. Not recommended for children.
Q2: What are the common side effects?
A: Common side effects include dizziness, lightheadedness, diarrhea, cough, and fatigue.
Q3: Can this drug be used during pregnancy?
A: No, Aliskiren + Hydrochlorothiazide is contraindicated during pregnancy due to the risk of fetal harm.
Q4: What should I monitor in patients taking this medication?
A: Closely monitor blood pressure, renal function (serum creatinine, electrolytes, particularly potassium), and be vigilant for signs of angioedema.
Q5: What are the key drug interactions?
A: Important drug interactions include other antihypertensives (additive effects), potassium-sparing diuretics (hyperkalemia risk), lithium (increased lithium levels), and NSAIDs (reduced antihypertensive effect).
Q6: How is this combination different from using aliskiren or hydrochlorothiazide alone?
A: The combination provides a synergistic effect in lowering blood pressure by targeting two different mechanisms: renin inhibition and diuresis. It is used when monotherapy with either agent is insufficient.
Q7: Can this combination be used in patients with renal impairment?
A: It is not recommended in patients with creatinine clearance less than 30 mL/min. No dosage adjustments are needed for patients with CrCl greater than 30 mL/min.
Q8: What are the contraindications for this medication?
A: Contraindications include pregnancy, hypersensitivity, anuria, and concurrent use with direct renin inhibitors or ACE inhibitors/ARBs in diabetic patients.
Q9: What are the signs of angioedema, and what should be done if it occurs?
A: Angioedema presents as swelling of the face, lips, tongue, or throat, and can cause difficulty breathing. If angioedema occurs, immediately discontinue the medication and provide emergency medical care.
