What is the effect of Aldoril (Methyldopa and Hydrochlorothiazide)?

From the Guidelines

Aldoril, a combination of methyldopa and hydrochlorothiazide, is not typically recommended as a first-line treatment for hypertension due to its side effect profile and the availability of newer agents with better tolerability. Aldoril works through two mechanisms: methyldopa converts to alpha-methylnorepinephrine in the body, stimulating central alpha-2 receptors to reduce sympathetic outflow, while hydrochlorothiazide is a thiazide diuretic that increases sodium and water excretion 1.

Key Points to Consider

• Typical dosing starts at Aldoril 250 (250mg methyldopa/25mg hydrochlorothiazide) once or twice daily, potentially increasing to Aldoril 500 if needed.
• Common side effects include drowsiness, dry mouth, dizziness, increased urination, and electrolyte disturbances.
• Patients should monitor for signs of liver dysfunction (yellowing skin/eyes, dark urine), take it consistently with or without food, and have regular blood pressure checks and blood tests to monitor electrolytes and liver function.
• The use of thiazide diuretics like hydrochlorothiazide in Aldoril may increase insulin resistance, dyslipidemia, and hyperuricemia, and accelerate conversion to overt diabetes, particularly in patients with metabolic syndrome 1.
• However, data from ALLHAT suggest that chlorthalidone, a thiazide-like diuretic, was associated with only a small increase in fasting glucose levels and did not translate into increased cardiovascular disease risk at a later date 1.
• In specific situations, such as pregnancy-related hypertension, methyldopa has established safety and may be considered as a treatment option.

Clinical Considerations

• The choice of antihypertensive medication should be individualized based on the patient's clinical profile, including the presence of comorbidities such as metabolic syndrome.
• Lifestyle modification, including dietary changes, weight reduction, and exercise, is essential for managing hypertension and metabolic syndrome.
• Regular monitoring of blood pressure, electrolytes, and liver function is crucial for patients taking Aldoril.
• Alternative antihypertensive agents with more favorable side effect profiles may be preferred in certain patient populations.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Aldoril Overview

• Aldoril is a combination medication used to treat high blood pressure
• It typically consists of a thiazide diuretic (such as hydrochlorothiazide) and an ACE inhibitor or other antihypertensive agent

Combination Therapy in Hypertension

• More than 70% of adults treated for primary hypertension will eventually require at least two antihypertensive agents, either initially as combination therapy or as add-on therapy if monotherapy and lifestyle modifications do not achieve adequate blood pressure control 2
• Four main classes of medications are used in combination therapy for the treatment of hypertension: thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) 2
• ACEIs and ARBs should not be used simultaneously 2

Efficacy of Different Antihypertensive Combinations

• Different combinations of antihypertensive therapy, including lisinopril, losartan, or valsartan alone or in combination with hydrochlorothiazide, are equally effective and well tolerated for the reduction of both systolic and diastolic blood pressure and improve arterial stiffness in patients with essential hypertension 3
• The mean reductions in systolic blood pressure were from -11.7 to -23.2 mmHg and diastolic blood pressure reductions varied from -5.5 to -13.4 mmHg 3

Rationale for Combination Therapy

• The goal of antihypertensive therapy is to abolish the risks associated with blood pressure elevation without adversely affecting quality of life 4
• Available data suggest that at least 75% of patients will require combination therapy to achieve contemporary blood pressure targets 4
• Combination therapy with an angiotensin II receptor blocker, a calcium channel blocker, and a thiazide diuretic is a rational approach to improve blood pressure control 5

Ultra-low-dose Quadruple Combination Therapy

• A single-pill combination of 4 blood pressure-lowering agents each at a quarter dose may provide a simple, safe, and effective blood pressure-lowering solution which may also improve long-term adherence 6
• The Quadruple UltrA-low-dose tReaTment for hypErTension (QUARTET) double-blind, active-controlled, randomized clinical trial will examine whether ultra-low-dose quadruple combination therapy is more effective than guideline-recommended standard care in lowering blood pressure 6