Generic Name

Methyldopa with Hydrochlorothiazide

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Classification

FDA Approved Indications

• Management of hypertension

Mechanism of Action

Methyldopa is a centrally acting antihypertensive that is converted to an active metabolite which stimulates alpha-2 adrenergic receptors in the brain, reducing sympathetic outflow. Hydrochlorothiazide is a thiazide diuretic that inhibits sodium reabsorption in the distal tubules of the kidney, leading to increased excretion of sodium and water, thereby lowering blood pressure.

Dosage and Administration

Adult: Dose varies; typical initial dose of methyldopa is 250 mg two to three times daily, titrated up as needed. Hydrochlorothiazide doses start at 12.5-25 mg once daily. Combination doses like Aldoril are adjusted based on patient response.

Pediatric: Use is generally not recommended for children due to limited data.

Geriatric: Start at lower doses due to increased sensitivity and risk of orthostatic hypotension.

Renal Impairment: Adjust dosage; contraindicated in severe renal impairment.

Hepatic Impairment: Use with caution; monitor closely.

Pharmacokinetics

Absorption: Well absorbed orally.

Distribution: Methyldopa crosses the blood-brain barrier; Hydrochlorothiazide distributed widely.

Metabolism: Methyldopa is metabolized in the liver; Hydrochlorothiazide undergoes minimal metabolism.

Excretion: Primarily renal excretion of unchanged drugs.

Half Life: Methyldopa: approximately 2-3 hours; Hydrochlorothiazide: approximately 6-15 hours.

Contraindications

• Hypersensitivity to methyldopa or hydrochlorothiazide.
• Concurrent use of monoamine oxidase inhibitors.

Precautions

• History of hepatic disease, especially with methyldopa.
• Liver function should be monitored during therapy.
• Use in patients with renal impairment requires caution and dose adjustments.
• Pregnancy: Methyldopa is classified as pregnancy category B and is preferred antihypertensive in pregnancy.

Adverse Reactions - Common

• Drowsiness or fatigue (Common)
• Orthostatic hypotension (Common)
• Gastrointestinal disturbances (Common)

Adverse Reactions - Serious

• Hemolytic anemia (Rare)
• Hepatitis or hepatic dysfunction (Rare)
• Blood dyscrasias, including leukopenia, agranulocytosis (Rare)

Drug-Drug Interactions

• MAO inhibitors (risk of hypertensive crisis with methyldopa)
• Other antihypertensives (additive effect)
• Digoxin (monitor levels)

Drug-Food Interactions

• Alcohol (may enhance hypotensive effects)

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Take medication exactly as prescribed.
• Notify healthcare provider if signs of jaundice, sore throat, fever, or unusual bleeding occur.
• Rise slowly from sitting or lying position to prevent orthostatic hypotension.
• Avoid alcohol and sedatives unless approved by healthcare provider.

Special Considerations

Black Box Warnings:

• Potential for hemolytic anemia and hepatic injury with methyldopa.

Genetic Factors: Less relevant for this combination.

Lab Test Interference: May cause false-positive Coombs' test with methyldopa.

Overdose Management

Signs/Symptoms: Hypotension, dizziness, dehydration, electrolyte disturbances.

Treatment: Discontinue medication, treat hypotension with fluid replacement, correct electrolyte imbalances.

Storage and Handling

Storage: Store at room temperature, away from moisture and light.

Stability: Stable under normal conditions.