ALDORIL D50
Clinical safety rating
cautionComprehensive clinical and safety monograph for ALDORIL D50 (ALDORIL D50).
Aldoril D50 is a combination of methyldopa and hydrochlorothiazide. Methyldopa is a centrally-acting alpha-2 adrenergic agonist that reduces sympathetic outflow from the brainstem, decreasing peripheral vascular resistance and blood pressure. Hydrochlorothiazide is a thiazide diuretic that inhibits sodium reabsorption in the distal convoluted tubule, reducing plasma volume and further lowering blood pressure.
| Metabolism | Methyldopa is extensively metabolized in the liver via conjugation and O-methylation, with involvement of catechol-O-methyltransferase (COMT). Hydrochlorothiazide is not extensively metabolized; it is eliminated largely unchanged by the kidneys. |
| Excretion | Renal: 50% as unchanged drug and 20% as metabolites; biliary/fecal: ~25% (as metabolites); total renal clearance accounts for ~70% of elimination. |
| Half-life | 3–6 hours (terminal elimination half-life); clinical context: requires twice-daily dosing for sustained blood pressure control; prolonged in renal impairment. |
| Protein binding | ~20% bound to albumin; minimal binding to other plasma proteins. |
| Volume of Distribution | 0.2–0.3 L/kg (moderately low Vd, indicating limited extravascular distribution and predominantly plasma water distribution). |
| Bioavailability | Oral: 30–40% (due to extensive first-pass metabolism); IV: 100%. |
| Onset of Action | Oral: 2–3 hours; IV: 1–2 hours (peak effect). |
| Duration of Action | Oral: 12–24 hours (antihypertensive effect persists for 12–24 hours with single dose, but twice-daily dosing is needed for consistent 24-hour control); IV: 4–6 hours. |
| Molecular Weight | Methyldopa: 211.22 Da; Hydrochlorothiazide: 297.74 Da |
1 tablet (hydrochlorothiazide 25 mg + methyldopa 250 mg) orally twice daily; maximum dose: 2 tablets (50 mg + 500 mg) twice daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR < 30 mL/min; for GFR 30-50 mL/min: reduce dose and monitor electrolytes. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50% and monitor; Class C: contraindicated. |
| Pediatric use | Not recommended; inadequate safety data. |
| Geriatric use | Start with 1 tablet (hydrochlorothiazide 12.5 mg + methyldopa 125 mg) once daily; increase slowly; monitor for hypotension and electrolyte imbalance. |
| 1st trimester | Methyldopa/hydrochlorothiazide combination use in the first trimester is not recommended due to possible teratogenic effects (neural tube defects, cardiovascular malformations) associated with hydrochlorothiazide and limited safety data for methyldopa. Use only if potential benefit outweighs risk. |
| 2nd trimester | Use in the second trimester may be associated with fetal hypotension, electrolyte imbalances, and decreased placental perfusion due to hydrochlorothiazide. Methyldopa is generally considered first-line for chronic hypertension in pregnancy, but the combination should be avoided due to thiazide risks. |
| 3rd trimester | Use in the third trimester can cause neonatal electrolyte disturbances, thrombocytopenia, and jaundice due to hydrochlorothiazide. Methyldopa remains acceptable, but combination therapy should be avoided. Consider alternative agents. |
Clinical note
Comprehensive clinical and safety monograph for ALDORIL D50 (ALDORIL D50).
| Placental transfer | Methyldopa crosses the placenta readily with fetal plasma levels similar to maternal. Hydrochlorothiazide also crosses the placenta and can cause adverse fetal/neonatal effects. Evidence indicates significant placental transfer for both components. |
| Breastfeeding | Methyldopa is excreted into breast milk in small amounts, and effects on the infant are unknown; monitoring for hypotension and sedation is advised. Hydrochlorothiazide is excreted into breast milk and may suppress lactation. Avoid use in breastfeeding women, especially when milk supply is critical. Use alternative antihypertensive agents if necessary. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | Hydrochlorothiazide (HCTZ) is Pregnancy Category B in first trimester and Category D in second/third trimesters. Methyldopa (M) is Category B. HCTZ use in second/third trimester may cause fetal/neonatal effects including electrolyte disturbances, jaundice, thrombocytopenia, and possible fetal growth restriction. Methyldopa has not shown teratogenicity. Aldoril D50 (M 500mg/HCTZ 50mg) is not recommended during pregnancy, especially after first trimester. |
| Fetal Monitoring | Monitor maternal blood pressure, electrolytes, renal function, and fetal growth (ultrasound). Check infant for electrolyte disturbances, jaundice, and thrombocytopenia if HCTZ used near term. |
| Fertility Effects | Hydrochlorothiazide may cause transient erectile dysfunction in males; no significant impact on female fertility. Methyldopa may cause gynecomastia or menstrual irregularities; overall effects on fertility are minimal. |
■ FDA Black Box Warning
None
| Serious Effects |
Anuria (due to hydrochlorothiazide)Renal impairment (creatinine clearance <30 mL/min or oliguria)Sulfonamide allergy (hydrochlorothiazide is a sulfonamide derivative)Active hepatic disease or cirrhosis (methyldopa hepatotoxicity)Concomitant MAO inhibitor therapy (methyldopa interaction)
| Precautions | Sedation and drowsiness common; avoid driving or hazardous activities. Risk of Coombs-positive hemolytic anemia with methyldopa (discontinue if anemia develops). Hepatotoxicity and liver function abnormalities (discontinue if jaundice occurs). Orthostatic hypotension; caution in volume-depleted patients. Electrolyte imbalances (particularly hypokalemia, hyponatremia) with hydrochlorothiazide; monitor serum electrolytes. Sulfonamide cross-sensitivity possible. Exacerbation of systemic lupus erythematosus. Avoid abrupt withdrawal of methyldopa (may cause rebound hypertension). |
| Food/Dietary | Avoid potassium supplements or salt substitutes containing potassium without consulting doctor. Limit alcohol intake. Avoid excessive grapefruit juice. Maintain adequate potassium intake through diet to prevent hypokalemia. |
| Clinical Pearls | ALDORIL D50 combines methyldopa and hydrochlorothiazide. Monitor for orthostatic hypotension, especially in volume-depleted patients. May cause positive Coombs test, hemolytic anemia, and lupus-like syndrome. Avoid in pheochromocytoma. Use caution in hepatic disease. |
| Patient Advice | Take exactly as prescribed; do not skip doses or double up. · May cause dizziness or drowsiness; avoid driving until you know how it affects you. · Report unexplained fever, jaundice, or dark urine immediately. · Avoid sudden discontinuation; may cause rapid increase in blood pressure. · Stay hydrated but do not overhydrate; monitor for signs of electrolyte imbalance. |
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