ALDORIL D50
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALDORIL D50 (ALDORIL D50).
| Breastfeeding | Both methyldopa and HCTZ are excreted in breast milk. Methyldopa M/P ratio approximately 1.0; HCTZ M/P ratio variable, small amounts. Use during breastfeeding may suppress lactation due to HCTZ diuretic effect. Monitor infant for signs of hypotension, electrolyte imbalance. Caution recommended; use only if clearly needed. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Active hepatic disease (cirrhosis, hepatitis) associated with methyldopa therapy; previous methyldopa-induced liver disorders. Anuria or hypersensitivity to thiazide diuretics or sulfonamide-derived drugs. Concomitant use with MAO inhibitors. Severe renal impairment (creatinine clearance <30 mL/min) or electrolyte depletion due to hydrochlorothiazide. Concurrent lithium therapy (risk of lithium toxicity).
| 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. |
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| 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. |
| 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. |