ALDORIL 25
Clinical safety rating
cautionComprehensive clinical and safety monograph for ALDORIL 25 (ALDORIL 25).
Combination of methyldopa, a centrally acting alpha-2 adrenergic agonist that reduces sympathetic outflow, and hydrochlorothiazide, a thiazide diuretic that inhibits sodium reabsorption in the distal convoluted tubule, reducing plasma volume.
| Metabolism | Methyldopa is metabolized primarily via hepatic conjugation and renal excretion; hydrochlorothiazide is not significantly metabolized and is excreted unchanged in urine. |
| Excretion | Renal: ~85% unchanged. Biliary/fecal: ~15% as metabolites. |
| Half-life | 7-16 hours (terminal). In renal impairment, half-life may exceed 24 hours, requiring dose adjustment. |
| Protein binding | Methyldopa: less than 10% bound to plasma proteins. Hydrochlorothiazide: ~70% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Methyldopa: 0.3-0.6 L/kg (distributes widely, including CNS). Hydrochlorothiazide: 0.8-1.5 L/kg (distributes into extracellular fluid). |
| Bioavailability | Methyldopa: oral bioavailability ~25% (first-pass metabolism). Hydrochlorothiazide: oral bioavailability ~60-80%. |
| Onset of Action | Oral: 2-4 hours for methyldopa component; thiazide component (hydrochlorothiazide) begins diuresis within 2 hours. |
| Duration of Action | Methyldopa: 12-24 hours; hydrochlorothiazide: 6-12 hours. Antihypertensive effect lasts up to 24 hours with once-daily dosing. |
| Molecular Weight | Methyldopa: 211.22 Da; Hydrochlorothiazide: 297.74 Da |
Oral: 1 tablet (hydrochlorothiazide 25 mg/methyldopa 250 mg) twice daily; increase as needed to max 2 tablets twice daily.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: use with caution, reduce dose. GFR <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B or C: contraindicated due to methyldopa hepatotoxicity risk. |
| Pediatric use | Not established; avoid use in children. |
| Geriatric use | Start at lowest dose (1 tablet daily); monitor for orthostatic hypotension, sedation, and electrolyte imbalance. |
| 1st trimester | Use only if clearly needed. Risk of fetotoxicity and neonatal hypotension. Avoid in pregnancy-induced hypertension as it decreases placental perfusion. |
| 2nd trimester | Use only if clearly needed. May cause fetal hypotension, bradycardia, and decreased placental perfusion. |
| 3rd trimester | Use only if clearly needed. Risk of neonatal hypotension, bradycardia, and electrolyte disturbances. |
Clinical note
Comprehensive clinical and safety monograph for ALDORIL 25 (ALDORIL 25).
| Placental transfer | Methyldopa crosses the placenta extensively. Hydrochlorothiazide crosses the placenta and is found in cord blood. Both reach fetal serum levels similar to maternal levels. |
| Breastfeeding | Methyldopa and hydrochlorothiazide are excreted into breast milk in low amounts. Methyldopa may cause sedation and bradycardia in infants. Hydrochlorothiazide may suppress lactation. Monitor infant for signs of hypotension, bradycardia, and electrolyte imbalance. Use cautiously in nursing mothers. |
| Lactation Rating | L3 (Moderately Safe) - use with caution |
| Teratogenic Risk | First trimester: Limited human data, but animal studies show no teratogenicity at therapeutic doses. Second and third trimesters: Associated with fetal hypotension, oligohydramnios, and renal dysfunction due to methyldopa component. Hydrochlorothiazide may cause fetal electrolyte imbalances. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and electrolytes. Perform fetal ultrasound for growth and amniotic fluid volume assessment. Nonstress test and biophysical profile in third trimester. |
| Fertility Effects | No significant adverse effects on fertility reported. Methyldopa may theoretically affect prolactin levels, but clinical relevance is minimal. |
■ FDA Black Box Warning
None
| Serious Effects |
Active hepatic disease (e.g., acute hepatitis, cirrhosis)History of previous methyldopa therapy associated with liver disordersHypersensitivity to methyldopa, hydrochlorothiazide, or sulfonamidesAnuriaConcomitant use with MAO inhibitors
| Precautions | May cause sedation, depression, positive direct Coombs test, hemolytic anemia, hepatotoxicity, fluid/electrolyte imbalance, and sensitivity reactions; monitor liver function, CBC, and electrolytes. |
| Food/Dietary | Avoid high-sodium foods to optimize antihypertensive effect. Limit alcohol intake. Do not consume large amounts of potassium-rich foods (e.g., bananas, oranges, spinach) unless advised by a healthcare provider, as hydrochlorothiazide can alter potassium levels. |
| Clinical Pearls | ALDORIL 25 is a fixed-dose combination of methyldopa (250 mg) and hydrochlorothiazide (25 mg). Monitor for hypotension, especially during initial therapy or with volume depletion. Methyldopa may cause a positive direct Coombs test and hemolytic anemia; discontinue if anemia develops. Hydrochlorothiazide can cause electrolyte imbalances, hyperglycemia, and hyperuricemia. Avoid use in patients with pheochromocytoma or active liver disease. |
| Patient Advice | Take this medication exactly as prescribed, usually once or twice daily. · Rise slowly from sitting or lying to prevent dizziness from low blood pressure. · Avoid alcohol, which can increase dizziness and drowsiness. · Report any signs of infection, unusual tiredness, or yellowing of skin/eyes. · Use sun protection as hydrochlorothiazide may increase sun sensitivity. · Do not use potassium supplements or salt substitutes without consulting your doctor. |
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