ALDORIL 25
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALDORIL 25 (ALDORIL 25).
| Breastfeeding | Methyldopa is excreted in breast milk with M/P ratio of approximately 0.2-0.5; hydrochlorothiazide M/P ratio ~0.5-0.6. Considered compatible with breastfeeding by AAP, but monitor infant for hypotension and electrolyte disturbances. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to methyldopa, hydrochlorothiazide, or sulfonamides; active hepatic disease; anuria; history of methyldopa-induced liver disorders.
| 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. |
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| 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. |
| 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. |