HYDRO-D
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HYDRO-D (HYDRO-D).
Thiazide diuretic that inhibits the sodium-chloride symporter (NCC) in the distal convoluted tubule, reducing sodium and water reabsorption and increasing potassium excretion.
| Metabolism | Not extensively metabolized; undergoes hepatic metabolism via CYP450 enzymes to a minor extent (primarily hydroxylation). |
| Excretion | Renal: approximately 50% as unchanged drug; biliary/fecal: approximately 50% as metabolites and minor unchanged drug. |
| Half-life | Terminal elimination half-life: 5.6 to 15 hours; prolonged in renal impairment and in patients with heart failure. |
| Protein binding | 99% bound, primarily to albumin. |
| Volume of Distribution | 3.6 to 5.5 L/kg; extensive tissue distribution including placenta and breast milk. |
| Bioavailability | Oral: 65–85% due to first-pass metabolism; may be reduced in patients with hepatic dysfunction. |
| Onset of Action | Oral: 1 hour; Intravenous: 15 minutes; onset of diuresis within 1 hour after oral dose. |
| Duration of Action | Oral: 12–24 hours; Intravenous: 2–6 hours; diuretic effect may persist for 6–12 hours after oral administration. |
| Molecular Weight | 297.74 |
25-100 mg orally once daily in the morning.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR < 30 mL/min. For GFR 30-50 mL/min, reduce dose by 50%. |
| Liver impairment | Contraindicated in Child-Pugh class C. For Child-Pugh class B, reduce dose by 50%. |
| Pediatric use | 2-4 mg/kg orally once daily; maximum 100 mg/day. |
| Geriatric use | Start at 12.5-25 mg orally once daily; titrate slowly due to increased risk of electrolyte disturbances. |
| 1st trimester | Hydrochlorothiazide crosses the placenta and is associated with increased risk of congenital malformations, particularly neural tube defects, when used in the first trimester. It is generally contraindicated unless no safer alternative is available. |
| 2nd trimester | Use during second trimester may cause fetal or neonatal effects such as jaundice, thrombocytopenia, and electrolyte imbalances. Limited data suggests potential for adverse effects, so use is not recommended unless clearly needed. |
| 3rd trimester | Use in third trimester can result in fetal or neonatal dehydration, hypotension, electrolyte disturbances, and possible oligohydramnios. It may also interfere with labor. Contraindicated in pregnancy-induced hypertension and preeclampsia. |
Clinical note
Comprehensive clinical and safety monograph for HYDRO-D (HYDRO-D).
| Placental transfer | Hydrochlorothiazide crosses the placenta readily, with fetal serum concentrations reaching 75-100% of maternal levels. It distributes into amniotic fluid and fetal tissues. |
| Breastfeeding |
■ FDA Black Box Warning
Sulfonamide hypersensitivity: Can cause anaphylaxis, Stevens-Johnson syndrome, and other severe allergic reactions in patients with sulfonamide allergy.
| Serious Effects |
AnuriaRenal failure (creatinine clearance <30 mL/min)Hypersensitivity to hydrochlorothiazide or sulfonamide-derived drugsHepatic coma or pre-comaSevere electrolyte abnormalities (e.g., hypercalcemia, hypokalemia refractory to treatment)Pregnancy (especially second and third trimesters) for routine hypertension
| Precautions | Hypokalemia (monitor potassium levels), Hyperglycemia (may impair glucose tolerance), Hyperuricemia (may precipitate gout), Volume depletion (risk of hypotension), Electrolyte disturbances (sodium, magnesium), Sulfonamide cross-reactivity |
| Food/Dietary | Avoid high-sodium foods and excessive alcohol. Limit caffeine intake. Ensure adequate potassium intake (e.g., bananas, oranges, potatoes) unless advised otherwise by a physician. No specific food interactions beyond electrolyte balance. |
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| Hydrochlorothiazide is excreted into breast milk in low amounts (<0.1 mg/day). Although generally considered compatible with breastfeeding, it may suppress lactation, especially at high doses. Monitor infant for electrolyte imbalances and dehydration, particularly in newborns or premature infants. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | First trimester: Use of thiazide diuretics during the first trimester is generally avoided due to risk of fetal hypotension and decreased placental perfusion, though no consistent teratogenic effects have been demonstrated. Second/third trimester: May cause fetal hypovolemia, electrolyte disturbances, and possible hypoglycemia; use only if clearly needed. |
| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (sodium, potassium), renal function, and fetal growth/amniotic fluid volume. Assess for signs of fetal bradycardia or hypoglycemia if used near delivery. |
| Fertility Effects | No direct adverse effects on fertility reported in women. In men, isolated reports of erectile dysfunction but no consistent effect on spermatogenesis. |
| Clinical Pearls | Hydrochlorothiazide (HCTZ) is a thiazide diuretic used for hypertension and edema. Monitor serum potassium, sodium, and magnesium; hypokalemia is common. May cause hyperuricemia and gout attacks. Sulfa allergy is a relative contraindication. Onset of diuresis within 2 hours, peak at 4 hours, duration 6-12 hours. Dose adjustment in renal impairment (CrCl <30 mL/min: not effective). Use with caution in diabetes as it may increase blood glucose. Can cause photosensitivity. Synergistic effect with ACE inhibitors/ARBs. |
| Patient Advice | Take this medication in the morning to prevent nighttime urination. · Avoid prolonged sun exposure; use sunscreen and protective clothing. · Monitor for signs of low potassium (muscle weakness, cramps, irregular heartbeat) and report to your doctor. · May increase blood sugar; monitor glucose if diabetic. · Avoid alcohol as it can increase dizziness and dehydration. · Do not take with other medications without consulting your doctor, especially lithium, NSAIDs, and certain antidepressants. |