ZIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZIDE (ZIDE).
Hydrochlorothiazide is a thiazide diuretic that inhibits the sodium-chloride symporter in the distal convoluted tubule of the nephron, reducing reabsorption of sodium and chloride and increasing excretion of water, sodium, chloride, potassium, and bicarbonate.
| Metabolism | Hydrochlorothiazide is not extensively metabolized; it is primarily excreted unchanged in the urine via glomerular filtration and active tubular secretion. |
| Excretion | Renal: 70% unchanged; Biliary/fecal: 30% (as metabolites and parent compound). |
| Half-life | 6-8 hours in normal renal function; prolonged to 20-40 hours in severe renal impairment (eGFR <30 mL/min). |
| Protein binding | 70-80% bound, primarily to albumin. |
| Volume of Distribution | 0.2-0.4 L/kg; predominantly remains in intravascular space. |
| Bioavailability | Oral: 50-70% (reduced by food). |
| Onset of Action | Oral: 1-2 hours; IV: 15-30 minutes. |
| Duration of Action | Oral: 6-12 hours; IV: 4-6 hours. Duration extended in renal impairment. |
| Molecular Weight | 297.74 |
10 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in anuria. For GFR 30-50 mL/min: no adjustment; GFR 15-29 mL/min: cautiously use 5 mg once daily; GFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: start at 5 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established for pediatric patients. |
| Geriatric use | Initiate at 5 mg once daily due to increased sensitivity; monitor electrolytes and renal function closely. |
| 1st trimester | Hydrochlorothiazide crosses the placenta; risk of neonatal electrolyte disturbances and thrombocytopenia. Avoid use in first trimester unless necessary. |
| 2nd trimester | Use with caution; may cause maternal electrolyte imbalance and reduced placental perfusion. |
| 3rd trimester | Use avoided due to risk of neonatal electrolyte disturbances, thrombocytopenia, and jaundice. |
Clinical note
Comprehensive clinical and safety monograph for ZIDE (ZIDE).
| Placental transfer | Crosses placenta; detected in fetal blood at concentrations similar to maternal blood. |
| Breastfeeding | Hydrochlorothiazide is excreted in breast milk in small amounts; may suppress lactation. Use with caution in nursing mothers, especially if high doses or other diuretics are used. |
■ FDA Black Box Warning
None
| Serious Effects |
AnuriaHypersensitivity to hydrochlorothiazide or sulfonamidesSevere renal impairment (CrCl <30 mL/min)Severe hepatic impairment (risk of hepatic encephalopathy)
| Precautions | Electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia, hypercalcemia), Hyperuricemia and precipitation of gout, Hypotension, Worsening of diabetes mellitus, Systemic lupus erythematosus exacerbation, Photosensitivity, Acute angle-closure glaucoma, Non-melanoma skin cancer risk with cumulative use |
| Food/Dietary | Avoid potassium-rich foods and salt substitutes containing potassium. Limit alcohol intake. Maintain a consistent fluid intake to prevent dehydration. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: No increased risk of major malformations in available studies. Second and third trimesters: Associated with fetal/neonatal adverse effects including oligohydramnios, renal dysfunction, and hypotension due to reduced placental perfusion. |
| Fetal Monitoring | Maternal: Blood pressure, serum electrolytes, renal function, and uric acid levels. Fetal: Ultrasound for amniotic fluid volume (assess for oligohydramnios) and fetal growth in second/third trimesters. Neonatal: Observe for hypotension, hypoglycemia, and electrolyte imbalance. |
| Fertility Effects | No known direct effect on human fertility; however, use may be associated with conditions (e.g., hypertension) that impact pregnancy outcomes. Animal studies show no impairment of fertility at clinically relevant doses. |
| Clinical Pearls |
| Monitor serum electrolytes (especially potassium and sodium) and renal function at baseline and periodically. Use with caution in patients with severe renal impairment (CrCl <30 mL/min) or hepatic impairment. Avoid concomitant use with other diuretics, NSAIDs, or drugs prolonging QT interval due to increased risk of arrhythmias. |
| Patient Advice | Take ZIDE exactly as prescribed, usually once daily in the morning to avoid nocturia. · Avoid excessive intake of potassium-rich foods (e.g., bananas, oranges, spinach) due to risk of hyperkalemia. · Report symptoms of electrolyte imbalance: muscle cramps, weakness, irregular heartbeat, or excessive thirst. · Avoid alcohol and NSAIDs (e.g., ibuprofen) as they can increase risk of kidney injury. · Monitor blood pressure regularly if prescribed for hypertension. |