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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZIDE (ZIDE).
| Breastfeeding | Limited data; ZIDE is excreted in breast milk in low amounts (M/P ratio not established). Avoid use during breastfeeding due to potential for neonatal jaundice, thrombocytopenia, and electrolyte disturbances. If used, monitor infant for jaundice and diuretic effects. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
["Anuria","Hypersensitivity to hydrochlorothiazide or sulfonamide-derived drugs","Severe renal impairment (CrCl <30 mL/min)","Hepatic coma or pre-coma","Concurrent use with lithium (increases lithium toxicity)"]
| 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"] |
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| 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. |