HYDRO-RX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HYDRO-RX (HYDRO-RX).
Hydrochlorothiazide is a thiazide diuretic that inhibits the sodium-chloride symporter (NCC) in the distal convoluted tubule of the nephron, reducing sodium and chloride reabsorption, leading to increased diuresis, decreased plasma volume, and vasodilation. It also reduces peripheral vascular resistance.
| Metabolism | Hydrochlorothiazide is not extensively metabolized; it is primarily excreted unchanged in the urine (~95%). A small amount may undergo hepatic metabolism via CYP450, but specific enzymes are not well-defined. |
| Excretion | Renal excretion of unchanged drug accounts for 60% of elimination; biliary/fecal excretion accounts for 30%; 10% metabolized. |
| Half-life | Terminal elimination half-life is 8-12 hours in adults with normal renal function; extended to 20-30 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 95% bound to albumin; minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.3-0.5 L/kg, indicating distribution primarily into extracellular fluid. |
| Bioavailability | Oral: 75-85% (first-pass metabolism reduces bioavailability); Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-10 minutes. |
| Duration of Action | Oral: 8-12 hours; Intravenous: 6-8 hours; duration may be prolonged in hepatic impairment. |
Initial: 25 mg orally once daily; may increase to 50 mg once daily after 2 weeks based on response. Maximum: 50 mg daily.
| Dosage form | POWDER |
| Renal impairment | GFR 30-59 mL/min: 25 mg once daily. GFR <30 mL/min: Not recommended. |
| Liver impairment | Child-Pugh Class A: 25 mg once daily. Child-Pugh Class B: 12.5 mg once daily. Child-Pugh Class C: Avoid use. |
| Pediatric use | Children ≥6 years: 0.5 mg/kg orally once daily; maximum 25 mg daily. Safety and efficacy not established for children <6 years. |
| Geriatric use | Start at 12.5 mg orally once daily; titrate cautiously to 25 mg once daily based on tolerance and renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HYDRO-RX (HYDRO-RX).
| Breastfeeding | Excreted in human milk; M/P ratio 0.8. Potential for infant toxicity. Use with caution, monitor infant for sedation and poor feeding. |
| Teratogenic Risk | First trimester: Increased risk of major malformations (cardiac, CNS) based on animal studies and limited human data. Second/third trimester: Risk of fetal growth restriction, oligohydramnios, and preterm birth. Avoid use unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Anuria","Hypersensitivity to hydrochlorothiazide or sulfonamide-derived drugs (cross-sensitivity possible)","Severe renal impairment (creatinine clearance <30 mL/min)","Hypercalcemia","Severe hepatic impairment (risk of hepatic encephalopathy)","Addison's disease (relative)"]
| Precautions | ["Hypokalemia: Risk increases with higher doses or concomitant use of other potassium-wasting drugs.","Hypomagnesemia, hyponatremia, hypercalcemia, and metabolic alkalosis.","Hyperuricemia may precipitate gout.","Acute angle-closure glaucoma (rare, idiosyncratic reaction).","Photosensitivity, systemic lupus erythematosus exacerbation, and pancreatitis have been reported.","Electrolyte monitoring is recommended."] |
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| Maternal: Blood pressure, renal function, liver enzymes, complete blood count. Fetal: Serial ultrasound for growth and amniotic fluid volume; nonstress test and biophysical profile weekly after 32 weeks. |
| Fertility Effects | May reduce fertility in females through hormonal disruption; reversible upon discontinuation. No known adverse effects on male fertility. |