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. |
| Molecular Weight | 312.4 |
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 | Contraindicated: known teratogenic effects (neural tube defects, cardiac malformations). |
| 2nd trimester | Contraindicated: risk of oligohydramnios and fetal renal impairment. |
| 3rd trimester | Contraindicated: may cause premature closure of ductus arteriosus and pulmonary hypertension. |
Clinical note
Comprehensive clinical and safety monograph for HYDRO-RX (HYDRO-RX).
| Placental transfer | High; crosses placenta readily with fetal concentrations similar to maternal levels. |
| Breastfeeding | Excreted into breast milk in low quantities; potential for severe adverse effects in infants (hypotension, renal impairment) based on mechanism of action. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
PregnancyHistory of allergic reaction to HYDRO-RXSevere renal impairment (eGFR <30 mL/min/1.73m²)Concomitant use with strong CYP3A4 inducers
| 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. |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, potatoes, tomatoes, spinach) in large amounts. Do not use potassium-containing salt substitutes. Grapefruit juice may increase drug levels; limit intake. Avoid alcohol as it may enhance hypotension. |
Loading safety data…
| L4 (Possibly Hazardous) |
| 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 | 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. |
| Clinical Pearls | Monitor serum potassium closely, especially in patients with renal impairment or those taking ACE inhibitors, ARBs, or potassium-sparing diuretics. Start low and go slow: initial dose 12.5 mg twice daily, titrating based on BP response. Caution in patients with history of angioedema or hereditary angioedema due to potential for increased risk. Not recommended in pregnant or breastfeeding women. Assess renal function before initiation and periodically. |
| Patient Advice | Take this medication exactly as prescribed, usually once or twice daily. · Do not stop taking this medication abruptly without consulting your doctor. · Avoid salt substitutes containing potassium unless approved by your doctor. · Inform your doctor if you have kidney disease, are on dialysis, or have a history of angioedema. · If you become pregnant or plan to become pregnant, contact your healthcare provider immediately. · Do not use this medication if you are breastfeeding. · Report any signs of allergic reaction: swelling of face, lips, tongue, or throat; difficulty breathing; or severe rash. · Take your blood pressure regularly as directed and keep a log to share with your doctor. |