HYDROCHLOROTHIAZIDE; VALSARTAN
Clinical safety rating: avoid
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Use in pregnancy can cause injury and death to the developing fetus.
Hydrochlorothiazide is a thiazide diuretic that inhibits the sodium-chloride symporter in the distal convoluted tubule, reducing sodium and water reabsorption. Valsartan is an angiotensin II receptor blocker (ARB) that selectively blocks the binding of angiotensin II to AT1 receptors, causing vasodilation and reduced aldosterone secretion.
| Metabolism | Hydrochlorothiazide is not metabolized and is excreted unchanged in urine. Valsartan is primarily metabolized by CYP2C9 to an inactive metabolite, with minor metabolism by CYP3A4. |
| Excretion | Hydrochlorothiazide: ~70% renal (unchanged) via tubular secretion; ~30% biliary/fecal. Valsartan: 83% fecal (unchanged); 13% renal (unchanged and metabolites). |
| Half-life | Hydrochlorothiazide: 6-15 hours (terminal); clinical effect persists due to tubular secretion. Valsartan: 6 hours (terminal); no accumulation with once-daily dosing. |
| Protein binding | Hydrochlorothiazide: 68% bound to albumin. Valsartan: 94-97% bound to albumin (primarily). |
| Volume of Distribution | Hydrochlorothiazide: 3-4 L/kg; extensive distribution into extracellular fluid. Valsartan: 0.17 L/kg; limited tissue distribution. |
| Bioavailability | Hydrochlorothiazide: oral, 65-75% (estimated). Valsartan: oral, 25% (variable, 10-35%) due to extensive first-pass metabolism. |
| Onset of Action | Hydrochlorothiazide: oral, 2 hours (diuresis); peak antihypertensive effect 4-6 hours. Valsartan: oral, 2 hours (antihypertensive); peak effect 4-6 hours. |
| Duration of Action | Hydrochlorothiazide: 12-16 hours (diuresis); 24 hours (antihypertensive) with chronic use. Valsartan: 24 hours (antihypertensive) with once-daily dosing. |
Oral, 12.5-25 mg hydrochlorothiazide / 80-320 mg valsartan once daily. Maximum dose: 25 mg hydrochlorothiazide / 320 mg valsartan per day.
| Dosage form | TABLET |
| Renal impairment | GFR ≥30 mL/min/1.73 m²: no adjustment. GFR 15-29 mL/min/1.73 m²: not recommended due to limited data; avoid use. GFR <15 mL/min/1.73 m²: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: caution; maximum dose 80 mg valsartan component. Child-Pugh C: contraindicated. |
| Pediatric use | Not approved for use in pediatric patients under 18 years of age. |
| Geriatric use | Start at lower end of dosing range (e.g., 12.5 mg hydrochlorothiazide / 80 mg valsartan) due to increased risk of hypotension and electrolyte disturbances; monitor renal function and electrolytes closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Use in pregnancy can cause injury and death to the developing fetus.
| FDA category | Contraindicated |
| Breastfeeding | Hydrochlorothiazide is excreted in breast milk in small amounts (<0.1% of maternal dose); M/P ratio not clearly defined. Valsartan is not known to be excreted in human milk. Due to potential for adverse effects (e.g., oligohydramnios in infants), not recommended during breastfeeding. |
| Teratogenic Risk |
■ FDA Black Box Warning
Fetal toxicity: Drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.
| Common Effects | heart failure |
| Serious Effects |
["Anuria","Hypersensitivity to sulfonamide-derived drugs (hydrochlorothiazide)","History of angioedema with ARBs","Concomitant use with aliskiren in patients with diabetes","Pregnancy (second and third trimesters)"]
| Precautions | ["Hypotension in volume-depleted patients","Electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia)","Renal function impairment","Acute angle-closure glaucoma (hydrochlorothiazide)","Sulfonamide allergy cross-reactivity","Exacerbation of systemic lupus erythematosus","Metabolic effects (hyperglycemia, hyperuricemia)"] |
Loading safety data…
| Pregnancy Category D. First trimester: Potential fetotoxicity, but limited data. Second and third trimesters: Fetal hypotension, oligohydramnios, renal dysfunction, skull ossification defects, and neonatal anuria or hyperkalemia. ARBs cause fetotoxicity in second and third trimesters. |
| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes, renal function, and urine output. Fetal ultrasound for oligohydramnios, fetal growth, and renal function. Neonates exposed in utero should be observed for hypotension, hyperkalemia, and oliguria. |
| Fertility Effects | No significant adverse effects on fertility reported in animal studies or human data. Hydrochlorothiazide does not impair fertility. Valsartan has no known effects on fertility. |