VALSARTAN; HYDROCHLOROTHIAZIDE
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.
Valsartan is an angiotensin II receptor blocker (ARB) that selectively blocks the binding of angiotensin II to the AT1 receptor, leading to vasodilation and reduced aldosterone secretion. Hydrochlorothiazide is a thiazide diuretic that inhibits the sodium-chloride symporter in the distal convoluted tubule, increasing excretion of sodium and water.
| Metabolism | Valsartan is primarily metabolized by CYP2C9; minimal hepatic metabolism. Hydrochlorothiazide is not metabolized and is excreted unchanged in urine. |
| Excretion | Valsartan: primarily excreted unchanged in feces (70%) via biliary elimination, with renal excretion accounting for about 30% (mostly unchanged). Hydrochlorothiazide: eliminated by renal excretion, with approximately 95% of the absorbed dose excreted unchanged in urine via tubular secretion. |
| Half-life | Valsartan: terminal half-life is approximately 6 hours. Hydrochlorothiazide: terminal half-life ranges from 5.6 to 14.8 hours, with an average of about 8 hours; prolonged in renal impairment. |
| Protein binding | Valsartan: highly bound to serum proteins (94-97%), primarily albumin. Hydrochlorothiazide: approximately 40-68% bound to plasma proteins, mainly albumin. |
| Volume of Distribution | Valsartan: apparent volume of distribution is about 17 L (0.24 L/kg), indicating distribution into extracellular fluid. Hydrochlorothiazide: volume of distribution is approximately 0.8-1.2 L/kg, suggesting distribution into total body water. |
| Bioavailability | Valsartan: oral bioavailability is about 25% due to extensive first-pass metabolism. Hydrochlorothiazide: oral bioavailability is 60-80%, varying with formulation. |
| Onset of Action | Valsartan: peak plasma concentrations occur 2-4 hours after oral administration; antihypertensive effect begins within 2 hours. Hydrochlorothiazide: diuretic effect begins within 2 hours, peak effect at 4-6 hours; antihypertensive effect may take 3-4 days. |
| Duration of Action | Valsartan: antihypertensive effect lasts for about 24 hours, allowing once-daily dosing. Hydrochlorothiazide: diuretic effect persists for 6-12 hours; antihypertensive effect with chronic dosing lasts 24 hours. |
80-320 mg valsartan / 12.5-25 mg hydrochlorothiazide once daily orally, titrated based on blood pressure response.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR <30 mL/min/1.73m². For GFR 30-60 mL/min/1.73m², maximum dose 160/25 mg once daily. Monitor electrolytes and renal function. |
| Liver impairment | For mild-to-moderate hepatic impairment (Child-Pugh A or B): maximum valsartan dose 80 mg once daily; no adjustment for hydrochlorothiazide. Contraindicated in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established in children <18 years. Not recommended. |
| Geriatric use | Start at lowest dose (80/12.5 mg once daily) with careful monitoring of blood pressure, electrolytes, and renal function due to age-related changes. |
| 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 | Valsartan is present in breast milk in low concentrations; no data on hydrochlorothiazide with valsartan. M/P ratio not available. Avoid breastfeeding due to potential adverse effects on infant kidney function and electrolytes. |
| Teratogenic Risk | First trimester: Risk of teratogenicity limited but potential for fetotoxicity increases with exposure. Second and third trimesters: Exposure associated with fetal renal hypoperfusion, oligohydramnios, skull ossification defects, anuria, renal failure, hypotension, and death. Hydrochlorothiazide may cause fetal jaundice, electrolyte disturbances. |
■ 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 pregnancy is detected.
| Common Effects | heart failure |
| Serious Effects |
Pregnancy, anuria, hypersensitivity to valsartan, hydrochlorothiazide, or sulfonamide-derived drugs
| Precautions | Hypotension, renal impairment, hyperkalemia, electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia), acute angle-closure glaucoma, exacerbation of systemic lupus erythematosus, fetal/neonatal morbidity, anaphylactic reactions, angioedema |
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| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN), electrolytes, and urine output. Fetal ultrasonography to assess amniotic fluid index, fetal growth, and renal anatomy. Monitor for oligohydramnios and fetal distress. |
| Fertility Effects | Data insufficient. Animal studies with valsartan showed no adverse effects on fertility. Hydrochlorothiazide has no known direct effect on fertility. However, the combination may theoretically affect reproductive function through hemodynamic changes. |