VALSARTAN AND 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 inhibits the binding of angiotensin II to the AT1 receptor, thereby antagonizing angiotensin II-induced vasoconstriction, aldosterone secretion, and renal sodium reabsorption. Hydrochlorothiazide is a thiazide diuretic that inhibits the sodium-chloride symporter in the distal convoluted tubule, reducing sodium and water reabsorption.
| Metabolism | Valsartan is minimally metabolized (approximately 20%) via CYP2C9 to an inactive metabolite; the majority is excreted unchanged in bile and urine. Hydrochlorothiazide is not metabolized significantly and is excreted unchanged by the kidneys. |
| Excretion | Valsartan: 83% eliminated via feces (biliary), 13% via urine; Hydrochlorothiazide: ≥95% eliminated unchanged via urine. |
| Half-life | Valsartan: Terminal half-life ~6 hours; Hydrochlorothiazide: Terminal half-life ~6-15 hours (prolonged in renal impairment). |
| Protein binding | Valsartan: 94-97% bound to serum albumin; Hydrochlorothiazide: 40-68% bound to serum albumin. |
| Volume of Distribution | Valsartan: Vd ~17 L (0.24 L/kg); Hydrochlorothiazide: Vd ~3-4 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Valsartan: Oral bioavailability ~25% (range 10-35%); Hydrochlorothiazide: Oral bioavailability ~65-70%. |
| Onset of Action | Oral: Valsartan and Hydrochlorothiazide combination: Antihypertensive effect begins within 2 hours, peak effect at 4-6 hours. |
| Duration of Action | Oral: Antihypertensive effect persists for 24 hours; duration of diuretic effect of hydrochlorothiazide is 6-12 hours. |
Oral, one tablet once daily. Starting dose: 160/12.5 mg or 80/12.5 mg. Titrate to 160/25 mg or 320/12.5 mg-320/25 mg based on response. Max: 320/25 mg/day.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR <30 mL/min/1.73m2. For GFR 30-60 mL/min/1.73m2: no dose adjustment needed; monitor renal function and electrolytes. Total daily dose of hydrochlorothiazide should not exceed 25 mg. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Maximum valsartan 80 mg/day; monitor. Child-Pugh C: Contraindicated due to hydrochlorothiazide. Valsartan: caution, no specific dose recommendations; avoid if severe hepatic impairment. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). Not recommended. |
| Geriatric use | Initiate at lower dose (e.g., 80/12.5 mg) due to risk of renal impairment and electrolyte disturbances. Monitor blood pressure, renal function, and serum electrolytes closely. Avoid use if GFR <30 mL/min/1.73m2. |
| 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 excreted in human milk at low levels; estimated infant dose <1% of maternal weight-adjusted dose; no M/P ratio reported. Hydrochlorothiazide is excreted in milk in low amounts; may suppress lactation and cause neonatal electrolyte disturbances. Combination is not recommended during breastfeeding due to potential adverse effects on the infant, particularly from HCTZ. If used, monitor infant for hypotension and electrolyte imbalances. |
■ FDA Black Box Warning
Fetal toxicity: Use during pregnancy can cause injury and death to the developing fetus. Discontinue as soon as pregnancy is detected.
| Common Effects | heart failure |
| Serious Effects |
["Anuria (hydrochlorothiazide component)","Hypersensitivity to sulfonamide-derived drugs (hydrochlorothiazide)","Pregnancy","Concomitant use with aliskiren in patients with diabetes (due to valsartan component)"]
| Precautions | ["Avoid use in pregnancy and breastfeeding","Monitor renal function and electrolytes (especially potassium, sodium, and magnesium)","Hypotension and syncope may occur, especially in volume-depleted patients","May worsen renal function in patients with renal artery stenosis or severe heart failure","Hydrochlorothiazide may cause acute angle-closure glaucoma or myopia (sulfonamide effect)","Hyperuricemia and gout may occur with thiazide use","May increase serum lithium levels and toxicity"] |
Loading safety data…
| Teratogenic Risk |
| First trimester: Potential for teratogenic effects from angiotensin receptor blocker (ARB) component; risk of fetal renal dysfunction, oligohydramnios, and skull ossification defects. Second and third trimesters: ARB exposure causes fetal renal hypoperfusion, oligohydramnios, anuria, renal failure, pulmonary hypoplasia, and death. Hydrochlorothiazide (HCTZ) is associated with fetal/neonatal jaundice, electrolyte disturbances, and thrombocytopenia. Both ARBs and HCTZ are contraindicated in the second and third trimesters. Risk Summary: ARBs are teratogenic and fetotoxic in all trimesters; HCTZ poses risks later in pregnancy. |
| Fetal Monitoring | Maternal: Blood pressure, serum creatinine, BUN, electrolytes (especially potassium, sodium, chloride, bicarbonate), uric acid, and urine output. Fetal: Ultrasound monitoring of amniotic fluid volume and fetal kidney function if ARB exposure after first trimester. Monitor for oligohydramnios and fetal growth restriction. Neonatal: Observe for hypotension, hyperkalemia, and renal dysfunction if exposure occurred in utero. |
| Fertility Effects | No definitive studies on fertility effects in humans. ARBs may theoretically affect reproductive function via renin-angiotensin system modulation, but clinical significance unknown. HCTZ has no known significant impact on fertility. Overall, no evidence of major fertility impairment. |