DIOVAN HCT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIOVAN HCT (DIOVAN HCT).
Valsartan is an angiotensin II receptor blocker (ARB) that selectively blocks the binding of angiotensin II to the AT1 receptor, causing vasodilation and reduced aldosterone secretion. Hydrochlorothiazide is a thiazide diuretic that inhibits the sodium-chloride cotransporter in the distal convoluted tubule, increasing excretion of sodium and water.
| Metabolism | Valsartan is primarily metabolized by CYP2C9 (minor) and eliminated unchanged in bile and urine. Hydrochlorothiazide is not extensively metabolized and is excreted unchanged in urine. |
| Excretion | Valsartan: primarily biliary (83%) and renal (13%) as unchanged drug; hydrochlorothiazide: renal (≥95%) as unchanged drug. |
| Half-life | Valsartan: 6 hours; hydrochlorothiazide: 6–15 hours (mean 9.6 hours). Clinical context: allows once-daily dosing; half-life prolonged in renal impairment. |
| Protein binding | Valsartan: 94–97% (primarily albumin); hydrochlorothiazide: 68% (albumin). |
| Volume of Distribution | Valsartan: 17 L (≈0.24 L/kg for 70 kg); hydrochlorothiazide: 3.6–7.8 L/kg (≈0.5–1.1 L/kg). Clinical meaning: Valsartan distributes mainly in plasma; HCTZ widely distributed into tissues. |
| Bioavailability | Valsartan: 25% (oral, with food reduces absorption by 40%); hydrochlorothiazide: 65–75% (oral). |
| Onset of Action | Valsartan: 2 hours (antihypertensive effect); hydrochlorothiazide: 2 hours (diuresis) with peak effect at 4 hours. |
| Duration of Action | Valsartan: 24 hours; hydrochlorothiazide: 6–12 hours (diuretic effect), 24 hours (antihypertensive effect). |
One tablet orally once daily. Available strengths: 80 mg/12.5 mg, 160 mg/12.5 mg, 160 mg/25 mg, 320 mg/12.5 mg, 320 mg/25 mg. Titrate to blood pressure response; maximum dose 320 mg/25 mg daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in anuria. For GFR 30-60 mL/min, use cautiously; consider lower starting doses. GFR <30 mL/min: not recommended due to thiazide component. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: use caution; valsartan exposure increases significantly. Child-Pugh C: avoid use. |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | No initial dose adjustment required, but consider lower starting doses due to greater sensitivity to antihypertensive effects; monitor renal function and electrolytes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIOVAN HCT (DIOVAN HCT).
| Breastfeeding | The active metabolites hydrochlorothiazide is excreted in low amounts in breast milk; low M/P ratio of approximately 0.25; valsartan excretion unknown; because of potential adverse effects on the nursing infant, especially renal effects, use is not recommended; alternative therapies are preferred. |
| Teratogenic Risk | First trimester: Potential risk based on mechanism (angiotensin II receptor blockade and thiazide diuretic); second and third trimesters: Known fetal toxicity including oligohydramnios, fetal renal dysfunction, skull ossification defects, and neonatal hypotension; avoid in pregnancy, especially after 20 weeks gestation. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Anuria","Hypersensitivity to valsartan, hydrochlorothiazide, or sulfonamide-derived drugs","Pregnancy (second and third trimesters)","Severe hepatic impairment (Child-Pugh class C)","Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR <60 mL/min)"]
| Precautions | ["Fetal toxicity: avoid use during pregnancy; can cause oligohydramnios and fetal renal dysfunction.","Hypotension in volume-depleted patients.","Electrolyte imbalances (e.g., hypokalemia, hyponatremia) due to thiazide component.","Renal impairment: monitor renal function; may exacerbate in bilateral renal artery stenosis.","Acute angle-closure glaucoma (thiazide component).","Sulfonamide allergy (cross-reactivity with thiazide).","Exacerbation of lupus erythematosus."] |
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| Fetal Monitoring | Monitor fetal ultrasound for amniotic fluid volume and fetal renal function during third trimester if exposure occurs; neonatal monitoring for hypotension, oliguria, and hyperkalemia after birth. |
| Fertility Effects | No specific data on fertility impairment with DIOVAN HCT; class effects of angiotensin receptor blockers may theoretically affect reproductive function; thiazide diuretics have no known direct fertility effects. |