DIOVAN HCT
Clinical safety rating
cautionComprehensive 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). |
| Molecular Weight | Valsartan: 435.5 Da; Hydrochlorothiazide: 297.7 Da |
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 | Avoid; potential fetal renal effects and oligohydramnios due to ARB (valsartan) component; HCTZ may cause fetal electrolyte disturbances. |
| 2nd trimester | Avoid; ARB use in second and third trimesters is associated with fetal renal impairment, oligohydramnios, skull hypoplasia; HCTZ may cause neonatal jaundice, thrombocytopenia. |
| 3rd trimester | Avoid; ARB exposure increases risk of fetal renal failure, anuria, oligohydramnios, and death; HCTZ may cause fetal or neonatal jaundice, electrolyte disturbances. |
Clinical note
Comprehensive clinical and safety monograph for DIOVAN HCT (DIOVAN HCT).
| Placental transfer | Valsartan crosses the placenta; HCTZ crosses the placenta and appears in cord blood. |
| Breastfeeding | Valsartan is excreted in breast milk at low concentrations; HCTZ is excreted in breast milk and may suppress lactation. Use with caution, especially in neonates or preterm infants; monitor for dehydration and electrolyte imbalance. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
AnuriaHypersensitivity to valsartan, hydrochlorothiazide, or sulfonamide-derived drugsConcomitant use with aliskiren in patients with diabetes
| 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. |
| Food/Dietary | Avoid grapefruit juice as it may alter drug metabolism. Limit high-potassium foods (e.g., bananas, oranges, potatoes, spinach) if potassium levels rise. Reduce sodium intake (less than 2 g/day) to enhance antihypertensive effect. Avoid excessive alcohol consumption. Maintain adequate fluid intake to prevent dehydration. |
| Clinical Pearls | Diovan HCT combines valsartan (ARB) and hydrochlorothiazide (thiazide diuretic). Monitor renal function, electrolytes (especially potassium and sodium), and blood pressure. Avoid use in pregnancy; contraindicated in anuria and severe renal impairment. Use caution in patients with pre-existing electrolyte imbalances, diabetes, or history of gout. May cause hyperkalemia with valsartan and hypokalemia with HCTZ; net effect requires monitoring. Onset of action within 2 hours, peak effect at 4-6 hours. Not recommended for initial therapy; titrate from individual components. |
| Patient Advice | Take exactly as prescribed, usually once daily. Do not skip doses. · Avoid potassium supplements or salt substitutes without doctor approval. · Report symptoms of electrolyte imbalance: muscle cramps, weakness, irregular heartbeat, excessive thirst. · May cause dizziness or lightheadedness; avoid driving until you know how it affects you. · This medication can make you urinate more frequently; take in the morning to minimize nighttime urination. · Avoid alcohol, which can increase dizziness and blood pressure lowering effects. · Notify your doctor if you become pregnant or plan to become pregnant; this drug can harm the fetus. · Stay hydrated, especially in hot weather or during exercise, to prevent dehydration. · Tell your doctor about all other medications, especially NSAIDs, lithium, and other blood pressure drugs. · Do not stop taking without consulting your doctor; sudden discontinuation may worsen blood pressure. |
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