Dosing and uses of Diovan HCT (valsartan-hydrochlorothiazide)
Adult dosage forms and strengths
valsartan/hydrochlorothiazide
tablet
- 80mg/12.5mg
- 160mg/12.5mg
- 320mg/12.5mg
- 160mg/25mg
- 320mg/25mg
Hypertension
1 tablet/day PO (80-160 mg valsartan/12.5-25 mg hydrochlorothiazide); may be titrated after 1-2 weeks of therapy; not to exceed 320 mg valsartan/25 mg hydrochlorothiazide daily
Pediatric dosage forms and strengths
Safety and efficacy not established
Diovan HCT (valsartan-hydrochlorothiazide) adverse (side) effects
1-10%
Valsartan
- Hyperkalemia (4-10%)
- Dizziness (2-8%)
- Hypotension (1-7%)
- Fatigue (3%)
Frequency not defined
Hydrochlorothiazide
- Anaphylaxis
- Anemia
- Anorexia
- Confusion
- Dizziness
- Epigastric distress
- Erythema multiforme
- Exfoliative dermatitis, including toxic epidermal necrolysis
- Headache
- Hyperuricemia
- Hypokalemia or hypomagnesemia
- Orthostatic hypotension
- Photosensitivity
- Stevens-Johnson syndrome
Postmarketing Reports
Hypersensitivity: Angioedema (rare), urticaria
Digestive: Elevated liver enzymes, hepatitis (rare)
Renal: Impaired renal function, renal failure
Clinical laboratory tests: Hyperkalemia
Dermatologic: Alopecia, bullous dermatitis
Blood and lymphatic: Thrombocytopenia (rare)
Vascular: Vasculitis
Warnings
Black box warnings
Discontinue as soon as possible when pregnancy is detected; drug affects renin-angiotensin system, causing oligohydramnios, which may result in fetal injury or death
Contraindications
Hypersensitivity to valsartan, hydrochlorothiazide, or sulfonamides
Anuria
Do not coadminister with aliskiren in patients with diabetes
Not for initial treatment
Cautions
Orthostatic hypotension risk: Initiate combination therapy with 2 antihypertensive drugs cautiously in patients with diabetes or autonomic dysfunction and in geriatric patients
Acute transient myopia and acute angle-closure glaucoma have been reported, particularly with a history of sulfonamide or penicillin allergy (hydrochlorothiazide is a sulfonamide)
Avoid in severe renal impairment (ineffective)
Use with caution in severe hepatic impairment
Use with caution in renal artery stenosis; avoid in bilateral renal artery stenosis
CrCl <30 mL/min: Use loop diuretic instead of hydrochlorothiazide
Hyperkalemia, particularly when coadministered with potassium-sparing diuretics, potassium supplements, or salt substitutes; concurrent therapy with hydrochlorothiazide may reduce the frequency of this effect
Dual blockade of the renin-angiotensin system with ARBs, angiotensin-converting enzyme (ACE) inhibitors, or aliskiren is associated with increased risk of hypotension, hyperkalemia, and altered renal function (including acute renal failure) in comparison with monotherapy
Hydrochlorothiazide can cause hypokalemia and hyponatremia; hypomagnesemia can result in hypokalemia that appears difficult to treat despite potassium repletion
Drugs that inhibit the renin-angiotensin system can cause hyperkalemia; monitor serum electrolytes periodically
In certain patients receiving thiazide therapy, hyperuricemia may occur, or frank gout may be precipitated
Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides
Thiazides may decrease urinary calcium excretion
Pregnancy and lactation
Pregnancy category: 1st trimester, C; 2nd and 3rd trimesters, d
Lactation: Discontinue drug, or do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Diovan HCT (valsartan-hydrochlorothiazide)
Mechanism of action
Valsartan: Blocks binding of angiotensin II to type 1 angiotensin II receptors; blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II
Hydrochlorothiazide: Thiazide diuretic that inhibits sodium reabsorption in distal renal tubules; results in increased excretion of sodium ions and water, as well as potassium and hydrogen ions
Absorption
Valsartan
- Bioavailability: 25%
- Onset: 2 hr
- Duration: 24 hr
- Peak plasma time: 2-4 hr
- Peak response: 4-6 hr
Hydrochlorothiazide
- Onset: Diuresis, ~2 hr; hypertension, 3-4 days
- Peak plasma time: 1-2.5 hr
- Peak effect: Diuresis, 4-6 hr
Distribution
Valsartan
- Protein bound: 94-95%
- Vd: 17 L
Hydrochlorothiazide
- Protein bound: 68%
- Vd: 3.6-7.8 L/kg
Metabolism
Valsartan
- Minimally metabolized in liver
- Metabolites: Valeryl-4-hydroxyvalsartan (inactive)
Hydrochlorothiazide
- Minimally metabolized
Elimination
Valsartan
- Half-life: 6-9 hr
- Renal clearance: 0.62 L/hr
- Total body clearance: 2.2 L/hr
- Excretion: Feces (83%), urine (13%)
Hydrochlorothiazide
- Half-life: 5/6-14.8 hr
- Excretion: Urine
