|Biological half-life||6 hours|
|Excretion||Renal 30%, biliary 70%|
|Chemical and physical data|
|Molar mass||435.519 g/mol|
|3D model (Jmol)|
Valsartan (trade name Diovan) is an angiotensin II receptor antagonist (commonly called an ARB, or angiotensin receptor blocker), that is selective for the type I (AT1) angiotensin receptor. Valsartan is mainly used for treatment of high blood pressure, congestive heart failure, and to increase the chances of living longer after a heart attack.
There is contradictory evidence with regard to treating people with heart failure with a combination of an angiotensin receptor blocker like valsartan and an angiotensin-converting enzyme inhibitor, with two major clinical trials (CHARM-additive and ValHeFt) showing a reduction in death, and two others (VALIANT and ONTARGET) showing no benefits, and more adverse effects including heart attacks.
The packaging for valsartan includes a warning stating the drug should not be used with the renin inhibitor aliskiren in people with diabetes mellitus. It also states the drug should not be used in people with kidney disease.
Valsartan falls in FDA pregnancy category D and includes a black box warning for fetal toxicity. Discontinuation of these agents is recommended immediately after detection of pregnancy and an alternative medication should be started. The US labeling makes no recommendation regarding continuation or discontinuation of valsartan for breast-feeding mothers. The Canadian labeling does not recommend use by nursing women.
Rates of side effects depends on the reason the medication is used.
Rates of adverse effects are based on a comparison versus placebo in people with heart failure. Most common side effects include dizziness (17% vs 9% ), low blood pressure (7% vs 2%), and diarrhea (5% vs 4%). Less common side effects include joint pain, fatigue, and back pain (all 3% vs 2%).
Clinical trials for valsartan treatment for hypertension versus placebo demonstrate side effects like viral infection (3% vs 2%), fatigue (2% vs 1%) and abdominal pain (2% vs 1%). Minor side effects that occurred at >1% but were similar to rates from the placebo group include:
- upper respiratory infection
The US prescribing information lists the following drug interactions for valsartan:
- Other inhibitors of the renin-angiotensin system may increase the risks of low blood pressure, kidney problems, and hyperkalemia
- Potassium sparing diuretics, potassium supplements, salt substitutes containing potassium may increase the risk of hyperkalemia.
- NSAIDs may increase the risk of kidney problems and may interfere with blood pressure-lowering effects.
- Valsartan may increase the concentration of lithium.
Mechanism of action
Valsartan blocks the actions of angiotensin II, which include constricting blood vessels and activating aldosterone, to reduce blood pressure. The drug binds to angiotensin type I receptors (AT1), working as an antagonist. This mechanism of action is different than the ACE inhibitor drugs, which block the conversion of angiotensin I to angiotensin II. Since valsartan acts at the receptor, it can provide more complete angiotensin II antagonism since angiotensin II is generated by other enzymes as well as ACE. Also, valsartan does not affect the metabolism of bradykinin like ACE inhibitors do.
In 2010, valsartan (trade name Diovan) achieved annual sales of $2.052 billion in the United States and $6.053 billion worldwide. The patents for valsartan and valsartan/hydrochlorothiazide expired in September 2012.
In people with impaired glucose tolerance, valsartan may decrease the incidence of developing diabetes mellitus type 2. However, the absolute risk reduction is small (less than 1 percent per year) and diet, exercise or other drugs, may be more protective. In the same study, no reduction in the rate of cardiovascular events (including death) was shown.
A prospective study demonstrated a reduction in the incidence and progression of Alzheimer's disease and dementia.
Amlodipine and valsartan is a combination drugs for hypertension. The combination is not approved for use by anyone younger than 18 years old. For who have diabetes or kidney disease the combination drugs cannot be given with medication that contains aliskiren.
- Angiotensin II receptor antagonist
- Discovery and development of angiotensin receptor blockers
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