No

Angiotensin II Antagonists

Alone or in combination with other antihypertensive agents in treating essential hypertension; may have an advantage over losartan due to minimal metabolism requirements and consequent use in mild to moderate hepatic impairment

C/D (2nd and 3rd trimesters)

Breast-feeding/lactation: Although no human data exist, valsartan is known to be excreted in animal breast milk and should be avoided in lactating mothers if possible

Hypersensitivity to valsartan or any component; hypersensitivity to other A-II receptor antagonists; primary hyperaldosteronism; bilateral renal artery stenosis; pregnancy (2nd and 3rd trimesters)

Avoid use or use a smaller dose in patients who are volume depleted; correct depletion first. Deterioration in renal function can occur with initiation. Use with caution in unilateral renal artery stenosis and pre-existing renal insufficiency; significant aortic/mitral stenosis. Use caution in patients with severe renal impairment or significant hepatic dysfunction.

Similar incidence to placebo; independent of race, age, and gender.

Central nervous system: Dizziness (2% to 9%), drowsiness(2.1%), ataxia (1.4%), fatigue (2%)

Cardiovascular: Hypotension (6.9%)

Endocrine & metabolic: Increased serum potassium (4.4%)

Gastrointestinal: Abdominal pain (2%), dysgeusia (1.4%)

Hematologic: Neutropenia (1.9%)

Hepatic: Increased LFTs

Respiratory: Cough (2.9% versus 1.5% in placebo)

Miscellaneous: Viral infection (3%)

>1% but frequency less than or equal to placebo: Headache, upper respiratory infection, cough, diarrhea, rhinitis, sinusitis, nausea, pharyngitis, edema, arthralgia

<1% (Limited to important or life-threatening symptoms): Anemia, increased creatinine (0.8%), orthostatic effects, allergic reactions, asthenia, palpitations, pruritus, rash, constipation, xerostomia, dyspepsia, flatulence, back pain, muscle cramps, myalgia, anxiety, insomnia, paresthesia, somnolence, dyspnea, vertigo, impotence, chest pain, syncope, anorexia, vomiting, angioedema, decreased hematocrit, decreased hemoglobin, increased serum transaminases, increased total bilirubin, tachycardia, depression, neuralgia, polyuria, conjunctivitis, epistaxis, joint pain. May be associated with worsening of renal function in patients dependent on renin-angiotensin-aldosterone system, alopecia

Case report: Antisynthetase syndrome without myositis

Only mild toxicity (hypotension, bradycardia, hyperkalemia) has been reported with large overdoses (up to 5 g of captopril and 300 mg of enalapril); no fatalities have been reported

Treatment is symptomatic (eg, fluids)

Lithium: Risk of toxicity may be increased by valsartan; monitor lithium levels.

Potassium-sparing diuretics (amiloride, potassium, spironolactone, triamterene): Increased risk of hyperkalemia.

Potassium supplements may increase the risk of hyperkalemia.

Trimethoprim (high dose) may increase the risk of hyperkalemia.

As a prodrug, valsartan produces direct antagonism of the angiotensin II (AT2) receptors, unlike the angiotensin-converting enzyme inhibitors. It displaces angiotensin II from the AT1 receptor and produces its blood pressure lowering effects by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses. This action results in more efficient blockade of the cardiovascular effects of angiotensin II and fewer side effects than the ACE inhibitors.

Distribution: V_d: 17 L (adults)

Protein binding: 94% to 97%

Metabolism: Metabolized to an inactive metabolite

Bioavailability: 23%

Half-life: 9 hours

Time to peak serum concentration: 2 hours (maximal effect: 4-6 hours)

Elimination: 13% and 83% excreted as unchanged drug in urine and feces, respectively

Adults: 80 mg/day; may be increased to 160 mg if needed (maximal effects observed in 4-6 weeks).

Dosing adjustment in hepatic impairment (mild - moderate): less than or equal to 80 mg/day

Dialysis: Not significantly removed

Baseline and periodic electrolyte panels, renal and liver function tests, urinalysis; symptoms of hypotension or hypersensitivity

The angiotensin II receptor antagonists appear to have similar indications as the ACE inhibitors. While these drugs have been shown to be effective in treating hypertension, their efficacy in heart failure is being vigorously evaluated. The angiotensin II antagonists are especially useful in providing an alternative therapy in those patients who have intractable cough in response to ACE-inhibitor therapy. Similar to ACE inhibitors, pre-existing volume depletion caused by diuretic therapy may potentiate hypotension in response to angiotensin II antagonists.

May cause dizziness or drowsiness

May rarely cause neutropenia; use caution with clozapine and carbamazepine; barbiturates and carbamazepine may increase the metabolism of valsartan

No information available to require special precautions

No effects or complications reported

Take exactly as directed; do not discontinue without consulting prescriber. Take first dose at bedtime. This drug does not eliminate need for diet or exercise regimen as recommended by prescriber. May cause dizziness, fainting, lightheadedness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); mild hypotension use caution when changing position (rising from sitting or lying position) until response to therapy is established; decreased libido (will resolve). Report chest pain or palpitations; unrelenting headache; swelling of extremities, face, or tongue; muscle weakness or pain; difficulty in breathing or unusual cough; flu-like symptoms; or other persistent adverse reactions. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate contraceptive measures. If you are, or plan to be pregnant, notify your prescriber at once. Do not breast-feed.

Capsule: 80 mg, 160 mg

Munger MA and Furniss SM, "Angiotensin II Receptor Blockers: Novel Therapy for Heart Failure?" Pharmacotherapy, 1996, 16(2 Pt 2):59S-68S.