Valsartan (ARB)

Snapshot from Phun Pharm facts
Angiotensin II receptor antagonist (ARB)
  Use: htn, safe in pts with impaired glucose intolerance

·         Action: blocking the binding of angiotensin II to the AT ₁ receptor in vascular smooth muscle and the adrenal gland, producing decreased BP.

·         SE:  headache and dizziness

·         CI: preg/lact

·          Interactions: Lithium, Potassium-sparing diuretics (eg, spironolactone), potassium supplements

Today's med: Valsartan (val SAR tan) 
(brand name: Diovan)

Drug Class: Angiotensin II receptor antagonist

Other Drugs in this class: Valsartan/hydrochlorothiazide, Losartan,Olmesartan, Irbesartan, 
Candesartan,Telmisartan, Losartan/hydrochlorothiazide,Azilsartan, Eprosartan,Telmisartan/hydrochlorothiazide, 
Losartan Potassium, Aliskiren/Valsartan,Candesartan cilexetil,Amlodipine/Valsartan/Hydrochlorothiazide,
Telmisartan/Amlodipine,Candesartan/Hydrochlorothiazide,Irbesartan/Hydrochlorothiazide,Amlodipine/Olmesartan,Olmesartan/Hydrochlorothiazide,Olmesartan/Amlodipine/Hydrochlorothiazide,Eprosartan mesylate, Amlodipine/Valsartan,Azilsartan kamedoxomil,Azilsartan/Chlorthalidone,Eprosartan/Hydrochlorothiazide, 
Olmesartan medoxomil

Indications: Alone or in combination with other antihypertensive agents in the treatment of essential hypertension; reduction of cardiovascular mortality in patients with left ventricular dysfunction postmyocardial infarction; treatment of heart failure (NYHA Class II-IV)

Action: Valsartan produces direct antagonism of the angiotensin II (AT2) receptors, unlike the ACE 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.

Contraindications: Hypersensitivity to valsartan or any component of the formulation; concomitant use with aliskiren in patients with diabetes mellitus

Adverse Effects: >10%:Central nervous system: Dizziness (heart failure trials 17%)

Renal: BUN increased >50% (heart failure trials 17%)

1% to 10%:

Cardiovascular: Hypotension (heart failure trials 7%; MI trial 1%), orthostatic hypotension (heart failure trials 2%), syncope (up to >1%)

Central nervous system: Dizziness (hypertension trial 2% to 8%), fatigue (heart failure trials 3%; hypertension trial 2%), postural dizziness (heart failure trials 2%), headache (heart failure trials >1%), vertigo (up to >1%)

Endocrine & metabolic: Serum potassium increased by >20% (4% to 10%), hyperkalemia (heart failure trials 2%)

Gastrointestinal: Diarrhea (heart failure trials 5%), abdominal pain (2%), nausea (heart failure trials >1%), upper abdominal pain (heart failure trials >1%)

Hematologic: Neutropenia (2%)

Neuromuscular & skeletal: Arthralgia (heart failure trials 3%), back pain (up to 3%)

Ocular: Blurred vision (heart failure trials >1%)

Renal: Creatinine doubled (MI trial 4%), creatinine increased >50% (heart failure trials 4%), renal dysfunction (up to >1%)

Respiratory: Cough (1% to 3%)

Miscellaneous: Viral infection (3%)

All indications: <1% (Limited to important or life-threatening): Allergic reactions, alopecia, anaphylaxis, anemia, angioedema, anorexia, anxiety, chest pain, constipation, dyspepsia, dyspnea, flatulence, hematocrit/hemoglobin decreased, hepatitis (rare), impotence, insomnia, liver function tests increased, microcytic anemia, muscle cramps, myalgia, palpitation, paresthesia, photosensitivity, pruritus, rash, renal failure, rhabdomyolysis, somnolence, taste disorder, thrombocytopenia (very rare), vasculitis, vomiting, weakness, xerostomia

Concerns related to adverse effects:

• Hyperkalemia: May occur; risk factors include renal dysfunction, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use with caution with these agents; monitor potassium closely.

• Hypotension: During the initiation of therapy, hypotension may occur, particularly in patients with heart failure or post-MI patients. Symptomatic hypotension may occur upon initiation in patients who are salt- or volume-depleted (eg, those treated with high-dose diuretics); correct volume depletion prior to administration. This transient hypotensive response is not a contraindication to further treatment with valsartan.

• Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose glomerular filtration rate (GFR) is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function.

Disease-related concerns:

• Aortic/mitral stenosis: Use with caution in patients with significant aortic/mitral stenosis.

• Heart failure: Use caution when initiating in heart failure; may need to adjust dose, and/or concurrent diuretic therapy, because of valsartan-induced hypotension. Careful monitoring of BUN, serum creatinine, and potassium is necessary especially if preexisting renal disease exists.

• Hepatic impairment: Use caution in patients with significant hepatic impairment since clearance is significantly reduced.

• Renal artery stenosis: Use valsartan with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks.

• Renal impairment: Use with caution with pre-existing renal insufficiency and severe renal impairment.

Concurrent drug therapy issues:

• Angiotensin-converting enzyme (ACE) inhibitors and renin inhibitors: Concomitant use of an ACE-inhibitor or renin inhibitor (eg, aliskiren) is associated with an increased risk of hypotension, hyperkalemia, and renal dysfunction. Concomitant use with aliskiren should be avoided in patients with GFR <60 mL/minute and is contraindicated in patients with diabetes mellitus (regardless of GFR).

Special populations:

• Pediatrics: Canadian labeling: Use is not approved in patients <18 years of age.

• Pregnancy: [U.S. Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.

Pregnancy Risk Factor D

Standard Dosing: Oral:  Hypertension:

Children 6-16 years: Initial: 1.3 mg/kg once daily (maximum: 40 mg/day); dose may be increased to achieve desired effect; doses >2.7 mg/kg (maximum: 160 mg) have not been studied

Adults: Initial: 80 mg or 160 mg once daily (in patients who are not volume depleted); dose may be increased to achieve desired effect; maximum recommended dose: 320 mg daily

Heart failure: Adults: Initial: 40 mg twice daily; titrate dose to 80-160 mg twice daily, as tolerated; maximum daily dose: 320 mg

Left ventricular dysfunction after MI: Adults: Initial: 20 mg twice daily; titrate dose to target of 160 mg twice daily as tolerated; may initiate ≥12 hours following MI

Administer with or without food.

Drug interactions: http://www.drugs.com/drug-interactions/valsartan.html

A total of 376 drugs (1787 brand and generic names) are known to interact with valsartan.

• 43 major drug interactions (196 brand and generic names)
• 331 moderate drug interactions (1586 brand and generic names)
• 2 minor drug interactions (5 brand and generic names)

Show all medications in the database that may interact with valsartan.

ACE Inhibitors: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of ACE Inhibitors. Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function.Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Monitor therapy

Val's-ARB-tan.