What are the treatment guidelines and potential side effects for a patient taking Diovan (valsartan) for hypertension or heart failure?

Diovan (Valsartan) for Hypertension and Heart Failure

Treatment Guidelines

For hypertension, start valsartan at 80-160 mg once daily and titrate up to 320 mg once daily as needed; for heart failure, initiate at 40 mg twice daily and uptitrate to the target dose of 160 mg twice daily. 1, 2

Hypertension Dosing

• Initial dose: 80 mg once daily, typically taken upon awakening 3, 4
• Titration: May increase to 160 mg once daily if blood pressure control is inadequate 1, 2
• Maximum dose: 320 mg once daily for optimal cardiovascular outcomes 5, 2
• Dose-response relationship: Valsartan exhibits predictable dose-dependent efficacy over the 80-320 mg range, with the 160 mg dose providing an optimal efficacy/tolerability ratio 4
• Combination therapy: If monotherapy is insufficient, add hydrochlorothiazide 12.5-25 mg rather than exceeding 160 mg valsartan alone 6, 7

Heart Failure Dosing

• Initial dose: 40 mg twice daily 1, 2
• Titration schedule: Increase to 80 mg twice daily, then to target dose of 160 mg twice daily 1
• Titration frequency: Make dose adjustments no more frequently than every 2 weeks 1
• Target achievement: At least 50% of the target dose (80 mg twice daily minimum) must be achieved for adequate treatment effect 1
• Clinical evidence: The 160 mg twice daily dose reduced the combined endpoint of mortality and morbidity by 13.2% compared to placebo in the Val-HeFT trial 5
• Important caveat: There is no evidence that valsartan provides added benefits when used with an adequate dose of an ACE inhibitor 2

Post-Myocardial Infarction Dosing

• Target dose: 160 mg twice daily for clinically stable patients with left ventricular failure or dysfunction 5, 2
• Evidence: The VALIANT trial demonstrated valsartan was noninferior to captopril for reducing cardiovascular events 5

Potential Side Effects and Monitoring

Common Side Effects

Hypertension patients: 2, 3

• Headache
• Dizziness
• Flu symptoms
• Tiredness
• Abdominal pain

Heart failure patients: 2

• Dizziness (most common)
• Low blood pressure
• Diarrhea
• Joint and back pain
• Tiredness
• High blood potassium

Post-MI patients (leading to discontinuation): 2

• Low blood pressure
• Cough
• Elevated blood creatinine (decreased kidney function)

Serious Warnings and Precautions

Fetal toxicity (BLACK BOX WARNING): 2

• Discontinue immediately when pregnancy is detected
• Use during second and third trimesters causes fetal renal dysfunction, oligohydramnios, skull hypoplasia, anuria, hypotension, renal failure, and death
• Do not breastfeed during treatment 2

Hypotension: 2

• Rarely seen (0.1%) in uncomplicated hypertension 2
• More common in volume-depleted patients or those on high-dose diuretics 2
• In heart failure trials: 5.5% with valsartan vs 1.8% with placebo 2
• In post-MI patients: led to permanent discontinuation in 1.4% of patients 2
• Management: Correct volume depletion before initiating therapy; if excessive hypotension occurs, place patient supine and give IV normal saline if necessary 2

Impaired renal function: 2

• Monitor renal function periodically, especially in patients with renal artery stenosis, chronic kidney disease, severe heart failure, or volume depletion 2
• Consider withholding or discontinuing if clinically significant decrease in renal function develops 2
• No dose adjustment needed for creatinine clearance >10 mL/min 8

Hyperkalemia: 2

• More likely in patients with pre-existing renal impairment 2
• Monitor potassium levels regularly, especially when combined with potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes 2
• May require dosage reduction or discontinuation 2

Drug Interactions Requiring Monitoring

Check levels regularly with: 2

• Lithium (valsartan increases lithium levels)
• Potassium-containing medicines or supplements
• NSAIDs (may worsen renal function)
• Other blood pressure medications

Tolerability Advantages

• Significantly lower incidence of cough compared to ACE inhibitors 5, 3
• Rare reports of angioedema (unlike ACE inhibitors where this is a class effect) 3
• Side effect profile comparable to placebo in most studies 5
• Better tolerated than hydrochlorothiazide alone when used in combination 3

Special Populations

Hepatic dysfunction: 8

• Do not exceed 80 mg once daily
• Not recommended for severe hepatic dysfunction or biliary cirrhosis

Pediatric patients (≥1 year): 2

• Pharmacist will prepare liquid suspension for children 1-5 years or older children who cannot swallow tablets
• Shake suspension well for at least 10 seconds before each dose 2

Clinical Outcomes Evidence

Cardiovascular benefits demonstrated: 5

• Significant reductions in heart failure hospitalizations (24% in Val-HeFT, 17% in CHARM-Added) 6
• 40% reduction in stroke incidence when added to conventional therapy in high-risk Japanese hypertensive patients (JIKEI HEART study) 6
• Comparable magnitude of effect to ACE inhibitors for mortality and morbidity reduction 5
• Improvements in NYHA functional class, ejection fraction, and quality of life 5