Dosing and uses of Diovan (valsartan)
Adult dosage forms and strengths
tablet
- 40mg
- 80mg
- 160mg
- 320mg
Hypertension
80-160 mg/day PO
Maintenance: 80-320 mg/day PO
Congestive Heart Failure
40 mg PO q12hr
Maintenance: 40-160 mg PO q12hr; not to exceed 320 mg/day
Post-MI Therapy in Left Ventricular Dysfunction
May be initiated >12 hours after myocardial infarction (MI)
20 mg PO q12hr initially, 12 hrs after MI, then increased to 40 mg PO q12hr within 7 days
Maintenance: Titrated to 160 mg PO q12hr as tolerated
Administration
Although food may decrease absorption (by 40%), manufacturer states drug may be administered without regard to meals
Drug may also be given in combination with hydrochlorothiazide (Diovan HCT) or amlodipine (Exforge)
Dosing Modifications
Renal impairment
- CrCl ≥30 mL/min: No dose adjustment necessary in adults
- CrCl <30 mL/min: Use with caution in adults; not studied in children
Hepatic impairment
- Mild to moderate liver impairment: No adjustment necessary; use with caution in liver disease
- Severe liver impairment: Not studied
Dosing Considerations
Generally, adjust dosage monthly (maximal reduction of BP attained after 4 weeks); adjust more aggressively in high-risk patients and patients with cormorbidities
Pediatric dosage forms and strengths
tablet
- 40mg
- 80mg
- 160mg
- 320mg
Hypertension
<6 years: Safety and efficacy not established
≥6 years: 1.3 mg/kg/day PO (not to exceed 40 mg/day); maintenance: 1.3-2.7 mg/kg/day PO (not to exceed 160 mg/day)
Diovan (valsartan) adverse (side) effects
>10%
Dizziness (17%; heart failure)
Increased blood urea nitrogen (BUN; 17%)
1-10%
Hyperkalemia (4-10%)
Dizziness (2-8%; hypertension)
Hypotension (1-7%; heart failure)
Fatigue (3%)
Viral infection (3%)
Neutropenia (2%)
Syncope (>1%)
Upper abdominal pain (>1%)
Vertigo (>1%)
Frequency not defined
Headache
Cough (rare)
Postmarketing Reports
Hypersensitivity: Angioedema (rare)
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
Do not coadminister with aliskiren in patients with diabetes mellitus
Cautions
Use caution in hereditary angioedema, volume depletion, severe congestive heart failure (CHF), hyperkalemia, hepatic or renal impairment, aortic or mitral valve stenosis, surgery, anesthesia
Discontinue immediately if patient is pregnant; potential risk of congenital abnormalities
Concomitant use with angiotensin-converting enzyme (ACE) inhibitor and beta blocker is not recommended in CHF patients
Post-MI treatment: Consider dosage reduction if hypotension or renal dysfunction occurs after MI
Angioedema, hypotension, hyperkalemia, and renal function deterioration may occur; monitor
Dosage reduction or discontinuance may be required if hyperkalemia or increased serum creatinine occurs
Use with caution in renal artery stenosis; avoid in bilateral renal artery stenosis
Dual blockade of the renin-angiotensin system with angiotensin-receptor blockers (ARBs), ACE inhibitors, or aliskiren is associated with increased risk of hypotension, hyperkalemia, and altered renal function (including acute renal failure) in comparison with monotherapy; closely monitor blood pressure
Avoid coadministration with aliskiren in patients with renal impairment (ie, GFR <60 mL/min/1.73 m²)
Pregnancy and lactation
Pregnancy category: d
Discontinue as soon as pregnancy detected; during the second and third trimesters of pregnancy, resulting oligohydramnios may cause fetal injury (eg, hypotension, neonatal skull hypoplasia, anuria, reversible and irreversible renal failure) and death
Neonates with a history of in utero exposure: Direct attention toward support of blood pressure and renal perfusion; exchange transfusions or dialysis may be required
Lactation: No human data; use with caution
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 (valsartan)
Mechanism of action
Blocks binding of angiotensin II to type 1 angiotensin II receptors, causing a lowering in blood pressure; blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II
Absorption
Bioavailability: 25%
Onset: 2 hr
Duration: 24 hr
Peak serum time: 2-4 hr
Peak response: 4-6 hr
Distribution
Protein bound: 94-95%
Vd: 17 L
Metabolism
Minimally metabolized in liver
Metabolites: Valeryl-4-hydroxyvalsartan (inactive)
Elimination
Half-life: 6-9 hr
Renal clearance: 0.62 L/hr
Total body clearance: 2.2 L/hr
Excretion: Feces (83%), urine (13%)
