Overview
11 DESCRIPTION PREXXARTAN™ (valsartan) is a nonpeptide, orally active, and specific angiotensin II receptor blocker acting on the AT 1 receptor subtype. Valsartan is chemically described as N -(1-oxopentyl)- N -[[2´-(1 H -tetrazol-5-yl) [1,1´-biphenyl]-4-yl]methyl]-L-valine. Its empirical formula is C 2 4H 29 N 5 O 3 , its molecular weight is 435.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Valsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT 1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis.
Indications
- 1 INDICATIONS AND USAGE PREXXARTAN™ is an angiotensin II receptor blocker (ARB) indicated for: • Hypertension in adults and children six years and older, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions ( 1.1 ) • Heart failure (NYHA class II-IV); PREXXARTAN™ significantly reduces hospitalization for heart failure in patients who are unable to swallow valsartan tablets ( 1.
Common Doses
- 80 mg
- 160 mg
- 0.65 mg
- 40 mg
Dosage
2 DOSAGE AND ADMINISTRATION Indication Starting Dose Dose Range Target Maintenance Dose* Hypertension - adults( 2.1 ) 40 or 80 mg twice daily 40 -160 mg twice daily --- Hypertension—age 6 to16 years ( 2.2 ) 0.65 mg/kg twice daily (up to 40 mg total) 0.65-1.35 mg/kg twice daily (up to 40 mg-160 mg total) --- Heart Failure ( 2.3 ) 40 mg twice daily 40 mg-160 mg twice daily 160 mg twice daily Post-Myocardial Infarction ( 2.4 ) 20 mg twice daily 20 mg-160 mg twice daily 160 mg twice daily * As tolerated by patient 2.
Black Box Warning
WARNING: FETAL TOXICITY When pregnancy is detected, discontinue PREXXARTAN TM as soon as possible. ( 5.1 ) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. ( 5.1 ) WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue PREXXARTAN TM as soon as possible. ( 5.1 ) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. ( 5.1 )
Contraindications
- 4 CONTRAINDICATIONS Do not use in patients with known hypersensitivity to any component. Do not coadminister aliskiren with PREXXARTAN™ in patients with diabetes [see Drug Interactions (7) ]. Known hypersensitivity Patients with diabetes on aliskiren ( 4 )
Side Effects
- 6 ADVERSE REACTIONS Hypertension: Most common adverse reactions are headache, dizziness, fatigue and abdominal pain ( 6.1 ) Heart Failure: Most common adverse reactions are dizziness, hypotension, diarrhea, arthralgia, back pain, fatigue and hyperkalemia ( 6.1 ) Post-Myocardial Infarction: Most common adverse reactions which caused patients to discontinue therapy are hypotension, cough and increased blood creatinine ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Carmel Biosciences, Inc. at 1-855-462-3186 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.
Interactions
- 7 DRUG INTERACTIONS • Potassium-sparing diuretics, potassium supplements or salt substitutes may lead to increases in serum potassium, and in heart failure patients, increases in serum creatinine ( 7.1 ) • Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) increase risk of renal impairment and loss of antihypertensive effect ( 7.2 ) • Dual inhibition of the Renin-Angiotensin System (RAS): Increased risk of renal impairment, hypotension, and hyperkalemia ( 7.3 ) • Lithium: Increases in serum lithium level and lithiumtoxicity ( 7.4 ) 7.