Cardene I.V. Product Overview

Cardene I.V. Product Overview

	Overview
	Cardene, or nicardipine hydrochloride, is a IV calcium channel blocker (i.e. "calcium ion influx inhibitor") available for the short-term treatment of hypertension, or high blood pressure, when oral therapy is not feasible or desirable.
		Active ingredient: nicardipine hydrochloride
		AHA / ECC and ASA guidelines recommend nicardipine as first-line treatment
	Disease State
	Hypertension affects nearly 1 in 3 adults in the United States and can directly increase one's risk of coronary heart disease, which may lead to stroke or heart attack.¹ There are approximately 26 million patients treated annually with a hypertension drug in a hospital setting, 3.1 million of whom are administered an IV antihypertensive drug.² Often, hospitalized patients experiencing hypertension may not be able to take certain medications because they are awaiting surgery or may be intubated and therefore cannot take oral medication.
	Hypertensive Emergency
	A number of clinical circumstances may require rapid reduction of blood pressure (BP). These circumstances, termed hypertensive crises, may be separated into emergencies, which require immediate (within minutes to a few hours) lowering of BP to safe levels, and urgencies, which can be safely treated with oral antihypertensive drugs with early follow-up.³ The distinction between emergencies and urgencies is based on the presence of end-organ damage and not on a specific BP level, although organ dysfunction is uncommon with diastolic blood pressure (DBP) <130 mm Hg. In addition, the absolute BP level may not be as important as the rate of increase.⁴ Hypertensive emergencies are uncommon and probably occur in less than 1% to 2% of the hypertensive population with hypertension.³ Nevertheless, because of the high prevalence of hypertension in the United States, about 500,000 patients experience a hypertensive emergency annually.³
	End-Organ Damage in Hypertensive Crises
	Examples of end-organ damage observed most often in a hypertensive emergency are shown on this slide. Patients may experience any of the following:
		Hypertensive encephalopathy with or without stroke
		Unstable angina, acute heart failure, acute myocardial infarction (MI), or dissecting aortic aneurysm
		Retinal hemorrhages, exudates, or papilledema
		Hematuria, proteinuria, or decreasing renal function

	Pathophysiology of Hypertensive Emergency
	Regardless of the underlying cause of the hypertensive emergency, it is hypothesized that the final common pathway is a sudden increase in systemic vascular resistance (SVR) and, consequently, an increase in BP due to the action of circulating vasoconstrictors, such as catecholamines and angiotensin, on arterioles.^5-8 The resulting increase in BP damages the endothelium, leading to the release of local vasoconstrictors, such as endothelin, which cause further vasoconstriction, often with intravascular hypovolemia.^5-8 Damage to the endothelium impairs autoregulatory function. Autoregulation refers to the inherent ability of arteries to dilate or constrict in response to changing perfusion pressures in order to maintain a relatively constant blood flow. Further release of humoral vasoconstrictors perpetuates the "vicious circle."^5,7,8 It is important to note that, in this setting, hypovolemia is often due to 2 factors:⁵
		An initial pressure natriuresis and diuresis accompany the onset of the hypertensive episode
		Fluid intake usually decreases as the episode and symptoms progress
	The resultant hypovolemia contributes to end-organ damage.⁵

	Goal of Therapy in Hypertensive Crises
	The goal in treating a hypertensive crisis is to lower BP immediately but in a controlled manner, so as not to fall off the autoregulatory curve and risk ischemia and additional end-organ damage.⁴ It is recommended that resting mean arterial pressure (MAP) not to be reduced >25%.³ It is recommended that BP be initially decreased by 10% to 15%.⁴ Treatment of many patients with severe, uncomplicated hypertension may be overly aggressive.⁹ "Aggressive dosing with IV or even oral antihypertensive agents to lower BP rapidly is not without risk."⁹
	Efficacy and Safety of Cardene I.V.
	Intravenous Cardene has been well studied and is approved for the short-term treatment of acute hypertension. The drug has been shown to effectively and safely control the acute increase in blood pressure in patients with severe hypertension with and without end-organ damage. Because postoperative hypertension occurs in 4-30% of patients after cardiac and noncardiac surgery, rapid control of the condition is desirable. In a randomized study involving patients who had undergone cardiac or noncardiac surgery, intravenous Cardene was effective in controlling blood pressure in 92% of patients. A therapeutic response was achieved in a mean time of 10-12 minutes.¹¹
	Cardene I.V. offers rapid, precise blood pressure control in a variety of patient types, and has been proven to be as effective as sodium nitroprusside with fewer dose adjustments and lower risk of hypotension.^10,12 Cardene improves left ventricular diastolic distensibility, offering a reduced risk of ischemia. Close monitoring of blood pressure is required during treatment, although minimal dose adjustments are required because there is no correlation between patient weight and dose response.
	Studies have also shown that Cardene I.V. is both effective and well tolerated for controlling blood pressure in emergency situations.¹²
	BP treatment goal achieved with CARDENE I.V. in multiple studies.

	*Patient type = postoperative hypertension within 24 hours of surgery; entry criteria = SBP 200 mm Hg or DBP 110 mm Hg; BP treatment goal = >15% decrease from pretreatment. The initial infusion dose used for CARDENE I.V. in this study (10 mg/hr) differs from the recommended initial dose in the package insert (5 mg/hr). †Patient type = acute medical; entry criteria = SBP >200 mm Hg or DBP >120 mm Hg; BP treatment goal = SBP 180 mm Hg or 20 mm Hg decrease from baseline. ‡Patient type = postoperative hypertension within 24 hours of surgery; entry criteria = SBP 140 mm Hg or DBP 95 mm Hg; BP treatment goal = 15% decrease from pretreatment baseline. §Patient type = severe hypertension; entry criteria = SBP >200 mm Hg or DBP >120 mm Hg; BP treatment goal = DBP 95 mm Hg; decrease in DBP 25 mm Hg or SBP 160 mm Hg; decrease in SBP 50 mm Hg.
	Click here for Safety and Tolerability Information
	Please see Important Safety Information at the bottom of the page.
	Well-documented safety profile

	How Cardene Works
	Cardene I.V., which is administered directly into the bloodstream, prevents calcium ions from entering cardiac and vascular smooth muscle cells through specific ion channels in the cell membrane, thus preventing the vascular smooth muscle from contracting. The drug, which is more selective for vascular muscle cells, causes arteries to dilate (relax) and blood pressure to decrease.
	Cardene I.V. is administered as a slow continuous infusion at a concentration of 0.1 mg/mL. Ampuls must be diluted before infusion. For rapid blood pressure control, therapy is initiated at a loading dose of 50 mL/hr (5 mg/hr) and titrated by 2.5 mg/hour every 5 minutes up to 15 mg/hour until the desired results are achieved. Then, the infusion rate is decreased to 30 mL/hr (3 mg/hr). For gradual reduction in blood pressure, the infusion rate is increased every 15 minutes until desired blood pressure is reached; for prolonged control, patients should be transferred to oral medication as soon as their clinical condition permits.

Important Safety Information

Close monitoring of the blood pressure is required during therapy. CARDENE I.V. is contraindicated in patients with known hypersensitivity to the drug and in patients with advanced aortic stenosis. Reduction of diastolic pressure and reduced afterload may worsen rather than improve myocardial oxygen balance. Caution is advised when administering CARDENE I.V. to patients with impaired renal or hepatic function, in combination with a beta-blocker in patients with congestive heart failure, or portal hypertension. Observe caution in patients with significant left ventricular dysfunction due to possible negative inotropic effect. CARDENE I.V. gives no protection against the dangers of abrupt beta-blocker withdrawal; beta-blocker dosage should be gradually reduced. Levels of cyclosporine should be closely monitored during therapy. The most common side effects of CARDENE I.V. are headache (14.6%), hypotension (5.6%), nausea/vomiting (4.9%), and tachycardia (3.5%). Less frequent adverse effects, in each case occurring at 1.4%, include ECG abnormalities, postural hypotension, ventricular extrasystoles, injection-site reaction, dizziness, sweating and polyuria.

Please see full prescribing information.

	References
	1.	American Heart Association. Heart Disease and Stroke Statistics, 2006 update. Available at: http://americanheart.org/presenter.jhtml?identifier=1928.
	2.	Hospital in-patient data from Premier Healthcare Informatics, Rx Market Advisor [database], 2005.
	3.	Mansoor GA, Frishman WH. Comprehensive management of hypertension emergencies and urgencies. Heart Dis. 2002;4:358-371.
	4.	Varon J, Marik PE. The diagnosis and management of hypertension crises. Chest. 2000;118:214-227.
	5.	Ault NJ, Ellrodt AG. Pathophysiological events leading to the end-organ effects of acute hypertension. Am J Emerg Med. 1985;3(6 suppl):10-15.
	6.	Wallach R et al. Pathogenesis of paroxysmal hypertension developing during and after coronary bypass surgery: a study of hemodynamic and humoral factors. Am J Cardiol. 1980;46:559-565.
	7.	Varon J, Marik PE. The diagnosis and management of hypertension crises. Chest. 2000;118:214-227.
	8.	Kincaid-Smith P. J Hypertens. 1991;9:893-899.
	9.	Nishiyama T, Yokoyama T, Matsukawa T, Hanaoka K. Continuous nicardipine infusion to control blood pressure after evacuation of acute cerebral hemorrhage. Can J Anesth. 2000;47:1196-1201.
	10.	Halpern NA, Goldberg M, Neely C, et al. Postoperative hypertension: a multicenter, prospective, randomized comparison between intravenous nicardipine and sodium nitroprusside. Crit Care Med. 1992;20:1637-1643.
	11.	Fischell TA, Maheshwari A. Current applications for nicardipine in invasive and interventional cardiology. J Invasive Cardiol. 2004;16:428-432.
	12.	Neutel JM, Smith DHG, Wallin D, et al. A comparison of intravenous nicardipine and sodium nitroprusside in the immediate treatment of severe hypertension. Am J Hypertens. 1994;7:623-628.