CARDENE® SR is a sustained release formulation of CARDENE®. CARDENE SR capsules for oral administration each contain 30 mg, 45 mg or 60 mg of nicardipine hydrochloride. Nicardipine hydrochloride is a calcium ion influx inhibitor (slow channel blocker or calcium entry blocker).

Nicardipine hydrochloride is a dihydropyridine derivative with the IUPAC (International Union of Pure and Applied Chemistry) chemical name (±)-2-(benzyl-methyl amino)ethyl methyl 1,4-dihydro-2,6 dimethyl- 4-(m-nitrophenyl)-3,5-pyridinedicarboxylate monohydrochloride, and it has the following structure:

Nicardipine hydrochloride is a greenish-yellow, odorless, crystalline powder that melts at about 169°C. It is freely soluble in chloroform, methanol and glacial acetic acid, sparingly soluble in anhydrous ethanol, slightly soluble in n-butanol, water, 0.01 M potassium dihydrogen phosphate, acetone and dioxane, very slightly soluble in ethyl acetate, and practically insoluble in benzene, ether and hexane. It has a molecular weight of 515.99.

CARDENE SR is available in hard gelatin capsules containing 30 mg, 45 mg or 60 mg nicardipine hydrochloride. All strengths contain a two component capsule fill. A powder component containing 25% of total nicardipine hydrochloride dose contains pregelatinized starch and magnesium stearate as inactive ingredients. A spherical granule component containing 75% of total nicardipine hydrochloride dose also contains microcrystalline cellulose, starch, lactose and methacrylic acid copolymer Type C as inactive ingredients.

The colorants used in the 30-mg capsules are titanium dioxide, FD& Red No. 40 and red iron oxide, and the colorants used in the 45-mg and 60-mg capsules are titanium dioxide and FD&C Blue No. 2.

Last updated on RxList: 6/19/2009

CARDENE SR is indicated for the treatment of hypertension. CARDENE SR may be used alone or in combination with other antihypertensive drugs.

The dose of CARDENE SR should be individually adjusted according to the blood pressure response beginning with 30 mg two times daily. The effective doses in clinical trials have ranged from 30 mg to 60 mg two times daily. The maximum blood pressure lowering effect at steady-state is sustained from 2 hours until 6 hours after dosing.

When initiating therapy or upon increasing dose, blood pressure should be measured 2 to 4 hours after the first dose or dose increase, as well as at the end of a dosing interval.

The total daily dose of immediate release nicardipine (CARDENE) may not be a useful guide to judging the effective dose of CARDENE SR. Patients currently receiving immediate release nicardipine may be titrated with CARDENE SR starting at their current total daily dose of immediate release nicardipine and then reexamined to assess the adequacy of blood pressure control.

Concomitant Use With Other Antihypertensive Agents

• Diuretics: CARDENE may be safely coadministered with thiazide diuretics.
• Beta-Blockers: CARDENE may be safely coadministered with betablockers (see DRUG INTERACTIONS).

Special Patient Populations

Renal Insufficiency: Although there is no evidence that CARDENE SR impairs renal function, careful dose titration beginning with 30-mg CARDENE SR bid is advised (see PRECAUTIONS).

Hepatic Insufficiency: CARDENE SR has not been studied in patients with severe liver impairment (see PRECAUTIONS).

Congestive Heart Failure: Caution is advised when titrating CARDENE SR dosage in patients with congestive heart failure (see WARNINGS).

CARDENE® SR 30-mg capsules are available in opaque pink-pink hard gelatin capsules. The capsule cap is printed with CARDENE SR 30 mg and the capsule body is printed with PDL BioPharma. These are supplied in bottles of 60 (NDC 67286-0813-2) and bottles of 200 (NDC 67286-0813-1).

CARDENE® SR 45-mg capsules are available in opaque powder bluepowder blue hard gelatin capsules. The capsule cap is printed with CARDENE SR 45 mg and the capsule body is printed with PDL BioPharma. These are supplied in bottles of 60 (NDC 67286-0813-4) and bottles of 200 (NDC 67286-0813-3).

CARDENE® SR 60-mg capsules are available in opaque light blue-white hard gelatin capsules. The capsule cap is printed with CARDENE SR 60 mg and the capsule body is printed with PDL BioPharma. These are supplied in bottles of 60 (NDC 67286-0813-5).

Store bottles at 15° to 30°C (59° to 86°F) and dispense in light-resistant containers, such as the manufacturer's original container.

For questions of a medical nature or to report an adverse event, call 1-866-437-7742.

Marketed by: PDL BioPharma, Inc., Redwood City, CA 94063. Revised: January 2007.

Last updated on RxList: 6/19/2009

In multiple-dose US and foreign controlled studies, 667 patients received CARDENE SR. In these studies adverse events were elicited by nondirected and in some cases directed questioning; adverse events were generally not serious and about 9% of patients withdrew prematurely from the studies because of them.

Hypertension

The incidence rates of adverse events in hypertensive patients were derived from placebo-controlled clinical trials. Following are the rates of adverse events for CARDENE SR (n=322) and placebo (n=140), respectively, that occurred in 0.6% of patients or more on CARDENE SR. These represent events considered probably drug related by the investigator. Where the frequency of adverse events for CARDENE SR and placebo is similar, causal relationship is uncertain. The only dose-related effect was pedal edema.

Percentage of Patients With Probably Drug Related Adverse Events in Placebo-Controlled Studies

Incidence (%) of Discontinuations Due to Any Adverse Event in Placebo-Controlled Studies

Uncontrolled experience in over 300 patients with hypertension treated for up to 27.5 months with CARDENE SR has shown no unexpected adverse events or increase in incidence of adverse events compared to the controlled clinical trials.

Rare Events

The following rare adverse events have been reported in clinical trials or the literature:

Body as a Whole: infection, allergic reaction

Cardiovascular: hypotension, atypical chest pain, peripheral vascular disorder, ventricular extrasystoles, ventricular tachycardia, angina pectoris

Digestive: sore throat, abnormal liver chemistries

Musculoskeletal: arthralgia

Nervous: hot flashes, vertigo, hyperkinesia, impotence, depression, confusion, anxiety

Respiratory: rhinitis, sinusitis

Special Senses: tinnitus, abnormal vision, blurred vision

Angina

Data are available from only 91 patients with chronic stable angina pectoris who received CARDENE SR 30 to 60 mg administered twice daily in open-label clinical trials. Fifty-eight of these patients were treated for at least 30 days. The four most frequently reported adverse events thought by the investigators to be probably related to the use of CARDENE SR were vasodilatation (5.5%), pedal edema (4.4%), asthenia (4.4%), and dizziness (3.3%).

Beta-Blockers

In controlled clinical studies, adrenergic beta-receptor blockers have been frequently administered concomitantly with CARDENE. The combination is well tolerated.

Cimetidine

Cimetidine increases CARDENE plasma levels. Patients receiving the two drugs concomitantly should be carefully monitored.

Digoxin

Some calcium blockers may increase the concentration of digitalis preparations in the blood. CARDENE usually does not alter the plasma levels of digoxin; however, serum digoxin levels should be evaluated after concomitant therapy with CARDENE is initiated.

Fentanyl Anesthesia

Severe hypotension has been reported during fentanyl anesthesia with concomitant use of a beta-blocker and a calcium channel blocker. Even though such interactions were not seen during clinical studies with CARDENE, an increased volume of circulating fluids might be required if such an interaction were to occur.

Cyclosporine

Concomitant administration of nicardipine and cyclosporine results in elevated plasma cyclosporine levels. Plasma concentrations of cyclosporine should therefore be closely monitored, and its dosage reduced accordingly, in patients treated with nicardipine.

When therapeutic concentrations of furosemide, propranolol, dipyridamole, warfarin, quinidine or naproxen were added to human plasma (in vitro), the plasma protein binding of CARDENE was not altered.

Last updated on RxList: 6/19/2009

Increased Angina in Patients With Angina

In short-term, placebo-controlled angina trials with CARDENE (an immediate release oral dosage form of nicardipine), about 7% of patients on CARDENE (compared with 4% of patients on placebo) have developed increased frequency, duration or severity of angina. Comparisons with beta-blockers also show a greater frequency of increased angina, 4% vs 1%. The mechanism of this effect has not been established.

Use in Patients With Congestive Heart Failure

Although preliminary hemodynamic studies in patients with congestive heart failure have shown that CARDENE reduced afterload without impairing myocardial contractility, it has a negative inotropic effect in vitro and in some patients. Caution should be exercised when using the drug in congestive heart failure patients, particularly in combination with a beta-blocker.

Beta-Blocker Withdrawal

CARDENE is not a beta-blocker and therefore gives no protection against the dangers of abrupt beta-blocker withdrawal; any such withdrawal should be by gradual reduction of the dose of beta-blocker, preferably over 8 to 10 days.

General

Blood Pressure

Because CARDENE decreases peripheral resistance, careful monitoring of blood pressure during the initial administration and titration of CARDENE is suggested. CARDENE, like other calcium channel blockers, may occasionally produce symptomatic hypotension. Caution is advised to avoid systemic hypotension when administering the drug to patients who have sustained an acute cerebral infarction or hemorrhage.

Use in Patients With Impaired Hepatic Function

Since the liver is the major site of biotransformation and since CARDENE is subject to firstpass metabolism, CARDENE should be used with caution in patients having impaired liver function or reduced hepatic blood flow. Patients with severe liver disease developed elevated blood levels (fourfold increase in AUC) and prolonged half-life (19 hours) of CARDENE.

Use in Patients With Impaired Renal Function

When 45-mg CARDENE SR bid was given to hypertensive patients with moderate renal impairment, mean AUC and Cmax values were approximately 2-fold to 3-fold higher than in patients with mild renal impairment. Doses in these patients must be adjusted. Mean AUC and Cmax values were similar in patients with mildly impaired renal function and normal volunteers (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Rats treated with nicardipine in the diet (at concentrations calculated to provide daily dosage levels of 5, 15 or 45 mg/kg/day) for 2 years showed a dose-dependent increase in thyroid hyperplasia and neoplasia (follicular adenoma/carcinoma). One- and 3-month studies in the rat have suggested that these results are linked to a nicardipine-induced reduction in plasma thyroxine (T₄) levels with a consequent increase in plasma levels of thyroid stimulating hormone (TSH). Chronic elevation of TSH known to cause hyperstimulation of the thyroid. In rats on an iodine deficient diet, nicardipine administration for 1 month was associated with thyroid hyperplasia that was prevented by T₄ supplementation. Mice treated with nicardipine in the diet (at concentrations calculated to provide daily dosage levels of up to 100 mg/kg/day) for up to 18 months showed no evidence of neoplasia of any tissue and no evidence of thyroid changes. There was no evidence of thyroid pathology in dogs treated with up to 25 mg nicardipine/kg/day for 1 year and no evidence of effects of nicardipine on thyroid function (plasma T4 and TSH) in man.

There was no evidence of a mutagenic potential of nicardipine in battery of genotoxicity tests conducted on microbial indicator organisms, in micronucleus tests in mice and hamsters, or in a sister chromatid exchange study in hamsters.

No impairment of fertility was seen in male or female rats administered nicardipine at oral doses as high as 100 mg/kg/day (50 times the maximum recommended daily dose in man, assuming a patient weight of 60 kg).

Pregnancy

Pregnancy Category C

Nicardipine was embryocidal when administered orally to pregnant Japanese White rabbits, during organogenesis, at 150 mg/kg/day (a dose associated with marked body weight gain suppression in the treated doe) but not at 50 mg/kg/day (25 times the maximum recommended dose in man). No adverse effects on the fetus were observed when New Zealand albino rabbits were treated, during organogenesis, with up to 100 mg nicardipine/kg/day (a dose associated with significant mortality in the treated doe). In pregnant rats administered nicardipine orally at up to 100 mg/kg/day (50 times the maximum recommended human dose) there was no evidence of embryolethality or teratogenicity. However, dystocia, reduced birth weights, reduced neonatal survival and reduced neonatal weight gain were noted. There are no adequate and well-controlled studies in pregnant women. CARDENE SR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Studies in rats have shown significant concentrations of nicardipine in maternal milk following oral administration. For this reason it is recommended that women who wish to breastfeed should not take this drug.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Pharmacokinetic parameters did not differ significantly between elderly hypertensive subjects (mean age: 70 years) and younger hypertensive subjects (mean age: 44 years) after 1 week of treatment with CARDENE SR (see CLINICAL PHARMACOLOGY: Geriatric Pharmacokinetics).

Clinical studies of nicardipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Last updated on RxList: 6/19/2009

Three overdosages with CARDENE or CARDENE SR have been reported. Two occurred in adults, 1 of whom ingested 600 mg of CARDENE and the other 2160 mg of CARDENE SR. Symptoms included marked hypotension, bradycardia, palpitations, flushing, drowsiness, confusion, and slurred speech. All symptoms resolved without sequelae. The third overdosage occurred in a 1-year-old child who ingested half of the powder in a 30-mg CARDENE capsule. The child remained asymptomatic.

Based on results obtained in laboratory animals, overdosage may cause systemic hypotension, bradycardia (following initial tachycardia) and progressive atrioventricular conduction block. Reversible hepatic function abnormalities and sporadic focal hepatic necrosis were noted in some animal species receiving very large doses of nicardipine.

For treatment of overdose standard measures (for example, evacuation of gastric contents, elevation of extremities, attention to circulating fluid volume, and urine output) including monitoring of cardiac and respiratory functions should be implemented. The patient should be positioned so as to avoid cerebral anoxia. Frequent blood pressure determinations are essential. Vasopressors are clinically indicated for patients exhibiting profound hypotension. Intravenous calcium gluconate may help reverse the effects of calcium entry blockade.

CARDENE is contraindicated in patients with hypersensitivity to the drug. Because part of the effect of CARDENE is secondary to reduced afterload, the drug is also contraindicated in patients with advanced aortic stenosis. Reduction of diastolic pressure by any means in these patients may worsen rather than improve myocardial oxygen balance.

Last updated on RxList: 6/19/2009

Mechanism of Action

Nicardipine is a calcium entry blocker (slow channel blocker or calcium ion antagonist) that inhibits the transmembrane influx of calcium ions into cardiac muscle and smooth muscle without changing serum calcium concentrations. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. The effects of nicardipine are more selective to vascular smooth muscle than cardiac muscle. In animal models, nicardipine produces relaxation of coronary vascular smooth muscle at drug levels that cause little or no negative inotropic effect.

Pharmacokinetics and Metabolism

Nicardipine is completely absorbed following oral doses administered as capsules, and the systemic bioavailability is about 35% following 30-mg oral dose at steady-state. The pharmacokinetics of nicardipine are nonlinear due to saturable hepatic first-pass metabolism.

Following oral administration of CARDENE SR, plasma levels are detectable as early as 20 minutes and maximal plasma levels are achieved as a broad peak generally between 1 and 4 hours. The average terminal plasma half-life of nicardipine is 8.6 hours. Following oral administration increasing doses result in disproportionate increases in plasma levels. Steady-state Cmax values following 30-, 45- and 60-mg doses every 12 hours averaged 13.4, 34.0, and 58.4 ng/mL, respectively. Hence, increasing the dose twofold increases maximum plasma levels 4-fold to 5-fold. A similar disproportionate increase is observed with AUC. In comparison with equivalent daily doses of CARDENE capsules, CARDENE SR shows a significant reduction in Cmax. CARDENE SR also has somewhat lower bioavailability than CARDENE except at the highest dose. Minimum plasma levels produced by equivalent daily doses are similar. CARDENE SR thus exhibits significantly reduced fluctuation in plasma levels in comparison to CARDENE capsules.

When CARDENE SR was administered with a high-fat breakfast, mean Cmax was 45% lower, AUC was 25% lower and trough levels were 75% higher than when CARDENE SR was given in the fasting state. Thus, taking CARDENE SR with the meal reduced the fluctuation in plasma levels. Clinical trials establishing the safety and efficacy of CARDENE SR were carried out in patients without regard to the timing of meals.

Nicardipine is highly protein bound ( > 95%) in human plasma over wide concentration range.

Nicardipine is metabolized extensively by the liver; less than 1% of intact drug is detected in the urine. Following a radioactive oral dose in solution, 60% of the radioactivity was recovered in the urine and 35% in feces. Most of the dose (over 90%) was recovered within 48 hours of dosing. Nicardipine does not induce its own metabolism and does not induce hepatic microsomal enzymes.

Nicardipine plasma levels following administration of CARDENE SR in hypertensive patients with moderate renal impairment (creatinine clearance 10 to 55 mL/min) were significantly higher following a single-oral dose and at steady-state than in hypertensive patients with mildly nicardipine hydrochloride impaired renal function (creatinine clearance > 55 mL/min). After 45-mg CARDENE SR bid at steady-state, Cmax and AUC were 2-fold to 3-fold higher in the patients with moderate renal impairment. Plasma levels in patients with mildly impaired renal function were similar to those in normal subjects.

In patients with severe renal impairment undergoing routine hemodialysis, plasma levels following a single dose of CARDENE SR were not significantly different from those patients with mildly impaired renal function.

Because nicardipine is extensively metabolized by the liver, the plasma levels of the drug are influenced by changes in hepatic function. Following administration of CARDENE capsules, nicardipine plasma levels were higher in patients with severe liver disease (hepatic cirrhosis confirmed by liver biopsy or presence of endoscopically-confirmed esophageal varices) than in normal subjects. After 20-mg CARDENE bid at steady-state, Cmax and AUC were 1.8-fold and 4-fold higher, and the terminal half-life was prolonged to 19 hours in these patients. CARDENE SR has not been studied in patients with severe liver disease.

Geriatric Pharmacokinetics

The pharmacokinetics of CARDENE SR in elderly hypertensive subjects mean age 70 years) were compared to those in younger hypertensive subjects (mean age 44 years). After a single dose and after 1 week of dosing with CARDENE SR there were no significant differences in Cmax, Tmax, AUC or clearance between the young and elderly subjects. In both groups of subjects, steady-state plasma levels were significantly higher than following a single dose. In the elderly subjects, a disproportional increase in plasma levels with dose was observed similar to that observed in normal subjects.

Hemodynamics

In man, nicardipine produces a significant decrease in systemic vascular resistance. The degree of vasodilation and the resultant hypotensive effects are more prominent in hypertensive patients. In hypertensive patients, nicardipine reduces the blood pressure at rest and during isometric and dynamic exercise. In normotensive patients, a small decrease of about 9 mm Hg in systolic and 7 mm Hg in diastolic blood pressure may accompany this fall in peripheral resistance. An increase in heart rate may occur in response to the vasodilation and decrease in blood pressure, and in a few patients this heart rate increase may be pronounced. In clinical studies mean heart rate at time of peak plasma levels was usually increased by 5 to 10 beats per minute compared to placebo, with the greater increases at higher doses, while there was no difference from placebo at the end of the dosing interval. Hemodynamic studies following intravenous dosing in patients with coronary artery disease and normal or moderately abnormal left ventricular function have shown significant increases in ejection fraction and cardiac output CARDENE® SR (nicardipine hydrochloride) with no significant change, or a small decrease, in left ventricular enddiastolic pressure (LVEDP). Although there is evidence that nicardipine increases coronary blood flow, there is no evidence that this property plays any role in its effectiveness in stable angina. In patients with coronary artery disease, intracoronary administration of nicardipine caused no direct myocardial depression. CARDENE does, however, have a negative inotropic effect in some patients with severe left ventricular dysfunction and could, in patients with very impaired function, lead to worsened failure.

“Coronary Steal,” the detrimental redistribution of coronary blood flow in patients with coronary artery disease (diversion of blood from underperfused areas toward better perfused areas), has not been observed during nicardipine treatment. On the contrary, nicardipine has been shown to improve systolic shortening in normal and hypokinetic segments of myocardial muscle, and radionuclide angiography has confirmed that wall motion remained improved during an increase in oxygen demand. Nonetheless, occasional patients have developed increased angina upon receiving nicardipine. Whether this represents steal in those patients, or is the result of increased heart rate and decreased diastolic pressure, is not clear.

In patients with coronary artery disease nicardipine improves L.V. diastolic distensibility during the early filling phase, probably due to a faster rate of myocardial relaxation in previously underperfused areas. There is little or no effect on normal myocardium, suggesting the improvement is mainly by indirect mechanisms such as afterload reduction and reduced ischemia. Nicardipine has no negative effect on myocardial relaxation at therapeutic doses. The clinical consequences of these properties are as yet undemonstrated.

Electrophysiologic Effects

In general, no detrimental effects on the cardiac conduction system were seen with the use of CARDENE.

Nicardipine increased the heart rate when given intravenously during acute electrophysiologic studies and prolonged the corrected QT interval to a minor degree. The sinus node recovery times and SA conduction times were not affected by the drug. The PA, AH and HV intervals* and the functional and effective refractory periods of the atrium were not prolonged by nicardipine and the relative and effective refractory periods

of the His-Purkinje system were slightly shortened after intravenous nicardipine.

Renal Function

There is a transient increase in electrolyte excretion, including sodium. CARDENE does not cause generalized fluid retention, as measured by weight changes.

Effects in Hypertension

CARDENE SR produced decreases in both systolic and diastolic blood pressure throughout the dosing interval in clinical trials. The antihypertensive efficacy of CARDENE SR administered twice daily has been demonstrated using in-clinic blood pressure measures in placebocontrolled trials involving patients with mild to moderate hypertension and in trials using 12 or 24 hour ambulatory blood pressure monitoring.

REFERENCES

*PA=conduction time from high to low right atrium, AH=conduction time from low right atrium to His bundle deflection or AV nodal conduction time, HV=conduction time through the His bundle and the bundle branch-Purkinje system.

Last updated on RxList: 6/19/2009

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 6/19/2009

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

NICARDIPINE CAPSULE - ORAL

(nye-KAR-di-peen)

COMMON BRAND NAME(S): Cardene

USES: Nicardipine is used with or without other medications to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Nicardipine is called a calcium channel blocker. It works by relaxing blood vessels so blood can flow more easily.

Nicardipine is also used to prevent certain types of chest pain (angina). It may help to increase your ability to exercise and decrease the frequency of angina attacks. This medication must be taken regularly to be effective. It should not be used to treat attacks of chest pain when they occur. Use other medications (such as sublingual nitroglycerin) to relieve attacks of chest pain as directed by your doctor. Consult your doctor or pharmacist for details.

HOW TO USE: Take this medication by mouth, usually 3 times daily with or without food or as directed by your doctor.

The dosage is based on your medical condition and response to treatment. Your doctor may gradually increase your dose. Follow your doctor's instructions carefully.

Avoid eating grapefruit or drinking grapefruit juice while taking this medication unless your doctor instructs you otherwise. Grapefruit can increase the amount of certain medications in your bloodstream. Consult your doctor or pharmacist for more details.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick.

Tell your doctor if your condition persists or worsens (for example, your routine blood pressure readings remain high or increase, your chest pain is more frequent or severe).

SIDE EFFECTS: Dizziness, lightheadedness, headache, flushing, or swelling ankles/feet may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To reduce dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: fainting, fast/irregular/pounding heartbeat.

Tell your doctor immediately if this rare but very serious side effect occurs: vision changes.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking nicardipine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have a certain medical condition. Before using this medicine, consult your doctor or pharmacist if you have: a certain structural heart problem (aortic stenosis).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, kidney disease.

Before having surgery, tell your doctor or dentist that you are taking this medication.

This drug may make you dizzy. Use caution while driving, using machinery, or doing any other activities that require alertness. Limit alcoholic beverages.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known if this medication passes into breast milk. Breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: See also the How to Use section.

Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: cyclosporine.

Other medications can affect the removal of nicardipine from your body, which may affect how nicardipine works. Examples include cimetidine, azole antifungals (such as itraconazole), macrolide antibiotics (such as erythromycin), rifamycins (such as rifabutin), St. John's wort, drugs used to treat seizures (such as carbamazepine, phenytoin), among others.

Check the labels on all your medicines (such as cough-and-cold products, diet aids, nonsteroidal anti-inflammatory drugs-NSAIDs for pain/fever) because they may contain ingredients that could increase your blood pressure or heart rate (such as pseudoephedrine, phenylephrine, ibuprofen, naproxen). Ask your pharmacist about using these products safely.

Cimetidine is a nonprescription drug that is commonly used to treat extra stomach acid. Because cimetidine may interact with nicardipine, ask your pharmacist about other products to treat stomach acid.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Talk with your doctor about making changes to your lifestyle that may help this medication work better (such as stress reduction programs, exercise, and dietary changes.)

Laboratory and/or medical tests (such as liver function tests, blood pressure, electrocardiograms) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Check your blood pressure regularly while taking this medication, especially when you first start this drug or when your doctor changes your dose. Learn how to monitor your own blood pressure at home, and share the results with your doctor.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature away from light and moisture. Different brands of this medication have different storage needs. Check the product package for instructions on how to store your brand, or ask your pharmacist. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised September 2008 Copyright(c) 2008 First DataBank, Inc.