Data from FDA - Curated by EPG Health - Last updated 30 August 2017

Indication(s)

INDICATIONS AND USAGE CARDENE SR is indicated for the treatment of hypertension. CARDENE SR may be used alone or in combination with other anti-hypertensive drugs.

Learning Zones

An epgonline.org Learning Zone (LZ) is an area of the site dedicated to providing detailed self-directed medical education about a disease, condition or procedure.

Acute and Advanced Heart Failure

Acute and Advanced Heart Failure

What are the most effective treatments for acute heart failure? Can you define advanced heart failure? Discover here...

+ 3 more

Allergic Rhinitis

Allergic Rhinitis

Allergic rhinitis causes great strain on the workforce. Help to reduce sick days and improve productivity with appropriate treatment options.

+ 4 more

Anticoagulation Therapy for Stroke Prevention

Anticoagulation Therapy for Stroke Prevention

Anticoagulation therapy for Stroke Prevention Learning Zone offers a deep-dive into atrial fibrillation causes, consequences, diagnosis and management to help you deliver optimal care and prevent strokes in patients living with this common arrhythmia.

Load more

Related Content

Advisory information

contraindications
CONTRAINDICATIONS 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.
Special warnings and precautions
PRECAUTIONS General 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. Blood Pressure: Since the liver is the major site of biotransformation and since CARDENE is subject to first-pass 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 Hepatic Function: When 45-mg CARDENE SR bid was given to hypertensive patients with moderate renal impairment, mean AUC and C 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 C values were similar in patients with mildly impaired renal function and normal volunteers (see and ). Use in Patients With Impaired Renal Function: max max CLINICAL PHARMACOLOGY DOSAGE AND ADMINISTRATION Drug Interactions In controlled clinical studies, adrenergic beta-receptor blockers have been frequently administered concomitantly with CARDENE. The combination is well tolerated. Beta-Blockers: Cimetidine increases CARDENE plasma levels. Patients receiving the two drugs concomitantly should be carefully monitored. Cimetidine: 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. Digoxin: 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. Fentanyl Anesthesia: 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. Cyclosporine: 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. 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 is 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 a 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.
Adverse reactions
ADVERSE REACTIONS In multiple-dose US and foreign controlled studies, 667 patients received CARDENE SR. In these studies adverse events were elicited by non-directed 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 Adverse Event CARDENE SR (n=322) Placebo (n=140) Headache 6.2 7.1 Pedal Edema 5.9 1.4 Vasodilatation 4.7 1.4 Palpitation 2.8 1.4 Nausea 1.9 0.7 Dizziness 1.6 0.7 Asthenia 0.9 0.7 Postural Hypotension 0.9 0 Increased UrinaryFrequency 0.6 0 Pain 0.6 0 Rash 0.6 0 Sweating Increased 0.6 0 Vomiting 0.6 0 Incidence (%) of Discontinuations Due to Any Adverse Event in Placebo-Controlled Studies Adverse Event CARDENE SR (n=322) Placebo (n=140) Headache 2.5 1.4 Palpitation 2.2 0.7 Dizziness 1.9 0.7 Asthenia 1.9 0 Pedal Edema 1.2 0 Nausea 1.2 0 Rash 0.9 0.7 Diarrhea 0.9 0 Tachycardia 0.9 0 Blurred Vision 0.6 0 Chest Pain 0.6 0 Face Edema 0.6 0 Myocardial Infarct 0.6 0 Vasodilatation 0.6 0 Vomiting 0.6 0 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: infection, allergic reaction Body as a Whole: hypotension, atypical chest pain, peripheral vascular disorder, ventricular extrasystoles, ventricular tachycardia, angina pectoris Cardiovascular: sore throat, abnormal liver chemistries Digestive: arthralgia Musculoskeletal: hot flashes, vertigo, hyperkinesia, impotence, depression, confusion, anxiety Nervous: rhinitis, sinusitis Respiratory: tinnitus, abnormal vision, blurred vision Special Senses: 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%).

Usage information

Dosing and administration
DOSAGE AND ADMINISTRATION 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: : CARDENE may be safely coadministered with thiazide diuretics. Diuretics : CARDENE may be safely coadministered with beta-blockers (see ). Beta-Blockers Drug Interactions Special Patient Populations Although there is no evidence that CARDENE SR impairs renal function, careful dose titration beginning with 30-mg CARDENE SR bid is advised (see ). Renal Insufficiency: PRECAUTIONS CARDENE SR has not been studied in patients with severe liver impairment (see ). Hepatic Insufficiency: PRECAUTIONS Caution is advised when titrating CARDENE SR dosage in patients with congestive heart failure (see ). Congestive Heart Failure: WARNINGS
Pregnancy and lactation
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.

Interactions

Drug Interactions In controlled clinical studies, adrenergic beta-receptor blockers have been frequently administered concomitantly with CARDENE. The combination is well tolerated. Beta-Blockers: Cimetidine increases CARDENE plasma levels. Patients receiving the two drugs concomitantly should be carefully monitored. Cimetidine: 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. Digoxin: 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. Fentanyl Anesthesia: 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. Cyclosporine: 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.

More information

Category Value
Authorisation number NDA020005
Agency product number K5BC5011K3
Orphan designation No
Product NDC 68151-0089
Date Last Revised 06-08-2016
Type HUMAN PRESCRIPTION DRUG
RXCUI 858587
Marketing authorisation holder Carilion Materials Management