FDA

Cardene

Approved 30 Jan 1992InjectionInjectable

The FDA lists this product in 3 strengths and forms.

Indications

CARDENE I.V. is a calcium channel blocker indicated for the short-term treatment of hypertension when oral therapy is not feasible. ( 1.1 )

1.1Hypertension

CARDENE I.V. (nicardipine hydrochloride) is indicated for the short-term treatment of hypertension when oral therapy is not feasible or not desirable. For prolonged control of blood pressure, transfer patients to oral medication as soon as their clinical condition permits [see Dosage and Administration (2.1) ] .

Contraindications

Do not use in patients with advanced aortic stenosis ( 4.1 ).

4.1Advanced Aortic Stenosis

CARDENE I.V. is contraindicated in patients with advanced aortic stenosis because part of the effect of CARDENE I.V. is secondary to reduced afterload. Reduction of diastolic pressure in these patients may worsen rather than improve myocardial oxygen balance.

Warnings and precautions

Closely monitor response in patients with angina, heart failure, impaired hepatic function, or renal impairment. ( 5.1 , 5.2 , 5.3 , 5.4 )
To reduce the possibility of venous thrombosis, phlebitis, and vascular impairment, do not use small veins, such as those on the dorsum of the hand or wrist. Exercise extreme care to avoid intra-arterial administration or extravasation. ( 5.5 )
To minimize the risk of peripheral venous irritation, change the site of infusion of CARDENE I.V. every 12 hours. ( 5.5 )

5.1Exacerbation of Angina Increases

in frequency, duration, or severity of angina have been seen in chronic therapy with oral nicardipine. Induction or exacerbation of angina has been seen in less than 1% of coronary artery disease patients treated with CARDENE I.V. The mechanism of this effect has not been established.

5.2Exacerbation of Heart Failure

Titrate slowly when using CARDENE I.V., particularly in combination with a beta-blocker, in patients with heart failure or significant left ventricular dysfunction because of possible negative inotropic effects.

At a glance

Brand name: Cardene
Active substance: nicardipine hydrochloride
Route: Injection
Dosage form: Injectable
Applicant: Chiesi
Status: Prescription
FDA approval: 30 Jan 1992
Application: NDA019734-001

Indications

CARDENE I.V. is a calcium channel blocker indicated for the short-term treatment of hypertension when oral therapy is not feasible. ( 1.1 )

1.1Hypertension

Contraindications

Do not use in patients with advanced aortic stenosis ( 4.1 ).

4.1Advanced Aortic Stenosis

Warnings and precautions

Closely monitor response in patients with angina, heart failure, impaired hepatic function, or renal impairment. ( 5.1 , 5.2 , 5.3 , 5.4 )
To reduce the possibility of venous thrombosis, phlebitis, and vascular impairment, do not use small veins, such as those on the dorsum of the hand or wrist. Exercise extreme care to avoid intra-arterial administration or extravasation. ( 5.5 )
To minimize the risk of peripheral venous irritation, change the site of infusion of CARDENE I.V. every 12 hours. ( 5.5 )

5.1Exacerbation of Angina Increases

5.2Exacerbation of Heart Failure

Pregnancy and breastfeeding

8.1Pregnancy

There are no adequate and well-controlled studies of nicardipine use in pregnant women. However, limited human data in pregnant women with preeclampsia or pre-term labor are available. In animal studies, no embryotoxicity occurred in rats with oral doses 8 times the maximum recommended human dose (MRHD) based on body surface area (mg/m 2 ), but did occur in rabbits with oral doses at 24 times the maximum recommended human dose (MRHD) based on body surface area (mg/m 2 ).

CARDENE I.V. should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Hypotension, reflex tachycardia, postpartum hemorrhage, tocolysis, headache, nausea, dizziness, and flushing have been reported in pregnant women who were treated with intravenous nicardipine for hypertension during pregnancy. Fetal safety results ranged from transient fetal heart rate decelerations to no adverse events.

Neonatal safety data ranged from hypotension to no adverse events. Adverse events in women treated with intravenous nicardipine during pre-term labor include pulmonary edema, dyspnea, hypoxia, hypotension, tachycardia, headache, and phlebitis at site of injection. Neonatal adverse events include acidosis (pH<7.25). In embryofetal toxicity studies, nicardipine was administered intravenously to pregnant rats and rabbits during organogenesis at doses up to 0.14 times the MRHD based on body surface area (mg/m 2 ) (5 mg/kg/day) (rats) and 0.03 times the MRHD based on body surface area (mg/m 2 ) (0.5 mg/kg/day) (rabbits).

No embryotoxicity or teratogenicity was seen at these doses. Embryotoxicity, but no teratogenicity was seen at 0.27 times the MRHD based on body surface area (mg/m 2 ) (10 mg/kg/day) in rats and at 0.05 times the MRHD based on body surface area (mg/m 2 ) (1 mg/kg/day) in rabbits. In other animal studies, pregnant Japanese White rabbits received oral nicardipine during organogenesis, at doses 8 and 24 times the MRHD based on body surface area (mg/m 2 ) (50 and 150 mg/kg/day).

Embryotoxicity occurred at the high dose along with signs of maternal toxicity (marked maternal weight gain suppression). New Zealand albino rabbits received oral nicardipine during organogenesis, at doses up to 16 times the MRHD based on body surface area (mg/m 2 )(100 mg nicardipine/kg/day). While significant maternal mortality occurred, no adverse effects on the fetus were observed. Pregnant rats received oral nicardipine from day 6 through day 15 of gestation at doses up to 8 times the MRHD based on body surface area (mg/m 2 ) (100 mg/kg/day).

There was no evidence of embryotoxicity or teratogenicity; however, dystocia, reduced birth weights, reduced neonatal survival, and reduced neonatal weight gain were noted.

Adverse reactions

Most common adverse reactions: are headache (15%), hypotension (6%), tachycardia (4%) and nausea/vomiting (5%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare Corporation at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Two hundred forty-four patients participated in two multicenter, double-blind, placebo-controlled trials of CARDENE I.V. Adverse experiences were generally not serious and most were expected consequences of vasodilation. Adverse experiences occasionally required dosage adjustment. Therapy was discontinued in approximately 12% of patients, mainly due to hypotension, headache, and tachycardia. The table below shows percentage of patients with adverse events where the rate is >3% more common on CARDENE I.V. than placebo.

Adverse Event CARDENE I.V. (N=144) Placebo (N=100) Body as a Whole Headache, n (%) 21 (15) 2 (2) Cardiovascular Hypotension, n (%) 8 (6) 1 (1) Tachycardia, n (%) 5 (4) 0 Digestive Nausea/vomiting, n (%) 7 (5) 1 (1) Other adverse events have been reported in clinical trials or in the literature in association with the use of intravenously administered nicardipine: Body as a Whole: fever, neck pain Cardiovascular: angina pectoris, atrioventricular block, ST segment depression, inverted T wave, deep-vein thrombophlebitis Digestive : dyspepsia Hemic and Lymphatic: thrombocytopenia Metabolic and Nutritional: hypophosphatemia, peripheral edema Nervous: confusion, hypertonia Respiratory: respiratory disorder Special Senses: conjunctivitis, ear disorder, tinnitus Urogenital: urinary frequency Sinus node dysfunction and myocardial infarction, which may be due to disease progression, have been seen in patients on chronic therapy with orally administered nicardipine.

6.2Postmarketing Experience

Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or to establish a causal relationship to drug exposure. The following adverse reaction has been identified during post-approval use of CARDENE I.V.: decreased oxygen saturation (possible pulmonary shunting).

Cardene

Indications

1.1Hypertension

Contraindications

4.1Advanced Aortic Stenosis

Warnings and precautions

5.1Exacerbation of Angina Increases

5.2Exacerbation of Heart Failure

At a glance

Two medicines in one question?

Cardene

Indications

1.1Hypertension

Contraindications

4.1Advanced Aortic Stenosis

Warnings and precautions

5.1Exacerbation of Angina Increases

5.2Exacerbation of Heart Failure

At a glance

Two medicines in one question?

5.5Local Irritation

Interactions

7.1Beta-Blockers

7.2Cimetidine

7.3Cyclosporine

7.4Tacrolimus

7.5In Vitro Interaction

Pregnancy and breastfeeding

8.1Pregnancy

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information