CARDENE®
NICARDIPINE HCI
20 mg and 30 mg capsules
ACTION AND CLINICAL PHARMACOLOGY
Cardene (nicardipine HCI) is a calcium ion influx inhibitor (calcium entry blocker or calcium ion antagonist).
Mechanism of Action: The therapeutic effect of this group of drugs is believed to be related to their specific cellular action of selectively inhibiting transmembrane influx of calcium ions into cardiac muscle and vascular smooth muscle.
Pharmacokinetics and Metabolism: Nicardipine is rapidly and completely absorbed following oral administration and is subject to extensive first-pass effect giving absolute bioavailability of about 35%.
INDICATIONS
Chronic Stable Angina: Cardene (nicardipine) is indicated for the management of chronic stable angina (effort-associated angina) in patients who remain symptomatic despite adequate doses of beta-blockers and/or organic nitrates or who cannot tolerate those agents. Cardene may be tried in combination with beta-adrenergic blocking drugs in chronic stable angina in patients with normal ventricular function. When such concomitant therapy is introduced, care must be taken to monitor blood pressure closely since hypotension can occur from the combined effects of drugs. Hypertension: Cardene is indicated in the treatment of mild to moderate essential hypertension. Cardene should normally be used in those patients in whom treatment with diuretics or beta-blockers has been associated with unacceptable adverse effects. Cardene can be tried as initial agent in those patients in whom the use of diuretics and/or beta-blockers is contraindicated or in patients with medical conditions in which these drugs frequently cause serious adverse effect. Combination of Cardene with a diuretic or a beta blocker has been found to be compatible and showed additive antihypertensive effect. Safety of concurrent use of Cardene with other antihypertensive agents has not been established and such use cannot be recommended at this time.
CONTRAINDICATIONS
Cardene (nicardipine) is contraindicated in patients with hypersensitivity to the drug. Since a major part of the effect of nicardipine is secondary to reduced afterload, the drug should not be given to patients with advanced valvular aortic stenosis. Reduction of diastolic pressure in these patients may worsen rather than improve myocardial oxygen balance.
WARNINGS
Congestive Heart Failure: Because Cardene (nicardipine) has a negative inotropic effect in vitro and is some patients, it should be used with caution and under careful medical supervision in patients with congestive cardiac failure, particularly when used in combination with a beta-blocker (see Hemodynamic and Electrophysiologic effects). Hypertension: Because nicardipine decreases peripheral resistance, careful monitoring of blood pressure during the initial administration and titration of nicardipine is suggested.
PRECAUTIONS
Peripheral Edema: Mild to moderate peripheral edema associated with arterial vasodilation has been reported to occur in patients treated with Cardene (nicardipine). Care should be taken to differentiate this peripheral edema from the effects of increasing left ventricular dysfunction.
DRUG INTERACTIONS
Beta-blockers: When beta-adrenergic receptor blocking drugs are administered concomitantly with nicardipine, blood pressure and pulmonary signs and symptoms of congestive failure should be carefully monitored since the antihypertensive effect of beta-blockers may be argumented by nicardipine’s reduction in peripheral vascular resistance.
ADVERSE REACTIONS
ANGINA: Adverse effects were derived from multicenter, controlled clinical trials in 520 angina patients. Adverse effects were reported on Cardene (nicardipine) and required discontinuation of treatment in 9%. The most common effects were: pedal edema, headache, dizziness, flushing, asthenia, angina, palpitation, nausea, dyspepsia, tachycardia, rash, dry mouth and somnolence. In addition, the following events were reported: Cardiovascular: sustained tachycardia, syncope, atrial fibrillation, myocardial infarction, cerebral ischemia, sudden death, ventricular and supraventricular tachycardia, hypotension, atypical chest pain, peripheral vascular disorder, postural hypotension, ventricular extrasystoles, AV block and sinus node dysfunction. Central nervous system: somnolence, paresthesia, nervousness, tremor, insomnia, apathy, abnormal dreams, ataxia, confusion, depression, hot flashes, vertigo and hyperkinesia. Gastrointestinal: constipation, flatulence, diarrhea, vomiting. Dermatologic: burning sensation, pruritus, rash. Musculoskeletal: myalgia, arthralgia. Respiratory: dyspnea. Special Senses: abnormal or blurred vision, tinnitus, taste perversion. Others: malaise, edema, polyuria, increased sweating.
DOSAGE AND ADMINISTRATION
Angina: The dose of Cardene (nicardipine) should be individually titrated for each patient beginning with 20 mg three times daily. Doses in the range of 20-40 mg three times daily have been shown to be effective. At least three days should be allowed before increasing the nicardipine dose to ensure achievement of steady state plasma drug concentration. Hypertension: Therapy should be individualized for each patient according to the blood pressure response beginning with 20 mg three times daily. Doses of 20 mg to 40 mg three times a day have been effective in clinical trials. Because of the prominent difference in the peak and through plasma levels of nicardipine, careful monitoring of blood pressure is required during initiation of therapy to ensure acceptable control of blood pressure during the interval. At least three days should be allowed before increasing the nicardipine dose to ensure achievement of steady state plasma drug concentrations.
AVAILABILITY OF DOSAGE FORMS
Cardene (nicardipine) is available as hard gelatin capsules in strengths of 20 mg and 30 mg in bottles of 100. The 20 mg capsule is available as an opaque white/white capsule imprinted «Syntex» and «Cardene 20 mg» and the 30 mg capsule is available as an opaque powder blue/opaque light blue capsule imprinted «Syntex» and «Cardene 30 mg».
