NICARDIPINE HYDROCHLORIDE
Generic: NICARDIPINE HYDROCHLORIDE
Basic Information
Manufacturer
Amici Pharma Inc
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
edda985c-004e-4487-b856-13cf2cdb900f
Indications & Usage
INDICATIONS AND USAGE I.
Stable Angina Nicardipine hydrochloride capsules are indicated for the management of patients with chronic stable angina (effort-associated angina).
Nicardipine hydrochloride capsules may be used alone or in combination with beta-blockers.
II.
Hypertension Nicardipine hydrochloride capsules are indicated for the treatment of hypertension.
Nicardipine hydrochloride capsules may be used alone or in combination with other antihypertensive drugs.
In administering nicardipine hydrochloride it is important to be aware of the relatively large peak to trough differences in blood pressure effect (See DOSAGE AND ADMINISTRATION ).
Stable Angina Nicardipine hydrochloride capsules are indicated for the management of patients with chronic stable angina (effort-associated angina).
Nicardipine hydrochloride capsules may be used alone or in combination with beta-blockers.
II.
Hypertension Nicardipine hydrochloride capsules are indicated for the treatment of hypertension.
Nicardipine hydrochloride capsules may be used alone or in combination with other antihypertensive drugs.
In administering nicardipine hydrochloride it is important to be aware of the relatively large peak to trough differences in blood pressure effect (See DOSAGE AND ADMINISTRATION ).
Warnings
WARNINGS Increased Angina About 7% of patients in short-term, placebo-controlled angina trials have developed increased frequency, duration or severity of angina on starting nicardipine hydrochloride capsules or at the time of dosage increases, compared with 4% of patients on placebo.
Comparisons with beta-blockers also show a greater frequency of increased angina, 4% vs 1%.
The mechanism of this effect has not been established (see ADVERSE REACTIONS ).
Use in Patients With Congestive Heart Failure Although preliminary hemodynamic studies in patients with congestive heart failure have shown that nicardipine hydrochloride capsules 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 Nicardipine hydrochloride capsules are 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.
Comparisons with beta-blockers also show a greater frequency of increased angina, 4% vs 1%.
The mechanism of this effect has not been established (see ADVERSE REACTIONS ).
Use in Patients With Congestive Heart Failure Although preliminary hemodynamic studies in patients with congestive heart failure have shown that nicardipine hydrochloride capsules 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 Nicardipine hydrochloride capsules are 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.
Adverse Reactions
ADVERSE REACTIONS In multiple-dose U.S.
and foreign controlled short-term (up to 3 months) studies 1910 patients received nicardipine hydrochloride capsules alone or in combination with other drugs.
In these studies adverse events were reported spontaneously; adverse experiences were generally not serious but occasionally required dosage adjustment and about 10% of patients left the studies prematurely because of them.
Peak responses were not observed to be associated with adverse effects during clinical trials, but physicians should be aware that adverse effects associated with decreases in blood pressure (tachycardia, hypotension, etc.) could occur around the time of the peak effect.
Most adverse effects were expected consequences of the vasodilator effects of nicardipine hydrochloride capsules.
Angina The incidence rates of adverse effects in anginal patients were derived from multicenter, controlled clinical trials.
Following are the rates of adverse effects for nicardipine hydrochloride capsules (n=520) and placebo (n=310), respectively, that occurred in 0.4% of patients or more.
These represent events considered probably drug-related by the investigator (except for certain cardiovascular events that were recorded in a different category).
Where the frequency of adverse effects for nicardipine hydrochloride capsules and placebo is similar, causal relationship is uncertain.
The only dose-related effects were pedal edema and increased angina.
Table 2 Percent of Patients With Adverse Effects in Controlled Studies (Incidence of Discontinuations Shown in Parentheses) ADVERSE EXPERIENCE NICARDIPINE HYDROCHLORIDE CAPSULES (n= 520) PLACEBO (n= 310) Pedal Edema 7.1 (0) 0.3 (0) Dizziness 6.9 (1.2) 0.6 (0) Headache 6.4 (0.6) 2.6 (0) Asthenia 5.8 (0.4) 2.6 (0) Flushing 5.6 (0.4) 1.0 (0) Increased Angina 5.6 (3.5) 4.2 (1.9) Palpitations 3.3 (0.4) 0.0 (0) Nausea 1.9 (0) 0.3 (0) Dyspepsia 1.5 (0.6) 0.6 (0.3) Dry Mouth 1.4 (0) 0.3 (0) Somnolence 1.4 (0) 1.0 (0) Rash 1.2 (0.2) 0.3 (0) Tachycardia 1.2 (0.2) 0.6 (0) Myalgia 1.0 (0) 0.0 (0) Other Edema 1.0 (0) 0.0 (0) Paresthesia 1.0 (0.2) 0.3 (0) Sustained Tachycardia 0.8 (0.6) 0.0 (0) Syncope 0.8 (0.2) 0.0 (0) Constipation 0.6 (0.2) 0.6 (0) Dyspnea 0.6 (0) 0.0 (0) Abnormal ECG 0.6 (0.6) 0.0 (0) Malaise 0.6 (0) 0.0 (0) Nervousness 0.6 (0) 0.3 (0) Tremor 0.6 (0) 0.0 (0) In addition, adverse events were observed that are not readily distinguishable from the natural history of the atherosclerotic vascular disease in these patients.
Adverse events in this category each occurred in <0.4% of patients receiving nicardipine hydrochloride capsules and included myocardial infarction, atrial fibrillation, exertional hypotension, pericarditis, heart block, cerebral ischemia, and ventricular tachycardia.
It is possible that some of these events were drug-related.
Hypertension The incidence rates of adverse effects in hypertensive patients were derived from multicenter, controlled clinical trials.
Following are the rates of adverse effects for nicardipine hydrochloride capsules (n= 1390) and placebo (n= 211), respectively, that occurred in 0.4% of patients or more.
These represent events considered probably drug-related by the investigator.
Where the frequency of adverse effects for nicardipine hydrochloride capsules and placebo is similar, causal relationship is uncertain.
The only dose-related effect was pedal edema.
Table 3 Percent of Patients with Adverse Effects in Controlled Studies (Incidence of Discontinuations Shown in Parentheses) ADVERSE EXPERIENCE NICARDIPINE HYDROCHLORIDE CAPSULES (n = 1390) PLACEBO (n = 211) Flushing 9.7 (2.1) 2.8 (0) Headache 8.2 (2.6) 4.7 (0) Pedal Edema 8.0 (1.8) 0.9 (0) Asthenia 4.2 (1.7) 0.5 (0) Palpitations 4.1 (1.0) 0.0 (0) Dizziness 4.0 (1.8) 0.0 (0) Tachycardia 3.4 (1.2) 0.5 (0) Nausea 2.2 (0.9) 0.9 (0) Somnolence 1.1 (0.1) 0.0 (0) Dyspepsia 0.8 (0.3) 0.5 (0) Insomnia 0.6 (0.1) 0.0 (0) Malaise 0.6 (0.1) 0.0 (0) Other Edema 0.6 (0.3) 1.4 (0) Abnormal Dreams 0.4 (0) 0.0 (0) Dry Mouth 0.4 (0.1) 0.0 (0) Nocturia 0.4 (0) 0.0 (0) Rash 0.4 (0.4) 0.0 (0) Vomiting 0.4 (0.4) 0.0 (0) 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, postural hypotension, atypical chest pain, peripheral vascular disorder, ventricular extrasystoles, ventricular tachycardia 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 Urogenital: increased urinary frequency
and foreign controlled short-term (up to 3 months) studies 1910 patients received nicardipine hydrochloride capsules alone or in combination with other drugs.
In these studies adverse events were reported spontaneously; adverse experiences were generally not serious but occasionally required dosage adjustment and about 10% of patients left the studies prematurely because of them.
Peak responses were not observed to be associated with adverse effects during clinical trials, but physicians should be aware that adverse effects associated with decreases in blood pressure (tachycardia, hypotension, etc.) could occur around the time of the peak effect.
Most adverse effects were expected consequences of the vasodilator effects of nicardipine hydrochloride capsules.
Angina The incidence rates of adverse effects in anginal patients were derived from multicenter, controlled clinical trials.
Following are the rates of adverse effects for nicardipine hydrochloride capsules (n=520) and placebo (n=310), respectively, that occurred in 0.4% of patients or more.
These represent events considered probably drug-related by the investigator (except for certain cardiovascular events that were recorded in a different category).
Where the frequency of adverse effects for nicardipine hydrochloride capsules and placebo is similar, causal relationship is uncertain.
The only dose-related effects were pedal edema and increased angina.
Table 2 Percent of Patients With Adverse Effects in Controlled Studies (Incidence of Discontinuations Shown in Parentheses) ADVERSE EXPERIENCE NICARDIPINE HYDROCHLORIDE CAPSULES (n= 520) PLACEBO (n= 310) Pedal Edema 7.1 (0) 0.3 (0) Dizziness 6.9 (1.2) 0.6 (0) Headache 6.4 (0.6) 2.6 (0) Asthenia 5.8 (0.4) 2.6 (0) Flushing 5.6 (0.4) 1.0 (0) Increased Angina 5.6 (3.5) 4.2 (1.9) Palpitations 3.3 (0.4) 0.0 (0) Nausea 1.9 (0) 0.3 (0) Dyspepsia 1.5 (0.6) 0.6 (0.3) Dry Mouth 1.4 (0) 0.3 (0) Somnolence 1.4 (0) 1.0 (0) Rash 1.2 (0.2) 0.3 (0) Tachycardia 1.2 (0.2) 0.6 (0) Myalgia 1.0 (0) 0.0 (0) Other Edema 1.0 (0) 0.0 (0) Paresthesia 1.0 (0.2) 0.3 (0) Sustained Tachycardia 0.8 (0.6) 0.0 (0) Syncope 0.8 (0.2) 0.0 (0) Constipation 0.6 (0.2) 0.6 (0) Dyspnea 0.6 (0) 0.0 (0) Abnormal ECG 0.6 (0.6) 0.0 (0) Malaise 0.6 (0) 0.0 (0) Nervousness 0.6 (0) 0.3 (0) Tremor 0.6 (0) 0.0 (0) In addition, adverse events were observed that are not readily distinguishable from the natural history of the atherosclerotic vascular disease in these patients.
Adverse events in this category each occurred in <0.4% of patients receiving nicardipine hydrochloride capsules and included myocardial infarction, atrial fibrillation, exertional hypotension, pericarditis, heart block, cerebral ischemia, and ventricular tachycardia.
It is possible that some of these events were drug-related.
Hypertension The incidence rates of adverse effects in hypertensive patients were derived from multicenter, controlled clinical trials.
Following are the rates of adverse effects for nicardipine hydrochloride capsules (n= 1390) and placebo (n= 211), respectively, that occurred in 0.4% of patients or more.
These represent events considered probably drug-related by the investigator.
Where the frequency of adverse effects for nicardipine hydrochloride capsules and placebo is similar, causal relationship is uncertain.
The only dose-related effect was pedal edema.
Table 3 Percent of Patients with Adverse Effects in Controlled Studies (Incidence of Discontinuations Shown in Parentheses) ADVERSE EXPERIENCE NICARDIPINE HYDROCHLORIDE CAPSULES (n = 1390) PLACEBO (n = 211) Flushing 9.7 (2.1) 2.8 (0) Headache 8.2 (2.6) 4.7 (0) Pedal Edema 8.0 (1.8) 0.9 (0) Asthenia 4.2 (1.7) 0.5 (0) Palpitations 4.1 (1.0) 0.0 (0) Dizziness 4.0 (1.8) 0.0 (0) Tachycardia 3.4 (1.2) 0.5 (0) Nausea 2.2 (0.9) 0.9 (0) Somnolence 1.1 (0.1) 0.0 (0) Dyspepsia 0.8 (0.3) 0.5 (0) Insomnia 0.6 (0.1) 0.0 (0) Malaise 0.6 (0.1) 0.0 (0) Other Edema 0.6 (0.3) 1.4 (0) Abnormal Dreams 0.4 (0) 0.0 (0) Dry Mouth 0.4 (0.1) 0.0 (0) Nocturia 0.4 (0) 0.0 (0) Rash 0.4 (0.4) 0.0 (0) Vomiting 0.4 (0.4) 0.0 (0) 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, postural hypotension, atypical chest pain, peripheral vascular disorder, ventricular extrasystoles, ventricular tachycardia 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 Urogenital: increased urinary frequency