Nicardipineside effects

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 0.3 Dizziness 6.9 0.6 Headache 6.4 2.6 Asthenia 5.8 2.6 Flushing 5.6

1.0 Increased

Angina 5.6 4.2 Palpitations 3.3 0.0 Nausea 1.9 0.3 Dyspepsia 1.5 0.6 Dry Mouth 1.4 0.3 Somnolence 1.4 1.0 Rash 1.2 0.3 Tachycardia 1.2 0.6 Myalgia 1.0 0.0 Other Edema 1.0 0.0 Paresthesia 1.0

0.3 Sustained

Tachycardia 0.8 0.0 Syncope 0.8 0.0 Constipation 0.6 0.6 Dyspnea 0.6 0.0 Abnormal ECG 0.6 0.0 Malaise 0.6 0.0 Nervousness 0.6 0.3 Tremor 0.6 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 2.8 Headache 8.2 4.7 Pedal Edema 8.0 0.9 Asthenia 4.2 0.5 Palpitations 4.1 0.0 Dizziness 4.0 0.0 Tachycardia 3.4 0.5 Nausea 2.2 0.9 Somnolence 1.1 0.0 Dyspepsia 0.8 0.5 Insomnia 0.6 0.0 Malaise 0.6 0.0 Other Edema 0.6

1.4 Abnormal

Dreams 0.4 0.0 Dry Mouth 0.4 0.0 Nocturia 0.4 0.0 Rash 0.4 0.0 Vomiting 0.4

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