Nicardipine Hydrochloride

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 ).

DOSAGE AND ADMINISTRATION Angina The dose should be individually titrated for each patient beginning with 20 mg three times daily. Doses in the range of 20 to 40 mg three times a day have been shown to be effective. At least 3 days should be allowed before increasing the nicardipine hydrochloride capsules dose to ensure achievement of steady-state plasma drug concentrations. Concomitant Use With Other Antianginal Agents Sublingual NTG may be taken as required to abort acute anginal attacks during nicardipine hydrochloride capsules therapy. Prophylactic Nitrate Therapy : nicardipine hydrochloride capsules may be safely co-administered with short- and long-acting nitrates. Beta-blockers : Nicardipine hydrochloride capsules may be safely co-administered with beta- blockers (see Drug Interactions ) . Hypertension The dose of nicardipine hydrochloride capsules should be individually adjusted according to the blood pressure response beginning with 20 mg three times daily. The effective doses in clinical trials have ranged from 20 mg to 40 mg three times daily. The maximum blood pressure lowering effect occurs approximately 1 to 2 hours after dosing. To assess the adequacy of blood pressure response, the blood pressure should be measured at trough (8 hours after dosing). Because of the prominent peak effects of nicardipine, blood pressure should be measured 1 to 2 hours after dosing, particularly during initiation of therapy (see PRECAUTIONS: Blood Pressure , INDICATIONS AND USAGE , CLINICAL PHARMACOLOGY, Effects in Hypertension ). At least 3 days should be allowed before increasing the nicardipine hydrochloride capsules dose to ensure achievement of steady-state plasma drug concentrations. Concomitant Use With Other Antihypertensive Agents Diuretics : nicardipine hydrochloride capsules may be safety co-administered with thiazide diuretics. Beta-blockers : nicardipine hydrochloride capsules may be safely co-administered with beta-blocker (see PRECAUTIONS , Drug Interactions ) Special Patient Population Renal Insufficiency Although there is no evidence that nicardipine hydrochloride capsules impair renal function, careful dose titration beginning with 20 mg tid is advised (see PRECAUTIONS ). Hepatic Insufficiency Nicardipine hydrochloride capsules should be administered cautiously in patients with severely impaired hepatic function. A suggested starting dose of 20 mg twice a day is advised with individual titration based on clinical findings maintaining the twice a day schedule (see PRECAUTIONS ). Congestive Heart Failure Caution is advised when titrating nicardipine hydrochloride capsules dosage in patients with congestive heart failure (see WARNINGS ).

CONTRAINDICATIONS Nicardipine hydrochloride capsules are contraindicated in patients with hypersensitivity to the drug. Because part of the effect of nicardipine hydrochloride capsules are secondary to reduced afterload, the drug is also contraindicated in patients with advanced aortic stenosis. Reduction of diastolic pressure in these patients may worsen rather than improve myocardial oxygen balance.

ADVERSE REACTIONS In multiple-dose US 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. 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. 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 …

Drug Interactions Beta Blockers In controlled clinical studies, adrenergic beta-receptor blockers have been frequently administered concomitantly with nicardipine hydrochloride capsules. The combination is well tolerated. Cimetidine Cimetidine increases nicardipine hydrochloride capsules plasma levels. Patients receiving the two drugs concomitantly should be carefully monitored. Digoxin Some calcium blockers may increase the concentration of digitalis preparations in the blood. Nicardipine hydrochloride capsules usually do not alter the plasma levels of digoxin; however, serum digoxin levels should be evaluated after concomitant therapy with nicardipine hydrochloride capsules are initiated. Maalox® Coadministration of Maalox TC had no effect on nicardipine hydrochloride capsules absorption. Fentanyl Anesthesia 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 nicardipine hydrochloride capsules, an increased volume of circulating fluids might be required if such an interaction were to occur. Cyclosporine Concomitant administration of oral or intravenous nicardipine and cyclosporine results in elevated plasma cyclosporine levels through nicardipine inhibition of hepatic microsomal enzymes, including CYP3A4. Plasma concentrations of cyclosporine should therefore be closely monitored, and its dosage reduced accordingly, in patients treated with nicardipine. Tacrolimus: Concomitant administration of oral or intravenous nicardipine and tacrolimus may result in elevated plasma tacrolimus levels through nicardipine inhibition of hepatic microsomal enzymes, including CYP3A4. Closely monitor plasma concentrations of tacrolimus during nicardipine administration, and adjust the dose of tacrolimus accordingly. When therapeutic concentrations of furosemide, propranolol, dipyridamole, warfarin, quinidine or naproxen were added to human plasma (in vitro), the plasma protein binding of nicardipine hydrochloride capsules were 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 40 mg tid maximum recommended antianginal or antihypertensive dose in man, assuming a patient weight of 60 kg). Pregnancy 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 …

​Mechanism of Action Nicardipine hydrochloride capsules are a calcium entry blocker (slow channel blocker or calcium ion antagonist) that inhibits the transmembrane influx of calcium ions into cardiac muscle and smooth muscle without changing serum calcium concentrations. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. The effects of nicardipine hydrochloride capsules are more selective to vascular smooth muscle than cardiac muscle. In animal models, nicardipine hydrochloride capsules produce relaxation of coronary vascular smooth muscle at drug levels that cause little or no negative inotropic effect.

DESCRIPTION Nicardipine hydrochloride capsules for oral administration each contain 20 mg or 30 mg of nicardipine hydrochloride. Nicardipine hydrochloride capsules are a calcium ion influx inhibitor (slow channel blocker or calcium channel blocker). Nicardipine hydrochloride is a dihydropyridine structure with the IUPAC (International Union of Pure and Applied Chemistry) chemical name 2-(benzyl-methyl amino)ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate monohydrochloride, and it has the following structure: Nicardipine hydrochloride is a greenish-yellow, odorless, crystalline powder that melts at about 169°C. It is freely soluble in chloroform, methanol and glacial acetic acid, sparingly soluble in anhydrous ethanol, slightly soluble in n-butanol, water, 0.01 M potassium dihydrogen phosphate, acetone and dioxane, very slightly soluble in ethyl acetate, and practically insoluble in benzene, ether and hexane. It has a molecular weight of 515.99. Nicardipine hydrochloride capsules are available in hard gelatin capsules containing 20 mg or 30 mg nicardipine hydrochloride with colloidal silicon dioxide, lactose monohydrate, magnesium stearate, pregelatinized starch, and sodium starch glycolate as the inactive ingredients. The 20-mg strength is provided in white opaque body and light blue opaque cap, hard gelatin capsules imprinted “NIC 1” in black ink on cap and body, filled with yellow color granular powder, while the 30-mg capsules are light blue opaque body and blue opaque cap, hard gelatin capsules imprinted “NIC 2” in black ink on cap and body, filled with yellow color granular powder. The capsule shells contain black imprint ink, FD&C blue #1, gelatin, and titanium dioxide. The black imprinting ink contains black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, shellac, and strong ammonia solution. structure

OVERDOSAGE Overdosage with a 600-mg single dose (15 times to 30 times normal clinical dose) has been reported. Marked hypotension (blood pressure unobtainable) and bradycardia (heart rate 20 bpm in normal sinus rhythm) occurred, along with drowsiness, confusion and slurred speech. Supportive treatment with a vasopressor resulted in gradual improvement with normal vital signs approximately 9 hours posttreatment. Based on results obtained in laboratory animals, overdosage may cause systemic hypotension, bradycardia (following initial tachycardia) and progressive atrioventricular conduction block. Reversible hepatic function abnormalities and sporadic focal hepatic necrosis were noted in some animal species receiving very large doses of nicardipine. For treatment of overdose standard measures (for example, evacuation of gastric contents, elevation of extremities, attention to circulating fluid volume, and urine output) including monitoring of cardiac and respiratory functions should be implemented. The patient should be positioned so as to avoid cerebral anoxia. Frequent blood pressure determinations are essential. Vasopressors are clinically indicated for patients exhibiting profound hypotension. Intravenous calcium gluconate may help reverse the effects of calcium entry blockade.

HOW SUPPLIED Nicardipine Hydrochloride Capsules 20 mg are available in size ‘3’ hard gelatin capsules with a light blue opaque cap and a white opaque body, imprinted with “Y” on the cap and “120” on the body in black ink and filled with yellow powder. These are supplied as follows: Bottles of 90 Capsules, NDC 68462-120-90 Bottles of 500 Capsules, NDC 68462-120-05 Nicardipine Hydrochloride Capsules 30 mg are available in size ‘2’ hard gelatin capsules with a blue opaque cap and a light blue opaque body, imprinted with “Y” on the cap and “121” on the body in black ink and filled with yellow powder. These are supplied as follows: Bottles of 90 Capsules, NDC 68462-121-90 Bottles of 500 Capsules, NDC 68462-121-05 Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Dispense contents in a tight, light-resistant container as defined in the USP. All trademarks are the property of their respective owners. Distributed by: Glenmark Pharmaceuticals Inc., USA Elmwood Park, NJ 07407 Questions? 1 (888) 721-7115 www.glenmarkpharma-us.com August 2025 glenmarklogo