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NiCARdipine

Medically reviewed by Drugs.com. Last updated on Aug 6, 2020.

Pronunciation

(nye KAR de peen)

Index Terms

  • Cardene
  • Nicardipine HCl
  • Nicardipine Hydrochloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as hydrochloride:

Generic: 20 mg, 30 mg

Solution, Intravenous [preservative free]:

Generic: 20 mg/200 mL in NaCl 0.9% (200 mL); 40 mg/200 mL in NaCl 0.9% (200 mL)

Solution, Intravenous, as hydrochloride:

Cardene IV: 20 mg (200 mL); 40 mg (200 mL)

Generic: 2.5 mg/mL (10 mL)

Solution, Intravenous, as hydrochloride [preservative free]:

Generic: 2.5 mg/mL (10 mL)

Brand Names: U.S.

  • Cardene IV

Pharmacologic Category

  • Antianginal Agent
  • Antihypertensive
  • Calcium Channel Blocker
  • Calcium Channel Blocker, Dihydropyridine

Pharmacology

Inhibits calcium ion from entering the “slow channels” or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, producing a relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina

Absorption

Oral: ~100%, but large first-pass effect.

Distribution

Vd: 8.3 L/kg.

Metabolism

Hepatic; extensive first-pass effect (saturable); major pathway is via cytochrome P450 isoenzyme CYP3A4, 2C8, and 2D6.

Excretion

Urine (oral: 60% as metabolites; IV: 49% as metabolites; <1% as unchanged drug); feces (oral: 35%; IV: 43%).

Clearance: Decreased in patients with hepatic impairment; may be decreased in patients with renal impairment.

Onset of Action

IV: Within minutes (constant infusion); Oral: 0.5 to 2 hours.

Peak effect: Oral: 1 to 2 hours. IV continuous infusion: 50% of the maximum effect is seen by 45 minutes.

Time to Peak

Serum: Oral: 30 to 120 minutes (mean: 1 hour).

Duration of Action

IV: ≤8 hours. Upon discontinuation of continuous infusion, a 50% decrease in effect is seen in ~30 minutes with gradual discontinuing antihypertensive effects for ~50 hours.

Oral: ≤8 hours.

Half-Life Elimination

Follows dose-dependent (nonlinear) pharmacokinetics; “apparent” or calculated half-life is dependent upon serum concentrations.

Oral: Half-life over the first 8 hours after oral dosing is 2 to 4 hours; terminal half-life: 8.6 hours.

IV: After IV infusion, serum concentrations decrease tri-exponentially; alpha half-life: 3 minutes; beta half-life: 45 minutes; terminal half-life: 14 hours (Note: Terminal half-life can only be seen after long-term infusions).

Protein Binding

>95%.

Special Populations: Renal Function Impairment

IV: Significantly lower systemic clearance and higher AUC in patients with mild to moderate renal impairment.

Oral: Cmax and AUC were ~2-fold higher in patients with mild renal impairment.

Special Populations: Hepatic Function Impairment

In patients with severe hepatic impairment, plasma concentrations were elevated and the half-life was prolonged

Use: Labeled Indications

Angina: Management of chronic stable angina (oral only).

Hypertension: Management of hypertension (oral and IV); parenteral only for short-term use when oral treatment is not feasible or not desirable.

Off Label Uses

Acute ischemic stroke, blood pressure management

The American Heart Association/American Stroke Association (AHA/ASA) guideline for the early management of patients with acute ischemic stroke recommends nicardipine as an antihypertensive treatment option for the management of BP before, during, and after reperfusion with a thrombolytic [AHA/ASA [Powers 2019]].

Intracerebral hemorrhage, blood pressure management

Data from prospective, randomized clinical trials and a retrospective chart review of patients with intracerebral hemorrhage or subarachnoid hemorrhage (SAH) suggest that nicardipine is effective and safe for the management of BP in this population [Koga 2012], [Ortega-Gutierrez 2013], [Qureshi 2016].

The American College of Cardiology (ACC)/AHA guideline for the prevention, detection, evaluation, and management of high BP in adults and the AHA/ASA guideline for the management of spontaneous intracerebral hemorrhage recommend nicardipine as an antihypertensive treatment option for the management of BP in patients with intracerebral hemorrhage [ACC/AHA [Hemphill 2015]], [AHA/ASA [Whelton 2018]].

Subarachnoid hemorrhage, blood pressure management

Data from prospective and retrospective clinical trials are supportive of nicardipine use in patients with SAH for BP management. Nicardipine appears to have more beneficial outcomes than sodium nitroprusside and labetalol; however, only a small number of studies have compared the agents directly [Liu-DeRyke 2013], [Ortega-Gutierrez 2013], [Roitberg 2008], [Woloszyn 2012].

The AHA/ASA guideline for the management of aneurysmal SAH recommends the use of antihypertensives during the period between onset of SAH and aneurysm repair [AHA/ASA [Connolly 2012]].

Contraindications

Hypersensitivity to nicardipine or any component of the formulation; advanced aortic stenosis

Dosing: Adult

Angina: Oral: 20 mg 3 times daily; usual dosage: 20 to 40 mg 3 times daily (allow ≥3 days between dose increases).

Hypertension: Oral: Initial: 20 mg 3 times daily; usual dosage: 20 to 40 mg 3 times daily (allow ≥3 days between dose increases).

Acute hypertension: Continuous IV infusion: Initial: 5 mg/hour; may increase by 2.5 mg/hour every 5 minutes (for rapid titration) to every 15 minutes (for gradual titration) up to a maximum of 15 mg/hour; adjust infusion rate as needed to maintain desired response; in rapidly titrated patients, consider reduction to 3 mg/hour after response is achieved. Discontinue infusion if unacceptable hypotension or tachycardia occurs.

Acute ischemic stroke, blood pressure management (off-label use):

Patient otherwise eligible for reperfusion treatment (eg, alteplase) except blood pressure >185/110 mm Hg:

Continuous IV infusion: Initiate 5 mg/hour; titrate by 2.5 mg/hour at 5- to 15-minute intervals (maximum dose: 15 mg/hour). When goal BP is obtained, adjust dose to maintain proper BP limits. If BP remains >185/110 mm Hg, do not administer thrombolytic (ACC/AHA [Whelton 2018]; AHA/ASA [Powers 2019]; Liu-DeRyke 2013).

Management of blood pressure during and after reperfusion treatment (eg, alteplase):

Continuous IV infusion: Initiate 5 mg/hour; titrate by 2.5 mg/hour at 5- to 15-minute intervals (maximum dose: 15 mg/hour). Target BP <180/105 mm Hg for first 24 hours after reperfusion treatment. If hypertension is refractory or diastolic BP >140 mm Hg, consider alternative therapy (ACC/AHA [Whelton 2018]; AHA/ASA [Powers 2019]).

Hypertensive emergency:

Note: In general, reduce mean arterial BP ~10% to 20% over the first hour, then 5% to 15% over the next 23 hours, unless there is a compelling indication (eg, acute aortic dissection, severe preeclampsia, eclampsia) for more rapid BP and heart rate control (ACC/AHA [Whelton 2018]; Elliott 2020).

Continuous IV infusion: Initiate 5 mg/hour; titrate by 2.5 mg/hour at 5- to 15-minute intervals to goal target mean arterial pressure (maximum dose: 15 mg/hour) (ACC/AHA [Whelton 2018]; Peixoto 2019).

Intracerebral hemorrhage, blood pressure management (off-label use):

Note: In patients who present within 6 hours of acute intracerebral hemorrhage and have systolic BP between 150 and 220 mm Hg, decreasing systolic BP to <140 mm Hg is not beneficial and can be harmful (ACC/AHA [Whelton 2018]).

Patients who present with systolic BP >220 mm Hg:

Continuous IV infusion: Initiate 5 mg/hour; titrate by 2.5 mg/hour at 5- to 15-minute intervals to recommended target systolic BP (maximum dose: 15 mg/hour) (AHA/ASA [Broderick 2007]; Mocco 2006; Ortega-Gutierrez 2013).

Subarachnoid hemorrhage, blood pressure management (off-label use):

Note: Optimal therapy is not well established. Cautious use of antihypertensive therapy to decrease the risk of rebleeding may be appropriate in some patients with systolic BP >160 mm Hg or mean arterial pressure >110 mm Hg with adequate cerebral perfusion pressure (AHA/ASA [Connolly 2012]; Diringer 2011).

Continuous IV infusion: Initiate 5 mg/hour; titrate by 2.5 mg/hour at 5- to 15-minute intervals to goal target systolic BP or mean arterial pressure (maximum dose: 15 mg/hour) (Mocco 2006).

Substitution for oral therapy (approximate equivalents):

20 mg every 8 hours oral, equivalent to 0.5 mg/hour IV infusion.

30 mg every 8 hours oral, equivalent to 1.2 mg/hour IV infusion.

40 mg every 8 hours oral, equivalent to 2.2 mg/hour IV infusion.

Conversion to oral antihypertensive agent: Initiate oral antihypertensive at the same time that IV nicardipine is discontinued; if transitioning to oral nicardipine, start oral nicardipine 1 hour prior to IV discontinuation.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Initiate at the low end of the dosage range. Specific guidelines for adjustment of nicardipine are not available, but careful monitoring is warranted and adjustment may be necessary.

Dosing: Pediatric

Hypertension: Note: Use should be reserved for acute severe hypertension: Limited data available: Infants, Children, and Adolescents: Continuous IV infusion: Bolus dose (optional): Initial: 30 mcg/kg, maximum dose: 2 mg/dose; followed by continuous infusion: Initial: 0.5 to 1 mcg/kg/minute; titrate dose according to blood pressure; rate of infusion may be increased every 15 to 30 minutes; maximum dose: 4 to 5 mcg/kg/minute (AAP [Flynn 2017]; Flynn 2000; Flynn 2001). In a retrospective analysis (n=29; mean age: 7.8 ± 6 years [range: 2 days to 17.9 years]), the mean initial dose was 0.8 ± 0.3 mcg/kg/minute (range: 0.2 to 1.3 mcg/kg/minute), the mean effective dose was 1.8 ± 1 mcg/kg/minute (range: 0.3 to 4 mcg/kg/minute); blood pressure was controlled within 2.7 ± 2.1 hours (range: 0.5 to 9 hours) after starting nicardipine continuous infusion (Flynn 2001).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Reconstitution

Parenteral:

Premixed bags: No further dilution needed.

Vial: Dilute 25 mg vial with 240 mL of compatible IV solution (eg, D5W, NS) to provide a 250 mL total volume solution and a final concentration of 0.1 mg/mL.

Administration

Oral: Administer without regards to meals.

IV:

Administer as a slow continuous infusion via central line or through a large peripheral vein. Peripheral venous irritation may be minimized by changing the site of infusion every 12 hours.

Premixed bags: Do not combine or run in the same line as other medications.

Storage

IV:

Premixed bags: Store at 20°C to 25°C (68°F to 77°F). Protect from light and excessive heat. Do not freeze.

Vials: Store at 20°C to 25°C (68°F to 77°F). Protect from light. Freezing does not adversely affect the product, but exposure to elevated temperatures should be avoided. Diluted solution (0.1 mg/mL) in D5W with KCl 40 mEq, D51/2NS, D5NS, D5W, NS, or 1/2NS is stable at room temperature for 24 hours in glass or PVC containers. Stability has also been demonstrated at room temperature at concentrations up to 0.5 mg/mL in PVC containers for 24 hours or in glass containers for up to 7 days (Baaske 1996).

Oral: Store at room temperature. Protect from light.

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs. Management: Concurrent use of felodipine or nisoldipine with itraconazole is specifically contraindicated. Frequent monitoring is warranted with any such combination; calcium channel blocker dose reductions may be required. Exceptions: Fluconazole; Isavuconazonium Sulfate. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Avoid combination

Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Monitor therapy

CarBAMazepine: May increase the metabolism of Calcium Channel Blockers (Dihydropyridine). Management: Consider calcium channel blocker (CCB) dose adjustments or alternative therapy in patients receiving concomitant carbamazepine. Nimodipine Canadian labeling contraindicates concurrent use with carbamazepine. Consider therapy modification

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CycloSPORINE (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination. Some combinations are specifically contraindicated by manufacturers; others may have recommended dose adjustments. If combined, monitor for increased substrate effects. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Efavirenz: May decrease the serum concentration of Calcium Channel Blockers. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fluconazole: May increase the serum concentration of Calcium Channel Blockers. Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Calcium Channel Blockers may decrease the serum concentration of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Consider therapy modification

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Grapefruit Juice: May increase the serum concentration of NiCARdipine. Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification

Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy

Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phenytoin: Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers. Management: Avoid use of nimodipine or nifedipine with phenytoin. Monitor for phenytoin toxicity and/or decreased calcium channel blocker effects with any concurrent use. Consider therapy modification

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

QuiNIDine: Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Rifamycin Derivatives: May decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

SUNItinib: NiCARdipine may increase the serum concentration of SUNItinib. Monitor therapy

Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

Thioridazine: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Test Interactions

May lead to false-negative aldosterone/renin ratio (ARR) (Funder 2016)

Adverse Reactions

1% to 10%:

Cardiovascular: Flushing (6% to 10%), pedal edema (dose related; 7% to 8%), exacerbation of angina pectoris (dose related; 6%), hypotension (IV 6%), palpitations (3% to 4%), tachycardia (1% to 4%), chest pain (IV 1%), extrasystoles (IV 1%), hemopericardium (IV 1%), hypertension (IV 1%), supraventricular tachycardia (IV 1%), edema (≤1%)

Central nervous system: Headache (6% to 15%), dizziness (4% to 7%), hypoesthesia (1%), intracranial hemorrhage (1%), pain (1%), somnolence (1%)

Dermatologic: Diaphoresis (1%), skin rash (≤1%)

Endocrine & metabolic: Hypokalemia (IV 1%)

Gastrointestinal: Nausea and vomiting (IV 5%), nausea (2%), dyspepsia (≤2%), abdominal pain (IV 1%), xerostomia (≤1%)

Genitourinary: Hematuria (1%)

Local: Injection site reaction (IV 1%), pain at injection site (IV 1%)

Neuromuscular & skeletal: Weakness (4% to 6%), myalgia (1%), paresthesia (1%)

<1%, postmarketing, and/or case reports: Abnormal dreams, abnormal hepatic function tests, abnormal vision, angina pectoris, anxiety, arthralgia, atrial fibrillation (not distinguishable from natural history of atherosclerotic vascular disease), atrioventricular block, atypical chest pain, blurred vision, cerebral ischemia (not distinguishable from natural history of atherosclerotic vascular disease), confusion, conjunctivitis, constipation, deep vein thrombophlebitis, depression, depression of ST segment on ECG, dyspnea, ear disease, ECG abnormal, fever, gingival hyperplasia, heart block (not distinguishable from natural history of atherosclerotic vascular disease), hot flash, hyperkinesia, hypersensitivity reaction, hypertonia, hypophosphatemia, impotence, infection, insomnia, inversion T wave on ECG, malaise, myocardial infarction (chronic therapy; may be due to disease progression), neck pain, nervousness, nocturia, orthostatic hypotension, oxygen saturation decreased (possible pulmonary shunting), parotitis, pericarditis (not distinguishable from natural history of atherosclerotic vascular disease), peripheral vascular disease, respiratory tract disease, rhinitis, sinus node dysfunction (chronic therapy; may be due to disease progression), sinusitis, sore throat, sustained tachycardia, syncope, thrombocytopenia, tinnitus, tremor, urinary frequency, ventricular extrasystoles, ventricular tachycardia, vertigo, vomiting

Warnings/Precautions

Concerns related to adverse effects:

• Angina/MI: Increased angina (frequency, duration, or severity) and/or MI has occurred. Reflex tachycardia may occur resulting in angina and/or MI in patients with obstructive coronary disease, especially in the absence of concurrent beta blockade.

• Hypotension/syncope: Symptomatic hypotension with or without syncope may rarely occur; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Avoid systemic hypotension in acute cerebral infarction or hemorrhage. Close monitoring of heart rate and blood pressure, especially during initial therapy and dosage titration, is required.

• Peripheral edema: A common side effect is peripheral edema (dose-dependent); occurs within 2 to 3 weeks of starting therapy.

• Tachycardia: May occur; close monitoring of heart rate is required.

Disease-related concerns:

• Aortic stenosis: Use with caution in patients with mild to moderate aortic stenosis; may reduce coronary perfusion resulting in ischemia. Use is contraindicated in patients with advanced aortic stenosis.

• Heart failure: Use in patients with heart failure (HF) or severe left ventricular dysfunction, particularly with concomitant beta-blockade, may experience worsened symptoms of HF due to mild negative inotropic effects of nicardipine. The ACC/AHA heart failure guidelines recommend to avoid use in patients with heart failure due to lack of benefit and/or worse outcomes with calcium channel blockers in general (ACC/AHA [Yancy 2013]).

• Hepatic impairment: Use with caution in patients with hepatic impairment or reduced hepatic blood flow. Consider lower starting dose and closely monitor response.

• Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (ACC/AHA [Gersh 2011]).

• Renal impairment: Use with caution in patients with renal impairment. Increase dose cautiously in patients with renal impairment since clearance of nicardipine is diminished in this population.

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007).

Other warnings/precautions:

• Infusion sites: To minimize infusion site reactions, peripheral infusion sites (for IV therapy) should be changed every 12 hours; use of arteries or small peripheral veins should be avoided.

• Withdrawal: Abrupt withdrawal may cause rebound angina in patients with CAD.

Monitoring Parameters

BP, heart rate; consult individual institutional policies and procedures.

Pregnancy Risk Factor

C

Pregnancy Considerations

Nicardipine has limited placental transfer following maternal oral and IV administration (Bartels 2007; Carbonne 1993; Matsumura 2014).

Nicardipine has been shown to decrease maternal blood pressure without significant changes on placental perfusion or fetal hemodynamics (Cornette 2016). Although effective for the treatment of hypertension in pregnancy, nicardipine may have an increased risk of adverse maternal events (eg, headache, nausea, tachycardia) in comparison to other agents (Nooij 2014). Cases of acute pulmonary edema have been reported following use as a tocolytic (Melis 2015).

Chronic maternal hypertension may increase the risk of birth defects, low birth weight, preterm delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to duration and severity of maternal hypertension. Untreated hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, myocardial infarction, preeclampsia, stroke, and delivery complications (ACOG 203 2019).

Calcium channel blockers may be used to treat hypertension in pregnant women; however, agents other than nicardipine are more commonly used for chronic hypertension (ACOG 203 2019; ESC [Regitz-Zagrosek 2018]). Females with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]). Nicardipine may be used as an alternative agent for the treatment of acute onset, severe hypertension in pregnant females (ACOG 203 2019; ACOG 767 2019).

Patient Education

What is this drug used for?

• It is used to treat high blood pressure.

• It is used to treat a type of long-term chest pain (stable angina) in some people.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Flushing

• Headache

• Loss of strength and energy

• Vomiting

• Nausea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe dizziness

• Passing out

• Abnormal heartbeat

• Chest pain

• Fast heartbeat

• Shortness of breath

• Excessive weight gain

• Swelling of arms or legs

• Severe injection site pain, burning, swelling, or irritation

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.