nicardipine (Cardene, Cardene IV, Cardene SR)

Dosing and uses of Cardene, Cardene IV (nicardipine)

• Adult
• Pediatric
• Geriatric

 

Adult dosage forms and strengths

capsule

• 20mg
• 30mg

capsule, extended release

• 30mg
• 45mg
• 60mg

infusion solution

• 20mg/200mL
• 40mg/200mL

injectable solution

• 2.5mg/mL

 

Hypertension

PO: 20-40 mg (conventional) q8hr or 30-60 mg (extended release) q12hr

Extended-release form preferred because of less frequent dosing, potentially smoother BP control, and concerns raised by short-acting nifedipine

IV: 5 mg/hr by slow infusion (50 mL/hr) initially; may be increased by 2.5 mg/hr every 15 minutes; not to exceed 15 mg/hr

IV as substitute for conventional PO

• PO dose: 20 mg q8hr; equivalent IV infusion: 0.5 mg/hr
• PO dose: 30 mg q8hr; equivalent IV infusion: 1.2 mg/hr
• PO dose: 40 mg q8hr; equivalent IV infusion: 2.2 mg/hr
• If transitioning to PO nicardipine, initiate PO dosing 1 hr before discontinuance of IV

 

Chronic Stable Angina

20-40 mg (conventional) PO q8hr

Start at 20 mg, and allow 3 days between dose increases to achieve steady-state plasma drug concentration; usual dosage range, 60-120 mg/day

 

Dosing Modifications

Renal impairment

• Immediate release: 20 mg PO q8hr initially; titrated to effect every 3 days
• Extended release: 30 mg PO q12hr initially; titrated to effect every 3 days
• IV: Use with caution; guidelines for dose adjustments not available; monitor and adjust as necessary

Hepatic impairment

• Immediate release: 20 mg PO q12hr initially; titrated to effect every 3 days
• Daily immediate-release dose may not be directly equivalent to daily extended-release dose; use caution in converting
• IV: Use with caution; guidelines for dose adjustments not available; monitor and adjust as necessary

 

Pediatric dosage forms and strengths

capsule

• 20mg
• 30mg

capsule, extended release

• 30mg
• 45mg
• 60mg

infusion solution

• 20mg/200mL
• 40mg/200mL

injectable solution

• 2.5mg/mL

 

Hypertension (Off-label)

Not approved by FDA; limited data available

0.5-3 mcg/kg/min IV

 

Geriatric dosage forms and strengths

Use with caution; initiate at low end of adult dosing range; monitor closely

 

Cardene, Cardene IV (nicardipine) adverse (side) effects

>10%

Headache (IV; 15%)

 

1-10%

Flushing (6-10%)

Peripheral edema (PO; 6-8%)

Pedal edema (PO; 6.8%)

Headache (PO; 6.3%)

Hypotension (IV; 6%)

Exacerbation of angina (6%)

Asthenia (PO; 3%)

Nausea (PO; 1.6%)

Ventricular extrasystoles (IV; 1%)

Dizziness (1%)

Rash (PO; 1%)

Polyuria (IV; 1%)

 

<1% (selected)

Asthenia (IV)

Facial edema

Hypotension (PO)

Myalgia (PO)

Syncope (IV)

Tachycardia

 

Warnings

Contraindications

Hypersensitivity to nicardipine or other calcium-channel blockers

Advanced aortic stenosis

 

Cautions

May cause symptomatic hypotension or tachycardia; titrate slowly to avoid systemic hypotension and possible negative inotropic effects with congestive heart failure (CHF), angina, and left ventricular dysfunction (particularly during treatment initiation, after dose increase, or after withdrawal of beta blocker)

To reduce possibility of venous thrombosis, phlebitis, and vascular impairment, do not use small veins, such as those on dorsum of hand or wrist; avoid intraarterial administration or extravasation

Caution should be exercised when using the drug in congestive heart failure patients, particularly in combination with a beta-blocker; nicardipine gives no protection against dangers of abrupt beta-blocker withdrawal; any such withdrawal should be by gradual reduction of dose of beta-blocker, preferably over 8 to 10 days

Closely monitor response in patients with angina, congestive heart failure, impaired hepatic function, portal hypertension, and renal impairment and pheochromocytoma

Peripheral edema may occur

Exacerbation of angina or MI reported with dosage titration of dihydropyridine calcium-channel blockers

With acute cerebral infarction or hemorrhage, titrate slowly to avoid systemic hypotension

Use with caution in patients with hypertrophic cardiomyopathy and mild-to-moderate aortic stenosis

Use with caution in hepatic or renal impairment; lower doses may be required

Use with caution in hypertension associated with pheochromocytoma and portal hypertension when administering IV

Change infusion site every 12 hr to minimize risk of peripheral venous irritation

Blood pressure starts to fall within min of infusion; calcium channel blockers, may occasionally produce symptomatic hypotension; caution is advised to avoid systemic hypotension when administering drug to patients who have sustained acute cerebral infarction or hemorrhage

Extended-release form not recommended for angina

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Unknown whether drug is excreted in breast milk; avoid use

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Cardene, Cardene IV (nicardipine)

Mechanism of action

Calcium-channel blocker (dihydropyridine); inhibits transmembrane influx of extracellular calcium ions across membranes of myocardial cells and vascular smooth muscle cells without changing serum calcium concentrations; this inhibits cardiac and vascular smooth muscle contraction, thereby dilating main coronary and systemic arteries

Produces vasodilation and decreases peripheral resistance  

 

Absorption

Bioavailability: 35%

Onset: PO, 0.5-2 hr; IV, 10-20 min

Duration: Immediate release and IV, 8 hr; extended release, 8-12 hr

Peak plasma time: Immediate release, 0.5-2 hr; extended release, 2-4 hr

 

Distribution

Protein bound: 95%

Vd: 8.3 L/kg

 

Metabolism

Metabolized in liver by CYP3A4 (first pass)

Metabolites: Pyridine analogue (inactive)

 

Elimination

Half-life: 2-4 hr

Dialyzable: HD, no

Total plasma clearance: IV, 0.3-0.9 L/hr/kg; PO, 1.62-7.86 L/hr/kg

Excretion: Urine (60%), feces (35%)

 

Administration

IV Incompatibilities

Solution: Lactated Ringer solution, sodium bicarbonate 5%

Y-site: Ampicillin, ampicillin-sulbactam, cefoperazone, furosemide, heparin (may be compatible at low concentrations of both), thiopentaL

 

IV Compatibilities

Solution: D5/NS, D5/LR, D5W, Ns

Additive: Potassium chloride

Y-site (partial list): Amikacin, aminophylline, aztreonam, calcium gluconate, cefazolin, ceftazidime (incompatible at high concentrations of both), chloramphenicol, cimetidine, clindamycin, diltiazem, dobutamine, dopamine, enalapril, epinephrine, erythromycin, esmolol, famotidine, fentanyl, gentamicin, hydrocortisone, labetalol, lidocaine, lorazepam, magnesium sulfate, methylprednisolone, metronidazole, midazolam, morphine, nitroglycerin, nitroprusside sodium, penicillin G, phosphate, piperacillin, potassium chloride, ranitidine, tobramycin, trimethoprim-sulfamethoxazole, vancomycin

 

IV Preparation

Dilute ampules before infusion: 25 mg diluted in 240 mL IV fluid (yielding 250 mL of 0.1 mg/mL solution)

Premixed infusion solution requires no dilution

 

IV Administration

Administer by slow continuous infusion