Nicardipine is a medication primarily used to treat high blood pressure and angina (chest pain). It belongs to a class of medications known as calcium channel blockers. Nicardipine works by relaxing the blood vessels, allowing blood to flow more easily and lowering blood pressure. This can help reduce the workload on the heart and improve blood flow to the heart muscle.

Nicardipine (Cardene) belongs to the class of dihydropyridine calcium channel blockers.

Nicardipine Uses:

• Angina:
  • It is used to treat long-term stable angina (oral immediate-release product only).
• Hypertension:
  • It is indicated for treating hypertension (oral immediate/ sustained release or intravenous forms).
  • In cases where oral medication cannot be delivered, intravenous delivery may be employed.

Guideline recommendations:

• If single-agent therapy is to be administered in the absence of comorbidities, the 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults suggests thiazide-like diuretics or dihydropyridine calcium channel blockers are preferred due to the prevention of heart failure and stroke.
• ARBs and ACE inhibitors can also be used alone. In high-risk individuals (such as those with stage 2 hypertension and an atherosclerotic cardiovascular disease risk of 10% or more), combination therapy is initially chosen.

Off Label Use of Nicardipine (Cardene) in adults:

• Arterial hypertension in acute ischemic stroke.
• Control of blood pressure in patients with spontaneous intracranial hemorrhage.
• Perioperative hypertension.
• Subarachnoid hemorrhage associated cerebral vasospasm.

Nicardipine (Cardene) dosage in adults:

Note: Cardene SR has been discontinued in the US for more than 1 year.

Nicardipine (Cardene) dose for the treatment of Angina:

• The typical starting dose with immediate-release tablets is 20 milligrams taken three times a day.
• Doctors may adjust this dose, usually increasing it every few days, but by no more than 20 to 40 milligrams each time.
• It's important to leave at least three days between these dose increases.

Nicardipine (Cardene) dose for the treatment of Hypertension: 

Immediate-release:

• The starting dose with immediate-release tablets is typically 20 milligrams taken three times daily.
• Doctors may then adjust the dose, usually increasing it every few days by 20 to 40 milligrams each time.
• It's essential to wait at least three days between these dose increases.

Sustained-release:

• The initial dose is usually 30 milligrams taken twice daily.
• This dose may be adjusted by your doctor, typically increasing it every few days, but by no more than 30 to 60 milligrams each time.

Nicardipine (Cardene) dose for the treatment of Acute hypertension:

• With nicardipine intravenously (IV), the initial dose is typically 5 milligrams per hour.
• The dosage can be adjusted by increasing it by 2.5 milligrams per hour every 5 minutes for rapid titration or every 15 minutes for gradual titration.
• The maximum dosage is 15 milligrams per hour.
• The infusion rate should be adjusted as needed to maintain the desired response.
• In patients who are rapidly titrated, it's important to consider reducing the dose to 3 milligrams per hour once the desired response is achieved.
• If unacceptable hypotension (low blood pressure) or tachycardia (fast heart rate) occurs, the infusion should be discontinued.

Nicardipine (Cardene) dose for the treatment of Arterial hypertension in acute ischemic stroke (off-label use):

• In treating arterial hypertension during an acute ischemic stroke, especially in patients eligible for reperfusion treatment like alteplase but with high blood pressure (BP) over 185/110 mm Hg, an IV infusion of nicardipine is typically initiated at a rate of 5 milligrams per hour.
• The dose can be adjusted by increasing it by 2.5 milligrams per hour at intervals of 5 to 15 minutes, up to a maximum dose of 15 milligrams per hour.
• Once the target BP is achieved, the dose should be adjusted to maintain proper BP levels.
• If BP remains high and exceeds 185/110 mm Hg, alteplase should not be administered.

Management of BP during and after reperfusion treatment to maintain BP ≤180/105 mm Hg:

• For managing BP during and after reperfusion treatment (e.g., alteplase) to maintain BP below or equal to 180/105 mm Hg, if systolic BP is between 180 to 230 mm Hg or diastolic BP is between 105 to 120 mm Hg, nicardipine infusion is initiated at 5 milligrams per hour and titrated by 2.5 milligrams per hour at 5 to 15-minute intervals, with a maximum dose of 15 milligrams per hour.
• If hypertension persists or if diastolic BP exceeds 140 mm Hg, other IV antihypertensives like nitroprusside may be considered.

Substitution for oral therapy (approximate equivalents):

• 20 milligrams every 8 hours orally is equivalent to a 0.5 milligrams/hour IV infusion.
• 30 milligrams every 8 hours orally is equivalent to a 1.2 milligrams/hour IV infusion.
• 40 milligrams every 8 hours orally is equivalent to a 2.2 milligrams/hour IV infusion.

Conversion to oral antihypertensive agent:

• When transitioning to oral antihypertensive agents, initiate the oral medication at the same time that the IV nicardipine is discontinued.

Nicardipine (Cardene) Dose in Children

Nicardipine dose in children for the treatment of hypertension:

Infants, Children, and Adolescents:

Nicardipine is typically administered intravenously through a continuous infusion.

• Bolus dose (optional): Initially, 30 micrograms per kilogram (mcg/kg) can be given, with a maximum dose of 2 milligrams per dose.
• This bolus dose is followed by a continuous infusion, initially starting at a rate of 0.5 to 1 mcg/kg/minute.
• The dosage is then adjusted based on the patient's blood pressure, and the infusion rate can be increased every 15 to 30 minutes.
• The maximum infusion rate is typically 4 to 5 mcg/kg/minute.

In a retrospective analysis involving 29 patients with a mean age of 7.8 years (ranging from 2 days to 17.9 years), the mean initial dose used was 0.8 mcg/kg/minute, with a range of 0.2 to 1.3 mcg/kg/minute. The mean effective dose was 1.8 mcg/kg/minute, ranging from 0.3 to 4 mcg/kg/minute. Blood pressure was usually controlled within an average of 2.7 hours after starting the nicardipine continuous infusion.

Pregnancy Risk Factor C

• Nicardipine is categorized as Pregnancy Risk Factor C, meaning adverse effects have been seen in animal studies.
• It's been used to treat severe hypertension and preterm labor during pregnancy, but it crosses the placenta, potentially affecting the fetus.
• Although rare, changes in fetal heart rate, neonatal hypotension, and acidosis have been noted with maternal use.
• Pregnant women may experience similar side effects to non-pregnant individuals, with pulmonary edema being a notable concern.
• It's advised to explore other treatment options for hypertension during pregnancy due to potential risks to both the mother and fetus associated with nicardipine use.

Nicardipine use during breastfeeding:

• Nicardipine is found in low levels in breast milk.
• In a study, peak concentrations in breast milk ranged from 1.9 to 18.8 micrograms per milliliter (mcg/mL) after mothers took oral doses of 40 to 150 milligrams per day.
• The amount of nicardipine passed to the breastfeeding baby was estimated to be around 0.073% of the mother's oral dose or 0.14% of the mother's IV dose, adjusted for the baby's weight.
• Some manufacturers advise against breastfeeding while using nicardipine.

Nicardipine dose adjustment in renal disease:

• When taken orally, the initial dose of nicardipine according to the manufacturer is 20 milligrams three times a day for immediate-release tablets or 30 milligrams twice daily for sustained-release tablets. It's advised to titrate the dose slowly.
• For intravenous (IV) administration, the manufacturer does not provide specific dosage adjustments. However, it's recommended to titrate the IV dose slowly while closely monitoring the patient, and dosage adjustments may be necessary based on individual response.

Nicardipine dose adjustment in liver disease:

• According to the manufacturer's instructions, when taking nicardipine orally, the typical starting dose is 20 milligrams twice daily for immediate-release tablets, and it's important to adjust the dose slowly.
• For intravenous (IV) administration, the manufacturer doesn't offer specific dosage adjustments. However, it's recommended to titrate the IV dose slowly while closely monitoring the patient, as dosage adjustments may be needed based on individual response.

Side Effects of Nicardipine (Cardene):

• Cardiovascular:
  • Flushing
  • Pedal Edema
  • Exacerbation Of Angina Pectoris
  • Hypotension
  • Palpitations
  • Tachycardia
  • Chest Pain
  • Extrasystoles
  • Hemopericardium
  • Hypertension
  • Supraventricular Tachycardia
  • Edema
• Central Nervous System:
  • Headache
  • Dizziness
  • Hypoesthesia
  • Intracranial Hemorrhage
  • Pain
  • Somnolence
• Dermatologic:
  • Diaphoresis
  • Skin Rash
• Endocrine & Metabolic:
  • Hypokalemia
• Gastrointestinal:
  • Nausea And Vomiting
  • Nausea
  • Dyspepsia
  • Abdominal Pain
  • Xerostomia
• Genitourinary:
  • Hematuria
• Local:
  • Injection Site Reaction
  • Pain At Injection Site
• Neuromuscular & Skeletal:
  • Weakness
  • Myalgia
  • Paresthesia

Contraindication to Nicardipine (Cardene):

• If someone is allergic to nicardipine or any part of the medication, or if they have advanced aortic stenosis, they shouldn't take nicardipine.

Warnings and precautions

Angina/Myocardial Infarction:

• For people with angina or a history of heart attacks (MI), nicardipine might increase angina symptoms like frequency, duration, or severity, and it could even lead to a heart attack.
• In some cases, nicardipine might cause reflex tachycardia, which means the heart beats faster in response to the medication, potentially worsening angina or triggering a heart attack, especially if the patient isn't also taking beta-blockers.

Hypotension/syncope

• Sometimes, nicardipine can cause low blood pressure, which may lead to feeling dizzy or fainting, although this is rare.
• It's crucial to adjust blood pressure gradually based on the patient's condition.
• In situations like acute stroke, it's important to avoid dropping blood pressure too much.
• Monitoring heart rate and blood pressure closely, especially when starting treatment or adjusting the dose, is essential.

Peripheral edema

• Peripheral edema, swelling in the arms or legs, is a frequent side effect of nicardipine, and its severity can depend on the dosage.
• This swelling typically develops within 2 to 3 weeks after starting the medication.

Tachycardia

• Tachycardia, or a fast heart rate, can sometimes happen with nicardipine use.
• It's important to keep a close eye on the heart rate and monitor it regularly while taking this medication.

Aortic stenosis

• Nicardipine should be used cautiously in individuals with mild to moderate aortic stenosis because it might decrease blood flow to the heart, leading to ischemia (reduced blood supply).
• However, it's not recommended for those with advanced aortic stenosis due to the increased risk of complications.

Heart failure:

• Nicardipine should be used cautiously in patients with heart failure or severe left ventricular dysfunction, especially if they're also taking beta-blockers.
• This combination might worsen heart failure symptoms because nicardipine can mildly reduce the heart's pumping ability.
• In fact, guidelines from the American College of Cardiology (ACC) and the American Heart Association (AHA) recommend avoiding calcium channel blockers, including nicardipine, in heart failure patients due to the potential lack of benefit and the possibility of worse outcomes.

Hepatic impairment

• If someone has liver problems or reduced blood flow to the liver, it's important to be cautious when using nicardipine.
• Doctors may start with a lower dose and closely watch how the person responds to the medication.

Hypertrophic cardiomyopathy with outflow tract obstruction (HCM)

• Nicardipine should be used cautiously in patients with hypertrophic cardiomyopathy (HCM) and outflow tract obstruction.
• This caution is because nicardipine can decrease the heart's workload, which might worsen symptoms in these individuals.

Renal impairment

• Nicardipine should be used cautiously in individuals with kidney problems.
• In patients with renal impairment, the clearance of nicardipine from the body is reduced, so any dosage adjustments should be made carefully.
• It's important to closely monitor these patients for any signs of adverse effects or changes in response to the medication.

Nicardipine: Drug Interaction

Monitoring parameters:

Blood Pressure and Heart Rate

• Consultation: Refer to individual institutional policies and procedures for guidance on monitoring blood pressure and heart rate.

Hypertension

• 2017 ACC/AHA Guidelines:
  • For confirmed hypertension with known cardiovascular disease (CVD) or a 10-year risk of atherosclerotic cardiovascular disease (ASCVD) ≥10%: Target blood pressure should be <130/80 mm Hg.
  • For confirmed hypertension without markers of increased ASCVD risk: A target blood pressure of <130/80 mm Hg may be reasonable.

Diabetes and Hypertension

• American Diabetes Association (ADA) Guidelines 2019:
  • For patients aged 18 to 65 without ASCVD and a 10-year ASCVD risk <15%: Target blood pressure is <140/90 mm Hg.
  • For patients aged 18 to 65 with known ASCVD or a 10-year ASCVD risk >15%: A target blood pressure of <130/80 mm Hg may be appropriate if safely attainable.
  • For patients aged over 65 (healthy or with complex/intermediate health): Target blood pressure is <140/90 mm Hg.
  • For patients aged over 65 (very complex/poor health): Target blood pressure is <150/90 mm Hg.

How to administer Nicardipine (Cardene)?

Oral Administration

• Dosing Caution: Be careful when converting between total daily doses of immediate-release and sustained-release formulations, as they may not be equivalent.
• Meal Consideration: Administer immediate-release nicardipine without regard to meals. Sustained-release nicardipine can be taken with a meal to reduce fluctuations in blood levels.
• Administration Instructions: Swallow sustained-release tablets whole; do not chew or crush. Avoid opening or cutting capsules.

IV Administration

• Method: Administer as a slow continuous infusion using a central line or a large peripheral vein.
• Peripheral Venous Irritation: Change the infusion site every 12 hours to minimize irritation.
• Premixed Bags: Do not mix nicardipine premixed bags with other medications, and avoid running them in the same line as other drugs.

Mechanism of action of Nicardipine (Cardene):

• Nicardipine works by blocking calcium ions from entering specific areas in the vascular smooth muscle and heart muscle during depolarization.
• This action leads to relaxation of the smooth muscle in the coronary blood vessels, causing them to widen (vasodilation).
• As a result, more oxygen-rich blood can flow to the heart muscle, which is particularly beneficial for patients with vasospastic angina, as it helps increase myocardial oxygen delivery.

Onset of Action:

• IV: Within minutes, when administered as a constant infusion.
• Oral: Takes 0.5 to 2 hours to take effect after ingestion.

Peak Effect:

• Immediate Capsules: 1 to 2 hours after ingestion.
• Sustained-Release Capsules (Steady State): Peak effect is sustained from 2 to 6 hours post-dose.
• IV Continuous Infusion: 50% of the maximum effect is observed by 45 minutes.

Duration:

• IV: Lasts up to 8 hours. After discontinuation of continuous infusion, the antihypertensive effects gradually decline over about 50 hours.
• Oral: Immediate-release lasts up to 8 hours; sustained-release lasts 8 to 12 hours.

Absorption:

• Oral: Approximately 100%, but there is a significant first-pass effect.

Distribution:

• Volume of Distribution: 8.3 L/kg.
• Protein Binding: More than 95%.

Metabolism:

• Hepatic metabolism, with a major pathway involving cytochrome P450 enzymes, particularly CYP3A4, 2C8, and 2D6.

Bioavailability:

• Oral: Approximately 35%.

Half-life Elimination:

• Follows dose-dependent (nonlinear) pharmacokinetics.
• Oral: Half-life over the first 8 hours is 2 to 4 hours, and the terminal half-life is 8.6 hours.
• IV: Serum concentrations decrease tri-exponentially, with an alpha half-life of 3 minutes, beta half-life of 45 minutes, and terminal half-life of 14 hours.

Time to Peak Serum Concentration:

• Oral: Immediate release: 30 to 120 minutes (average: 1 hour); Sustained release: 60 to 240 minutes.

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 also be decreased in patients with renal impairment.

Nicardipine Brand Names (International):

• Cardene IV
• Antagonil
• Barizin
• Binicapin
• Blistra
• Cardene
• Cardene SR
• Cardepine
• Cardepine SR
• Cardibloc SR
• Cardibrain
• Cardilon
• Cardimed
• Cardipene
• Carsive
• Convertal
• Dacarel
• Dafil
• Dipitenz
• Flusemide
• Karden
• Lincil
• Loxen
• Loxen LP
• Nerdipina
• Nicafer
• Nicardal
• Nicardin
• Nidaven
• Nimicor
• Perdipina
• Perdipine
• Perdipine LA
• Ridene
• Rydene
• Tensilo
• Vasonase
• Xian Li

Nicardipine Brand Names in Pakistan:

Nicapress-R 40 mg (Amson Vaccines and Pharmaceuticals)