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

Risk Factor C (Monitor therapy)
Alfuzosin	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Alpha1-Blockers	The hypotensive effects of calcium channel blockers may be strengthened.
Amphetamines	May lessen the effectiveness of antihypertensive agents.
Antipsychotic Agents (Second Generation [Atypical])	Antipsychotic drugs' hypotensive effects may be enhanced by blood pressure-lowering medications (Second Generation [Atypical]).
Aprepitant	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
ARIPiprazole	ARIPiprazole's serum levels may rise in response to CYP2D6 Inhibitors (Weak). Management: Keep an eye out for enhanced pharmacologic effects of aripiprazole. Depending on the concurrent therapy and/or the indication, aripiprazole dosage modifications may or may not be necessary. For detailed advice, refer to the complete interaction monograph.
Atosiban	Calcium channel blockers may intensify Atosiban's harmful or hazardous effects. Particularly, pulmonary edoema and/or dyspnea may be at higher risk.
Barbiturates	Calcium Channel Blockers' metabolic rate might be increased. Management: Keep an eye out for any diminished therapeutic effects of barbiturate medication when concurrently using calcium channel blockers. There may need to be dose modifications with calcium channel blockers. The concurrent use of phenobarbital and nimodipine is not recommended.
Barbiturates	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Benperidol	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Bosentan	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Brigatinib	May lessen the effectiveness of antihypertensive agents. Antihypertensive Agents' bradycardic action may be strengthened by brutinib.
Brimonidine (Topical)	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Calcium Channel Blockers (Nondihydropyridine)	Dihydropyridine, a calcium channel blocker, may increase the hypotensive effects of calcium channel blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may cause an increase in serum calcium channel blocker concentration (Dihydropyridine).
Calcium Salts	The hypotensive effects of calcium channel blockers may become weak.
Carvedilol	Carvedilol's hypotensive impact could be strengthened by nicARdipine. In people on Carvedilol who are vulnerable, NiCARdipine may accelerate the signs of heart failure. Carvedilol's serum levels may rise in response to NiCARdipine.
Clofazimine	May enhance the serum level of CYP3A4 substrates (High risk with Inducers).
Clopidogrel	Calcium channel blockers may reduce Clopidogrel's therapeutic efficacy.
CycloSPORINE (Systemic)	The serum concentration of CycloSPORINE may rise when Calcium Channel Blockers (Dihydropyridine) are taken (Systemic). Calcium Channel Blockers' serum levels may rise when CycloSPORINE (Systemic) is used (Dihydropyridine).
CYP3A4 Inducers (Moderate)	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
CYP3A4 Inhibitors (Moderate)	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Dapoxetine	The orthoststatic hypotensive effects of calcium channel blockers may be strengthened.
Deferasirox	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Dexmethylphenidate	May lessen the effectiveness of antihypertensive agents.
Diazoxide	The hypotensive effects of blood pressure-lowering medications may be strengthened.
DULoxetine	The hypotensive impact of DULoxetine may be enhanced by blood pressure lowering medications.
Duvelisib	May enhance the serum level of CYP3A4 substrates (High risk with Inducers).
Efavirenz	The hypotensive effects of calcium channel blockers may be decreased.
Erdafitinib	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Erdafitinib	May enhance the serum level of CYP3A4 substrates (High risk with Inducers).
Erdafitinib	P-glycoprotein/ABCB1 Substrates serum levels can rise.
Fluconazole	The hypotensive effects of calcium channel blockers may be strengthened.
Fosaprepitant	May enhance the serum level of CYP3A4 substrates (High risk with Inducers).
Fosnetupitant	May enhance the serum level of CYP3A4 substrates (High risk with Inducers).
Grapefruit Juice	NiCARdipine serum concentration can rise.
Herbs (Hypertensive Properties)	May lessen the effectiveness of antihypertensive agents.
Herbs (Hypotensive Properties)	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Hypotension-Associated Agents	The hypotensive action of hypotension-associated agents may be strengthened by blood pressure lowering medications.
Ivosidenib	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Larotrectinib	May enhance the serum level of CYP3A4 substrates (High risk with Inducers).
Levodopa-Containing Products	Levodopa-Containing Products' hypotensive effects may be strengthened by blood pressure-lowering medications.
Lormetazepam	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Magnesium Salts	Calcium channel blockers might make magnesium salts more harmful or poisonous. Calcium Channel Blockers' hypotensive effects may be strengthened by magnesium salts.
Melatonin	May reduce the effectiveness of calcium channel blockers as an antihypertensive (Dihydropyridine).
Methylphenidate	May lessen the effectiveness of antihypertensive agents.
Molsidomine	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Naftopidil	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Netupitant	May enhance the serum level of CYP3A4 substrates (High risk with Inducers).
Neuromuscular-Blocking Agents (Nondepolarizing)	The neuromuscular-blocking impact of neuromuscular-blocking agents may be enhanced by calcium channel blockers (Nondepolarizing).
Nicergoline	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Nicorandil	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Nitroprusside	Nitroprusside's hypotensive impact may be strengthened by blood pressure-lowering medications.
Palbociclib	May enhance the serum level of CYP3A4 substrates (High risk with Inducers).
Pentoxifylline	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Perhexiline	The quantity of perhexiline in the serum may rise in response to CYP2D6 Inhibitors (Weak).
P-glycoprotein/ABCB1 Inhibitors	P-glycoprotein/ABCB1 Substrates serum levels can rise. P-glycoprotein inhibitors may also make it easier for p-glycoprotein substrates to reach particular cells, tissues, and organs where p-glycoprotein is abundant (e.g., brain, T-lymphocytes, testes, etc.).
Pholcodine	Pholcodine's hypotensive impact may be strengthened by blood pressure lowering medications.
Phosphodiesterase 5 Inhibitors	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Prostacyclin Analogues	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Quinagolide	The hypotensive effects of blood pressure-lowering medications may be strengthened.
QuiNIDine	The serum concentration of QuiNIDine may be lowered by calcium channel blockers (Dihydropyridine). The serum concentration of QuiNIDine may rise in response to calcium channel blockers (Dihydropyridine). Calcium Channel Blockers' serum levels may rise in response to quinine (Dihydropyridine).
Ranolazine	May enhance the serum level of CYP3A4 substrates (High risk with Inducers).
Sarilumab	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Siltuximab	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Simeprevir	May enhance the serum level of CYP3A4 substrates (High risk with Inducers).
SUNItinib	NiCARdipine may boost SUNItinib's serum levels.
Tacrolimus (Systemic)	Tacrolimus serum levels may rise when Calcium Channel Blockers (Dihydropyridine) are used (Systemic).
Tocilizumab	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Yohimbine	May lessen the effectiveness of antihypertensive agents.
Risk Factor D (Consider therapy modification)
Amifostine	Amifostine's hypotensive impact may be strengthened by blood pressure lowering medications. Treatment: Blood pressure-lowering drugs need to be avoided for 24 hours before amifostine is administered when used at chemotherapeutic doses. Amifostine should not be given if blood pressure lowering treatment cannot be stopped.
Antifungal Agents (Azole Derivatives, Systemic)	Calcium Channel Blockers' harmful or toxic effects could be exacerbated. In particular, itraconazole may make verapamil or diltiazem's unfavourable inotropic effects worse. Calcium Channel Blockers' metabolism may be slowed down by antifungal agents (systemic azole derivatives). Fluconazole and isavuconazonium, which are covered in different monographs, probably have less powerful effects than those of other azoles. Treatment: Itraconazole should not be used concurrently with felodipine or nisoldipine. With any such combination, regular monitoring is advised; calcium channel blocker dose decreases might be necessary.
CarBAMazepine	Calcium Channel Blockers' metabolism could be accelerated (Dihydropyridine). In individuals receiving concurrent carbamazepine, consider adjusting the dosage of calcium channel blockers (CCBs) or switching to an alternative form of treatment. The Canadian labelling for nimodipine expressly forbids taking it alongside carbamazepine.
CYP3A4 Inducers (Strong)	May speed up CYP3A4 substrate metabolism (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label.
CYP3A4 Inhibitors (Strong)	May slow down CYP3A4 substrate metabolism (High risk with Inhibitors).
Dabrafenib	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: When possible, look for substitutes for the CYP3A4 substrate. If concurrent therapy cannot be avoided, pay special attention to the substrate's clinical consequences (particularly therapeutic effects).
Enzalutamide	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: Enzalutamide should not be used concurrently with CYP3A4 substrates that have a limited therapeutic index. Enzalutamide use, like with the use of any other CYP3A4 substrate, should be done cautiously and under close observation.
Fosphenytoin	Calcium channel blockers may raise the level of fosphenytoin in the blood. Monitoring for phenytoin toxicity while using a calcium channel blocker (CCB) at the same time or reduced phenytoin effects while stopping the CCB are the two management options. Check for diminished therapeutic effects of CCB. The Canadian labelling for nimodipine specifically forbids the use of phenytoin.
Lorlatinib	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Avoid using lorlatinib concurrently with any CYP3A4 substrates when even a small drop in serum levels of the substrate could result in adverse effects.
Macrolide Antibiotics	Calcium Channel Blockers' metabolic rate might be decreased. Use a noninteracting macrolide as a possible management strategy. The Canadian labelling for felodipine expressly advises against using it in conjunction with clarithromycin. Exceptions: Fidaxomicin, Roxithromycin, Spiramycin, and systemic azithromycin.
MiFEPRIStone	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: During and two weeks after mifepristone treatment, reduce doses of CYP3A4 substrates and keep an eye out for elevated amounts or toxicity. Fentanyl, pimozide, quinidine, sirolimus, and tacrolimus should all be avoided. Cyclosporine should also be avoided.
Mitotane	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: When administered in individuals receiving mitotane, doses of CYP3A4 substrates may need to be significantly modified.
Obinutuzumab	The hypotensive effects of blood pressure-lowering medications may be strengthened. Management: Take into account temporarily stopping blood pressure-lowering drugs 12 hours before the start of the obinutuzumab infusion and keeping them off until 1 hour after the infusion is finished.
Phenytoin	The serum levels of phenytoin may rise when calcium channel blockers are used. Calcium Channel Blockers' serum levels may be reduced by phenytoin. Avoid combining nimodipine or nifedipine with phenytoin for management. With any concurrent use, keep an eye out for phenytoin toxicity and/or diminished calcium channel blocker effects.
Rifamycin Derivatives	Calcium Channel Blockers' serum concentration can drop. This predominantly affects calcium channel blockers used orally. Management: Using rifampin with certain calcium channel blockers is not advised according to the labelling in the US and Canada. Look up the relevant labelling.
Sincalide	The therapeutic benefit of Sincalide may be reduced by medications that affect gallbladder function. Prior to using sincalide to induce gallbladder contraction, you should think about stopping any medications that can impair gallbladder motility.
St John's Wort	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label.
Stiripentol	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: Due to the increased potential for side effects and toxicity, stiripentol should not be used with CYP3A4 substrates that are thought to have a narrow therapeutic index. Use of stiripentol with any CYP3A4 substrate necessitates closer observation.
Risk Factor X (Avoid combination)
Bromperidol	The hypotensive impact of bromperidol may be enhanced by blood pressure lowering medications. Blood Pressure Lowering Agents' hypotensive effects may be lessened by bromperidol.
Conivaptan	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Fusidic Acid (Systemic)	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Idelalisib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

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)