What Is Nicardipine?
Nicardipine is an FDA-approved medication for hypertension (high blood pressure). It is a medication primarily used to control blood pressure, particularly in situations where rapid and precise management is needed. Nicardipine is often administered as a continuous intravenous infusion, with the dosage carefully adjusted to achieve and maintain a target blood pressure range. This approach helps to lower blood pressure, which can be critical in various medical conditions.
Beyond its approved use, nicardipine is also being investigated in clinical trials for several other conditions where blood pressure control is important. These include various forms of cerebral hemorrhage, acute ischemic stroke, cerebral vasospasm, and coronary artery disease. The drug has been studied in 34 clinical trials involving a total of 6,630 participants, with the first trial initiated in 2004.
Uses and Conditions Under Study
Nicardipine is primarily studied for its role in managing blood pressure across a range of cardiovascular and neurological conditions. For conditions related to high blood pressure, such as Hypertension, nicardipine helps to lower and control elevated blood pressure. It is being studied in 4 trials specifically for hypertension, 2 trials for Coronary Artery Disease, and 1 trial for Coronary Artery Bypass Grafting, where blood pressure management is crucial during and after surgery.
The medication is also extensively investigated for various conditions affecting the brain, where precise blood pressure control can prevent further damage or complications. These include:
- Intracerebral Hemorrhage (3 trials): Bleeding within the brain tissue.
- Subarachnoid Hemorrhage (2 trials): Bleeding in the space between the brain and the surrounding membrane.
- Aneurysmal Subarachnoid Hemorrhage (2 trials): A specific type of subarachnoid hemorrhage caused by a ruptured aneurysm.
- Cerebral Hemorrhage (1 trial): A general term for bleeding in the brain.
- Acute Ischemic Stroke (2 trials): A stroke caused by a blockage in a blood vessel supplying the brain.
- Cerebral Vasospasm (2 trials): Narrowing of blood vessels in the brain, often a complication of subarachnoid hemorrhage.
- CVA (Cerebrovascular Accident) (1 trial): Another term for stroke.
In these neurological conditions, timely control of hypertension is directly related to patient outcomes, and nicardipine is being evaluated for its effectiveness in achieving this control.
Dosing
Nicardipine has been studied in several dosage forms and administration methods, tailored to the specific condition being treated. The most common method involves intravenous administration for blood pressure control.
- Intravenous Infusion: For postoperative blood pressure control, nicardipine is typically administered as a continuous intravenous infusion. Dosing often starts at 5 mg/hour and is titrated upward by 1 mg/hour every 5 minutes based on the patient's blood pressure response. Another regimen involves an initial dose of 1 mcg/kg administered intravenously over 10 minutes, followed by a maintenance infusion of 0.2 to 1 mcg/kg/hour.
- Intracoronary Injection: For procedures like percutaneous coronary intervention (PCI), nicardipine can be given as an intracoronary injection. A typical dose is 200 mcg prior to PCI, with additional 100 mcg doses administered 2-4 times depending on the complexity of the procedure.
- Intrathecal Administration: For the prevention of symptomatic vasospasm in patients with subarachnoid hemorrhage, nicardipine has been studied for intrathecal administration. This involves delivering 10 mL of preservative-free solution via a lumbar cerebrospinal fluid drain every 24 hours for up to 14 days.
Other dosage forms under investigation include NicaPlant®, though specific dosing details for this form are not provided in the available trial data.
Side Effects
In a study (NCT01176565) evaluating intensive blood pressure reduction (which included Nicardipine) compared to standard blood pressure reduction in patients with acute cerebral hemorrhage, serious adverse events were reported. Over a 90-day period, 58.4% of patients in the intensive reduction arm experienced any serious adverse event, compared to 46.5% in the standard reduction arm. Treatment-related serious adverse events within 72 hours occurred in 3.7% of patients in the intensive arm and 2.8% in the standard arm.
Neurological deterioration within 24 hours was observed in 25.1% of patients in the intensive blood pressure reduction arm, compared to 18.6% in the standard reduction arm. Hypotension (low blood pressure) within 72 hours occurred in 2.7% of patients receiving intensive blood pressure reduction, versus 1.4% in the standard reduction group.
In another study (NCT00415610) of antihypertensive treatment in acute cerebral hemorrhage, specific adverse events were reported across different treatment tiers. Neurological deteriorations (defined as a decrease of 2 or more points on the GCS score or an increase of 4 or more points on the NIHSS score) during the 24-hour treatment period occurred in 1 participant in Tier 1, 2 participants in Tier 2, and 4 participants in Tier 3. Serious adverse events within the initial 72 hours were reported in 0 participants in Tier 1, 1 participant in Tier 2, and 3 participants in Tier 3.
Clinical Trial Results
Acute Cerebral Hemorrhage
In a study (NCT01176565) comparing intensive blood pressure reduction (which included Nicardipine) to standard blood pressure reduction in patients with acute cerebral hemorrhage, several outcomes were assessed. Hematoma expansion (an increase of 33% or more in the size of the brain bleed) within 24 hours occurred in 38.8% of patients in the intensive reduction arm, compared to 48.4% in the standard reduction arm.
However, regarding long-term outcomes, the intensive blood pressure reduction arm did not show better results. At 90 days, 15.1% of patients in the intensive reduction arm achieved a good outcome (no death or significant disability, mRS 0-2), while 84.2% of patients in the standard reduction arm achieved a good outcome. Quality of life at 90 days, measured by the EuroQol Visual Analog Scale (EQ VAS), showed a median score of 62.5 units for the intensive reduction arm and 70 units for the standard reduction arm (higher scores indicate better quality of life).
Another study (NCT00415610) in acute cerebral hemorrhage evaluated Nicardipine across different treatment tiers. Participants who achieved and maintained systolic blood pressure goals for each treatment tier included 25 participants in Tier 1, 25 participants in Tier 2, and 37 participants in Tier 3. Furthermore, participants who achieved blood pressure reduction and maintained treatment goals for 18-24 hours without neurological deterioration or death included 18 participants in Tier 1, 20 participants in Tier 2, and 22 participants in Tier 3.
Blood Pressure Control in the Emergency Department
A trial (NCT00765648) comparing intravenous Nicardipine to Labetalol in the emergency department found that 91.7% of patients receiving Nicardipine achieved a pre-defined target systolic blood pressure within 30 minutes, compared to 82.5% of patients receiving Labetalol. Fewer patients on Nicardipine required intravenous rescue medications (15.5%) compared to Labetalol (22.4%). The median time to transition to oral medication was shorter for Nicardipine at 4.9 hours, compared to 6.4 hours for Labetalol. Both medications had a median emergency department time to disposition decision of 4.6 hours.
Blood Pressure Control During Craniotomy Emergence
In a study (NCT01951950) comparing Nicardipine to Esmolol for blood pressure control during craniotomy emergence, Nicardipine was more effective at controlling systolic blood pressure. Only 1 participant receiving Nicardipine failed to control systolic blood pressure below 140 mmHg, compared to 11 participants receiving Esmolol.
Neuroprotection in Aortic Surgery
In a study (NCT00508118) investigating Nicardipine for neuroprotection during aortic surgery, the median duration from the start of cardiopulmonary bypass to electrocerebral silence (a state where brain activity stops, sometimes induced during surgery) was 45 minutes in the Nicardipine group.