lercanidipine

Action and Spectrum

Actions and Spectrum: 

Action: 

lercanidipine is a medication primarily used in the management of hypertension. It belongs to a class of drugs known as dihydropyridine calcium channel blockers. These medications work by inhibiting the influx of calcium ions into smooth muscle cells lining blood vessels, leading to their relaxation and subsequent vasodilation. This vasodilatory effect reduces the resistance in the arteries, lowering blood pressure. lercanidipine targets the L-type calcium channels in the vascular smooth muscle cells, effectively dilating peripheral and coronary arteries. This dual action helps to alleviate the workload on the heart and enhance blood flow, making it a practical choice in treating hypertension and, potentially, angina. 

Spectrum: 

The spectrum of action of lercanidipine centers around its cardiovascular effects. By dilating peripheral arteries, it decreases the resistance against which the heart pumps blood, reducing blood pressure. This is particularly important in individuals with hypertension, as it helps to lower their risk of cardiovascular complications like stroke and heart attack. Additionally, the vasodilation of coronary arteries improves blood flow to the heart muscle itself, potentially alleviating symptoms of angina (chest pain due to reduced blood supply to the heart). lercanidipine’s selective action on vascular smooth muscle cells and its sustained-release formulation contribute to its efficacy and tolerability.

Drug Interaction

Adverse Reaction

Frequency not defined 

Headache 

Dizziness 

Flushing 

Swollen ankles 

Palpitations 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity: Individuals who have demonstrated a hypersensitivity or allergic reaction to lercanidipine or other dihydropyridine calcium channel blockers should not use this medication. 
• Severe Aortic Stenosis: lercanidipine is contraindicated in patients with severe aortic stenosis, a condition characterized by narrowing the aortic valve. Calcium channel blockers like lercanidipine may exacerbate this condition by reducing cardiac output. 
• Unstable Angina: lercanidipine is generally not recommended for use in individuals with unstable angina, where chest pain becomes more frequent and severe or occurs at rest. Calcium channel blockers could potentially worsen blood supply to the heart in such cases. 
• Cardiogenic Shock: Cardiogenic shock is a critical condition where the heart cannot pump sufficient blood to meet the body’s needs. The use of lercanidipine in individuals with cardiogenic shock is contraindicated due to the potential to worsen cardiovascular function. 
• Acute Myocardial Infarction (Heart Attack): lercanidipine is contraindicated shortly after a heart attack, as it could worsen cardiovascular instability and other complications that arise during the acute phase. 
• Severe Hepatic Impairment: Individuals with severe hepatic (liver) impairment should avoid using lercanidipine, as the medication’s metabolism may be compromised in such cases, leading to potential accumulation and adverse effects. 
• Pregnancy and Breastfeeding: lercanidipine is generally not recommended during pregnancy and breastfeeding. Adequate studies on its safety during these periods might be limited. 
• Children: lercanidipine is typically not used in children and adolescents due to limited data on its safety and efficacy in this age group. 
• Co-administration with Strong CYP3A4 Inhibitors: The concomitant use of lercanidipine with potent inhibitors of the enzyme CYP3A4 (which is involved in drug metabolism) can lead to increased levels of lercanidipine in the body, potentially increasing the risk of adverse effects. 

Caution 

• Elderly Patients: Elderly individuals may be more sensitive to the effects of lercanidipine. Dosing adjustments might be necessary to avoid excessive blood pressure lowering or other adverse effects. 
• Renal Impairment: Patients with impaired kidney function should be monitored closely while taking lercanidipine, as the medication’s elimination may be affected. Dose adjustments might be needed to prevent accumulation and potential side effects. 
• Liver Impairment: Patients with mild to moderate liver impairment should use lercanidipine cautiously, as its metabolism could be altered. However, individuals with severe liver impairment should avoid this medication altogether (contraindication). 
• Heart Failure: lercanidipine should be used cautiously in individuals with heart failure. While some calcium channel blockers are contraindicated in heart failure, a healthcare professional must carefully evaluate lercanidipine’s specific effects. 
• Hypotension: lercanidipine’s vasodilatory effects can sometimes lead to low blood pressure (hypotension), especially at the start of treatment or with dose adjustments. Patients should be educated on the signs of hypotension and advised to rise slowly from a sitting/lying position to minimize the risk. 
• Driving and Machinery Operation: lercanidipine might cause dizziness, particularly at the beginning of treatment or when changing doses.  
• Concomitant Medications: Patients taking other medications, especially antihypertensive drugs, should be closely monitored when initiating lercanidipine therapy. Dose adjustments might be necessary to prevent additive hypotensive effects. 
• Electrolyte Imbalance: lercanidipine’s effects on blood pressure could alter electrolyte balance. Patients with conditions that already impact electrolyte levels (e.g., kidney disorders) should be monitored carefully. 
• Pregnancy and Breastfeeding: lercanidipine should be avoided during pregnancy and breastfeeding due to limited data on its safety during these periods. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk: Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• <b>Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

lercanidipine is a dihydropyridine calcium channel blocker that exerts its pharmacological effects by selectively inhibiting L-type calcium channels in vascular smooth muscle cells. Doing so reduces the influx of calcium ions into these cells, leading to relaxation and dilation of peripheral and coronary arteries. This vasodilation results in decreased vascular resistance and improved blood flow, effectively lowering blood pressure.

lercanidipine’s selectivity for vascular smooth muscle cells over cardiac muscle cells minimizes adverse inotropic effects on the heart, making it a preferred choice in the treatment of hypertension. The medication’s prolonged duration of action and slow onset of binding contribute to its sustained antihypertensive effects and once-daily dosing regimen. 

Pharmacodynamics: 

Mechanism of action: lercanidipine’s mechanism of action is primarily centered around its role as a calcium channel blocker. It belongs to the dihydropyridine class of the calcium channel blockers, which exert their effects by selectively targeting L-type calcium channels. These channels are present in the cell membranes of various tissues, including smooth muscle cells in blood vessels. 

• Calcium Channels: Calcium ions regulate muscle contraction in vascular smooth muscle cells. L-type calcium channels allow calcium ions to enter these cells from the extracellular space. 
• Vasodilation: lercanidipine selectively and competitively inhibits L-type calcium channels, particularly in the vascular smooth muscle cells lining the walls of arteries. By blocking these channels, it prevents the influx of calcium ions into the cells. 
• Smooth Muscle Relaxation: When calcium ions can’t enter the smooth muscle cells, it decreases intracellular calcium concentration. This, in turn, reduces the contraction of smooth muscle cells and results in the relaxation of the blood vessel walls. 
• Vasodilatory Effects: The relaxation of smooth muscle cells leads to vasodilation or the widening of the arteries. This dilation diminishes the resistance to blood flow within the arteries, which decreases blood pressure. As a result, the workload on the heart is reduced, and blood flow to organs and tissues improves. 
• Blood Pressure Reduction: lercanidipine effectively lowers blood pressure by dilating both peripheral and coronary arteries. Its effects are particularly beneficial in individuals with hypertension, as it helps to bring blood pressure within a healthier range and reduces the risk of associated cardiovascular complications. 

Pharmacokinetics: 

Absorption 

lercanidipine is well-absorbed after oral administration. Food, particularly high-fat meals, can affect its absorption, which can slow down the absorption rate. Taking lercanidipine on an empty stomach or at least one hour before meals is generally recommended to ensure consistent and optimal absorption. 

Distribution 

lercanidipine is extensively bound to plasma proteins, primarily to albumin. This binding influences its distribution and interaction with other bodily substances within the bloodstream. The medication’s distribution into tissues, including vascular smooth muscle cells and possibly other target organs, contributes to its therapeutic effects. 

Metabolism 

lercanidipine undergoes extensive first-pass metabolism in the liver before reaching the systemic circulation. It is generally metabolized by the cytochrome P450 enzyme system, with the main enzyme involved being CYP3A4. The metabolism forms several metabolites, but the parent compound is responsible for most of the drug’s activity. 

Elimination and Excretion 

After metabolism, lercanidipine and its metabolites are excreted primarily via the biliary route (in feces) rather than the renal route (in urine). The enterohepatic circulation contributes to the prolonged duration of the drug’s effects. Renal excretion is minimal, accounting for only a tiny fraction of the total elimination. 

Adminstartion

Administration: 

lercanidipine is typically available in tablet form and is taken orally. The dosing and administration instructions for lercanidipine may vary based on the patient’s condition and the specific product available.  

• Dosage: The usual starting dose of lercanidipine for hypertension (high blood pressure) is around 10 mg once daily. The dosage might be adjusted based on the patient’s response and tolerability. Higher doses (up to 20 mg) might sometimes be required. The maximum recommended dose is generally 20 mg per day. 
• Time of Administration: lercanidipine is usually taken once daily, preferably in the morning. Taking it simultaneously each day can help maintain a consistent level of the medication in the body. 
• Administration: lercanidipine tablets should be swallowed whole with a glass of water. They should not be crushed, chewed, or divided unless otherwise specified by a healthcare professional. 
• Food Interactions: food, particularly high-fat meals, can affect lercanidipine’s absorption. Taking lercanidipine on an empty stomach or at least one hour before meals is generally recommended for optimal absorption.  
• Compliance: It’s essential to adhere to the prescribed dosing schedule and not miss doses. Skipping doses can affect the effectiveness of the medication in controlling blood pressure. 
• Duration of Treatment: lercanidipine is typically used as a long-term treatment for hypertension. However, the duration of treatment will be determined by the patient’s condition and healthcare provider’s recommendations. 
• Titration and Monitoring: Dose adjustments should only be made under the guidance of a healthcare professional. Blood pressure should be regularly monitored to assess the medication’s effectiveness and make any necessary dose changes. 
• Other Medications: Interactions and potential additive effects should be considered if the patient takes other medications, especially other antihypertensive drugs.  
• Special Populations: Elderly patients and individuals with kidney or liver impairment may require dose adjustments. Patients with specific medical conditions should follow their healthcare provider’s recommendations closely. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: lercanidipine 

Why do we use lercanidipine? 

lercanidipine is primarily used in the treatment of hypertension, which is commonly known as high blood pressure. Hypertension is a chronic medical condition generally characterized by enhanced blood pressure levels that can enhance the risk of cardiovascular problems, including stroke, heart attack, and kidney disease. lercanidipine belongs to the class of medications known as dihydropyridine calcium channel blockers, and it exerts its effects by dilating blood vessels and reducing the resistance to blood flow, which helps in diminishing BP.  

• Hypertension: lercanidipine is indicated for treating essential hypertension, which refers to high blood pressure with no identifiable underlying cause. By relaxing the smooth muscles the lining the blood vessels and reducing the pressure against which the heart pumps, lercanidipine helps lower blood pressure, reducing the risk of cardiovascular complications which is associated with hypertension. 
• Stable Angina: lercanidipine’s ability to dilate coronary arteries could potentially alleviate symptoms of stable angina, which is chest pain or discomfort due to reduced blood flow to the heart muscle. However, other anti-anginal medications are often preferred for this purpose. 
• Vascular Conditions: The vasodilation caused by lercanidipine might have implications in certain vascular conditions, like Raynaud’s phenomenon, where blood vessels narrow in response to cold or stress. However, its use for such conditions would be assessed case-by-case.