nilvadipine

Action and Spectrum

Actions and Spectrum: 

nilvadipine is a medication that belongs to a class of drugs called calcium channel blockers. It is primarily used to treat high blood pressure; nilvadipine works by blocking calcium channels in the smooth muscles of band certain types of angina. nilvadipine works by blocking calcium channels in the smooth muscles of blood vessels, leading to relaxation and dilation of the blood vessels. This dilation reduces the resistance against which the heart pumps blood, lowering blood pressure and improving blood flow. 

Action: 

nilvadipine’s primary mechanism of action is its ability to block the calcium channels in the vascular smooth muscle cells. These calcium channels are responsible for allowing calcium ions to enter the cells. When calcium enters these cells, it promotes muscle contraction, including the contraction of blood vessel walls. By blocking these calcium channels, nilvadipine inhibits the influx of calcium ions, leading to the relaxation of the smooth muscle cells. This relaxation results in vasodilation, reducing peripheral vascular resistance and lowering blood pressure. 

Spectrum: 

nilvadipine primarily treats hypertension (high blood pressure) and stable angina. It’s important to note that nilvadipine, like other calcium channel blockers, is generally not the first-line choice for treating hypertension. It is often used when other antihypertensive medications have proven ineffective or have caused adverse effects. It can also be combined with other antihypertensive drugs to achieve better blood pressure control. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Headache  

Flushing  

Dizziness 

Fatigue 

Weakness 

Swelling in the ankles or feet 

Nausea 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity: nilvadipine should not be used in individuals with a known hypersensitivity or allergy to the medication or its components. 
• Severe Aortic Stenosis: nilvadipine is contraindicated in patients with severe aortic stenosis, a condition characterized by the narrowing the heart’s aortic valve. Using nilvadipine in such cases could lead to further impairment of cardiac function. 
• Cardiogenic Shock: It is a life-threatening condition where the heart fails to pump the enough blood to meet the body’s needs. nilvadipine is contraindicated in patients with cardiogenic shock, as it can worsen the condition by reducing cardiac output. 
• Acute Myocardial Infarction: nilvadipine is generally not recommended during the acute phase of myocardial infarction (heart attack) due to the potential for its adverse effects on cardiac function and blood pressure. 
• Unstable Angina: nilvadipine may not be suitable for patients with unstable angina, a type of chest pain characterized by its unpredictable nature. Other treatments may be more appropriate in this situation. 
• Severe Liver Impairment: Since nilvadipine is metabolized in the liver, individuals with severe liver impairment should use it cautiously. The medication’s dosage may need to be adjusted or an alternative treatment considered. 
• Pregnancy and Breastfeeding: nilvadipine is generally not recommended during pregnancy condition and breastfeeding due to limited safety data.  
• Combination with Strong CYP3A4 Inhibitors: nilvadipine is metabolized by the liver enzyme CYP3A4. Concomitant use with potent CYP3A4 inhibitors, like certain medications used to treat infections or HIV, can increase the levels of nilvadipine in the blood, leading to potential adverse effects. 
• Certain Medical Conditions: nilvadipine should be used cautiously in individuals with certain medical conditions, including heart failure, renal impairment, and arrhythmias. The dosage may need to be adjusted based on the severity of these conditions. 

Caution 

• Hypotension: nilvadipine’s primary action is to lower blood pressure by causing vasodilation. This can lead to low blood pressure, especially when transitioning from a seated or lying position to standing (orthostatic hypotension).  
• Liver Impairment: nilvadipine is metabolized by the liver, so individuals with mild to moderate liver impairment should use the medication cautiously. Dose adjustments might be necessary based on the degree of impairment. 
• Elderly Patients: They may be more sensitive to the effects of nilvadipine, including its blood pressure-lowering effects. Careful monitoring of blood pressure and potential adverse effects is essential. 
• Renal Impairment: While the kidneys do not primarily excrete nilvadipine, caution is still advised in patients with moderate to severe renal impairment. Adjustments to the dosage might be necessary. 
• Heart Failure: Individuals with heart failure should be monitored closely when using nilvadipine. While it can be used in heart failure patients, careful evaluation and management are essential to avoid exacerbating heart failure symptoms. 
• Grapefruit Juice Interaction: Grapefruit juice can inhibit the metabolism of nilvadipine, potentially leading to increased blood levels of the medication. Patients should avoid consuming grapefruit juice while taking nilvadipine. 
• Combination with Other Medications: Patients taking other medications, especially those that also affect blood pressure, should inform their healthcare provider. Some combinations may require dosage adjustments or close monitoring. 
• Pregnancy and Breastfeeding: As previously mentioned, nilvadipine is generally not recommended during pregnancy and breastfeeding due to limited safety data. Alternative treatments should be considered, and discussions with a healthcare provider are essential. 
• Driving and Operating Machinery: nilvadipine can cause dizziness or lightheadedness, which may impair one’s ability to drive or operate machinery. Patients should be cautious and avoid such activities if they experience these side effects. 
• Electrolyte Imbalance: nilvadipine’s effects on blood pressure can potentially lead to changes in electrolyte levels, such as potassium and magnesium. Regular monitoring of electrolytes may be recommended. 
• Surgery: Patients scheduled for surgery should inform their healthcare provider about using nilvadipine. The medication’s effects on blood pressure and potential interactions with anesthesia must be considered. 

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: 

nilvadipine is a dihydropyridine calcium channel blocker that exerts its pharmacological effects by selectively blocking L-type calcium channels in vascular smooth muscle cells. This inhibition leads to decreased intracellular calcium levels, resulting in relaxation and dilation of arterial smooth muscle. Consequently, peripheral vascular resistance is reduced, promoting vasodilation and lowering blood pressure. nilvadipine’s vasodilatory action is particularly beneficial in treating hypertension and stable angina, improving blood flow, and reducing cardiac workload. 

Pharmacodynamics: 

Mechanism of action: nilvadipine belongs to a class of drugs called dihydropyridine calcium channel blockers. Its mechanism of action is centered around its ability to block L-type calcium channels in vascular smooth muscle cells.  

• Calcium Channels and Vascular Smooth Muscle: Calcium ions (Ca2+) are crucial in various physiological processes, including muscle contraction. In vascular smooth muscle cells, calcium influx through L-type calcium channels triggers muscle contraction, leading to blood vessel constriction. This process contributes to increased peripheral vascular resistance, leading to elevated blood pressure. 
• Blocking Calcium Influx: nilvadipine selectively blocks these L-type calcium channels. Binding to these channels inhibits the entry of calcium ions into the smooth muscle cells. This action prevents the rise of intracellular calcium levels, which is essential for muscle contraction. As a result, the smooth muscle cells are less likely to contract and remain relaxed. 
• Vasodilation: The relaxation of vascular smooth muscle cells leads to vasodilation/the widening of blood vessels. When blood vessels dilate, the resistance against blood flow decreases. This reduction in peripheral vascular resistance results in lowered blood pressure. The vasodilatory effect also enhances blood flow to various tissues, including the heart itself, which is beneficial for conditions like angina. 
• Blood Pressure Regulation: nilvadipine’s primary vasodilation effect contributes to its antihypertensive action. Reducing vascular resistance and promoting relaxation of blood vessels helps lower blood pressure levels. 

Pharmacokinetics: 

Absorption 

nilvadipine is orally administered and is rapidly absorbed from the gastrointestinal tract after ingestion. However, its absorption can be affected by food, particularly high-fat meals, which may delay the absorption process. Therefore, taking nilvadipine on an empty stomach is often recommended to ensure consistent absorption. 

Distribution 

nilvadipine is extensively bound to plasma proteins, primarily albumin, which limits its distribution to various tissues. The medication crosses the blood-brain barrier to a limited extent, and its distribution into the central nervous system is relatively low. nilvadipine mainly accumulates in vascular smooth muscle cells, where its calcium channel-blocking action is exerted. 

Metabolism 

nilvadipine undergoes extensive metabolism in the liver through a process known as hepatic first-pass metabolism. The primary metabolite produced is known as nilvadipine glucuronide. The metabolism is mainly mediated by the enzyme cytochrome P450 3A4 (CYP3A4), which significantly breaks down the medication into its metabolites. 

Elimination and Excretion 

The metabolites of nilvadipine, including nilvadipine glucuronide, are excreted mainly through the bile into the feces. A small portion of the metabolites might also be excreted in the urine. The elimination half-life of nilvadipine is relatively short, which contributes to its need for once-daily dosing. 

Adminstartion

Administration: 

nilvadipine is typically available in oral tablet form and is taken by mouth. The administration of nilvadipine involves a few essential considerations to ensure its effectiveness and safety.  

• Dosage: Your healthcare provider will determine The dosage of nilvadipine based on your health status, blood pressure goals, and response to the medication. It’s essential to follow the prescribed dosage and not adjust it without consulting the healthcare provider. 
• Timing: nilvadipine is usually taken once a day, either in the morning or evening.  
• Food and Grapefruit Juice: nilvadipine should be taken on an empty stomach nearly 1 hour before or 2 hours after a meal. Food may interfere with the absorption of the medication. Additionally, as mentioned earlier, avoid consuming grapefruit juice while taking nilvadipine, as it can affect the metabolism of the medication. 
• Swallowing: Swallow the nilvadipine tablet whole with a glass of water. Do not crush, chew/break the tablet, as this could alter how the medication is absorbed. 
• Consistency: If a dose is missed, taking it as soon as possible is generally recommended. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time. It is key to avoid taking a double dose of the drug in order to compensate for the missed dose. 
• Monitoring: While taking nilvadipine, your healthcare provider should regularly monitor your blood pressure to ensure that it is being effectively managed and that you are not experiencing any adverse effects. 
• Duration: nilvadipine is typically a long-term treatment for hypertension or stable angina. Do not stop taking it without consulting your healthcare provider, even if you feel better, as abruptly discontinuing the medication can lead to a sudden increase in blood pressure. 
• Interaction with Other Medications: Inform your healthcare provider about all the drugs you are taking, including over-the-counter drugs, supplements, and herbal remedies. Certain medications may interact with nilvadipine and affect its efficacy or safety. 
• Storage: Store nilvadipine tablets in a cool, dry place, away from direct sunlight and moisture. Keep the medication out of reach of children. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: nilvadipine 

Why do we use nilvadipine? 

nilvadipine is a medication primarily used to treat high blood pressure and certain types of angina (chest pain).  

• Hypertension (High Blood Pressure): nilvadipine is commonly prescribed to manage high blood pressure. By blocking calcium channels in blood vessels, nilvadipine promotes vasodilation (relaxation of blood vessels), which reduces peripheral vascular resistance and lowers blood pressure. It is often used as a second-line or adjunctive treatment when other antihypertensive medications are insufficient to control blood pressure. 
• Stable Angina: nilvadipine can alleviate symptoms of stable angina, a condition with reduced blood flow to the heart muscle because of the narrowed coronary arteries. The vasodilatory effects of nilvadipine help increase blood flow to the heart, which can relieve chest pain and improve exercise tolerance. 
• Raynaud’s Phenomenon: Raynaud’s phenomenon is characterized by reduced blood flow to the fingers and toes, often triggered by cold temperatures or emotional stress. nilvadipine’s ability to dilate blood vessels may help improve blood flow in these situations, reducing the severity and frequency of symptoms.