Usage
- Efonidipine is prescribed for the management of hypertension (high blood pressure), including renal parenchymal hypertension (high blood pressure caused by kidney disease), and angina pectoris (chest pain).
- Pharmacological Classification: Dihydropyridine calcium channel blocker.
- Mechanism of Action: Efonidipine blocks both L-type and T-type calcium channels in vascular smooth muscle cells. This inhibition reduces calcium influx, leading to vasodilation (widening of blood vessels) and a decrease in blood pressure. The improved blood supply to the heart muscle, particularly in angina, increases oxygen delivery and relieves chest pain.
Alternate Names
- NZ-105
- Brand Name: Landel (Japan)
How It Works
- Pharmacodynamics: Efonidipine’s primary effect is lowering blood pressure by relaxing the blood vessels. It achieves this by blocking calcium channels, inhibiting smooth muscle contraction, and promoting vasodilation. In angina, this vasodilation improves coronary blood flow, thus alleviating chest pain.
- Pharmacokinetics: Efonidipine is orally administered and absorbed relatively quickly. It is primarily metabolized in the liver via the CYP3A4 enzyme system. The biliary route (through bile) constitutes the primary excretion pathway, with negligible amounts of unchanged drug found in urine. Deaminated efonidipine and its pyridine analogue are minor urinary metabolites.
- Mode of Action: Efonidipine binds to and blocks both L-type and T-type calcium channels in vascular smooth muscle cells and cardiac myocytes. This blockage inhibits calcium influx, reduces muscle contraction, and causes vasodilation. The drug also shows mild negative chronotropic and inotropic effects.
- Receptor Binding/Enzyme Inhibition: Efonidipine primarily acts by binding to L-type and T-type calcium channels. It is metabolized via the CYP3A4 enzyme system.
- Elimination Pathways: Primarily biliary excretion, with minimal renal excretion.
Dosage
Standard Dosage
Adults:
- Hypertension: Initial dose is 20 mg once daily, which can be titrated up to 40 mg once daily as needed. Doses up to 80 mg/day have been deemed safe and effective in clinical trials.
- Angina: 40 mg once daily.
Children:
- The safety and efficacy of efonidipine in children have not been established and therefore its use is not recommended.
Special Cases:
- Elderly Patients: Initiate treatment at a low dose (20 mg/day) with careful monitoring for hypotension. The dose may be reduced to 10 mg/day if 20 mg is not tolerated.
- Patients with Renal Impairment: Caution is advised, and dosage adjustments may be necessary in severe renal impairment or patients undergoing hemodialysis. A lower starting dose (20 mg) is recommended.
- Patients with Hepatic Dysfunction: Exercise caution and titrate dose slowly due to potential increased bioavailability. Dosage adjustment is recommended in mild to moderate hepatic impairment.
- Patients with Comorbid Conditions: Monitor closely, especially those with heart failure or sinoatrial node dysfunction.
Clinical Use Cases
- Efonidipine’s clinical use focuses on chronic hypertension and angina management. Its use in acute settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergencies has not been established.
Dosage Adjustments:
- Dosage modifications are based on patient response, tolerability, and renal or hepatic function. Genetic polymorphism related to CYP3A4 metabolism may also necessitate adjustments, although specific guidelines are lacking.
Side Effects
Common Side Effects:
- Headache
- Dizziness
- Flushing
- Palpitations
- Peripheral edema (swelling in the extremities)
- Nausea
- Stomach discomfort
- Abdominal pain
- Hot flashes
Rare but Serious Side Effects:
- Severe hypotension (low blood pressure)
- Bradycardia (slow heart rate)
- Hepatic dysfunction
- Allergic reactions
Long-Term Effects:
- Limited data exist regarding chronic complications of prolonged efonidipine use. Regular monitoring of blood pressure, liver function, and other relevant parameters is necessary.
Adverse Drug Reactions (ADR):
- Angioedema (severe swelling of the face, lips, tongue, or throat)
- Hypersensitivity reactions
Contraindications
- Hypersensitivity to efonidipine or its components
- Pregnancy and lactation
- Severe hepatic impairment
- Severe aortic stenosis
Drug Interactions
- Other Antihypertensives: Concomitant use with other antihypertensive agents (e.g., beta-blockers, ACE inhibitors, diuretics) may enhance the antihypertensive effects and increase the risk of hypotension.
- CYP3A4 Inhibitors: Drugs that inhibit CYP3A4 (e.g., ketoconazole, erythromycin, some protease inhibitors, grapefruit juice) may increase efonidipine plasma concentrations, potentially leading to increased side effects.
- CYP3A4 Inducers: Drugs that induce CYP3A4 (e.g., rifampin, St. John’s Wort) may decrease efonidipine levels, potentially reducing its efficacy.
- Other Interactions: Cimetidine, NSAIDs, and alcohol.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated. Efonidipine should not be used during pregnancy due to potential fetal harm.
- Breastfeeding: Efonidipine should not be used during breastfeeding as it is unknown whether it passes into breast milk.
Drug Profile Summary
- Mechanism of Action: Calcium channel blocker inhibiting both L-type and T-type calcium channels, leading to vasodilation and reduced blood pressure.
- Side Effects: Headache, dizziness, flushing, palpitations, peripheral edema, nausea.
- Contraindications: Hypersensitivity, pregnancy, lactation, severe hepatic impairment.
- Drug Interactions: Other antihypertensives, CYP3A4 inhibitors and inducers, grapefruit juice.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 20-40 mg once daily for hypertension; 40 mg once daily for angina. Adjust for renal/hepatic impairment and elderly patients.
- Monitoring Parameters: Blood pressure, heart rate, liver function tests, signs of edema.
Popular Combinations
- Efonidipine + Telmisartan: This combination is used for the management of stage II hypertension and combines the vasodilatory effects of both drugs.
- Efonidipine + Metoprolol: This combination is used for the management of hypertension by combining the vasodilating effects of efonidipine with the beta-blocking effects of metoprolol.
Precautions
- General Precautions: Assess for allergies, hepatic/renal dysfunction, and other relevant medical conditions before initiating treatment.
- Specific Populations: See “Dosage - Special Cases” section above.
- Lifestyle Considerations: Advise patients to limit alcohol intake and avoid grapefruit juice. Caution patients about potential dizziness and its impact on driving or operating machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Efonidipine?
A: The usual starting dose for adults is 20 mg once daily, titratable to 40 mg once daily as needed, up to a maximum of 80 mg daily. Elderly patients should start with a lower dose (20 mg/day) and be monitored closely for hypotension. Pediatric use is not recommended.
Q2: What are the common side effects of Efonidipine?
A: Common side effects include headache, dizziness, flushing, palpitations, and peripheral edema.
Q3: What are the contraindications for using Efonidipine?
A: Contraindications include hypersensitivity to efonidipine, pregnancy, breastfeeding, severe hepatic impairment, and severe aortic stenosis.
Q4: How does Efonidipine interact with other antihypertensive medications?
A: Combining efonidipine with other antihypertensives can enhance the blood pressure-lowering effects and may increase the risk of hypotension. Dosage adjustments may be needed.
Q5: Can Efonidipine be used during pregnancy or breastfeeding?
A: No, efonidipine is contraindicated during pregnancy and breastfeeding due to potential fetal harm and lack of safety data for infants.
Q6: Are there any special considerations for elderly patients taking Efonidipine?
A: Yes, elderly patients should start with a lower dose (20 mg/day) and be monitored closely for hypotension. Dosage adjustments may be necessary based on tolerability.
Q7: What should a patient do if they miss a dose of Efonidipine?
A: Take the missed dose as soon as remembered, unless it is close to the next scheduled dose. Do not double the dose.
Q8: Does Efonidipine interact with grapefruit juice?
A: Yes, grapefruit juice can inhibit the metabolism of efonidipine, leading to increased drug levels and a greater risk of side effects. Patients should avoid grapefruit juice while taking efonidipine.
Q9: How does Efonidipine affect the liver and kidneys?
A: Efonidipine is primarily metabolized in the liver. Patients with hepatic impairment may require dosage adjustments. Caution is also advised in patients with renal impairment, particularly those with severe renal dysfunction or undergoing hemodialysis.
