Benidipine

Usage

• Benidipine is prescribed for the treatment of hypertension (high blood pressure), renal parenchymal hypertension (high blood pressure caused by kidney disease), and angina pectoris (chest pain).
• Pharmacological Classification: Benidipine is a dihydropyridine calcium channel blocker.
• Mechanism of Action: Benidipine works by blocking L-type, T-type, and N-type calcium channels in the heart and blood vessels. This action reduces calcium influx into cells, causing relaxation of vascular smooth muscle, leading to vasodilation (widening of blood vessels), decreased peripheral vascular resistance, and lowered blood pressure. The T-type calcium channel blockade also contributes to its anti-anginal effects.

Alternate Names

• Benidipine hydrochloride is the chemical name.
• Brand Names: Benidipine is marketed under various brand names such as Benidip, Benipine, Coniel, and Benpress in different regions. In Japan, it’s marketed under brand name Benidipine Hydrochloride tab. 4mg「SAWAI」 and Benidipine Hydrochloride tab. 8mg「OME」

How It Works

• Pharmacodynamics: Benidipine lowers blood pressure by causing vasodilation, primarily in the peripheral arteries and coronary vessels. It also reduces myocardial oxygen demand, thus relieving angina. It does not significantly affect heart rate.

• Pharmacokinetics:

  • Absorption: Benidipine is rapidly absorbed after oral administration, achieving peak plasma concentrations within 2 hours.
  • Metabolism: Benidipine is extensively metabolized in the liver, mainly via CYP3A4 enzyme.
  • Elimination: It is primarily eliminated via hepatic metabolism and biliary excretion, with a small portion excreted renally.

• Mode of Action: Benidipine binds to L-type, T-type, and N-type calcium channels, inhibiting calcium influx into vascular smooth muscle cells and cardiac myocytes. This inhibition leads to vasodilation and decreased myocardial contractility. It shows high affinity for the dihydropyridine binding site on L-type calcium channels, contributing to its long-lasting effect.

• Elimination Pathways: Primarily hepatic metabolism and biliary excretion. A small portion is excreted unchanged in urine.

Dosage

Standard Dosage

Adults:

• Hypertension and Renal Parenchymal Hypertension: Initial dose is 2-4 mg once daily, preferably after breakfast. The dose may be increased to a maximum of 8 mg once daily if needed. For severe hypertension, the starting dose may be 4-8 mg once daily.
• Angina Pectoris: 4 mg twice daily, after breakfast and dinner.

Children:

• Benidipine’s safety and efficacy have not been established in children; therefore, it is not recommended for pediatric use.

Special Cases:

• Elderly Patients: Start with a lower dose (2 mg/day) and titrate cautiously due to increased risk of hypotension.
• Patients with Renal Impairment: Generally, dose adjustment is not required, but caution is advised, and close monitoring is recommended.
• Patients with Hepatic Dysfunction: Initiate with a lower dose and titrate carefully due to reduced drug clearance. Close monitoring of liver function tests is essential.
• Patients with Comorbid Conditions: Dosage adjustments may be necessary depending on coexisting conditions like diabetes or cardiovascular disease. Individualized therapy is crucial.

Clinical Use Cases

• The use of benidipine in specific clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations is not routinely indicated or well-established. Its primary role remains in chronic management of hypertension and angina.

Dosage Adjustments

• Dose modifications should be based on individual patient response, tolerability, and renal/hepatic function. Genetic polymorphisms affecting drug metabolism, although not specifically studied for benidipine, should be considered.

Side Effects

Common Side Effects

• Headache
• Dizziness
• Flushing
• Palpitations
• Peripheral edema (swelling in the feet or ankles)
• Fatigue
• Sleepiness

Rare but Serious Side Effects

• Angioedema (severe swelling of face, lips, tongue, or throat)
• Hepatic dysfunction (liver damage)
• Severe hypotension (very low blood pressure)

Long-Term Effects

• The long-term effects of benidipine are generally related to its impact on cardiovascular health, including potential improvement in blood pressure control and reduction in angina episodes.

Adverse Drug Reactions (ADR)

• Angioedema, severe hypotension, and hepatotoxicity are serious ADRs requiring immediate medical attention.

Contraindications

• Cardiogenic shock
• Hypotension
• Hypersensitivity to benidipine
• Pregnancy (unless clearly needed)
• Breastfeeding

Drug Interactions

• CYP3A4 Inhibitors: Ketoconazole, itraconazole, erythromycin, and clarithromycin can increase benidipine levels and enhance its effects. Dose adjustments may be necessary.
• CYP3A4 Inducers: Rifampin, phenytoin, and carbamazepine can decrease benidipine levels and reduce its efficacy.
• Antihypertensives: Concurrent use of other antihypertensive medications can potentiate the blood pressure-lowering effects of benidipine. Close monitoring is required.
• Grapefruit Juice: Avoid grapefruit juice as it inhibits CYP3A4 and can significantly increase benidipine levels, leading to excessive hypotension.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Benidipine is generally avoided during pregnancy due to limited safety data. Its use should only be considered if the potential benefits outweigh the risks.
• Animal studies have shown some evidence of fetal harm.
• Breastfeeding: Benidipine is excreted in breast milk. Breastfeeding should be avoided while taking benidipine.

Drug Profile Summary

• Mechanism of Action: Calcium channel blocker (L, T, and N-type) causing vasodilation and reducing blood pressure.
• Side Effects: Headache, dizziness, flushing, palpitations, edema, fatigue. Rarely: angioedema, hepatic dysfunction, hypotension.
• Contraindications: Cardiogenic shock, hypotension, hypersensitivity, pregnancy, breastfeeding.
• Drug Interactions: CYP3A4 inhibitors/inducers, other antihypertensives, grapefruit juice.
• Pregnancy & Breastfeeding: Avoid during pregnancy and breastfeeding.
• Dosage: Hypertension: 2-8 mg once daily. Angina: 4 mg twice daily. Elderly/Hepatic dysfunction: Start low and titrate slowly.
• Monitoring Parameters: Blood pressure, heart rate, liver function tests, signs of edema, renal function.

Popular Combinations

• Benidipine is often used in combination with other antihypertensives, such as angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACE inhibitors), particularly in patients with chronic kidney disease or when monotherapy is insufficient to control blood pressure.

Precautions

• General Precautions: Assess liver and kidney function before and during treatment. Monitor blood pressure regularly.
• Specific Populations: Caution in elderly patients and those with hepatic/renal impairment. Avoid during pregnancy and breastfeeding.
• Lifestyle Considerations: Limit alcohol intake. Advise patients against operating heavy machinery or performing tasks requiring alertness if dizziness occurs.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Benidipine?

A: For hypertension, 2-4 mg once daily initially, up to 8 mg/day. For angina, 4 mg twice daily.

Q2: How should Benidipine be taken?

A: Orally, once daily for hypertension, twice daily for angina, preferably with food.

Q3: What are the common side effects of Benidipine?

A: Headache, dizziness, flushing, and peripheral edema are common.

Q4: What are the serious side effects of Benidipine?

A: Angioedema, severe hypotension, and hepatotoxicity are rare but serious.

Q5: Can Benidipine be used during pregnancy or breastfeeding?

A: No, it’s generally contraindicated due to potential fetal/neonatal risks.

Q6: What drugs interact with Benidipine?

A: CYP3A4 inhibitors/inducers, other antihypertensives, and grapefruit juice.

Q7: What should patients be cautious about while taking Benidipine?

A: Dizziness and hypotension. Avoid activities requiring alertness, especially initially.

Q8: How does Benidipine differ from other calcium channel blockers?

A: It blocks L, T, and N-type calcium channels, has a long duration of action, and potentially offers renal protective benefits.

Q9: Can Benidipine be used in patients with renal impairment?

A: Caution is advised. Close monitoring of renal function is recommended. Dose adjustment may be necessary depending on the severity of impairment.

Q10: What are the indications for using Benidipine?

A: Hypertension, renal parenchymal hypertension, and angina pectoris.