Verapamil

Usage

Verapamil is prescribed for various cardiovascular conditions, including:

• Hypertension (High Blood Pressure): It helps lower blood pressure by relaxing blood vessels.
• Angina Pectoris (Chest Pain): It reduces chest pain by improving blood flow to the heart and decreasing the heart’s workload.
• Supraventricular Tachycardia (Rapid Heartbeat): It slows down the rapid heart rate originating above the ventricles.
• Atrial Fibrillation/Flutter (Irregular Heartbeat): It helps control the heart rate in these conditions.
• Migraine Prophylaxis (Off-label): It can be used to prevent migraine headaches.

Pharmacological Classification: Verapamil belongs to the class of non-dihydropyridine calcium channel blockers.

Mechanism of Action: Verapamil inhibits the influx of calcium ions into vascular smooth muscle and cardiac cells, resulting in vasodilation and decreased heart rate and contractility.

Alternate Names

Verapamil hydrochloride is the chemical name. Brand names include Calan, Calan SR, Isoptin SR, Verelan, Verelan PM, Covera-HS, and others.

How It Works

Pharmacodynamics: Verapamil reduces peripheral vascular resistance, lowering blood pressure. It decreases myocardial contractility and slows atrioventricular (AV) node conduction, reducing heart rate. It also dilates coronary arteries, improving blood flow to the heart.

Pharmacokinetics:

• Absorption: Well absorbed orally.
• Metabolism: Extensive first-pass metabolism in the liver.
• Elimination: Primarily excreted in the urine and feces as metabolites.

Mode of Action: Verapamil binds to L-type calcium channels, blocking calcium influx into cells. This leads to smooth muscle relaxation, reduced cardiac contractility, and decreased AV node conduction.

Elimination Pathways: Primarily hepatic metabolism, with metabolites excreted in urine and feces. CYP3A4 is the major enzyme involved in its metabolism.

Dosage

Standard Dosage

Adults:

• Immediate-release tablets: 80-120 mg three times a day for angina, hypertension, and arrhythmias. Dosages can be adjusted up to a maximum of 480 mg/day.
• Extended-release formulations: Dosage varies depending on the specific formulation and condition, typically starting with 180-200 mg once daily and titrated up to a maximum of 480 mg/day.

Children:

• Supraventricular Tachycardia (IV): 0.1-0.3 mg/kg (maximum 5 mg) over 2 minutes; a second dose (maximum 10 mg) may be given after 30 minutes if the response is inadequate.
• Other conditions: Oral dosing should be determined by the physician based on the child’s weight, age, and the specific condition being treated.

Special Cases:

• Elderly Patients: Start with lower doses and titrate cautiously due to increased sensitivity.
• Patients with Renal Impairment: Reduce dose and monitor carefully, especially in severe renal dysfunction.
• Patients with Hepatic Dysfunction: Reduce dose and monitor carefully due to reduced clearance.
• Patients with Comorbid Conditions: Dose adjustment may be necessary in patients with other cardiovascular diseases or metabolic disorders.

Clinical Use Cases

Dosage in clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations should be individualized based on the patient’s specific needs and hemodynamic status. IV administration is preferred in these settings.

Dosage Adjustments

Dose adjustments are necessary based on patient factors, such as renal/hepatic dysfunction, other medications, and the patient’s response to therapy. Therapeutic drug monitoring can be helpful in optimizing dosage.

Side Effects

Common Side Effects:

• Constipation
• Headache
• Dizziness
• Nausea
• Peripheral edema
• Fatigue

Rare but Serious Side Effects:

• Bradycardia (slow heart rate)
• Hypotension (low blood pressure)
• Heart failure exacerbation
• Liver dysfunction
• Angioedema (swelling of face, lips, tongue)

Long-Term Effects:

Chronic use may lead to tolerance or dependence. Regular monitoring of liver function and cardiac function is recommended.

Adverse Drug Reactions (ADR):

Severe hypotension, bradycardia, AV block, and heart failure are serious ADRs requiring immediate intervention.

Contraindications

• Hypersensitivity to verapamil.
• Severe left ventricular dysfunction.
• Cardiogenic shock or severe hypotension.
• Sick sinus syndrome or second/third-degree AV block (unless a pacemaker is present).
• Atrial flutter/fibrillation with accessory bypass tract (e.g., Wolff-Parkinson-White syndrome).

Drug Interactions

Verapamil interacts with numerous medications, including:

• CYP3A4 inhibitors (e.g., grapefruit juice, ketoconazole): Increase verapamil levels.
• CYP3A4 inducers (e.g., rifampin, St. John’s wort): Decrease verapamil levels.
• Beta-blockers: Additive negative inotropic effects.
• Digoxin: Increased digoxin levels.
• Statins: Increased risk of statin-induced myopathy.
• Alcohol: Enhanced hypotensive effects.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (FDA). Use only if the potential benefit justifies the potential risk to the fetus.
• Breastfeeding: Verapamil passes into breast milk in small amounts. While generally considered safe, consider the risks and benefits and the infant’s age.

Drug Profile Summary

• Mechanism of Action: Calcium channel blocker, inhibits calcium influx into cells.
• Side Effects: Constipation, headache, dizziness, nausea, edema. Serious: bradycardia, hypotension, heart failure.
• Contraindications: Severe heart failure, hypotension, AV block, sick sinus syndrome.
• Drug Interactions: CYP3A4 inhibitors/inducers, beta-blockers, digoxin, statins.
• Pregnancy & Breastfeeding: Use with caution, monitor infant.
• Dosage: Variable, depending on condition and formulation. Adjust for age and organ function.
• Monitoring Parameters: Blood pressure, heart rate, ECG, liver function tests.

Popular Combinations

Verapamil may be combined with other antihypertensives like thiazide diuretics or ACE inhibitors for synergistic effects.

Precautions

Monitor patients for bradycardia, hypotension, and heart failure. Avoid abrupt withdrawal. Exercise caution in patients with hepatic or renal impairment, AV block, or bradycardia.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Verapamil?

A: Dosage varies depending on the condition and formulation. Adult doses for immediate-release tablets range from 80-120 mg three times daily, while extended-release formulations typically start at 180-200 mg once daily. Doses should be adjusted based on the patient’s response and comorbidities.

Q2: What are the common side effects of Verapamil?

A: Common side effects include constipation, headache, dizziness, nausea, and peripheral edema.

Q3: What are the serious side effects of Verapamil?

A: Serious side effects include bradycardia, hypotension, heart failure exacerbation, and liver dysfunction.

Q4: What are the contraindications for Verapamil?

A: Verapamil is contraindicated in patients with severe heart failure, cardiogenic shock, severe hypotension, sick sinus syndrome, second/third-degree AV block, and hypersensitivity to verapamil.

Q5: How does Verapamil interact with other medications?

A: Verapamil interacts with numerous medications, including CYP3A4 inhibitors and inducers, beta-blockers, digoxin, and statins. These interactions can either increase or decrease verapamil levels or enhance its effects.

Q6: Can Verapamil be used during pregnancy and breastfeeding?

A: Verapamil should be used with caution during pregnancy and breastfeeding. Consult a specialist to evaluate risks and benefits. Monitor the infant for potential side effects during breastfeeding.

Q7: What are the monitoring parameters for patients on Verapamil?

A: Patients on verapamil should be monitored for changes in blood pressure, heart rate, ECG, and liver function tests.

Q8: What precautions should be taken when prescribing Verapamil?

A: Start with a low dose and titrate carefully, especially in elderly patients and those with renal or hepatic impairment. Monitor for bradycardia, hypotension, and signs of heart failure. Avoid abrupt withdrawal.

Q9: How does verapamil affect the heart’s electrical activity?

A: Verapamil slows down AV node conduction, which can be beneficial in treating supraventricular tachycardias and controlling the ventricular rate in atrial fibrillation/flutter. However, it can also exacerbate AV block in susceptible individuals.