Disopyramide

Usage

Disopyramide is prescribed for the treatment of certain types of serious (potentially fatal) irregular heartbeats, primarily ventricular arrhythmias such as ventricular tachycardia, and for maintaining normal heart rhythm after procedures like electroconversion for atrial fibrillation or flutter. Its pharmacological classification is antiarrhythmic (Class IA). Disopyramide works by blocking sodium channels in the heart muscle, slowing the conduction of electrical impulses and prolonging the refractory period, thus stabilizing the heart rhythm.

Alternate Names

Disopyramide phosphate (salt form used in formulations) Brand names include Norpace®, Norpace CR®.

How It Works

Pharmacodynamics: Disopyramide decreases the rate of depolarization in cardiac tissues by blocking fast sodium channels, prolonging the action potential duration and effective refractory period. It also has antimuscarinic (anticholinergic) properties which contribute to its antiarrhythmic action but causes many of the adverse side effects.

Pharmacokinetics:

• Absorption: Well-absorbed orally.
• Metabolism: Primarily metabolized by the liver, with a portion excreted unchanged in the urine.
• Elimination: Both renal and hepatic pathways. Primarily eliminated through hepatic metabolism by CYP3A4, with a small portion excreted unchanged in the urine.

Mode of Action: Disopyramide binds to and blocks fast sodium channels in the heart, reducing the inward sodium current, slowing down the rapid depolarization phase of the action potential. It prolongs the action potential duration and the effective refractory period, helping to stabilize the heart rhythm. The drug also has anticholinergic effects, blocking the effects of acetylcholine, which can further impact heart rate and rhythm.

Dosage

Standard Dosage

Adults:

• Immediate-release: 100-150 mg every 6 hours, total daily dose 400-800 mg. Patients weighing less than 50 kg may receive a lower dose (400 mg/day divided every 6 hours).

• Extended-release: 200-300 mg every 12 hours, total daily dose 400-800 mg. It is not recommended for rapid control of arrhythmias.

Children:

Disopyramide is generally not recommended for use in children under 18 years old. Safety and efficacy have not been established. Some limited data suggest a starting dose of 10-30 mg/kg/day divided every 6 hours for children under 1 year old and adjusted based on age for older children. However, expert consultation is crucial for pediatric use.

Special Cases:

• Elderly Patients: Lower starting doses are recommended due to potential reduced renal and hepatic function. Dose adjustments should be made cautiously.

• Patients with Renal Impairment: Dosage adjustments are essential.

  • CrCl >40 mL/min: Standard dosing
  • CrCl 30-40 mL/min: Administer every 8 hours.
  • CrCl 15-30 mL/min: Administer every 12 hours.
  • CrCl <15 mL/min: Administer once daily.

• Patients with Hepatic Dysfunction: Reduced doses are recommended (e.g., 100 mg every 6 hours for immediate release or 200 mg every 12 hours for extended release).

• Patients with Comorbid Conditions: Caution should be used in patients with heart failure, glaucoma, myasthenia gravis, urinary retention, or prostatic hypertrophy. Dosage adjustments may be needed.

Clinical Use Cases

Disopyramide’s standard dosing is generally employed for indicated arrhythmias, whether occurring post-myocardial infarction, post-electroconversion, or in other settings. There is some indication for its use to suppress arrhythmias during surgical procedures, but specific dosage guidelines for these cases must be tailored to the individual patient’s needs and clinical status. Please refer to standard dosage section for more information.

Dosage Adjustments

Disopyramide should be administered with caution, usually at the lower end of the dosing range in elderly patients, and closely monitored. Dose adjustments are usually needed when treating patients with hepatic or renal impairment.

Side Effects

Common Side Effects

• Dry mouth
• Blurred vision
• Constipation
• Urinary hesitancy/retention
• Dizziness
• Fatigue
• Nausea

Rare but Serious Side Effects

• Severe hypotension
• Heart failure exacerbation
• Worsening of arrhythmias (proarrhythmic effect), including torsades de pointes.
• Hypoglycemia (low blood sugar)
• Agranulocytosis (low white blood cell count)
• Cholestatic jaundice

Long-Term Effects

• Chronic heart failure exacerbation
• Anticholinergic effects (e.g., cognitive impairment, urinary retention)

Adverse Drug Reactions (ADR)

• Torsades de pointes (a life-threatening arrhythmia).
• Acute heart failure decompensation.
• Severe hypotension.
• Agranulocytosis.

Contraindications

• Second- or third-degree atrioventricular block (without a pacemaker)
• Bundle branch block with first-degree AV block
• Bifasicular block (without a pacemaker)
• Cardiogenic shock
• Severe heart failure
• Pre-existing long QT syndrome
• Known hypersensitivity to disopyramide

Drug Interactions

• Other Class IA antiarrhythmics (additive effects, increased risk of toxicity).
• Drugs that prolong the QT interval (increased risk of torsades de pointes).
• Anticholinergic medications (additive anticholinergic effects).
• CYP3A4 inhibitors (increased disopyramide levels).
• CYP3A4 inducers (decreased disopyramide levels).

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C. Disopyramide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• Breastfeeding: Disopyramide is excreted in breast milk. Caution should be exercised when administering to breastfeeding mothers.

Drug Profile Summary

• Mechanism of Action: Blocks fast sodium channels in cardiac tissue, prolonging action potential duration and effective refractory period. Possesses anticholinergic properties.
• Side Effects: Dry mouth, blurred vision, constipation, urinary retention, dizziness, fatigue, nausea. Serious: Hypotension, heart failure, arrhythmias (torsades de pointes), hypoglycemia.
• Contraindications: 2nd/3rd degree AV block (unpaced), bundle branch block with 1st-degree AV block, bifasicular block (unpaced), cardiogenic shock, severe heart failure, long QT syndrome, hypersensitivity.
• Drug Interactions: Class IA antiarrhythmics, QT-prolonging drugs, anticholinergics, CYP3A4 inhibitors/inducers.
• Pregnancy & Breastfeeding: Category C; caution advised during breastfeeding.
• Dosage: Adults: Immediate-release: 400-800 mg/day divided every 6 hours; Extended-release: 400-800 mg/day divided every 12 hours. Adjustments needed for renal/hepatic impairment and low body weight (<50 kg).
• Monitoring Parameters: ECG (QT interval), heart rate, blood pressure, signs of heart failure, electrolyte levels (potassium, magnesium).

Popular Combinations

Disopyramide is not typically used in combination with other antiarrhythmics due to the increased risk of adverse effects.

Precautions

• Patients with glaucoma, myasthenia gravis, urinary retention, or prostatic hypertrophy should be carefully monitored due to the drug’s anticholinergic effects.
• Patients with pre-existing heart conditions or electrolyte abnormalities require close monitoring.
• Alcohol consumption should be avoided, as it may potentiate the drug’s sedative effects.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Disopyramide?

A: The recommended adult dose is 400-800 mg/day, divided into doses given every 6 hours for immediate-release or every 12 hours for extended-release formulations. Adjustments are necessary for renal/hepatic impairment, low body weight, and elderly patients.

Q2: What are the primary side effects of Disopyramide?

A: Common side effects include dry mouth, constipation, urinary hesitancy, blurred vision, dizziness, and fatigue. More serious side effects include heart failure exacerbation, hypotension, and proarrhythmia, including Torsades de pointes.

Q3: What are the absolute contraindications for using Disopyramide?

A: Disopyramide is contraindicated in patients with second- or third-degree heart block (without a pacemaker), bundle branch block with first-degree heart block, bifasicular block (without a pacemaker), cardiogenic shock, pre-existing long QT syndrome, and severe heart failure not related to arrhythmias.

Q4: How does Disopyramide interact with other antiarrhythmic drugs?

A: Combining disopyramide with other Class IA antiarrhythmics can increase the risk of additive effects and toxicity. Co-administration with QT-prolonging drugs increases the risk of torsades de pointes.

Q5: Can Disopyramide be used in patients with renal impairment?

A: Yes, but dosage adjustments are crucial. The dosing interval needs to be extended based on creatinine clearance levels.

Q6: Is Disopyramide safe to use during pregnancy?

A: Disopyramide is a Pregnancy Category C drug. Use it only if the potential benefit outweighs the potential risk to the fetus. Consult a specialist.

Q7: Does Disopyramide interact with any specific foods or drinks?

A: Alcohol should be avoided due to potential additive sedative effects. Grapefruit juice may inhibit CYP3A4, potentially increasing drug levels.

Q9: What monitoring parameters are essential for patients on Disopyramide?

A: Essential monitoring parameters include ECG (especially QT interval), heart rate, blood pressure, signs of heart failure, and electrolyte levels (potassium and magnesium). Regular follow-up is important.

Q10: How is Disopyramide metabolized and eliminated from the body?

A: Disopyramide is metabolized by the liver via CYP3A4 and eliminated via both renal and hepatic routes. A small portion is excreted unchanged in the urine.