Norpace CR 150mg Capsules

Manufacturer PFIZER Active Ingredient Disopyramide Controlled-Release Capsules(dye soe PEER a mide) Pronunciation dye soe PEER a mide
WARNING: This drug is only to be used to treat certain types of abnormal heartbeats. Other abnormal heartbeats have happened with this drug, which in rare cases can be deadly. Talk to the doctor if you have any questions about this drug. @ COMMON USES: It is used to treat certain types of abnormal heartbeats.It may be given to you for other reasons. Talk with the doctor.
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Drug Class
Antiarrhythmic
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Pharmacologic Class
Class Ia Antiarrhythmic (Sodium Channel Blocker)
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Pregnancy Category
Category C
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FDA Approved
Mar 1977
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DEA Schedule
Not Controlled

Overview

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What is this medicine?

Disopyramide is a medication used to treat certain types of irregular heartbeats (arrhythmias). It works by helping to stabilize the electrical activity in your heart, which can prevent dangerous fast or irregular rhythms. It's important to take this medication exactly as prescribed because too much or too little can be harmful.
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How to Use This Medicine

Taking Your Medication Correctly

To get the most benefit from your medication, it's essential to take it exactly as directed by your doctor. Carefully read all the information provided with your prescription, and follow the instructions closely. When taking your medication, swallow the tablets whole - do not chew, break, or crush them. Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better.

Storing and Disposing of Your Medication

To maintain the effectiveness and safety of your medication, store it at room temperature in a dry location, avoiding the bathroom. Keep all medications in a secure place, out of the reach of children and pets. When disposing of unused or expired medication, do not flush it down the toilet or pour it down the drain unless specifically instructed to do so. Instead, consult with your pharmacist for guidance on the best disposal method. You may also want to explore local drug take-back programs for a safe and environmentally friendly way to dispose of your medication.

What to Do If You Miss a Dose

If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
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Lifestyle & Tips

  • Take the medication exactly as prescribed, do not crush, chew, or break the controlled-release capsules.
  • Do not stop taking this medication without consulting your doctor, as it can worsen your heart condition.
  • Avoid alcohol, as it can worsen side effects or affect the medication's action.
  • Be aware of potential side effects like dizziness or blurred vision, and avoid driving or operating machinery until you know how the medication affects you.
  • Maintain adequate hydration and fiber intake to help manage anticholinergic side effects like dry mouth and constipation.
  • Report any new or worsening symptoms, especially heart-related symptoms, to your doctor immediately.

Dosing & Administration

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Adult Dosing

Standard Dose: 300 mg per day in two divided doses (e.g., 150 mg every 12 hours)
Dose Range: 300 - 400 mg

Condition-Specific Dosing:

severeArrhythmias: Up to 400 mg per day in two divided doses (e.g., 200 mg every 12 hours)
maintenance: 300-400 mg/day in two divided doses
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Pediatric Dosing

Neonatal: Not established
Infant: Not established
Child: Not established
Adolescent: Not established
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Dose Adjustments

Renal Impairment:

Mild: CrCl 40-30 mL/min: 150 mg every 12 hours or 150 mg every 24 hours
Moderate: CrCl 30-15 mL/min: 100 mg every 12 hours or 100 mg every 24 hours
Severe: CrCl <15 mL/min: 100 mg every 24 hours or 100 mg every 48 hours
Dialysis: Administer dose after dialysis; supplemental dose may be needed. Specific dosing should be guided by serum levels.

Hepatic Impairment:

Mild: Reduce dose by approximately 50% (e.g., 100 mg every 12 hours or 150 mg every 24 hours)
Moderate: Reduce dose by approximately 50% (e.g., 100 mg every 12 hours or 150 mg every 24 hours)
Severe: Reduce dose by approximately 50% (e.g., 100 mg every 12 hours or 150 mg every 24 hours)

Pharmacology

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Mechanism of Action

Disopyramide is a Class Ia antiarrhythmic agent. It exerts its antiarrhythmic effect by decreasing the rate of depolarization (Phase 0) and prolonging the action potential duration (APD) and effective refractory period (ERP) in atrial and ventricular myocardial fibers and accessory pathways. This is primarily achieved by blocking fast inward sodium channels in the myocardial cell membrane. It also possesses significant anticholinergic properties.
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Pharmacokinetics

Absorption:

Bioavailability: 80-90%
Tmax: 4-12 hours (for controlled-release formulation)
FoodEffect: Food may delay absorption but does not significantly affect the extent of absorption.

Distribution:

Vd: 0.8-1.2 L/kg
ProteinBinding: 20-60% (concentration-dependent)
CnssPenetration: Limited

Elimination:

HalfLife: 10-18 hours (for controlled-release formulation; can be prolonged in renal/hepatic impairment)
Clearance: Not available
ExcretionRoute: Renal (50-60%), Hepatic (15-20%)
Unchanged: 50-60%
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Pharmacodynamics

OnsetOfAction: 1-2 hours
PeakEffect: 4-12 hours (for controlled-release formulation)
DurationOfAction: 10-18 hours (consistent with half-life)

Safety & Warnings

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BLACK BOX WARNING

Disopyramide has a narrow therapeutic index and can cause serious adverse effects, including proarrhythmia (aggravation or induction of new arrhythmias, including ventricular tachycardia and fibrillation) and negative inotropic effects (worsening of heart failure). It should be reserved for patients with life-threatening ventricular arrhythmias because of its proarrhythmic potential. Patients should be hospitalized for initiation of therapy and for any dose adjustments.
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Side Effects

Serious Side Effects: Seek Medical Attention Immediately

Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you experience any of the following symptoms, contact your doctor or seek medical help right away:

Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of low blood sugar, including:
+ Dizziness
+ Headache
+ Feeling sleepy
+ Feeling weak
+ Shaking
+ Fast heartbeat
+ Confusion
+ Hunger
+ Sweating
New or worsening abnormal heartbeat
Chest pain or pressure
Changes in eyesight
Trouble passing urine, frequent urination, or urgent need to urinate
Muscle weakness
A type of abnormal heartbeat (prolonged QT interval) has been associated with this medication, which can increase the risk of another type of abnormal heartbeat (torsades de pointes). If you experience a fast or abnormal heartbeat, or if you pass out, contact your doctor right away.
Heart failure has been reported with this medication, as well as worsening heart failure in people with pre-existing heart disease. If you have heart disease, inform your doctor. Seek medical attention immediately if you experience:
+ Shortness of breath
+ Sudden weight gain
+ Abnormal heartbeat
+ New or worsening swelling in the arms or legs

Other Possible Side Effects

Like all medications, this drug can cause side effects. However, many people do not experience any side effects or only have mild ones. If you are bothered by any of the following side effects or if they do not go away, contact your doctor or seek medical help:

Headache
Constipation
Dry mouth, nose, or throat
Dry eyes
Dizziness
Fatigue
Weakness
Bloating
Gas
Upset stomach
Stomach pain

This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
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Seek Immediate Medical Attention If You Experience:

  • New or worsening palpitations
  • Dizziness or lightheadedness
  • Fainting spells (syncope)
  • Shortness of breath
  • Swelling in the ankles or feet
  • Unusual fatigue or weakness
  • Severe dry mouth, blurred vision, difficulty urinating, or severe constipation
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Before Using This Medicine

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following:

Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction and its symptoms.
Certain health conditions, including:
+ Heart problems, such as heart block without a functioning pacemaker, heart failure, a prolonged QT interval on an electrocardiogram (ECG), or low blood pressure.
+ Glaucoma or myasthenia gravis.
+ Difficulty urinating.
+ Kidney disease.
+ Abnormal potassium levels, either high or low.
+ Recent use of verapamil within the past 24 hours.

This medication can interact with numerous other drugs, which may increase the risk of severe, life-threatening, or fatal side effects. Therefore, it is crucial to:

Inform your doctor and pharmacist about all medications you are taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins.
Discuss your health problems with your doctor to ensure it is safe to take this medication.
* Never start, stop, or change the dose of any medication without first consulting your doctor.
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Precautions & Cautions

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. In some cases, your doctor may recommend that you start taking this drug in a hospital setting where your condition can be closely monitored.

If you have diabetes, it is crucial to closely monitor your blood sugar levels while taking this medication. Consult your doctor for guidance on managing your blood sugar.

Before consuming alcohol, discuss the potential risks with your doctor.

If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.

If you are pregnant, planning to become pregnant, or breastfeeding, inform your doctor. You and your doctor will need to discuss the potential benefits and risks of this medication to both you and your baby.
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Overdose Information

Overdose Symptoms:

  • Profound hypotension
  • Widening of QRS complex
  • Prolongation of QT interval
  • Ventricular tachycardia
  • Ventricular fibrillation
  • Asystole
  • Cardiogenic shock
  • Respiratory depression
  • Coma
  • Anticholinergic effects (e.g., severe dry mouth, dilated pupils, urinary retention, ileus)

What to Do:

Seek immediate medical attention. Call 911 or your local emergency number. For poison control, call 1-800-222-1222. Treatment is supportive and may include gastric lavage, activated charcoal, vasopressors for hypotension, atropine for bradycardia, and correction of electrolyte imbalances. Overdrive pacing or defibrillation may be necessary for severe arrhythmias. Hemodialysis is not effective.

Drug Interactions

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Contraindicated Interactions

  • Cisapride
  • Dronedarone
  • Pimozide
  • Thioridazine
  • Other drugs known to prolong QT interval and cause Torsades de Pointes (unless benefits outweigh risks and close monitoring is possible)
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Major Interactions

  • Amiodarone (increased disopyramide levels, additive QT prolongation)
  • Beta-blockers (additive negative inotropic effects, bradycardia)
  • Calcium channel blockers (e.g., Verapamil, Diltiazem - additive negative inotropic effects, bradycardia, AV block)
  • Macrolide antibiotics (e.g., Erythromycin, Clarithromycin - CYP3A4 inhibition, increased disopyramide levels, QT prolongation)
  • Azole antifungals (e.g., Ketoconazole, Itraconazole - CYP3A4 inhibition, increased disopyramide levels)
  • Ritonavir (CYP3A4 inhibition, increased disopyramide levels)
  • Phenytoin, Rifampin (CYP3A4 induction, decreased disopyramide levels)
  • Other Class Ia antiarrhythmics (additive proarrhythmic effects, QT prolongation)
  • Anticholinergic agents (additive anticholinergic effects)
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Moderate Interactions

  • Digoxin (may increase digoxin levels, additive bradycardia)
  • Diuretics (especially loop or thiazide - risk of hypokalemia/hypomagnesemia, increasing proarrhythmia risk)
  • Warfarin (potential for increased INR, though not consistently reported)
  • Grapefruit juice (CYP3A4 inhibition, potential for increased disopyramide levels)
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Minor Interactions

  • Antacids (may affect absorption, but generally not clinically significant)

Monitoring

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Baseline Monitoring

Electrocardiogram (ECG)

Rationale: To assess baseline cardiac rhythm, PR, QRS, and QTc intervals, and identify pre-existing conduction abnormalities or prolonged QT.

Timing: Prior to initiation of therapy

Serum Electrolytes (Potassium, Magnesium)

Rationale: Hypokalemia and hypomagnesemia can increase the risk of proarrhythmia, especially Torsades de Pointes.

Timing: Prior to initiation of therapy

Renal Function (BUN, Creatinine, CrCl)

Rationale: Disopyramide is primarily renally eliminated; dose adjustments are necessary in renal impairment.

Timing: Prior to initiation of therapy

Hepatic Function (ALT, AST, Bilirubin)

Rationale: Disopyramide is metabolized in the liver; dose adjustments are necessary in hepatic impairment.

Timing: Prior to initiation of therapy

Blood Pressure

Rationale: To assess baseline hemodynamic status, as disopyramide can cause hypotension.

Timing: Prior to initiation of therapy

Echocardiogram/Cardiac Function Assessment

Rationale: To assess left ventricular function, as disopyramide has negative inotropic effects and is contraindicated in cardiogenic shock or decompensated heart failure.

Timing: Prior to initiation of therapy, especially in patients with pre-existing heart disease

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Routine Monitoring

Electrocardiogram (ECG)

Frequency: Regularly, especially during dose titration and with changes in clinical status or concomitant medications. At least weekly during initiation, then monthly or quarterly.

Target: Maintain QTc < 450-460 ms (or < 25% increase from baseline); QRS duration < 120 ms (or < 25% increase from baseline)

Action Threshold: Discontinue or reduce dose if QTc prolongs significantly (>500 ms or >25% increase from baseline) or if QRS widens significantly (>25% increase from baseline or >120 ms), or if new arrhythmias occur.

Serum Disopyramide Levels

Frequency: During dose titration, with suspected toxicity, or if efficacy is suboptimal. Once stable, periodically.

Target: Therapeutic range: 2-5 mcg/mL (trough)

Action Threshold: Adjust dose to maintain levels within therapeutic range; levels >7 mcg/mL are associated with increased toxicity.

Serum Electrolytes (Potassium, Magnesium)

Frequency: Regularly, especially if on diuretics or with GI losses. At least monthly.

Target: Potassium 4.0-5.0 mEq/L; Magnesium 1.8-2.5 mg/dL

Action Threshold: Correct hypokalemia/hypomagnesemia promptly to reduce proarrhythmia risk.

Renal Function (BUN, Creatinine)

Frequency: Periodically, especially in elderly or those with risk factors for renal impairment. At least every 3-6 months.

Target: Stable within patient's baseline

Action Threshold: Adjust dose if renal function declines.

Hepatic Function (ALT, AST)

Frequency: Periodically, especially in those with pre-existing liver disease. At least every 3-6 months.

Target: Stable within patient's baseline

Action Threshold: Adjust dose if hepatic function declines.

Blood Pressure

Frequency: Regularly, especially during initiation and dose changes.

Target: Within patient's target range

Action Threshold: Manage hypotension if symptomatic or severe.

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Symptom Monitoring

  • Palpitations
  • Dizziness
  • Lightheadedness
  • Syncope
  • Shortness of breath
  • Swelling of ankles/feet (signs of heart failure)
  • Dry mouth
  • Blurred vision
  • Urinary retention
  • Constipation
  • Nausea
  • Abdominal pain
  • Fatigue

Special Patient Groups

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Pregnancy

Disopyramide is Pregnancy Category C. Animal studies have shown adverse effects on the fetus, but there are no adequate and well-controlled studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Trimester-Specific Risks:

First Trimester: Potential for teratogenicity based on animal data; use only if clearly needed.
Second Trimester: Potential for fetal adverse effects; use with caution.
Third Trimester: Potential for fetal adverse effects, including effects on fetal heart rate; use with caution.
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Lactation

Disopyramide is excreted into breast milk. The American Academy of Pediatrics considers it to be of 'unknown effect on nursing infant but may be of concern'. Due to potential for serious adverse reactions in the nursing infant (e.g., anticholinergic effects, cardiac effects), a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Infant Risk: L3 (Moderately safe; caution advised). Potential for anticholinergic effects (e.g., dry mouth, constipation, urinary retention) and cardiac effects (e.g., arrhythmias, bradycardia) in the infant.
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Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Use is generally not recommended.

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Geriatric Use

Elderly patients may be more susceptible to the anticholinergic effects (e.g., urinary retention, constipation, confusion) and negative inotropic effects of disopyramide. Renal function often declines with age, requiring dose adjustments. Close monitoring of ECG, renal function, and serum levels is crucial.

Clinical Information

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Clinical Pearls

  • Disopyramide has significant negative inotropic effects; use with extreme caution or avoid in patients with pre-existing heart failure or impaired left ventricular function.
  • Its anticholinergic properties are prominent and can lead to bothersome side effects like dry mouth, blurred vision, urinary retention (especially in men with BPH), and constipation.
  • Hypokalemia and hypomagnesemia must be corrected prior to and during disopyramide therapy to minimize the risk of proarrhythmia, particularly Torsades de Pointes.
  • Therapeutic drug monitoring (serum levels) is recommended due to its narrow therapeutic index and concentration-dependent protein binding.
  • Patients should be hospitalized for initiation and significant dose adjustments due to the risk of proarrhythmia and heart failure exacerbation.
  • Norpace CR (controlled-release) is designed for twice-daily dosing, improving patient adherence compared to immediate-release formulations.
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Alternative Therapies

  • Other Class Ia antiarrhythmics (e.g., Procainamide, Quinidine - though less commonly used due to side effects)
  • Class Ic antiarrhythmics (e.g., Flecainide, Propafenone - for supraventricular and ventricular arrhythmias in patients without structural heart disease)
  • Class III antiarrhythmics (e.g., Amiodarone, Sotalol, Dofetilide - for various arrhythmias, including life-threatening ventricular arrhythmias)
  • Beta-blockers (e.g., Metoprolol, Propranolol - for rate control and some antiarrhythmic effects)
  • Calcium channel blockers (e.g., Verapamil, Diltiazem - for rate control in supraventricular arrhythmias)
  • Catheter ablation (non-pharmacological alternative for certain arrhythmias)
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Cost & Coverage

Average Cost: $50 - $200 per 30 capsules (150mg CR)
Generic Available: Yes
Insurance Coverage: Tier 1 or Tier 2 (for generic)
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General Drug Facts

If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.