Norpace CR 100mg Capsules
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.
Drug Class
Antiarrhythmic
Pharmacologic Class
Class Ia Antiarrhythmic
Pregnancy Category
C
FDA Approved
Jan 1977
DEA Schedule
Not Controlled
Overview
What is this medicine?
Disopyramide is a medication used to treat certain types of irregular heartbeats (arrhythmias). It works by affecting the electrical signals in your heart to help it beat more regularly. The 'CR' in Norpace CR means 'controlled release,' which means the medicine is released slowly over time, so you take it less often.
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 bathrooms. Keep all medications in a secure place, out of reach of children and pets. Properly dispose of any unused or expired medication. Do not flush it down the toilet or pour it down the drain unless instructed to do so by your pharmacist or healthcare provider. If you have questions about disposing of your medication, consult with your pharmacist, who can also inform you about potential drug take-back programs in your area.
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. It's crucial not to take two doses at the same time or take extra doses to make up for the missed one.
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 bathrooms. Keep all medications in a secure place, out of reach of children and pets. Properly dispose of any unused or expired medication. Do not flush it down the toilet or pour it down the drain unless instructed to do so by your pharmacist or healthcare provider. If you have questions about disposing of your medication, consult with your pharmacist, who can also inform you about potential drug take-back programs in your area.
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. It's crucial not to take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Take the medication exactly as prescribed, do not crush or chew the controlled-release capsules.
- Avoid grapefruit juice as it can increase the levels of the medication in your body.
- Report any new or worsening symptoms of heart failure (e.g., shortness of breath, swelling) immediately.
- Report any new or worsening heart palpitations, dizziness, or fainting spells.
- Maintain adequate hydration and electrolyte balance, especially if you experience vomiting or diarrhea.
- Limit alcohol intake as it can affect heart rhythm and interact with medications.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
300 mg every 12 hours (Norpace CR)
Dose Range:
200 - 400 mg
Condition-Specific Dosing:
ventricularArrhythmias:
300 mg every 12 hours (Norpace CR) for patients weighing > 110 lbs (50 kg). For patients weighing < 110 lbs, 200 mg every 12 hours (Norpace CR).
severeHeartFailure:
Initial dose may be reduced to 100 mg every 12 hours (Norpace CR) with careful monitoring.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
CrCl 40-30 mL/min: 150 mg every 12 hours (Norpace CR)
Moderate:
CrCl 30-15 mL/min: 150 mg every 24 hours (Norpace CR)
Severe:
CrCl < 15 mL/min: 100 mg every 24 hours (Norpace CR)
Dialysis:
Administer dose after dialysis. Supplemental dose may be needed.
Hepatic Impairment:
Mild:
No specific adjustment, but monitor closely.
Moderate:
Reduce dose by approximately 25-50% (e.g., 100 mg every 12 hours Norpace CR), monitor plasma levels.
Severe:
Reduce dose by approximately 50% or more (e.g., 100 mg every 24 hours Norpace CR), monitor plasma levels.
Pharmacology
Mechanism of Action
Disopyramide is a Class Ia antiarrhythmic agent. It decreases the rate of depolarization (Phase 0) and prolongs the action potential duration (APD) and effective refractory period (ERP) in atrial and ventricular myocardial fibers and accessory pathways. It achieves this by blocking fast sodium channels, thereby reducing the maximum rate of depolarization (Vmax) and increasing the threshold for excitability. It also possesses anticholinergic properties.
Pharmacokinetics
Absorption:
Bioavailability:
80-90%
Tmax:
1-2 hours (immediate release); 4-6 hours (controlled release)
FoodEffect:
Food may delay absorption but does not significantly affect the extent of absorption.
Distribution:
Vd:
0.8-1.2 L/kg
ProteinBinding:
50-65% (concentration-dependent, decreases with higher concentrations)
CnssPenetration:
Limited
Elimination:
HalfLife:
5-8 hours (immediate release); 10-18 hours (controlled release)
Clearance:
Not available
ExcretionRoute:
Renal (50-60% unchanged), Hepatic (10-20% as metabolites)
Unchanged:
50-60%
Pharmacodynamics
OnsetOfAction:
30 minutes - 2 hours (immediate release)
PeakEffect:
1-3 hours (immediate release); 4-6 hours (controlled release)
DurationOfAction:
6-12 hours (immediate release); 12 hours (controlled release)
Safety & Warnings
BLACK BOX WARNING
Disopyramide may cause or worsen congestive heart failure (CHF) or hypotension. It has negative inotropic properties. It may also cause new or worsened arrhythmias (proarrhythmia), including ventricular tachycardia and ventricular fibrillation, particularly in patients with structural heart disease or electrolyte imbalances. Patients should be hospitalized for initiation of therapy and for dosage adjustments.
Side Effects
Serious Side Effects: Seek Medical Help Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention 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 lead to another type of unsafe abnormal heartbeat (torsades de pointes). If you experience a fast or abnormal heartbeat, or if you pass out, contact your doctor immediately.
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 right away 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. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or 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, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention 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 lead to another type of unsafe abnormal heartbeat (torsades de pointes). If you experience a fast or abnormal heartbeat, or if you pass out, contact your doctor immediately.
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 right away 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. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or 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, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Severe dizziness or fainting (syncope)
- New or worsening shortness of breath
- Swelling in the ankles, feet, or legs
- Chest pain
- New or worsening irregular heartbeats (palpitations)
- Blurred vision
- Difficulty urinating
- Severe dry mouth
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. Describe the allergic reaction you experienced, including the symptoms that occurred.
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 discuss the following with your doctor and pharmacist:
All prescription and over-the-counter (OTC) medications you are taking.
Any natural products or vitamins you are using.
* Your complete medical history, including all health problems.
Before starting, stopping, or changing the dose of any medication, including this one, you must consult with your doctor to ensure your safety. It is your responsibility to verify that it is safe to take this medication with all your other medications and health conditions.
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. Describe the allergic reaction you experienced, including the symptoms that occurred.
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 discuss the following with your doctor and pharmacist:
All prescription and over-the-counter (OTC) medications you are taking.
Any natural products or vitamins you are using.
* Your complete medical history, including all health problems.
Before starting, stopping, or changing the dose of any medication, including this one, you must consult with your doctor to ensure your safety. It is your responsibility to verify that it is safe to take this medication with all your other medications and health conditions.
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 (high blood sugar), it is crucial to closely monitor your blood sugar levels while taking this medication. 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. Additionally, if you are pregnant, planning to become pregnant, or breastfeeding, consult your doctor to discuss the potential benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- Profound hypotension (low blood pressure)
- Widening of QRS complex
- Prolonged QT interval
- Ventricular arrhythmias (e.g., Torsades de Pointes, ventricular fibrillation)
- Asystole
- Cardiogenic shock
- Respiratory depression
- Coma
- Anticholinergic effects (e.g., severe dry mouth, blurred vision, urinary retention, delirium)
What to Do:
Call 1-800-222-1222 (Poison Control). Seek immediate medical attention. Treatment is supportive and may include gastric lavage, activated charcoal, vasopressors for hypotension, atropine for bradycardia, and correction of electrolyte imbalances. Hemodialysis may be effective in removing disopyramide.
Drug Interactions
Contraindicated Interactions
- Other Class Ia antiarrhythmics (e.g., quinidine, procainamide)
- Class Ic antiarrhythmics (e.g., flecainide, propafenone)
- Drugs that prolong QT interval (e.g., amiodarone, sotalol, tricyclic antidepressants, macrolide antibiotics, some antipsychotics)
- Potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, clarithromycin) due to increased disopyramide levels
Major Interactions
- Beta-blockers (additive negative inotropic effects, bradycardia)
- Calcium channel blockers (e.g., verapamil, diltiazem - additive negative inotropic and chronotropic effects)
- Digoxin (may increase digoxin levels, additive bradycardia)
- Phenytoin, Rifampin (CYP3A4 inducers - decrease disopyramide levels)
- Diuretics (may cause hypokalemia/hypomagnesemia, increasing proarrhythmic risk)
- Anticholinergic drugs (additive anticholinergic effects)
Moderate Interactions
- Warfarin (potential for increased INR, though not consistently reported)
- Grapefruit juice (CYP3A4 inhibition, potential for increased disopyramide levels)
Minor Interactions
- Antacids (may affect absorption of immediate release, less relevant for CR)
Monitoring
Baseline Monitoring
Electrocardiogram (ECG)
Rationale: To assess baseline cardiac rhythm, PR, QRS, and QT 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.
Timing: Prior to initiation of therapy.
Renal Function (CrCl)
Rationale: Disopyramide is primarily renally excreted; dose adjustment is necessary in renal impairment.
Timing: Prior to initiation of therapy.
Hepatic Function (LFTs)
Rationale: Disopyramide is metabolized by the liver; dose adjustment may be necessary in hepatic impairment.
Timing: Prior to initiation of therapy.
Echocardiogram/Cardiac Function Assessment
Rationale: To assess left ventricular function, as disopyramide has significant negative inotropic effects.
Timing: Prior to initiation of therapy, especially in patients with pre-existing heart disease.
Routine Monitoring
Electrocardiogram (ECG)
Frequency: Regularly (e.g., weekly initially, then monthly or as clinically indicated)
Target: Maintain QRS duration < 25% increase from baseline, QTc interval < 500 ms (or < 450 ms if possible)
Action Threshold: Discontinue or reduce dose if QRS widens by > 25% or QTc prolongs significantly (> 500 ms or > 60 ms from baseline).
Serum Disopyramide Levels
Frequency: Initially after steady-state (3-4 days), then periodically or if toxicity/inefficacy suspected.
Target: Therapeutic range: 2-5 mcg/mL (for ventricular arrhythmias)
Action Threshold: Adjust dose to maintain levels within therapeutic range; levels > 7 mcg/mL are associated with increased toxicity.
Serum Electrolytes (Potassium, Magnesium)
Frequency: Periodically, especially if on diuretics or with GI losses.
Target: Maintain within normal limits (K 3.5-5.0 mEq/L, Mg 1.7-2.2 mg/dL)
Action Threshold: Correct hypokalemia/hypomagnesemia promptly.
Renal Function (CrCl)
Frequency: Periodically, especially in elderly or those with changing renal status.
Target: Not applicable
Action Threshold: Adjust dose if renal function declines.
Signs/Symptoms of Heart Failure
Frequency: At each visit
Target: Not applicable
Action Threshold: Discontinue or reduce dose if new or worsening heart failure develops.
Symptom Monitoring
- Palpitations
- Dizziness
- Lightheadedness
- Syncope
- Shortness of breath
- Swelling of ankles/feet
- Dry mouth
- Blurred vision
- Urinary retention
- Constipation
Special Patient Groups
Pregnancy
Use only if the potential benefit justifies the potential risk to the fetus. Disopyramide has been shown to cause uterine contractions and may induce labor.
Trimester-Specific Risks:
First Trimester:
Limited data, but potential for fetal harm cannot be excluded.
Second Trimester:
Potential for uterine contractions and premature labor.
Third Trimester:
Increased risk of uterine contractions and premature labor; potential for fetal bradycardia.
Lactation
Disopyramide is excreted into breast milk. 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 (Moderate risk) - Potential for infant exposure and adverse effects (e.g., anticholinergic effects, cardiac effects). Monitor infant for bradycardia, feeding difficulties, and anticholinergic signs.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Use is generally not recommended.
Geriatric Use
Elderly patients may be more susceptible to the anticholinergic effects and negative inotropic effects of disopyramide. Renal function often declines with age, necessitating dose adjustments. Start with lower doses and monitor closely.
Clinical Information
Clinical Pearls
- Disopyramide has significant negative inotropic effects, making it generally contraindicated in patients with pre-existing heart failure or severe left ventricular dysfunction (LVEF < 40%).
- Its anticholinergic properties can be problematic, especially in elderly patients or those with benign prostatic hyperplasia, glaucoma, or myasthenia gravis.
- Careful monitoring of ECG (QRS, QTc), serum electrolytes (K, Mg), and disopyramide levels is crucial due to its narrow therapeutic index and potential for proarrhythmia.
- Hypokalemia and hypomagnesemia must be corrected prior to and during disopyramide therapy to minimize proarrhythmic risk.
- Controlled-release formulation (Norpace CR) allows for twice-daily dosing, improving patient adherence compared to immediate-release formulations.
- Consider alternative antiarrhythmics if significant anticholinergic side effects or worsening heart failure are concerns.
Alternative Therapies
- Other Class Ia antiarrhythmics (e.g., quinidine, procainamide - though less commonly used due to side effects)
- Class Ic antiarrhythmics (e.g., flecainide, propafenone - for structurally normal hearts)
- Class III antiarrhythmics (e.g., amiodarone, sotalol, dofetilide)
- Beta-blockers (e.g., metoprolol, carvedilol)
- Calcium channel blockers (e.g., verapamil, diltiazem - for supraventricular arrhythmias)
- Catheter ablation (for certain arrhythmias)
Cost & Coverage
Average Cost:
Varies widely, typically $50-$200 per 30 capsules
Generic Available:
Yes
Insurance Coverage:
Tier 2-3 (generic), Tier 3-4 (brand)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to 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 seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.