ISOPTIN SR Verapamil Hydrochloride 180mg Sustained Release Tablet 30's
RXDRUG-DR-XY42927
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Indications/Uses
Verapamil hydrochloride (Isoptin) Solution for IV Injection: Verapamil hydrochloride injection is indicated in adults, neonates, infants, children, and adolescents for the treatment of supraventricular tachyarrhythmias, which includes the following: 1. Rapid conversion to sinus rhythm of paroxysmal supraventricular tachycardias, including those associated with accessory bypass tracts (Wolff-Parkinson-White [W-P-W] or Lown-Ganong-Levine [L-G-L] syndromes). When clinically advisable, appropriate vagal maneuvers (e.g., Valsalva maneuver) should be attempted prior to administration of verapamil hydrochloride.
2. Temporary control of rapid ventricular rate in atrial flutter or atrial fibrillation except when the atrial flutter and/or atrial fibrillation are associated with accessory bypass tracts (Wolff-Parkinson-White (W-P-W) or Lown-Ganong-Levine (L-G-L) syndromes).
Verapamil hydrochloride (Isoptin) Film-Coated Tablet/(Isoptin SR) Sustained-Release Tablet: Verapamil hydrochloride is indicated in adults, neonates, infants, children and adolescents for the treatment of: 1. Coronary artery disease (conditions characterized by inadequate oxygen supply to the cardiac muscle) including: chronic stable angina pectoris; unstable angina pectoris (crescendo angina, angina at rest); vasospastic angina pectoris (Prinzmetal's angina, variant angina); post-myocardial infarction angina in patients without heart failure if beta-blockers are not indicated.
2. Disturbance of cardiac rhythm in paroxysmal supraventricular tachycardia, atrial fibrillation/atrial flutter with rapid atrioventricular conduction (except in Wolff-Parkinson-White or Lown-Ganong-Levine syndromes).
3. High blood pressure (hypertension).
2. Temporary control of rapid ventricular rate in atrial flutter or atrial fibrillation except when the atrial flutter and/or atrial fibrillation are associated with accessory bypass tracts (Wolff-Parkinson-White (W-P-W) or Lown-Ganong-Levine (L-G-L) syndromes).
Verapamil hydrochloride (Isoptin) Film-Coated Tablet/(Isoptin SR) Sustained-Release Tablet: Verapamil hydrochloride is indicated in adults, neonates, infants, children and adolescents for the treatment of: 1. Coronary artery disease (conditions characterized by inadequate oxygen supply to the cardiac muscle) including: chronic stable angina pectoris; unstable angina pectoris (crescendo angina, angina at rest); vasospastic angina pectoris (Prinzmetal's angina, variant angina); post-myocardial infarction angina in patients without heart failure if beta-blockers are not indicated.
2. Disturbance of cardiac rhythm in paroxysmal supraventricular tachycardia, atrial fibrillation/atrial flutter with rapid atrioventricular conduction (except in Wolff-Parkinson-White or Lown-Ganong-Levine syndromes).
3. High blood pressure (hypertension).
Dosage/Direction for Use
Posology: Verapamil hydrochloride (Isoptin) Solution for IV Injection: Adults: The recommended intravenous doses of verapamil hydrochloride are as follows: Initial dose: 5 to 10 mg (0.075 to 0.15 mg/kg body weight) given as an intravenous bolus over at least two minutes.
Repeat dose: 10 mg (0.15 mg/kg body weight) 30 minutes after the first dose if the initial response is not adequate.
Special Populations: Pediatric population: The safety and efficacy of verapamil hydrochloride injection have been established in neonates, infants, children and adolescents: Initial Dose: 0 to 1 year: 0.1 to 0.2 mg/kg body weight (usual single dose range: 0.75 to 2 mg) should be administered as an intravenous bolus over at least two minutes under continuous ECG monitoring.
1 to 15 years: 0.1 to 0.3 mg/kg body weight (usual single dose range: 2 to 5 mg) should be administered as an intravenous bolus over at least two minutes. Do not exceed 5 mg.
Repeat Dose: 0 to 1 year: 0.1 to 0.2 mg/kg body weight (usual single dose range: 0.75 to 2 mg) 30 minutes after the first dose if the initial response is not adequate.
1 to 15 years: 0.1 to 0.3 mg/kg body weight (usual single dose range: 2 to 5 mg) 30 minutes after the first dose if the initial response is not adequate. Do not exceed 10 mg as a single dose.
Elderly patients: The dose should be administered over at least three minutes to minimize the risk of untoward drug effects.
Method of administration: For intravenous use only.
Verapamil hydrochloride should be given as a slow intravenous injection over at least a two minute period of time under continuous electrocardiographic and blood pressure monitoring.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Verapamil hydrochloride is physically compatible and chemically stable for at least 24 hours at 25°C protected from light in most common large volume parenteral solutions. Use only if solution is clear and vial seal is intact.
Unused amount of solution should be discarded immediately following withdrawal of any portion of contents.
For stability reasons this product is not recommended for dilution with sodium lactate injection, USP in polyvinyl chloride bags.
Admixing intravenous verapamil hydrochloride with albumin, amphotericin B, hydralazine hydrochloride or trimethoprim and sulfamethoxazole should be avoided.
Verapamil hydrochloride will precipitate in any solution with a pH above 6.0.
Posology: Verapamil hydrochloride (Isoptin) Film-Coated Tablet/(Isoptin SR) Sustained-Release Tablet: The dose of verapamil hydrochloride should be adjusted individually in accordance with the severity of disease. Long-standing clinical experience shows that the average daily dose in all indications is between 240 mg and 360 mg. The daily dose should not exceed 480 mg on a long-term basis, although a higher dose may be used for a short period. There is no limitation on the duration of use. Verapamil hydrochloride should not be discontinued abruptly after long-term use. It is recommended to taper the dosage.
Verapamil hydrochloride 40 mg tablets should be used for patients likely to display a satisfactory response to low doses (e.g., patients with hepatic dysfunction or elderly patients). For patients requiring higher dosages (e.g., 240 mg to 480 mg verapamil hydrochloride per day), formulations with a more suitable active drug content should be used.
Adults: Coronary artery disease, paroxysmal supraventricular tachycardia, atrial flutter and atrial fibrillation: IR: 120 to 480 mg in three or four divided doses.
SR: 120 to 480 mg in one or two divided doses.
Hypertension: IR: 120 to 480 mg in three divided doses.
SR: 120 to 480 mg in one or two divided doses.
Special Populations: Pediatric population: The safety and efficacy of verapamil hydrochloride have been established in children: Up to age 6 years: 80 mg to 120 mg Verapamil hydrochloride (Isoptin) in two to three divided doses.
Age 6-14 years: 80 mg to 360 mg Verapamil hydrochloride (Isoptin) in two to four divided doses.
Renal impairment: Currently available data are described in Precautions. Verapamil hydrochloride should be used cautiously and with close monitoring in patients with impaired renal function.
Liver impairment: In patients with impaired liver function, metabolism of the drug is delayed to a greater or lesser extent depending on the severity of hepatic dysfunction, thus potentiating and prolonging the effects of verapamil hydrochloride. Therefore, the dosage needs to be adjusted with special caution in patients with impaired liver function and low doses should be given initially (see Precautions).
Method of administration: For oral use only.
Tablets should be taken without sucking or chewing, with sufficient liquid, preferably with or shortly after meals.
Repeat dose: 10 mg (0.15 mg/kg body weight) 30 minutes after the first dose if the initial response is not adequate.
Special Populations: Pediatric population: The safety and efficacy of verapamil hydrochloride injection have been established in neonates, infants, children and adolescents: Initial Dose: 0 to 1 year: 0.1 to 0.2 mg/kg body weight (usual single dose range: 0.75 to 2 mg) should be administered as an intravenous bolus over at least two minutes under continuous ECG monitoring.
1 to 15 years: 0.1 to 0.3 mg/kg body weight (usual single dose range: 2 to 5 mg) should be administered as an intravenous bolus over at least two minutes. Do not exceed 5 mg.
Repeat Dose: 0 to 1 year: 0.1 to 0.2 mg/kg body weight (usual single dose range: 0.75 to 2 mg) 30 minutes after the first dose if the initial response is not adequate.
1 to 15 years: 0.1 to 0.3 mg/kg body weight (usual single dose range: 2 to 5 mg) 30 minutes after the first dose if the initial response is not adequate. Do not exceed 10 mg as a single dose.
Elderly patients: The dose should be administered over at least three minutes to minimize the risk of untoward drug effects.
Method of administration: For intravenous use only.
Verapamil hydrochloride should be given as a slow intravenous injection over at least a two minute period of time under continuous electrocardiographic and blood pressure monitoring.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Verapamil hydrochloride is physically compatible and chemically stable for at least 24 hours at 25°C protected from light in most common large volume parenteral solutions. Use only if solution is clear and vial seal is intact.
Unused amount of solution should be discarded immediately following withdrawal of any portion of contents.
For stability reasons this product is not recommended for dilution with sodium lactate injection, USP in polyvinyl chloride bags.
Admixing intravenous verapamil hydrochloride with albumin, amphotericin B, hydralazine hydrochloride or trimethoprim and sulfamethoxazole should be avoided.
Verapamil hydrochloride will precipitate in any solution with a pH above 6.0.
Posology: Verapamil hydrochloride (Isoptin) Film-Coated Tablet/(Isoptin SR) Sustained-Release Tablet: The dose of verapamil hydrochloride should be adjusted individually in accordance with the severity of disease. Long-standing clinical experience shows that the average daily dose in all indications is between 240 mg and 360 mg. The daily dose should not exceed 480 mg on a long-term basis, although a higher dose may be used for a short period. There is no limitation on the duration of use. Verapamil hydrochloride should not be discontinued abruptly after long-term use. It is recommended to taper the dosage.
Verapamil hydrochloride 40 mg tablets should be used for patients likely to display a satisfactory response to low doses (e.g., patients with hepatic dysfunction or elderly patients). For patients requiring higher dosages (e.g., 240 mg to 480 mg verapamil hydrochloride per day), formulations with a more suitable active drug content should be used.
Adults: Coronary artery disease, paroxysmal supraventricular tachycardia, atrial flutter and atrial fibrillation: IR: 120 to 480 mg in three or four divided doses.
SR: 120 to 480 mg in one or two divided doses.
Hypertension: IR: 120 to 480 mg in three divided doses.
SR: 120 to 480 mg in one or two divided doses.
Special Populations: Pediatric population: The safety and efficacy of verapamil hydrochloride have been established in children: Up to age 6 years: 80 mg to 120 mg Verapamil hydrochloride (Isoptin) in two to three divided doses.
Age 6-14 years: 80 mg to 360 mg Verapamil hydrochloride (Isoptin) in two to four divided doses.
Renal impairment: Currently available data are described in Precautions. Verapamil hydrochloride should be used cautiously and with close monitoring in patients with impaired renal function.
Liver impairment: In patients with impaired liver function, metabolism of the drug is delayed to a greater or lesser extent depending on the severity of hepatic dysfunction, thus potentiating and prolonging the effects of verapamil hydrochloride. Therefore, the dosage needs to be adjusted with special caution in patients with impaired liver function and low doses should be given initially (see Precautions).
Method of administration: For oral use only.
Tablets should be taken without sucking or chewing, with sufficient liquid, preferably with or shortly after meals.
Overdosage
Clinical Manifestations: Hypotension, bradycardia up to high degree AV block and sinus arrest, hyperglycemia, stupor, metabolic acidosis and acute respiratory distress syndrome. Fatalities have occurred as a result of overdose.
Treatment: Treatment of verapamil hydrochloride overdose should be mainly supportive and individualized. Beta-adrenergic stimulation and/or parenteral administration of calcium injection (calcium chloride) have been effectively used in treatment of deliberate overdosage with oral verapamil hydrochloride. Clinically significant hypotensive reactions or high-degree AV block should be treated with vasopressor agents or cardiac pacing, respectively. Asystole should be handled by the usual measures including beta adrenergic stimulation (e.g., isoproterenol hydrochloride), other vasopressor agents or cardiopulmonary resuscitation.
Due to the potential for delayed absorption of the sustained release product, patients may require observation and hospitalization for up to 48 hours. Verapamil hydrochloride cannot be removed by hemodialysis.
Treatment: Treatment of verapamil hydrochloride overdose should be mainly supportive and individualized. Beta-adrenergic stimulation and/or parenteral administration of calcium injection (calcium chloride) have been effectively used in treatment of deliberate overdosage with oral verapamil hydrochloride. Clinically significant hypotensive reactions or high-degree AV block should be treated with vasopressor agents or cardiac pacing, respectively. Asystole should be handled by the usual measures including beta adrenergic stimulation (e.g., isoproterenol hydrochloride), other vasopressor agents or cardiopulmonary resuscitation.
Due to the potential for delayed absorption of the sustained release product, patients may require observation and hospitalization for up to 48 hours. Verapamil hydrochloride cannot be removed by hemodialysis.
Administration
Should be taken with food: Take w/ or shortly after meals. Swallow whole, do not suck/chew.
Contraindications
Hypersensitivity to verapamil hydrochloride or to any of the inactive ingredients.
Cardiogenic shock.
Second- or third-degree AV block (except in patients with a functioning artificial pacemaker).
Sick sinus syndrome (except in patients with a functioning artificial pacemaker).
Heart failure with reduced ejection fraction of less than 35%, and/or pulmonary wedge pressure above 20 mmHg (unless secondary to a supraventricular tachycardia amenable to verapamil therapy).
Atrial fibrillation/flutter in the presence of an accessory bypass tract (e.g., Wolff-Parkinson-White, Lown-Ganong-Levine syndromes). These patients are at risk to develop ventricular tachyarrhythmia including ventricular fibrillation if verapamil hydrochloride is administered.
Combination with Ivabradine (see Interactions).
Verapamil hydrochloride (Isoptin) Solution for IV Injection: Verapamil hydrochloride is contraindicated in: Severe hypotension.
Patients receiving intravenous beta-adrenergic blocking drugs (e.g., propranolol). Intravenous verapamil hydrochloride and intravenous beta-adrenergic blocking drugs, should not be administered in close proximity to each other (within a few hours), since both may have a depressant effect on myocardial contractility and AV conduction.
Ventricular tachycardia: Administration of intravenous verapamil hydrochloride to patients with wide-complex ventricular tachycardia (QRS > 0.12 seconds) can result in marked hemodynamic deterioration and ventricular fibrillation. Proper pretherapy diagnosis and differentiation from wide-complex supraventricular tachycardia is imperative in the emergency room setting.
Cardiogenic shock.
Second- or third-degree AV block (except in patients with a functioning artificial pacemaker).
Sick sinus syndrome (except in patients with a functioning artificial pacemaker).
Heart failure with reduced ejection fraction of less than 35%, and/or pulmonary wedge pressure above 20 mmHg (unless secondary to a supraventricular tachycardia amenable to verapamil therapy).
Atrial fibrillation/flutter in the presence of an accessory bypass tract (e.g., Wolff-Parkinson-White, Lown-Ganong-Levine syndromes). These patients are at risk to develop ventricular tachyarrhythmia including ventricular fibrillation if verapamil hydrochloride is administered.
Combination with Ivabradine (see Interactions).
Verapamil hydrochloride (Isoptin) Solution for IV Injection: Verapamil hydrochloride is contraindicated in: Severe hypotension.
Patients receiving intravenous beta-adrenergic blocking drugs (e.g., propranolol). Intravenous verapamil hydrochloride and intravenous beta-adrenergic blocking drugs, should not be administered in close proximity to each other (within a few hours), since both may have a depressant effect on myocardial contractility and AV conduction.
Ventricular tachycardia: Administration of intravenous verapamil hydrochloride to patients with wide-complex ventricular tachycardia (QRS > 0.12 seconds) can result in marked hemodynamic deterioration and ventricular fibrillation. Proper pretherapy diagnosis and differentiation from wide-complex supraventricular tachycardia is imperative in the emergency room setting.
Special Precautions
Acute Myocardial Infarction: Use with caution in acute myocardial infarction complicated by bradycardia, marked hypotension, or left ventricular dysfunction.
Heart Block/1st Degree AV block/Bradycardia/Asystole: Verapamil hydrochloride affects the AV and SA nodes and prolongs AV conduction time. Use with caution as development of second- or third-degree AV block (contraindication) or unifascicular, bifascicular or trifascicular bundle branch block requires discontinuation in subsequent doses of verapamil hydrochloride and institution of appropriate therapy, if needed.
Verapamil hydrochloride affects the AV and SA nodes and rarely may produce second- or third-degree AV block, bradycardia, and, in extreme cases, asystole. This is more likely to occur in patients with a sick sinus syndrome (SA nodal disease), which is more common in older patients.
Asystole in patients other than those with sick sinus syndrome is usually of short duration (few seconds or less), with spontaneous return to AV nodal or normal sinus rhythm. If this does not occur promptly, appropriate treatment should be initiated immediately. See Adverse Reactions.
Antiarrhythmics, Beta-blockers: Mutual potentiation of cardiovascular effects (higher-grade AV block, higher-grade lowering of heart rate, induction of heart failure and potentiated hypotension). Asymptomatic bradycardia (36 beats/minute) with a wandering atrial pacemaker has been observed in a patient receiving concomitant timolol (a beta-adrenergic blocker) eye drops and oral verapamil hydrochloride.
Digoxin: If verapamil is administered concomitantly with digoxin, reduce digoxin dosage. See Interactions.
Heart Failure: Heart failure patients with ejection fraction higher than 35% should be compensated before starting verapamil treatment and should be adequately treated throughout.
Hypotension: Intravenous verapamil hydrochloride often produces a decrease in blood pressure below baseline levels that is usually transient and asymptomatic but may result in dizziness.
HMG-CoA Reductase Inhibitors ("Statins"): See Interactions.
Neuromuscular transmission disorders: Verapamil hydrochloride should be used with caution in the presence of diseases in which neuromuscular transmission is affected (myasthenia gravis, Lambert-Eaton syndrome, advanced Duchenne muscular dystrophy).
Other: Special Populations: Renal impairment: Although impaired renal function has been shown in robust comparator studies to have no effect on verapamil pharmacokinetics in patients with end-stage renal failure, several case reports suggest that verapamil should be used cautiously and with close monitoring in patients with impaired renal function.
Verapamil cannot be removed by hemodialysis.
Liver impairment: Use with caution in patients with severely impaired liver function (see also Liver impairment under Dosage & Administration).
Verapamil hydrochloride (Isoptin) Solution for IV Injection: Verapamil hydrochloride injection should be given as a slow intravenous injection over at least a two-minute period of time under continuous ECG and blood pressure monitoring.
A small fraction of patients treated with verapamil hydrochloride respond with life-threatening adverse responses including (rapid ventricular rate (in atrial flutter/fibrillation in the presence of an accessory bypass tract), marked hypotension or extreme bradycardia/asystole).
Antiarrhythmics: Digitalis: Intravenous verapamil hydrochloride has been used concomitantly with digitalis preparations. Since both drugs slow AV conduction, patients should be monitored for AV block or excessive bradycardia.
Quinidine: Intravenous verapamil hydrochloride has been administered to a small number of patients receiving oral quinidine. A few cases of hypotension have been reported in patients taking oral quinidine who received intravenous verapamil hydrochloride. Caution should therefore be used when employing this combination of drugs.
Flecainide: A study in healthy volunteers showed that the concomitant administration of flecainide and verapamil hydrochloride may have additive effects reducing myocardial contractility, prolonging AV conduction and prolonging repolarization.
Disopyramide: Until data on possible interactions between verapamil hydrochloride and disopyramide are obtained, disopyramide should not be administered within 48 hours before or 24 hours after verapamil hydrochloride administration.
Beta-adrenergic blocking drugs: Intravenous verapamil hydrochloride has been administered to patients receiving oral beta-blockers. Since both drugs may depress myocardial contractility or AV conduction, the possibility of detrimental interactions should be considered. The concomitant administration of intravenous beta-blockers and intravenous verapamil hydrochloride has resulted in serious adverse reactions (see Contraindications), especially in patients with severe cardiomyopathy, congestive heart failure or recent myocardial infarction.
Effects on ability to drive and use machines: Due to its antihypertensive effect, depending on the individual response, verapamil hydrochloride may affect the ability to react to the point of impairing the ability to drive a vehicle, operate machinery or work under hazardous conditions. This applies all the more at the start of treatment, when the dose is raised, when switching from another drug and in conjunction with alcohol. Verapamil may increase the blood levels of alcohol and slow its elimination. Therefore, the effects of alcohol may be exaggerated.
Heart Block/1st Degree AV block/Bradycardia/Asystole: Verapamil hydrochloride affects the AV and SA nodes and prolongs AV conduction time. Use with caution as development of second- or third-degree AV block (contraindication) or unifascicular, bifascicular or trifascicular bundle branch block requires discontinuation in subsequent doses of verapamil hydrochloride and institution of appropriate therapy, if needed.
Verapamil hydrochloride affects the AV and SA nodes and rarely may produce second- or third-degree AV block, bradycardia, and, in extreme cases, asystole. This is more likely to occur in patients with a sick sinus syndrome (SA nodal disease), which is more common in older patients.
Asystole in patients other than those with sick sinus syndrome is usually of short duration (few seconds or less), with spontaneous return to AV nodal or normal sinus rhythm. If this does not occur promptly, appropriate treatment should be initiated immediately. See Adverse Reactions.
Antiarrhythmics, Beta-blockers: Mutual potentiation of cardiovascular effects (higher-grade AV block, higher-grade lowering of heart rate, induction of heart failure and potentiated hypotension). Asymptomatic bradycardia (36 beats/minute) with a wandering atrial pacemaker has been observed in a patient receiving concomitant timolol (a beta-adrenergic blocker) eye drops and oral verapamil hydrochloride.
Digoxin: If verapamil is administered concomitantly with digoxin, reduce digoxin dosage. See Interactions.
Heart Failure: Heart failure patients with ejection fraction higher than 35% should be compensated before starting verapamil treatment and should be adequately treated throughout.
Hypotension: Intravenous verapamil hydrochloride often produces a decrease in blood pressure below baseline levels that is usually transient and asymptomatic but may result in dizziness.
HMG-CoA Reductase Inhibitors ("Statins"): See Interactions.
Neuromuscular transmission disorders: Verapamil hydrochloride should be used with caution in the presence of diseases in which neuromuscular transmission is affected (myasthenia gravis, Lambert-Eaton syndrome, advanced Duchenne muscular dystrophy).
Other: Special Populations: Renal impairment: Although impaired renal function has been shown in robust comparator studies to have no effect on verapamil pharmacokinetics in patients with end-stage renal failure, several case reports suggest that verapamil should be used cautiously and with close monitoring in patients with impaired renal function.
Verapamil cannot be removed by hemodialysis.
Liver impairment: Use with caution in patients with severely impaired liver function (see also Liver impairment under Dosage & Administration).
Verapamil hydrochloride (Isoptin) Solution for IV Injection: Verapamil hydrochloride injection should be given as a slow intravenous injection over at least a two-minute period of time under continuous ECG and blood pressure monitoring.
A small fraction of patients treated with verapamil hydrochloride respond with life-threatening adverse responses including (rapid ventricular rate (in atrial flutter/fibrillation in the presence of an accessory bypass tract), marked hypotension or extreme bradycardia/asystole).
Antiarrhythmics: Digitalis: Intravenous verapamil hydrochloride has been used concomitantly with digitalis preparations. Since both drugs slow AV conduction, patients should be monitored for AV block or excessive bradycardia.
Quinidine: Intravenous verapamil hydrochloride has been administered to a small number of patients receiving oral quinidine. A few cases of hypotension have been reported in patients taking oral quinidine who received intravenous verapamil hydrochloride. Caution should therefore be used when employing this combination of drugs.
Flecainide: A study in healthy volunteers showed that the concomitant administration of flecainide and verapamil hydrochloride may have additive effects reducing myocardial contractility, prolonging AV conduction and prolonging repolarization.
Disopyramide: Until data on possible interactions between verapamil hydrochloride and disopyramide are obtained, disopyramide should not be administered within 48 hours before or 24 hours after verapamil hydrochloride administration.
Beta-adrenergic blocking drugs: Intravenous verapamil hydrochloride has been administered to patients receiving oral beta-blockers. Since both drugs may depress myocardial contractility or AV conduction, the possibility of detrimental interactions should be considered. The concomitant administration of intravenous beta-blockers and intravenous verapamil hydrochloride has resulted in serious adverse reactions (see Contraindications), especially in patients with severe cardiomyopathy, congestive heart failure or recent myocardial infarction.
Effects on ability to drive and use machines: Due to its antihypertensive effect, depending on the individual response, verapamil hydrochloride may affect the ability to react to the point of impairing the ability to drive a vehicle, operate machinery or work under hazardous conditions. This applies all the more at the start of treatment, when the dose is raised, when switching from another drug and in conjunction with alcohol. Verapamil may increase the blood levels of alcohol and slow its elimination. Therefore, the effects of alcohol may be exaggerated.
Use In Pregnancy & Lactation
Pregnancy: Teratogenic Effects: There are no adequate and well-controlled study data in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed (see Pharmacology: Toxicology: Preclinical Safety Data under Actions).
Lactation: Verapamil crosses the placental barrier and can be detected in umbilical vein blood at delivery.
Verapamil hydrochloride/metabolites are excreted in human milk. Limited human data from oral administration has shown that the infant relative dose of verapamil is low (0.1-1% of the mother's oral dose) and that verapamil use may be compatible with breastfeeding.
A risk to the newborns/infants cannot be excluded. Due to the potential for serious adverse reactions in nursing infants, verapamil should only be used during lactation if it is essential for the welfare of the mother.
Lactation: Verapamil crosses the placental barrier and can be detected in umbilical vein blood at delivery.
Verapamil hydrochloride/metabolites are excreted in human milk. Limited human data from oral administration has shown that the infant relative dose of verapamil is low (0.1-1% of the mother's oral dose) and that verapamil use may be compatible with breastfeeding.
A risk to the newborns/infants cannot be excluded. Due to the potential for serious adverse reactions in nursing infants, verapamil should only be used during lactation if it is essential for the welfare of the mother.
Adverse Reactions
The following adverse reactions have been reported with verapamil from clinical studies, postmarketing surveillance or Phase IV clinical trials and are listed as follows by system organ class. Frequencies are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).
The most commonly reported ADRs were headache, dizziness, gastrointestinal disorders: nausea, constipation and abdominal pain, as well as bradycardia, tachycardia, palpitations, hypotension, flushing, edema peripheral and fatigue. (See Table 1.)
Reporting of suspected adverse reactions: Reporting of suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product.
The most commonly reported ADRs were headache, dizziness, gastrointestinal disorders: nausea, constipation and abdominal pain, as well as bradycardia, tachycardia, palpitations, hypotension, flushing, edema peripheral and fatigue. (See Table 1.)
Reporting of suspected adverse reactions: Reporting of suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product.
Drug Interactions
In rare instances, including when patients with severe cardiomyopathy, congestive heart failure or recent myocardial infarction were given intravenous beta-adrenergic blocking agents or disopyramide concomitantly with intravenous verapamil hydrochloride, serious adverse effects have occurred. Concomitant use of verapamil hydrochloride injection with agents that decrease adrenergic function may result in an exaggerated hypotensive response.
In vitro metabolic studies indicate that verapamil hydrochloride is metabolized by cytochrome P450 CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. Verapamil has been shown to be an inhibitor of CYP3A4 enzymes and P-glycoprotein (P-gp). Clinically significant interactions have been reported with inhibitors of CYP3A4 causing elevation of plasma levels of verapamil hydrochloride while inducers of CYP3A4 have caused a lowering of plasma levels of verapamil hydrochloride, therefore, patients should be monitored for drug interactions. Co-administration of verapamil and a drug primarily metabolized by CYP3A4 or being a P-gp substrate may be associated with elevations in drug concentrations that could increase or prolong both therapeutic and adverse effects of the concomitant drug.
The following table provides a list of potential drug interactions due to pharmacokinetic reasons: See Table 2.
Other Drug Interactions and Additional Drug Interaction Information: HIV antiviral agents: Due to the metabolic inhibitory potential of some of the HIV antiviral agents, such as ritonavir, plasma concentrations of verapamil may increase. Caution should be used or the dose of verapamil may be decreased.
Lithium: Increased sensitivity to the effects of lithium (neurotoxicity) has been reported during concomitant verapamil hydrochloride-lithium therapy with either no change or an increase in serum lithium levels. The addition of verapamil hydrochloride, however, has also resulted in the lowering of the serum lithium levels in patients receiving chronic stable oral lithium. Patients receiving both drugs should be monitored carefully.
Neuromuscular blocking agents: Clinical data and animal studies suggest that verapamil hydrochloride may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing). It may be necessary to decrease the dose of verapamil hydrochloride and/or the dose of the neuromuscular blocking agent when the drugs are used concomitantly.
Acetylsalicylic acid: Increased tendency to bleed.
Ethanol (alcohol): Elevation of ethanol plasma levels.
HMG Co-A Reductase Inhibitors ("Statins"): Treatment with HMG CoA reductase inhibitors (e.g. simvastatin, atorvastatin or lovastatin) in a patient taking verapamil should be started at the lowest possible dose and titrated upwards. If verapamil treatment is to be added to patients already taking an HMG CoA reductase inhibitor (e.g. simvastatin, atorvastatin or lovastatin), consider a reduction in the statin dose and retitrate against serum cholesterol concentrations.
Fluvastatin, pravastatin and rosuvastatin are not metabolized by CYP3A4 and are less likely to interact with verapamil.
Antihypertensives, diuretics, vasodilators: Potentiation of the hypotensive effect.
Verapamil hydrochloride (Isoptin) Solution for IV Injection: Protein-bound drugs: As verapamil hydrochloride is highly bound to plasma proteins, it should be administered with caution to patients receiving other highly protein-bound drugs.
Inhalation anesthetics: When used concomitantly, inhalation anesthetics and calcium antagonists, such as verapamil hydrochloride injection, should each be titrated carefully to avoid excessive cardiovascular depression.
In vitro metabolic studies indicate that verapamil hydrochloride is metabolized by cytochrome P450 CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. Verapamil has been shown to be an inhibitor of CYP3A4 enzymes and P-glycoprotein (P-gp). Clinically significant interactions have been reported with inhibitors of CYP3A4 causing elevation of plasma levels of verapamil hydrochloride while inducers of CYP3A4 have caused a lowering of plasma levels of verapamil hydrochloride, therefore, patients should be monitored for drug interactions. Co-administration of verapamil and a drug primarily metabolized by CYP3A4 or being a P-gp substrate may be associated with elevations in drug concentrations that could increase or prolong both therapeutic and adverse effects of the concomitant drug.
The following table provides a list of potential drug interactions due to pharmacokinetic reasons: See Table 2.
Other Drug Interactions and Additional Drug Interaction Information: HIV antiviral agents: Due to the metabolic inhibitory potential of some of the HIV antiviral agents, such as ritonavir, plasma concentrations of verapamil may increase. Caution should be used or the dose of verapamil may be decreased.
Lithium: Increased sensitivity to the effects of lithium (neurotoxicity) has been reported during concomitant verapamil hydrochloride-lithium therapy with either no change or an increase in serum lithium levels. The addition of verapamil hydrochloride, however, has also resulted in the lowering of the serum lithium levels in patients receiving chronic stable oral lithium. Patients receiving both drugs should be monitored carefully.
Neuromuscular blocking agents: Clinical data and animal studies suggest that verapamil hydrochloride may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing). It may be necessary to decrease the dose of verapamil hydrochloride and/or the dose of the neuromuscular blocking agent when the drugs are used concomitantly.
Acetylsalicylic acid: Increased tendency to bleed.
Ethanol (alcohol): Elevation of ethanol plasma levels.
HMG Co-A Reductase Inhibitors ("Statins"): Treatment with HMG CoA reductase inhibitors (e.g. simvastatin, atorvastatin or lovastatin) in a patient taking verapamil should be started at the lowest possible dose and titrated upwards. If verapamil treatment is to be added to patients already taking an HMG CoA reductase inhibitor (e.g. simvastatin, atorvastatin or lovastatin), consider a reduction in the statin dose and retitrate against serum cholesterol concentrations.
Fluvastatin, pravastatin and rosuvastatin are not metabolized by CYP3A4 and are less likely to interact with verapamil.
Antihypertensives, diuretics, vasodilators: Potentiation of the hypotensive effect.
Verapamil hydrochloride (Isoptin) Solution for IV Injection: Protein-bound drugs: As verapamil hydrochloride is highly bound to plasma proteins, it should be administered with caution to patients receiving other highly protein-bound drugs.
Inhalation anesthetics: When used concomitantly, inhalation anesthetics and calcium antagonists, such as verapamil hydrochloride injection, should each be titrated carefully to avoid excessive cardiovascular depression.
Caution For Usage
Incompatibilities: Verapamil hydrochloride will precipitate in any solution with a pH above 6.0.
Verapamil hydrochloride (Isoptin) Solution for IV Injection: For stability reasons verapamil hydrochloride injection is not recommended for dilution with sodium lactate injection, in polyvinyl chloride bags. Admixing intravenous verapamil hydrochloride with albumin, amphotericin B, hydralazine hydrochloride or trimethoprim and sulfamethoxazole should be avoided.
Special precautions for disposal and other handling: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Unused amount of solution should be discarded immediately following withdrawal of any portion of contents in accordance with local requirements.
Verapamil hydrochloride (Isoptin) Solution for IV Injection: For stability reasons verapamil hydrochloride injection is not recommended for dilution with sodium lactate injection, in polyvinyl chloride bags. Admixing intravenous verapamil hydrochloride with albumin, amphotericin B, hydralazine hydrochloride or trimethoprim and sulfamethoxazole should be avoided.
Special precautions for disposal and other handling: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Unused amount of solution should be discarded immediately following withdrawal of any portion of contents in accordance with local requirements.
Storage
Shelf life: Verapamil hydrochloride (Isoptin) 40 mg Film-Coated Tablet: 36 Months.
Verapamil hydrochloride (Isoptin) 80 mg Film-Coated Tablet: 36 Months.
Verapamil hydrochloride (Isoptin SR) 180 mg Sustained-Release Tablet: 36 Months.
Verapamil hydrochloride (Isoptin SR) 240 mg Sustained-Release Tablet: 36 Months.
Verapamil hydrochloride (Isoptin) Solution for IV Injection: 36 Months.
Verapamil hydrochloride injection is physically compatible and chemically stable for at least 24 hours at 25°C protected from light in most common large volume parenteral solutions. Use only if solution is clear and vial seal is intact.
Verapamil hydrochloride (Isoptin) 40 mg & 80 mg Film-Coated Tablet: Store at temperatures not exceeding 30°C.
Verapamil hydrochloride (Isoptin SR) 180 mg Sustained-Release Tablet: Store at temperatures not exceeding 25°C.
Verapamil hydrochloride (Isoptin SR) 240 mg Sustained-Release Tablet: Store at temperatures not exceeding 25°C.
Verapamil hydrochloride (Isoptin) Solution for IV Injection: Store at temperatures not exceeding 30°C.
Verapamil hydrochloride (Isoptin) 80 mg Film-Coated Tablet: 36 Months.
Verapamil hydrochloride (Isoptin SR) 180 mg Sustained-Release Tablet: 36 Months.
Verapamil hydrochloride (Isoptin SR) 240 mg Sustained-Release Tablet: 36 Months.
Verapamil hydrochloride (Isoptin) Solution for IV Injection: 36 Months.
Verapamil hydrochloride injection is physically compatible and chemically stable for at least 24 hours at 25°C protected from light in most common large volume parenteral solutions. Use only if solution is clear and vial seal is intact.
Verapamil hydrochloride (Isoptin) 40 mg & 80 mg Film-Coated Tablet: Store at temperatures not exceeding 30°C.
Verapamil hydrochloride (Isoptin SR) 180 mg Sustained-Release Tablet: Store at temperatures not exceeding 25°C.
Verapamil hydrochloride (Isoptin SR) 240 mg Sustained-Release Tablet: Store at temperatures not exceeding 25°C.
Verapamil hydrochloride (Isoptin) Solution for IV Injection: Store at temperatures not exceeding 30°C.
Action
Pharmacotherapeutic group: Selective calcium channel blockers with direct cardiac effects, phenylalkylamine derivatives. ATC-Code: C08DA01.
Pharmacology: Pharmacodynamics: Verapamil hydrochloride is a white or practically white crystalline powder. It is practically odorless and has a bitter taste. It is soluble in water, freely soluble in chloroform, sparingly soluble in alcohol and practically insoluble in ether.
The chemical name of verapamil hydrochloride is benzeneacetonitrile, α-[3-[{2-(3,4-dimethoxyphenyl)ethyl}methylaminol] propyl]-3,4-dimethoxy-α-(1-methylethyl) hydrochloride.
It has a molecular weight of 491.07 and the molecular formula is C27H38N2O4 • HCl.
Mechanism of action and Pharmacodynamic effects: Verapamil inhibits the calcium ion (and possibly sodium ion) influx through slow channels into conductile and contractile myocardial cells and vascular smooth muscle cells. The antiarrhythmic effect of verapamil appears to be due to its effect on the slow channel in cells of the cardiac conductile system.
Electrical activity through the sinoatrial (SA) and atrioventricular (AV) nodes depends, to a significant degree, upon calcium influx through the slow channel. By inhibiting this influx, verapamil slows AV conduction and prolongs the effective refractory period within the AV node in a rate-related manner. This effect results in a reduction of the ventricular rate in patients with atrial flutter and/or atrial fibrillation and a rapid ventricular response. By interrupting reentry at the AV node, verapamil can restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardias (PSVT), including Wolff-Parkinson-White (W-P-W) syndrome. Verapamil has no effect on conduction across accessory bypass tracts.
Clinical efficacy and safety: Verapamil does not alter the normal atrial action potential or intraventricular conduction time, but depresses amplitude, velocity of depolarization and conduction in depressed atrial fibers.
In the isolated rabbit heart, concentrations of verapamil that markedly affect SA nodal fibers or fibers in the upper and middle regions of the AV node have very little effect on fibers in the lower AV node (NH region) and no effect on atrial action potentials or His bundle fibers.
Verapamil does not induce peripheral arterial spasm nor does it alter total serum calcium levels.
Verapamil reduces afterload and myocardial contractility. In most patients, including those with organic cardiac disease, the negative inotropic action of verapamil is countered by reduction of afterload and cardiac index is usually not reduced, but in patients with moderately severe to severe cardiac dysfunction (pulmonary wedge pressure above 20 mmHg, ejection fraction less than 30%), acute worsening of heart failure may be seen. Peak therapeutic effects occur within three to five minutes after a bolus injection of verapamil.
The commonly used intravenous doses of 5 to 10 mg verapamil hydrochloride produce transient, usually asymptomatic, reduction in normal systemic arterial pressure, systemic vascular resistance and contractility; left ventricular filling pressure is slightly increased.
Pharmacokinetics: Verapamil hydrochloride is a racemic mixture consisting of equal portions of the R-enantiomer and the S-enantiomer. Verapamil is extensively metabolized. Norverapamil is one of 12 metabolites identified in urine, has 10 to 20% of the pharmacologic activity of verapamil and accounts for 6% of excreted drug. The steady-state plasma concentrations of norverapamil and verapamil are similar. Steady state after multiple once daily dosing is reached after three to four days.
Absorption: Verapamil hydrochloride (Isoptin) Film-coated Tablet/(Isoptin SR) Sustained-Release Tablet only: Greater than 90% of verapamil is rapidly absorbed from the small intestine after oral administration. Mean systemic availability of the unchanged compound after a single dose of IR verapamil is 23% and that of SR verapamil approximately 32%, owing to an extensive hepatic first-pass metabolism. Bioavailability is about two times higher with repeated administration. Peak verapamil plasma levels are reached one to two hours after IR administration, and four to five hours after SR administration. The peak plasma concentration of norverapamil is attained approximately one and five hours after IR or SR administration, respectively. The presence of food has no effect on the bioavailability of verapamil.
Distribution (all formulations): Verapamil is widely distributed throughout the body tissues, the volume of distribution ranging from 1.8-6.8 L/kg in healthy subjects. Plasma protein binding of verapamil is approximately 90%.
Metabolism (all formulations): Verapamil is extensively metabolized. In vitro metabolic studies indicate that verapamil is metabolized by cytochrome P450 CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. In healthy men, orally administered verapamil hydrochloride undergoes extensive metabolism in the liver, with 12 metabolites having been identified, most in only trace amounts. The major metabolites have been identified as various N and O-dealkylated products of verapamil. Of these metabolites, only norverapamil has any appreciable pharmacological effect (approximately 20% that of the parent compound), which was observed in a study with dogs.
Elimination (all formulations): Following intravenous infusion, verapamil is eliminated bi-exponentially, with a rapid early distribution phase (half-life about four minutes) and a slower terminal elimination phase (half-life two to five hours). Following oral administration, the elimination half-life is three to seven hours. Approximately 50% of an administered dose is eliminated renally within 24 hours, 70% within five days. Up to 16% of a dose is excreted in the feces. About 3% to 4% of renally excreted drug is excreted as unchanged drug. The total clearance of verapamil is nearly as high as the hepatic blood flow, approximately 1 L/h/kg (range: 0.7-1.3 L/h/kg).
Special Populations: Pediatric: Limited information on the pharmacokinetics in the pediatric population is available. After intravenous dosing, the mean half-life of verapamil was 9.17 hours and the mean clearance was 30 L/h, whereas it is around 70 L/h for a 70-kg adult. Steady-state plasma concentrations appear to be somewhat lower in the pediatric population after oral dosing compared to those observed in adults.
Geriatric: Aging may affect the pharmacokinetics of verapamil given to hypertensive patients. Elimination half-life may be prolonged in the elderly. The antihypertensive effect of verapamil was found not to be age-related.
Renal insufficiency: Impaired renal function has no effect on verapamil pharmacokinetics, as shown by comparative studies in patients with end-stage renal failure and subjects with healthy kidneys. Verapamil and norverapamil are not significantly removed by hemodialysis.
Hepatic insufficiency: The half-life of verapamil is prolonged in patients with impaired liver function owing to lower oral clearance and a higher volume of distribution.
Toxicology: Preclinical safety data: Reproduction studies have been performed in rabbits and rats at oral verapamil doses up to 180mg/m2/day and 360 mg/m2/day (compared to a maximum recommended human oral daily dose of 300 mg/m2) and have revealed no evidence of teratogenicity. In the rat, however, a dose similar to the clinical dose (360 mg/m2) was embryocidal and retarded fetal growth and development. These effects occurred in the presence of maternal toxicity (reflected by reduced food consumption and weight gain of dams). This oral dose has also been shown to cause hypotension in rats.
There are, however, no adequate and well-controlled studies in pregnant women.
Pharmacology: Pharmacodynamics: Verapamil hydrochloride is a white or practically white crystalline powder. It is practically odorless and has a bitter taste. It is soluble in water, freely soluble in chloroform, sparingly soluble in alcohol and practically insoluble in ether.
The chemical name of verapamil hydrochloride is benzeneacetonitrile, α-[3-[{2-(3,4-dimethoxyphenyl)ethyl}methylaminol] propyl]-3,4-dimethoxy-α-(1-methylethyl) hydrochloride.
It has a molecular weight of 491.07 and the molecular formula is C27H38N2O4 • HCl.
Mechanism of action and Pharmacodynamic effects: Verapamil inhibits the calcium ion (and possibly sodium ion) influx through slow channels into conductile and contractile myocardial cells and vascular smooth muscle cells. The antiarrhythmic effect of verapamil appears to be due to its effect on the slow channel in cells of the cardiac conductile system.
Electrical activity through the sinoatrial (SA) and atrioventricular (AV) nodes depends, to a significant degree, upon calcium influx through the slow channel. By inhibiting this influx, verapamil slows AV conduction and prolongs the effective refractory period within the AV node in a rate-related manner. This effect results in a reduction of the ventricular rate in patients with atrial flutter and/or atrial fibrillation and a rapid ventricular response. By interrupting reentry at the AV node, verapamil can restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardias (PSVT), including Wolff-Parkinson-White (W-P-W) syndrome. Verapamil has no effect on conduction across accessory bypass tracts.
Clinical efficacy and safety: Verapamil does not alter the normal atrial action potential or intraventricular conduction time, but depresses amplitude, velocity of depolarization and conduction in depressed atrial fibers.
In the isolated rabbit heart, concentrations of verapamil that markedly affect SA nodal fibers or fibers in the upper and middle regions of the AV node have very little effect on fibers in the lower AV node (NH region) and no effect on atrial action potentials or His bundle fibers.
Verapamil does not induce peripheral arterial spasm nor does it alter total serum calcium levels.
Verapamil reduces afterload and myocardial contractility. In most patients, including those with organic cardiac disease, the negative inotropic action of verapamil is countered by reduction of afterload and cardiac index is usually not reduced, but in patients with moderately severe to severe cardiac dysfunction (pulmonary wedge pressure above 20 mmHg, ejection fraction less than 30%), acute worsening of heart failure may be seen. Peak therapeutic effects occur within three to five minutes after a bolus injection of verapamil.
The commonly used intravenous doses of 5 to 10 mg verapamil hydrochloride produce transient, usually asymptomatic, reduction in normal systemic arterial pressure, systemic vascular resistance and contractility; left ventricular filling pressure is slightly increased.
Pharmacokinetics: Verapamil hydrochloride is a racemic mixture consisting of equal portions of the R-enantiomer and the S-enantiomer. Verapamil is extensively metabolized. Norverapamil is one of 12 metabolites identified in urine, has 10 to 20% of the pharmacologic activity of verapamil and accounts for 6% of excreted drug. The steady-state plasma concentrations of norverapamil and verapamil are similar. Steady state after multiple once daily dosing is reached after three to four days.
Absorption: Verapamil hydrochloride (Isoptin) Film-coated Tablet/(Isoptin SR) Sustained-Release Tablet only: Greater than 90% of verapamil is rapidly absorbed from the small intestine after oral administration. Mean systemic availability of the unchanged compound after a single dose of IR verapamil is 23% and that of SR verapamil approximately 32%, owing to an extensive hepatic first-pass metabolism. Bioavailability is about two times higher with repeated administration. Peak verapamil plasma levels are reached one to two hours after IR administration, and four to five hours after SR administration. The peak plasma concentration of norverapamil is attained approximately one and five hours after IR or SR administration, respectively. The presence of food has no effect on the bioavailability of verapamil.
Distribution (all formulations): Verapamil is widely distributed throughout the body tissues, the volume of distribution ranging from 1.8-6.8 L/kg in healthy subjects. Plasma protein binding of verapamil is approximately 90%.
Metabolism (all formulations): Verapamil is extensively metabolized. In vitro metabolic studies indicate that verapamil is metabolized by cytochrome P450 CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. In healthy men, orally administered verapamil hydrochloride undergoes extensive metabolism in the liver, with 12 metabolites having been identified, most in only trace amounts. The major metabolites have been identified as various N and O-dealkylated products of verapamil. Of these metabolites, only norverapamil has any appreciable pharmacological effect (approximately 20% that of the parent compound), which was observed in a study with dogs.
Elimination (all formulations): Following intravenous infusion, verapamil is eliminated bi-exponentially, with a rapid early distribution phase (half-life about four minutes) and a slower terminal elimination phase (half-life two to five hours). Following oral administration, the elimination half-life is three to seven hours. Approximately 50% of an administered dose is eliminated renally within 24 hours, 70% within five days. Up to 16% of a dose is excreted in the feces. About 3% to 4% of renally excreted drug is excreted as unchanged drug. The total clearance of verapamil is nearly as high as the hepatic blood flow, approximately 1 L/h/kg (range: 0.7-1.3 L/h/kg).
Special Populations: Pediatric: Limited information on the pharmacokinetics in the pediatric population is available. After intravenous dosing, the mean half-life of verapamil was 9.17 hours and the mean clearance was 30 L/h, whereas it is around 70 L/h for a 70-kg adult. Steady-state plasma concentrations appear to be somewhat lower in the pediatric population after oral dosing compared to those observed in adults.
Geriatric: Aging may affect the pharmacokinetics of verapamil given to hypertensive patients. Elimination half-life may be prolonged in the elderly. The antihypertensive effect of verapamil was found not to be age-related.
Renal insufficiency: Impaired renal function has no effect on verapamil pharmacokinetics, as shown by comparative studies in patients with end-stage renal failure and subjects with healthy kidneys. Verapamil and norverapamil are not significantly removed by hemodialysis.
Hepatic insufficiency: The half-life of verapamil is prolonged in patients with impaired liver function owing to lower oral clearance and a higher volume of distribution.
Toxicology: Preclinical safety data: Reproduction studies have been performed in rabbits and rats at oral verapamil doses up to 180mg/m2/day and 360 mg/m2/day (compared to a maximum recommended human oral daily dose of 300 mg/m2) and have revealed no evidence of teratogenicity. In the rat, however, a dose similar to the clinical dose (360 mg/m2) was embryocidal and retarded fetal growth and development. These effects occurred in the presence of maternal toxicity (reflected by reduced food consumption and weight gain of dams). This oral dose has also been shown to cause hypotension in rats.
There are, however, no adequate and well-controlled studies in pregnant women.
MedsGo Class
Calcium Antagonists
Features
Brand
Isoptin SR
Full Details
Dosage Strength
180 mg
Drug Ingredients
- Verapamil
Drug Packaging
Sustained Release Tablet 30's
Generic Name
Verapamil Hcl
Dosage Form
Sustained Release Tablet
Registration Number
DR-XY42927
Drug Classification
Prescription Drug (RX)
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