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Verapamil Hydrochloride

Pronunciation

Class: Calcium-Channel Blocking Agents, Miscellaneous
VA Class: CV200
CAS Number: 152-11-4
Brands: Calan, Covera-HS, Isoptin SR, Tarka, Verelan

Introduction

Calcium-channel blocking agent; nondihydropyridine.353 401

Uses for Verapamil Hydrochloride

Supraventricular Tachyarrhythmias

IV management of supraventricular tachyarrhythmias, including rapid conversion to sinus rhythm of paroxysmal supraventricular tachycardias (PSVT) (e.g., those associated with Wolff-Parkinson-White or Lown-Ganong-Levine syndrome) and temporary control of rapid ventricular rate in atrial flutter or fibrillation.b 401

One of several preferred antiarrhythmic agents for the treatment of stable, narrow-complex supraventricular tachycardias (e.g., PSVT [reentry supraventricular tachycardia], ectopic or multifocal atrial tachycardia, junctional tachycardia) if the rhythm is not controlled by vagal maneuvers or adenosine and to control the ventricular response rate in atrial fibrillation or flutter when impaired ventricular function or heart failure is not present.401 Use only in patients with narrow-complex reentry SVT or arrhythmias known with certainty to be of supraventricular origin.401

An oral treatment of choice to prevent recurrent PSVT.118 171 181 182 183 184 185 186 187 188

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Oral management (alone172 173 174 176 177 178 or in combination with a cardiac glycoside) to control ventricular rate at rest and during stress in patients with chronic atrial fibrillation and/or flutter.118 171 172 173 174 175 176 177 178 179 180 181 182

Angina

Oral management of unstable or chronic stable angina pectoris.118 362

A drug of choice for the management of Prinzmetal variant angina.b

Hypertension

Oral management of hypertension (alone or in combination with other classes of antihypertensive agents).207 352 362 376

One of several preferred initial therapies in hypertensive patients with a high risk of developing coronary artery disease and/or diabetes mellitus.392

JNC 7 recommends that thiazides be used as initial therapy for the treatment of uncomplicated hypertension in most patients, either alone or combined with other classes of antihypertensive drugs with demonstrated benefit (e.g., ACE inhibitors, angiotensin II receptor antagonists, β-blockers, calcium-channel blockers).167 217 243 392

Hypertrophic Cardiomyopathy

Has been used as adjunctive therapy in the management of hypertrophic cardiomyopathy.266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 297

Recommended only when no other suitable agents are available.153 266 273 278 (See Hypertrophic Cardiomyopathy under Cautions.)

AMI

Can be considered for secondary prevention of AMI as an alternative to β-blockers (when β-blockers are contraindicated or poorly tolerated) in patients with preserved left ventricular function.358 (See Contraindications under Cautions.)

Bipolar Disorder

Has been used for management of manic manifestations of bipolar disorder;139 145 146 147 148 149 150 151 152 other more effective agents (e.g., lithium) available.b

Verapamil Hydrochloride Dosage and Administration

General

  • Individualize dosage according to patient response.b

Hypertension

  • Extended-release capsules or tablets, extended-release core tablets, or controlled extended-release capsules preferably353 should be used for management of hypertension.117 119 207 208 229 302 349 353 376

  • Fixed-combination verapamil/trandolapril tablets should not be used for initial treatment of hypertension.352

Supraventricular Tachyarrhythmias

  • Proper diagnosis and differentiation from wide-complex supraventricular tachycardia is imperative when administration of IV verapamil is considered.382 (See Contraindications under Cautions.)

Administration

Administer orally or by direct IV injection.b 401

Oral Administration

Extended-release Capsules (Verelan)

Administer orally once daily302 without regard to meals.b

Swallow capsules whole; do not chew or divide.302

Alternatively, open capsule and sprinkle contents (pellets) on a small amount of applesauce; swallow immediately without chewing.302 Follow with glass of cool water to ensure complete ingestion.302 Do not store mixture of applesauce and pellets for future use.302

Controlled Extended-release Capsules (Verelan PM)

Administer orally once daily at bedtime376 without regard to meals.b

Conventional Tablets (Calan)

Administer orally 2–4 times daily118 199 214 215 222 392 without regard to meals.b

Extended-release Tablets (Calan SR, Isoptin SR)

Administer orally once daily in the morning with food.117 207

Extended-release tablets are scored117 207 and may be halved without affecting oral bioavailability.b

Extended-release Core Tablets (Covera-HS)

Administer orally once daily at bedtime362 without regard to meals.b

Swallow tablets whole; do not break, chew, or crush.362

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Monitor BP and ECG continuously during IV therapy.382

Rate of Administration

Administer slowly by direct IV injection over ≥2 minutes or, in geriatric patients, ≥3 minutes.382 401

Dosage

Available as verapamil hydrochloride; dosage expressed in terms of the salt.117 118 207 241 302 350

Pediatric Patients

Supraventricular Tachyarrhythmias

See Pediatric Use under Cautions.

Conversion of PSVT to Sinus Rhythm
IV

Children 1–15 years of age: Initially, 0.1–0.3 mg/kg (maximum 5 mg; usual single dose range: 2–5 mg), given by IV injection over ≥2 minutes.382

If initial response is not adequate, may administer an additional 0.1–0.3 mg/kg (usual single dose range: 2–5 mg) 30 minutes after the first dose; maximum single dose of 10 mg.382

Ventricular Rate Control in Atrial Fibrillation or Flutter
IV

Children 1–15 years of age: Initially, 0.1–0.3 mg/kg (maximum 5 mg; usual single dose range: 2–5 mg), given by IV injection over ≥2 minutes.382

If initial response is not adequate, may administer an additional 0.1–0.3 mg/kg (usual single dose range: 2–5 mg) 30 minutes after the first dose; maximum single dose of 10 mg.382

Adults

Supraventricular Tachyarrhythmias
PSVT Prophylaxis
Oral

Usual dosage: 240–480 mg daily given in 3 or 4 divided doses as conventional tablets (Calan).118

PSVT, Junctional Tachycardia, Ectopic Tachycardia, Multifocal Atrial Tachycardia)
IV

Initially, 5–10 mg (0.075–0.15 mg/kg) given by IV injection over ≥2 minutes.382

If the patient tolerates but does not respond adequately to the initial IV dose, a second IV dose of 10 mg (0.15 mg/kg) may be given 30 minutes after the initial dose.382

Some experts recommend an initial IV dose of 2.5–5 mg administered over 2 minutes.401 If response is inadequate (i.e., conversion to normal sinus rhythm does not occur), give 5–10 mg every 15–30 minutes to a total dose of 20 mg.401 Alternatively, give 5 mg every 15 minutes to a total dose of 30 mg.401

Ventricular Rate Control in Atrial Fibrillation or Flutter
Oral

Usual dosage: 240–320 mg daily given in 3 or 4 divided doses as conventional tablets (Calan).118

IV

Initially, 5–10 mg (0.075–0.15 mg/kg) given by IV injection over ≥2 minutes.382

If the patient tolerates but does not respond adequately to the initial IV dose, a second IV dose of 10 mg (0.15 mg/kg) may be given 30 minutes after the initial dose.382

Some experts recommend an initial IV dose of 2.5–5 mg administered over 2 minutes.401 If response is inadequate, give 5–10 mg every 15–30 minutes to a total dose of 20 mg.401 Alternatively, give 5 mg every 15 minutes to a total dose of 30 mg.401

Angina
Oral

Usual initial dosage: 80 mg 3 or 4 times daily as conventional tablets (Calan).118 b Gradually increase dosage by 80-mg increments at weekly intervals or, in patients with unstable angina, at daily intervals until optimum control of angina is obtained.118

Alternatively, usual initial dosage of 180 mg at bedtime as extended-release core tablets (Covera-HS).349 If adequate response does not occur, may increase dosage to 240 mg daily, and subsequently by 120-mg increments to 480 mg daily at bedtime.349

Hypertension
Monotherapy
Oral

Recommended dosages vary by formulation. Adjust dosage at approximately monthly intervals (more aggressively in high-risk patients) to achieve BP control.392

When switching from conventional tablets (Calan) to extended-release capsules (Verelan) or tablets (Calan SR, Isoptin SR), can use same total daily dosage.117 302

Table 1. Recommended Dosages for Management of Hypertension

Formulation

Initial Dosage

Dosage Titration Regimen

Controlled extended-release capsules (Verelan PM)

200 mg once daily at bedtime376

Manufacturer states that dosage may be increased to 300 mg once daily and then to 400 mg once daily, if required376

JNC 7 recommends usual range of 120–360 mg once daily392

Extended-release capsules (Verelan)

120 mg once daily in the morning302

Manufacturer states that dosage may be increased to 180 mg once daily and then to 240 mg once daily, with subsequent increases in 120-mg increments to 480 mg once daily, if required302

120–240 mg once dailyb

Conventional tablets (Calan)

80 mg 3 times daily118

JNC 7 recommends usual range of 80–320 mg daily, given in 2 divided doses392

Extended-release tablets (CalanSR, Isoptin SR)

180 mg once daily in the morning117

Increase dosage to 240 mg each morning117

Subsequently, increase dosage to 360 mg daily, given in 2 divided doses (either 180 mg in the morning + 180 mg in the evening or 240 mg in the morning + 120 mg in the evening)117

Manufacturer states that dosage may be increased to 240 mg every 12 hours, if required117

JNC 7 recommends usual range of 120–360 mg daily, given in 1 or 2 divided doses392

Extended-release core tablets (Covera-HS)

180 mg once daily at bedtime362

Manufacturer states that dosage may be increased to 240 mg once daily, with subsequent increases to 360 mg once daily and then to 480 mg once daily, if required362

JNC 7 recommends usual range of 120–360 mg once daily392

Combination Therapy
Oral

If BP is not adequately controlled by monotherapy with verapamil (up to 240 mg daily) or trandolapril (up to 8 mg daily), can switch to fixed-combination tablets using tablets containing the same component doses.352

Special Populations

Hepatic Impairment

Reduce usual daily doses by up to 60–70% in patients with severe hepatic dysfunction.b

Angina
Oral

Usual dosage in patients with decreased hepatic function: 40 mg (as conventional tablets) 3 times daily.118

Hypertension
Oral

Controlled extended-release capsules (VerelanPM): Manufacturer states that initial dosage of 100 mg daily at bedtime rarely may be necessary in patients with impaired hepatic function.376

Renal Impairment

Supplemental doses not necessary in patients undergoing hemodialysis.117 118 281 290

Hypertension
Oral

Controlled extended-release capsules (VerelanPM): Manufacturer states that initial dosage of 100 mg daily at bedtime rarely may be necessary in patients with impaired renal function.376

Geriatric Patients

Supraventricular Tachyarrhythmias

Use slower infusion rates (over ≥3 minutes) in geriatric patients in order to minimize risk of adverse effects.382

Angina

Usual dosage: 40 mg (as conventional tablets) 3 times daily.118 b

Hypertension

Lower initial dosage recommended for treatment of hypertension in geriatric patients.117 118 207 302 376

Table 2. Recommended Initial Dosages for Management of Hypertension in Geriatric Patients

Formulation

Initial Dosage

Extended-release capsules (Verelan)

120 mg once daily in the morning302

Controlled extended-release capsules (Verelan PM)

100 mg daily at bedtime may rarely be necessary376

Conventional tablets (Calan)

40 mg 3 times daily118 119 214 215 222

Extended-release tablets (CalanSR, Isoptin)

120 mg once daily in the morning117 207

Small-stature Patients

Hypertension

Lower initial dosage recommended for treatment of hypertension in patients with small stature.117 118 207 302 376

Table 3. Recommended Initial Dosages for Management of Hypertension in Small-stature Patients

Formulation

Initial Dosage

Extended-release capsules (Verelan)

120 mg once daily in the morning302

Controlled extended-release capsules (Verelan PM)

100 mg daily at bedtime may rarely be necessary376

Conventional tablets (Calan)

40 mg 3 times daily118

Extended-release tablets (CalanSR, Isoptin)

120 mg once daily in the morning117 207

Cautions for Verapamil Hydrochloride

Contraindications

  • Severe left ventricular dysfunctionb (unless CHF is secondary to a supraventricular tachycardia amenable to verapamil therapy).382

  • Severe hypotension (SBP <90 mm Hg) or cardiogenic shock.118 b

  • Sick sinus syndrome (unless a functioning artificial ventricular pacemaker is present).118 b

  • Second- or third-degree AV block (unless a functioning artificial ventricular pacemaker is present).118 b

  • Atrial flutter or fibrillation associated with an accessory bypass tract (e.g., Wolff-Parkinson-White or Lown-Ganong-Levine syndrome).118 382 b

  • Patients currently receiving, or having recently received (i.e., within a few hours of IV verapamil therapy), IV β-adrenergic blocker therapy.382

  • Use of IV verapamil in patients with wide-complex ventricular tachycardia (QRS ≥0.12 seconds).382 (See Wide-Complex Ventricular Tachycardia under Cautions.)

  • Known hypersensitivity to verapamil or any ingredient in the formulation.118 382 b

Warnings/Precautions

Warnings

Cardiac Failure

Possible precipitation or acute worsening of CHF.117 118 207 376

Avoid use in patients with severe left ventricular dysfunction (e.g., pulmonary wedge pressure >20 mm Hg, ejection fraction <30%),117 118 207 unless the heart failure is caused by a supraventricular tachycardia amenable to verapamil therapy382 b or in patients with moderate to severe symptoms of cardiac failure.

Avoid use in patients with any degree of ventricular dysfunction who are receiving a β-adrenergic blocker concomitantly.117 118 207 376 382

Adequate treatment (e.g., with a cardiac glycoside and/or diuretic) recommended prior to initiation of verapamil therapy in patients with milder ventricular dysfunction.117 118 207 376

Wide-complex Ventricular Tachycardia

Possibly marked hemodynamic deterioration and ventricular fibrillation associated with use of IV verapamil in patients with wide-complex ventricular tachycardia (QRS of ≥0.12 seconds); IV verapamil contraindicated in these patients.382

Hypotension

Possible hypotension;117 118 207 376 monitor BP carefully.b

Hepatic Effects

Possible hepatocellular toxicity; monitor liver function tests periodically.117 118 207 376

Possible increases in serum AST/ALT concentrations with or without concomitant increases in alkaline phosphatase and bilirubin concentrations; may resolve despite continued therapy.117 118 207 376

Accessory Bypass Tract

Possible life-threatening ventricular fibrillation and/or cardiac arrest precipitated by accelerated AV conduction in patients with atrial flutter and/or fibrillation with an accessory bypass tract (Wolff-Parkinson-White or Lown-Ganong Levine syndrome); use contraindicated in these patients.117 118 207 376 382 b 401

Extreme Bradycardia/Asystole

Possible second- or third-degree AV block, bradycardia, or asystole, particularly in patients with sick sinus syndrome; use contraindicated in patients with sick sinus syndrome (unless a functioning artificial ventricular pacemaker is present).382

AV Block

Possible first-degree AV block or progression to second- or third-degree AV block; generally responds to discontinuance of IV verapamil, reduction of oral verapamil dosage, or, in the case of increased ventricular response rate, to cardioversion.118 382 b

If severe AV block occurs, discontinue the drug and initiate appropriate treatment (e.g., IV atropine, isoproterenol, calcium) as needed.382 b

Hypertrophic Cardiomyopathy

Possibly serious and sometimes fatal adverse cardiovascular effects (e.g., pulmonary edema, hypotension, second-degree AV block, sinus arrest) in patients with hypertrophic cardiomyopathy; use with caution in these patients.118 207 b

Duchenne’s Muscular Dystrophy

Possible precipitation of respiratory muscle failure with IV verapamil in patients with Duchenne’s muscular dystrophy; use with caution.382

Increased Intracranial Pressure

Possible increased intracranial pressure with IV verapamil in patients with supratentorial tumors at the time of anesthesia induction; use caution and monitor carefully.382

General Precautions

GI Effects

Certain extended-release tablets (e.g., Covera-HS) are nondeformable; use with caution in patients with preexisting severe GI narrowing.349

Use of Fixed Combinations

When verapamil is used in fixed combination with trandolapril, consider the cautions, precautions, and contraindications associated with trandolapril.352

Specific Populations

Pregnancy

Category C.117 118

Lactation

Distributed into milk; discontinue nursing or the drug.117 118

Pediatric Use

Possibly severe adverse cardiovascular effects (e.g., refractory hypotension, cardiac arrest) following IV administration of verapamil in neonates and infants.382 401 If used in children, caution advised.382 401 Some experts state that verapamil should not be used in infants.401

Safety and efficacy of oral verapamil not established in children <18 years of age.117 118 207 302 362 376

Geriatric Use

Consider the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.c Select dosage with caution;302 376 c titrate dosage carefully.c

Hepatic Impairment

Severe hepatic impairment prolongs elimination half-life of verapamil.118 207 (See Elimination: Special Populations, under Pharmacokinetics.) Dosage adjustments may be necessary.118 207 (See Hepatic Impairment under Dosage and Administration.)

Use with caution and with close monitoring for prolongation of the PR interval on ECG, BP changes, or other signs of overdosage.118 382 b

Renal Impairment

Use with caution and with close monitoring for prolongation of the PR interval on ECG, BP changes, or other signs of overdosage.117 118 382 b

Common Adverse Effects

Constipation,207 362 dizziness,207 362 382 nausea,207 362 382 hypotension,207 362 382 headache.207 362 382

Interactions for Verapamil Hydrochloride

Metabolized principally by CYP3A4, 1A2, and 2C.c

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inducers: Possible decreased plasma verapamil concentrations.c

CYP3A4 inhibitors: Possible increased plasma verapamil concentrations.c

Protein-bound Drugs

Potential for verapamil to be displaced from binding sites by, or to displace from binding sites, other protein-bound drugs.b Use with caution.b

Specific Drugs and Foods

Drug or Food

Interaction

Comment

ACE inhibitors

Additive hypotensive effectsb

Usually used to therapeutic advantage; monitor BPb

α-Adrenergic blocking agents (e.g., prazosin)

Increased hypotensive effect, possibly excessive in some patients118

β-Adrenergic blocking agents

(see entries for atenolol, metoprolol, and propranolol)

Additive negative effects on myocardial contractility, heart rate, and AV conduction356 357

Excessive bradycardia and AV block, including complete heart block, reported in hypertensive patientsb

Use with caution for oral management of hypertension; monitor closelyb

Concomitant use of IV verapamil and an IV β-adrenergic blocking agent within a few hours of each other is contraindicatedb

Alcohol

Inhibition of ethanol elimination, resulting in increased blood ethanol concentrations and prolonged intoxicating effects362 385 c

Antineoplastic agents

Increased serum concentrations and efficacy of doxorubicin376

Decreased verapamil absorption when used with COPP (cyclophosphamide, vincristine, procarbazine, prednisone) or VAC (vindesine, doxorubicin, cisplatin) regimen376

Decreased paclitaxel clearance (interaction with R-verapamil)376

Anesthetics, inhalation

Potentiation of cardiovascular depressionb

Titrate dosages carefullyb

Aspirin

Increased bleeding timesc

Atenolol

(see entry for β-Adrenergic blocking agents)

Pharmacokinetic interaction unlikely141 142

Carbamazepine

Increased plasma carbamazepine concentrations and subsequent toxicity104 105 106

Reduce carbamazepine dosage by 40–50% after initiating verapamil therapy104 105

Monitor for carbamazepine toxicity (e.g., diplopia, headache, ataxia, dizziness)104 105 362

Cimetidine

Variable effects on verapamil clearance and oral bioavailability reported109 110 111 112 113 114 117 118 207 362

Monitor for changes in verapamil's therapeutic and toxic effects if cimetidine is added to or eliminated from regimen109 110 362

Cyclosporine

Increased blood cyclosporine concentrations117 118 294 295 296

Monitor for cyclosporine toxicity294 296

Dantrolene

Cardiovascular collapse following concomitant use of IV verapamil and IV dantrolene in animalsb

Clinical relevance to humans unknownb

Digoxin

Increased serum digoxin concentrations and digoxin toxicity207 244 b

Monitor serum digoxin concentrations carefully and reduce digoxin dosage as necessary;b observe closely for digoxin toxicityb

Disopyramide

Possible additive effects and impairment of left ventricular functionb

Discontinue disopyramide 48 hours prior to initiating verapamil; do not reinstitute until 24 hours after verapamil has been discontinuedb

Diuretics

Additive hypotensive effectsb

Usually used to therapeutic advantage; monitor BPb

Erythromycin

Increased plasma verapamil concentrationsc

Flecainide

Possible additive effects on myocardial contractility, AV conduction, and repolarization;117 118 241 possible additive negative inotropic effect and prolongation of AV conduction362

Avoid concomitant use unless potential benefits outweigh risks292 293

Grapefruit juice

Increased plasma verapamil concentrationsc

Not considered clinically importantc

Lithium

Possible increased, decreased, or unchanged serum lithium concentrations;117 118 132 133 207 241 362 possible increased sensitivity to lithium’s neurotoxic effects207

Monitor for lithium toxicity;207 monitor serum lithium concentrations; adjust dosage as necessary117 118 132 133 207 241 362

Metoprolol

(see entry for β-Adrenergic blocking agents)

Increased oral bioavailability of metoprolol117 118 141 142 143 207

Avoid concomitant use, if possible;141 142 if used concomitantly, adjust metoprolol dosage and monitor patient closely142

Concomitant use of IV verapamil and IV metoprolol within a few hours of each other is contraindicatedb

Neuromuscular blocking agents

Potentiation of neuromuscular blockadeb

Monitor neuromuscular function; decrease dosage of verapamil and/or neuromuscular blocking agent as necessaryb

Nitrates

Possible additive beneficial effects; undesirable interactions unlikely376

Phenobarbital

Increased clearance of total and unbound verapamil,207 302 303 305 possibly via induction of hepatic metabolism303 304

Adjust verapamil dosage as necessary305

Propranolol

(see entry for β-Adrenergic blocking agents)

Increased incidence of CHF, arrhythmia, and severe hypotension, particularly if IV route or high propranolol dosages are used or if patient has moderately severe or severe CHF, severe cardiomyopathy, or recent MIb

Use with caution for oral management of hypertension; monitor closelyb

Concomitant use of IV verapamil and IV propranolol within a few hours of each other is contraindicatedb

Quinidine

Additive adrenergic blocking activity at α1- and α2-receptors154

Hypotensive effect in patients with hypertrophic cardiomyopathy117 118 153 207

Verapamil counteracts the effects of quinidine on AV conduction362

Possible increased plasma quinidine concentrations117 118 155 207

Avoid concomitant use in patients with hypertrophic cardiomyopathyb

Rifampin

Decreased oral bioavailability of verapamil117 118 134 135 136 137 138 207

Monitor closely if rifampin is added to or eliminated from regimen; adjust verapamil dosage as necessary134 135 136 137 138

Ritonavir

Increased plasma verapamil concentrationsc

Theophylline

Decreased clearance, elevated serum concentrations, and prolonged serum half-life of theophylline117 310 311 312 313

Monitor for theophylline toxicity312 313

Timolol, ophthalmic

Severe bradycardia 207 242 243 (associated with wandering atrial pacemaker 207 242 and transient asystole) reported243

Use with caution243

Vasodilators

Additive hypotensive effectsb

Usually used to therapeutic advantage; monitor BPb

Verapamil Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration as conventional tablets, but only about 20–35% of an oral dose reaches systemic circulation as unchanged drug because of first-pass metabolism.118 b

Oral bioavailability of extended-release capsules or tablets is comparable to that of conventional tablets following administration under fasting conditions.117 207 302

Peak plasma concentrations for conventional tablets are attained within 1–2 hours.118 b

Peak plasma concentrations for extended-release capsules or tablets are attained within 7–9 or 4–8 hours, respectively.b

Peak plasma concentrations for extended-release core tablets or controlled extended-release capsules are attained within about 11 hours.b

Onset

Antihypertensive effect evident within 1 week.118

Maximum antiarrhythmic effects generally are apparent within 48 hours after initiating a given oral verapamil dosage.118

After a single IV injection, hemodynamic effects peak within 5 minutes; effects on AV node occur within 1–2 minutes and peak at 10–15 minutes.382 b Conversion of PSVT to sinus rhythm generally occur rapidly (usually within 10 minutes following administration).382 b

Duration

After a single IV injection, hemodynamic effects generally persist for 10–20 minutes; effects on AV node usually persist for 30–60 minutes but may persist for up to 6 hours.b

Slowing of the ventricular rate in patients with atrial fibrillation or flutter generally persists for 30–60 minutes following a single IV injection.382

Food

Food decreases the rate and extent of absorption of extended-release tablets but produces smaller differences between peak and trough plasma concentrations of the drug.117 207

Food does not appear to substantially affect the absorption of conventional tablets,121 extended-release capsules,302 extended-release core tablets,349 or controlled extended-release capsules.376

Plasma Concentrations

Plasma concentrations >100 ng/mL usually are required for acute antiarrhythmic effect.b

PR-interval prolongation linearly correlates with plasma concentrations ranging from 10–250 ng/mL during initial dose titration, but this correlation may disappear during chronic therapy.b

Special Populations

In patients with hepatic dysfunction (e.g., cirrhosis), oral bioavailability may be substantially increased.127 128 129

Distribution

Extent

Verapamil and norverapamil distribute into the CNS.115 117 118 207

Verapamil crosses the placenta and is present in umbilical vein blood at delivery.b

Verapamil distributes into milk;103 117 118 207 122 123 124 concentrations in breast milk are similar to those in maternal plasma in some women.122 123 124

Plasma Protein Binding

Approximately 90%.118 b

Elimination

Metabolism

Rapidly and almost completely metabolized in the liver, principally by CYP3A4, 1A2, and 2C, to at least 12 dealkylated or demethylated metabolites; principal metabolite (norverapamil) has approximately 20% of the cardiovascular activity of verapamil.b c

Undergoes stereoselective first-pass metabolism, with the l-isomer being preferentially metabolized.101 102 127

Elimination Route

Eliminated mainly in urine (70%) and feces (16%).362 376 Only 3–4% of a dose is excreted in urine as unchanged drug.362 376

Neither verapamil nor norverapamil is appreciably removed by hemodialysis.117 118 281 290

Half-life

Biphasic or triphasic following IV administration; terminal elimination half-life is 2–8 hours.382 b

Plasma half-life of 2–8 or 4.5–12 hours after single oral dose or multiple oral doses, respectively.b

Special Populations

In patients with hepatic cirrhosis, plasma half-life is increased to 14–16 hours.118 b

In geriatric patients, plasma elimination half-life appears to be increased and clearance decreased.126 207

In infants, verapamil metabolism may differ.b Elimination half-life of 4.4–6.9 hours reported.125

Stability

Storage

Oral

Capsules and Tablets

Tightly closed container at room temperature (approximately 25°C); generally should be protected from light and moisture.117 118 207 302 362 376 Consult individual manufacturer's labeling for specific storage instructions.

Parenteral

Injection

15–30°C.382 Store ampuls and vials in carton to protect from light.382

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Will precipitate in any solution with a pH>6.382

Solution CompatibilityHID

Compatible

Dextran 40 10% in sodium chloride 0.9%

Dextrose 5% in Ringer’s injection

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% in sodium chloride 0.45 or 0.9%

Dextrose 5% in water

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Sodium lactate (1/6) M

Drug Compatibility
Admixture CompatibilityHID

Compatible

Amikacin sulfate

Amiodarone HCl

Ascorbic acid injection

Atropine sulfate

Calcium chloride

Calcium gluconate

Cefazolin sodium

Cefotaxime sodium

Cefoxitin sodium

Chloramphenicol sodium succinate

Clindamycin phosphate

Dexamethasone sodium phosphate

Diazepam

Digoxin

Dopamine HCl

Epinephrine HCl

Erythromycin lactobionate

Gentamicin sulfate

Heparin sodium

Hydrocortisone sodium succinate

Hydromorphone HCl

Isoproterenol HCl

Lidocaine HCl

Magnesium sulfate

Mannitol

Meperidine HCl

Methyldopate HCl

Methylprednisolone sodium succinate

Metoclopramide HCl

Morphine sulfate

Multivitamins

Naloxone HCl

Nitroglycerin

Norepinephrine bitartrate

Oxytocin

Pancuronium bromide

Penicillin G potassium

Penicillin G sodium

Pentobarbital sodium

Phenobarbital sodium

Phentolamine mesylate

Phenytoin sodium

Potassium chloride

Potassium phosphates

Procainamide HCl

Propranolol HCl

Protamine sulfate

Quinidine gluconate

Sodium bicarbonate

Sodium nitroprusside

Theophylline

Tobramycin sulfate

Vancomycin HCl

Vasopressin

Incompatible

Albumin human382 HID

Aminophylline

Amphotericin B382 HID

Co-trimoxazole382 HID

Hydralazine HCl382 HID

Variable

Ampicillin sodium

Dobutamine HCl

Furosemide

Nafcillin sodium

Oxacillin sodium

Y-Site CompatibilityHID

Compatible

Argatroban

Bivalirudin

Ciprofloxacin

Clonidine HCl

Dexmedetomidine HCl

Dobutamine HCl

Dopamine HCl

Famotidine

Fenoldopam mesylate

Hetastarch in lactated electrolyte injection (Hextend)

Hydralazine HCl

Linezolid

Meperidine HCl

Milrinone lactate

Nesiritide

Oxaliplatin

Penicillin G potassium

Incompatible

Albumin human

Amphotericin B cholesteryl sulfate complex

Ampicillin sodium

Nafcillin sodium

Oxacillin sodium

Propofol

Sodium bicarbonate

Actions

  • Inhibits calcium ion influx across membranes of myocardial cells and vascular smooth muscle, thereby inhibiting contractile processes of cardiac and vascular smooth muscle, with resultant dilation of main coronary and systemic arteries; dilation of systemic arteries results in decreased total peripheral resistance, systemic BP, and afterload of the heart.b

  • Increases myocardial oxygen delivery in patients with Prinzmetal variant angina (vasospastic angina) by inhibiting spontaneous and ergonovine-induced coronary artery spasm.b

  • Alleviates symptoms of unstable and chronic stable angina pectoris through reduction in afterload (at rest and with exercise) and its resultant decrease in oxygen consumption.b

  • Unlike nifedipine, verapamil has substantial inhibitory effects on the cardiac conduction system and is considered a class IV antiarrhythmic agent.b

  • May reduce resting heart rate and produce sinus arrest or SA block in patients with SA node disease (e.g., sick sinus syndrome).b (See Extreme Bradycardia/Asystole under Cautions.)

  • Slows conduction and prolongs refractoriness in the AV node, thereby prolonging the AH (atria-His bundle) interval; this usually also results in PR interval prolongation on ECG and, rarely, second- or third-degree AV block (even in patients without preexisting conduction defects).b (See AV Block under Cautions.)

  • Has little effect on the QT interval and minimal or no effects on antegrade or retrograde conduction of accessory bypass pathways.b

  • Negative inotropic effects of the drug usually offset by reduced afterload; cardiac index not reduced except in patients with moderately severe or severe heart failure.b (See Cardiac Failure under Cautions.)

Advice to Patients

  • Risk of precipitating or worsening cardiovascular disorders.b

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.b

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.b

  • Importance of informing patients of other important precautionary information.b (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Verapamil Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, controlled- and extended-release (containing pellets)

100 mg

Verelan PM

Schwarz

200 mg

Verelan PM

Schwarz

300 mg

Verelan PM

Schwarz

Capsules, extended-release (containing pellets)

120 mg*

Verapamil Hydrochloride Extended-Release Capsules

Verelan

Schwarz

180 mg*

Verapamil Hydrochloride Extended-Release Capsules

Verelan

240 mg*

Verapamil Hydrochloride Extended-Release Capsules

Verelan

Schwarz

360 mg

Verelan

Schwarz

Tablets, extended-release core, film-coated

180 mg

Covera-HS

Pfizer

240 mg

Covera-HS

Pfizer

Tablets, extended-release, film-coated

120 mg*

Calan SR Caplets

Pfizer

Isoptin SR

Abbott

Verapamil Hydrochloride Extended-Release

180 mg*

Calan SR Caplets (scored)

Pfizer

Isoptin SR (scored)

Abbott

240 mg*

Calan SR Caplets (scored)

Pfizer

Isoptin SR (scored)

Abbott

Tablets, film-coated

40 mg*

Calan

Pfizer

Verapamil Hydrochloride Tablets

80 mg*

Calan (scored)

Pfizer

120 mg*

Calan (scored)

Pfizer

Parenteral

Injection, for IV use

2.5 mg/mL*

Verapamil Hydrochloride Injection

Verapamil Hydrochloride Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release core (containing verapamil hydrochloride 180 mg), film-coated

180 mg with Trandolapril 2 mg

Tarka

Abbott

Tablets, extended-release core (containing verapamil hydrochloride 240 mg), film-coated

240 mg with Trandolapril 1 mg

Tarka

Abbott

Tablets, extended-release core (containing verapamil hydrochloride 240 mg), film-coated

240 mg with Trandolapril 2 mg

Tarka

Abbott

Tablets, extended-release core (containing verapamil hydrochloride 240 mg), film-coated

240 mg with Trandolapril 4 mg

Tarka

Abbott

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Calan 120MG Tablets (PFIZER U.S.): 90/$156.94 or 180/$300.39

Calan 40MG Tablets (PFIZER U.S.): 90/$69.29 or 270/$188.95

Calan 80MG Tablets (PFIZER U.S.): 30/$46.86 or 60/$85.00

Calan SR 120MG Controlled-release Tablets (PFIZER U.S.): 30/$75.59 or 90/$199.47

Calan SR 180MG Controlled-release Tablets (PFIZER U.S.): 30/$94.48 or 90/$251.96

Calan SR 240MG Controlled-release Tablets (PFIZER U.S.): 30/$112.00 or 90/$314.97

Covera-HS 180MG 24-hr Tablets (PFIZER U.S.): 30/$72.99 or 90/$209.96

Covera-HS 240MG 24-hr Tablets (PFIZER U.S.): 30/$102.89 or 90/$283.45

Tarka 1-240MG Controlled-release Tablets (ABBOTT): 30/$105.99 or 90/$285.96

Tarka 2-180MG Controlled-release Tablets (ABBOTT): 30/$113.99 or 90/$329.97

Tarka 2-240MG Controlled-release Tablets (ABBOTT): 30/$113.99 or 90/$319.98

Tarka 4-240MG Controlled-release Tablets (ABBOTT): 30/$115.99 or 90/$334.98

Trandolapril-Verapamil HCl 2-180MG Controlled-release Tablets (GLENMARK PHARMACEUTICALS): 30/$89.99 or 90/$249.97

Trandolapril-Verapamil HCl 2-240MG Controlled-release Tablets (GLENMARK PHARMACEUTICALS): 30/$89.99 or 90/$249.97

Trandolapril-Verapamil HCl 4-240MG Controlled-release Tablets (GLENMARK PHARMACEUTICALS): 30/$89.99 or 90/$249.97

Verapamil HCl 120MG Tablets (WATSON LABS): 90/$17.99 or 180/$25.97

Verapamil HCl 40MG Tablets (WATSON LABS): 90/$24.99 or 180/$39.97

Verapamil HCl 80MG Tablets (WATSON LABS): 90/$16.99 or 270/$44.95

Verapamil HCl CR 100MG 24-hr Capsules (KREMERS URBAN): 100/$189.98 or 300/$529.94

Verapamil HCl CR 120MG 24-hr Capsules (MYLAN): 30/$29.99 or 90/$69.97

Verapamil HCl CR 120MG Controlled-release Tablets (IVAX PHARMACEUTICALS): 30/$22.99 or 90/$52.97

Verapamil HCl CR 180MG 24-hr Capsules (MYLAN): 30/$26.99 or 90/$67.98

Verapamil HCl CR 180MG Controlled-release Tablets (IVAX PHARMACEUTICALS): 30/$18.99 or 90/$34.97

Verapamil HCl CR 200MG 24-hr Capsules (KREMERS URBAN): 30/$72.99 or 90/$195.98

Verapamil HCl CR 240MG 24-hr Capsules (MYLAN): 30/$25.99 or 60/$39.97

Verapamil HCl CR 240MG Controlled-release Tablets (IVAX PHARMACEUTICALS): 30/$21.99 or 60/$32.98

Verapamil HCl CR 300MG 24-hr Capsules (KREMERS URBAN): 30/$105.99 or 90/$280.97

Verapamil HCl CR 360MG 24-hr Capsules (WATSON LABS): 30/$61.99 or 90/$169.98

Verelan 180MG 24-hr Capsules (SCHWARZ PHARMA): 30/$115.99 or 90/$317.97

Verelan 240MG 24-hr Capsules (SCHWARZ PHARMA): 30/$136.00 or 90/$407.99

Verelan 360MG 24-hr Capsules (SCHWARZ PHARMA): 30/$237.98 or 90/$669.97

Verelan PM 100MG 24-hr Capsules (SCHWARZ PHARMA): 30/$123.99 or 90/$345.96

Verelan PM 200MG 24-hr Capsules (SCHWARZ PHARMA): 30/$139.98 or 90/$399.99

Verelan PM 300MG 24-hr Capsules (SCHWARZ PHARMA): 30/$207.99 or 90/$609.99

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 10, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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