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Verapamil (Monograph)

Brand names: Calan, Verelan
Drug class: Class IV Antiarrhythmics
- Nondihydropyridine Calcium-Channel Blocking Agents
- Calcium-Channel Blocking Agents, Nondihydropyridine
- Calcium Antagonists

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Calcium-channel blocking agent; nondihydropyridine.117 118 302 382

Uses for Verapamil

Supraventricular Arrhythmias

IV management of supraventricular tachycardia (SVT), 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.700 701

Vagal maneuvers and/or IV adenosine are considered first-line interventions for acute treatment of SVT when clinically indicated; if such measures are ineffective or not feasible, a nondihydropyridine calcium-channel blocker such as verapamil may be used.700 Use only in hemodynamically stable patients who do not have impaired ventricular function.700

Also has been used for treatment of other SVTs (e.g., atrial tachycardia† [off-label], junctional tachycardia† [off-label]).255 256 257 258 259 260 261 262 263 264 265 700

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

Oral management (alone† [off-label]172 173 174 176 177 178 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

Management of chronic stable angina, Prinzmetal variant angina, and unstable angina.118 362 1100 1101

A drug of choice for the management of Prinzmetal variant angina (used alone or in combination with nitrates).1100

β-Blockers are recommended as the anti-ischemic drugs of choice in most patients with chronic stable angina; calcium-channel blockers may be substituted or added in patients who do not tolerate or respond adequately to β-blockers.1101

Experts recommend a nondihydropyridine calcium-channel blocker (e.g., diltiazem, verapamil) for the relief of ongoing or recurrent ischemia when β-blocker therapy is inadequate, not tolerated, or contraindicated in patients with unstable angina who do not have clinically important left ventricular dysfunction, increased risk of cardiogenic shock, or AV block.1100

Hypertension

Oral management of hypertension, alone or in combination with other classes of antihypertensive agents.207 352 362 376 1200

Calcium-channel blockers are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics.501 502 503 504 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 503 504 1200 1213

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Previous hypertension guidelines generally have based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk, and have used higher BP thresholds and target BPs in elderly patients501 504 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.1200 1220 1229

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment recommended by ACC/AHA for all adults with hypertension.1200

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years of age are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200 Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.502 1200

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Calcium-channel blockers may be preferred in hypertensive patients with certain coexisting conditions (e.g., ischemic heart disease)195 212 281 285 286 523 and in geriatric patients, including those with isolated systolic hypertension.193 194 195 204 212 224 227 230 282 288 289 502 510 Nondihydropyridine calcium-channel blockers (e.g., diltiazem, verapamil) may be beneficial in hypertensive patients with coexisting atrial fibrillation and a rapid ventricular rate.118 171 172 173 174 175 176 177 178 179 180 181 182 353 502 504

Black hypertensive patients generally respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to other antihypertensive drug classes (e.g., ACE inhibitors, angiotensin II receptor antagonists).501 504 1200 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.1200

Hypertrophic Cardiomyopathy

Has been used as adjunctive therapy in the management of hypertrophic cardiomyopathy† [off-label].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.)

Acute MI

Used in the early treatment and secondary prevention of acute MI† [off-label]; an effective anti-ischemic agent, but mortality benefit not demonstrated.266 527 1100

Calcium-channel blockers generally are used for their anti-ischemic and BP-reducing properties in the MI setting, and only when β-blockers (which have been shown to reduce mortality after MI) are ineffective, not tolerated, or contraindicated.527 702 1100

Experts state that calcium-channel blockers may be used to relieve ischemic symptoms, lower BP, or control rapid ventricular response rate associated with atrial fibrillation in patients with ST-segment-elevation MI (STEMI) who are intolerant to β-blockers.527

Experts recommend a nondihydropyridine calcium-channel blocker for ongoing or recurrent ischemia in patients with non-ST-segment-elevation MI (NSTEMI) who have a contraindication to β-blockers and who do not have clinically important left ventricular dysfunction, increased risk of cardiogenic shock, or AV block.1100

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 Dosage and Administration

General

BP Monitoring and Treatment Goals

Supraventricular Arrhythmias

Administration

Administer orally or by direct IV injection.700

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 3 or 4 times daily118 199 214 215 222 without regard to meals.b

Extended-release Tablets (Calan 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

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

Dosage

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

Pediatric Patients

Supraventricular Arrhythmias

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 Arrhythmias
PSVT Prophylaxis
Oral

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

Ventricular Rate Control in PSVT
IV

Initially, 5–10 mg (0.075–0.15 mg/kg) given by IV injection over ≥2 minutes.382 700

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.382 700

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.382 701

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

Other SVTs (e.g., Junctional Tachycardia†, Atrial Tachycardia†)
IV

5–10 mg (0.075–0.15 mg/kg) administered over 2 minutes.700 If no response, can administer additional dose of 10 mg (0.15 mg/kg) 30 minutes after initial dose.700

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

Hypertension
Verapamil Therapy
Oral

Recommended dosages vary by formulation (see Table 2).

When switching from conventional tablets (Calan) to extended-release capsules (Verelan) or tablets (Calan SR), can use same total daily dosage.600 601 1200

Extended-release preparations may be preferred353 for management of hypertension (for less frequent dosing and potentially smoother BP control).117 119 207 208 229 302 353

Table 2. Recommended Dosages for Management of Hypertension

Formulation

Initial Dosage

Dosage Titration Regimen

Controlled extended-release capsules (Verelan PM)

200 mg once daily at bedtime376

Patients who may have increased response (e.g., elderly, low weight, impaired renal or hepatic function): 100 mg daily at bedtime may rarely be necessary376

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

Extended-release capsules (Verelan)

Usual dosage is 240 mg once daily in the morning600

Patients who may have increased response (elderly, small stature): 120 mg once daily in the morning600

If adequate response not achieved with 120 mg once daily, increase dosage to 180 mg once daily and then to 240 mg once daily, with subsequent increases in 120-mg increments up to 480 mg once daily, if required600 Some experts recommend a usual dosage range of 120–360 mg daily given as a single dose or in 2 divided doses1200

Conventional tablets (Calan)

80 mg 3 times daily118 199 214 215 222

Patients who may have increased response (elderly, small stature): 40 mg 3 times daily118 119 214 215 222

Some experts recommend a usual dosage range of 120–360 mg daily, given in 3 divided doses1200

Extended-release tablets (CalanSR)

Usual initial dosage: 180 mg once daily in the morning601

Patients who may have increased response (elderly, small stature): 120 mg once daily in the morning601

If adequate response not achieved with 180 mg once daily, increase dosage to 240 mg each morning601

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)601

Dosage may be increased to 240 mg every 12 hours, if required601

Some experts recommend a usual dosage range of 120–360 mg daily given as a single dose or in 2 divided doses1200
Verapamil/Trandolapril Fixed-combination Therapy
Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.352

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 (See Table 2.)

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 (See Table 2.)

Geriatric Patients

Supraventricular Arrhythmias

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 (See Table 2.)

Small-stature/Low-weight Patients

Hypertension

Lower initial dosage recommended for treatment of hypertension in patients with small stature or low weight.117 118 207 302 376 (See Table 2.)

Detailed Verapamil dosage information

Cautions for Verapamil

Contraindications

Warnings/Precautions

Warnings

Cardiac Failure

Possible precipitation or acute worsening of heart failure.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

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

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 If used in children, caution advised.382

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

Drug Interactions

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 heart failure, arrhythmia, and severe hypotension, particularly if IV route or high propranolol dosages are used or if patient has moderately severe or severe heart failure, 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 drug interactions (more detail)

Verapamil 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 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

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

Advice to Patients

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* 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, film-coated

120 mg*

Calan SR Caplets

Pfizer

Verapamil Hydrochloride Extended-Release

180 mg*

Calan SR Caplets (scored)

Pfizer

240 mg*

Calan SR Caplets (scored)

Pfizer

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

AHFS DI Essentials™. © Copyright 2024, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

References

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102. Vogelgesang B, Echizen H, Schmidt E et al. Stereoselective first-pass metabolism of highly cleared drugs: studies of the bioavailability of l- and d-verapamil examined with a stable isotope technique. Br J Clin Pharmacol. 1984; 18:733-40. http://www.ncbi.nlm.nih.gov/pubmed/6508982?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1463564&blobtype=pdf

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134. Rahn KH, Mooy J, Bohm R et al. Reduction of bioavailability of verapamil by rifampin. N Engl J Med. 1985; 312:920-1. http://www.ncbi.nlm.nih.gov/pubmed/3974676?dopt=AbstractPlus

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141. McLean AJ, Knight R, Harrison PM et al. Clearance-based oral drug interaction between verapamil and metoprolol and comparison with atenolol. Am J Cardiol. 1985; 55:1628-9. http://www.ncbi.nlm.nih.gov/pubmed/4003307?dopt=AbstractPlus

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182. Zipes DP. A consideration of antiarrhythmic therapy. Circulation. 1985; 72:949-56. http://www.ncbi.nlm.nih.gov/pubmed/3930087?dopt=AbstractPlus

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185. Pritchett EL, Hammill SC, Reiter MJ et al. Life-table methods for evaluating antiarrhythmic drug efficacy in patients with paroxysmal atrial tachycardia. Am J Cardiol. 1983; 52:1007-12. http://www.ncbi.nlm.nih.gov/pubmed/6356859?dopt=AbstractPlus

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187. Tonkin AM, Aylward PE, Joel SE et al. Verapamil in prophylaxis of paroxysmal atrioventricular nodal reentrant tachycardia. J Cardiovasc Pharmacol. 1980; 2:473-86. http://www.ncbi.nlm.nih.gov/pubmed/6157944?dopt=AbstractPlus

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189. Rose JS, Bhandari A, Rahimtoola SH et al. Effective termination of reentrant supraventricular tachycardia by single dose oral combination therapy with pindolol and verapamil. Am Heart J. 1986; 112:759-65. http://www.ncbi.nlm.nih.gov/pubmed/3766376?dopt=AbstractPlus

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192. Zusman RM. Alternatives to traditional antihypertensive therapy. Hypertension. 1986; 8:837-42. http://www.ncbi.nlm.nih.gov/pubmed/2875945?dopt=AbstractPlus

193. Kaplan NM. Initial treatment of adult patients with essential hypertension. Part II: alternating monotherapy is the preferred treatment. Pharmacotherapy. 1985; 5:195-200. http://www.ncbi.nlm.nih.gov/pubmed/4034407?dopt=AbstractPlus

194. Bauer JH. Stepped-care approach to the treatment of hypertension: is it obsolete? (unpublished observations)

195. Halperin AK, Cubeddu LX. The role of calcium channel blockers in the treatment of hypertension. Am Heart J. 1986; 111:363-82. http://www.ncbi.nlm.nih.gov/pubmed/3511651?dopt=AbstractPlus

196. Spivack C, Ocken S, Frishman WH. Calcium antagonists: clinical use in the treatment of systemic hypertension. Drugs. 1983; 25:154-77. http://www.ncbi.nlm.nih.gov/pubmed/6339198?dopt=AbstractPlus

197. Murphy MB. Treatment of hypertension with calcium antagonists. Int J Clin Pharm Res. 1985; 5:287-91.

198. Frishman W, Charlap S, Kimmel B et al. Twice-daily administration of oral verapamil in the treatment of essential hypertension. Arch Intern Med. 1986; 146:561-5. http://www.ncbi.nlm.nih.gov/pubmed/3954530?dopt=AbstractPlus

199. Cubeddu LX, Aranda J, Singh B et al. A comparison of verapamil and propranolol for the initial treatment of hypertension: racial differences in response. JAMA. 1986; 256:2214-21. http://www.ncbi.nlm.nih.gov/pubmed/3531560?dopt=AbstractPlus

200. Hornung RS, Jones RI, Gould BA et al. Propranolol versus verapamil for the treatment of essential hypertension. Am Heart J. 1984; 108:554-60. http://www.ncbi.nlm.nih.gov/pubmed/6382991?dopt=AbstractPlus

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