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Verapamil

Class: Calcium-Channel Blocking Agents, Miscellaneous
- Nondihydropyridine Calcium-Channel Blocking Agents
- Calcium-Channel Blocking Agents, Nondihydropyridine
- Calcium Antagonists
VA Class: CV200
CAS Number: 152-11-4
Brands: Calan, Verelan

Medically reviewed by Drugs.com on Oct 19, 2020. Written by ASHP.

Introduction

Calcium-channel blocking agent; nondihydropyridine.

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.

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. Use only in hemodynamically stable patients who do not have impaired ventricular function.

Also has been used for treatment of other SVTs (e.g., atrial tachycardia, junctional tachycardia).

An oral treatment of choice to prevent recurrent PSVT.

Oral management (alone 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.

Angina

Management of chronic stable angina, Prinzmetal variant angina, and unstable angina.

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

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.

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.

Hypertension

Oral management of hypertension, alone or in combination with other classes of antihypertensive agents.

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. 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.

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).

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

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. 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. These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.

Previous hypertension guidelines generally have based target BP goals on age and comorbidities. 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 patients compared with those recommended by the 2017 ACC/AHA hypertension guideline.

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.

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.

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

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%).

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.

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. Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.

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. 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.

Calcium-channel blockers may be preferred in hypertensive patients with certain coexisting conditions (e.g., ischemic heart disease) and in geriatric patients, including those with isolated systolic hypertension. Nondihydropyridine calcium-channel blockers (e.g., diltiazem, verapamil) may be beneficial in hypertensive patients with coexisting atrial fibrillation and a rapid ventricular rate.

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). 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.

Hypertrophic Cardiomyopathy

Has been used as adjunctive therapy in the management of hypertrophic cardiomyopathy.

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

Acute MI

Used in the early treatment and secondary prevention of acute MI; an effective anti-ischemic agent, but mortality benefit not demonstrated.

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.

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.

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.

Bipolar Disorder

Has been used for management of manic manifestations of bipolar disorder; other more effective agents (e.g., lithium) available.

Verapamil Dosage and Administration

General

  • Individualize dosage according to patient response.

BP Monitoring and Treatment Goals

  • Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.

  • If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.

  • If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., ACE inhibitor, angiotensin II receptor antagonist, thiazide diuretic). Many patients will require at least 2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved, add a third drug.

Supraventricular Arrhythmias

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

Administration

Administer orally or by direct IV injection.

Oral Administration

Extended-release Capsules (Verelan)

Administer orally once daily without regard to meals.

Swallow capsules whole; do not chew or divide.

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

Controlled Extended-release Capsules (Verelan PM)

Administer orally once daily at bedtime without regard to meals.

Conventional Tablets (Calan)

Administer orally 3 or 4 times daily without regard to meals.

Extended-release Tablets (Calan SR)

Administer orally once daily in the morning with food.

Extended-release tablets are scored and may be halved without affecting oral bioavailability.

IV Administration

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

Monitor BP and ECG continuously during IV therapy.

Rate of Administration

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

Dosage

Available as verapamil hydrochloride; dosage expressed in terms of the salt.

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.

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.

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.

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.

Adults

Supraventricular Arrhythmias
PSVT Prophylaxis
Oral

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

Ventricular Rate Control in PSVT
IV

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

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.

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).

IV

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

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.

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

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

Angina
Oral

Usual initial dosage: 80 mg 3 or 4 times daily as conventional tablets (Calan). 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.

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.

Extended-release preparations may be preferred for management of hypertension (for less frequent dosing and potentially smoother BP control).

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 bedtime

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

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

Extended-release capsules (Verelan)

Usual dosage is 240 mg once daily in the morning

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

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 required Some experts recommend a usual dosage range of 120–360 mg daily given as a single dose or in 2 divided doses

Conventional tablets (Calan)

80 mg 3 times daily

Patients who may have increased response (elderly, small stature): 40 mg 3 times daily

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

Extended-release tablets (CalanSR)

Usual initial dosage: 180 mg once daily in the morning

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

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

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)

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

Some experts recommend a usual dosage range of 120–360 mg daily given as a single dose or in 2 divided doses

Verapamil/Trandolapril Fixed-combination Therapy
Oral

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

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.

Special Populations

Hepatic Impairment

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

Angina
Oral

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

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. (See Table 2.)

Renal Impairment

Supplemental doses not necessary in patients undergoing hemodialysis.

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. (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.

Angina

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

Hypertension

Lower initial dosage recommended for treatment of hypertension in geriatric patients. (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. (See Table 2.)

Cautions for Verapamil

Contraindications

  • Severe left ventricular dysfunction (unless heart failure is secondary to a supraventricular tachycardia amenable to verapamil therapy).

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

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

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

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

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

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

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

Warnings/Precautions

Warnings

Cardiac Failure

Possible precipitation or acute worsening of heart failure.

Avoid use in patients with severe left ventricular dysfunction (e.g., pulmonary wedge pressure >20 mm Hg, ejection fraction <30%), unless the heart failure is caused by a supraventricular tachycardia amenable to verapamil therapy 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.

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

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.

Hypotension

Possible hypotension; monitor BP carefully.

Hepatic Effects

Possible hepatocellular toxicity; monitor liver function tests periodically.

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

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.

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).

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.

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

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.

Duchenne’s Muscular Dystrophy

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

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.

General Precautions

Use of Fixed Combinations

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

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk; discontinue nursing or the drug.

Pediatric Use

Possibly severe adverse cardiovascular effects (e.g., refractory hypotension, cardiac arrest) following IV administration of verapamil in neonates and infants. If used in children, caution advised.

Safety and efficacy of oral verapamil not established in children <18 years of age.

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. Select dosage with caution; titrate dosage carefully.

Hepatic Impairment

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

Renal Impairment

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

Common Adverse Effects

Constipation, dizziness, nausea, hypotension, headache.

Interactions for Verapamil

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

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inducers: Possible decreased plasma verapamil concentrations.

CYP3A4 inhibitors: Possible increased plasma verapamil concentrations.

Protein-bound Drugs

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

Specific Drugs and Foods

Drug or Food

Interaction

Comment

ACE inhibitors

Additive hypotensive effects

Usually used to therapeutic advantage; monitor BP

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

Increased hypotensive effect, possibly excessive in some patients

β-Adrenergic blocking agents (see entries for atenolol, metoprolol, and propranolol)

Additive negative effects on myocardial contractility, heart rate, and AV conduction

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

Use with caution for oral management of hypertension; monitor closely

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

Alcohol

Inhibition of ethanol elimination, resulting in increased blood ethanol concentrations and prolonged intoxicating effects

Antineoplastic agents

Increased serum concentrations and efficacy of doxorubicin

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

Decreased paclitaxel clearance (interaction with R-verapamil)

Anesthetics, inhalation

Potentiation of cardiovascular depression

Titrate dosages carefully

Aspirin

Increased bleeding times

Atenolol (see entry for β-Adrenergic blocking agents)

Pharmacokinetic interaction unlikely

Carbamazepine

Increased plasma carbamazepine concentrations and subsequent toxicity

Reduce carbamazepine dosage by 40–50% after initiating verapamil therapy

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

Cimetidine

Variable effects on verapamil clearance and oral bioavailability reported

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

Cyclosporine

Increased blood cyclosporine concentrations

Monitor for cyclosporine toxicity

Dantrolene

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

Clinical relevance to humans unknown

Digoxin

Increased serum digoxin concentrations and digoxin toxicity

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

Disopyramide

Possible additive effects and impairment of left ventricular function

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

Diuretics

Additive hypotensive effects

Usually used to therapeutic advantage; monitor BP

Erythromycin

Increased plasma verapamil concentrations

Flecainide

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

Avoid concomitant use unless potential benefits outweigh risks

Grapefruit juice

Increased plasma verapamil concentrations

Not considered clinically important

Lithium

Possible increased, decreased, or unchanged serum lithium concentrations; possible increased sensitivity to lithium’s neurotoxic effects

Monitor for lithium toxicity; monitor serum lithium concentrations; adjust dosage as necessary

Metoprolol (see entry for β-Adrenergic blocking agents)

Increased oral bioavailability of metoprolol

Avoid concomitant use, if possible; if used concomitantly, adjust metoprolol dosage and monitor patient closely

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

Neuromuscular blocking agents

Potentiation of neuromuscular blockade

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

Nitrates

Possible additive beneficial effects; undesirable interactions unlikely

Phenobarbital

Increased clearance of total and unbound verapamil, possibly via induction of hepatic metabolism

Adjust verapamil dosage as necessary

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 MI

Use with caution for oral management of hypertension; monitor closely

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

Quinidine

Additive adrenergic blocking activity at α1- and α2-receptors

Hypotensive effect in patients with hypertrophic cardiomyopathy

Verapamil counteracts the effects of quinidine on AV conduction

Possible increased plasma quinidine concentrations

Avoid concomitant use in patients with hypertrophic cardiomyopathy

Rifampin

Decreased oral bioavailability of verapamil

Monitor closely if rifampin is added to or eliminated from regimen; adjust verapamil dosage as necessary

Ritonavir

Increased plasma verapamil concentrations

Theophylline

Decreased clearance, elevated serum concentrations, and prolonged serum half-life of theophylline

Monitor for theophylline toxicity

Timolol, ophthalmic

Severe bradycardia (associated with wandering atrial pacemaker and transient asystole) reported

Use with caution

Vasodilators

Additive hypotensive effects

Usually used to therapeutic advantage; monitor BP

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.

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

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

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

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

Onset

Antihypertensive effect evident within 1 week.

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

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. Conversion of PSVT to sinus rhythm generally occur rapidly (usually within 10 minutes following administration).

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.

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

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.

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

Plasma Concentrations

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

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.

Special Populations

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

Distribution

Extent

Verapamil and norverapamil distribute into the CNS.

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

Verapamil distributes into milk; concentrations in breast milk are similar to those in maternal plasma in some women.

Plasma Protein Binding

Approximately 90%.

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.

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

Elimination Route

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

Neither verapamil nor norverapamil is appreciably removed by hemodialysis.

Half-life

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

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

Special Populations

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

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

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

Stability

Storage

Oral

Capsules and Tablets

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

Parenteral

Injection

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

Compatibility

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

Parenteral

Will precipitate in any solution with a pH>6.

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 human

Aminophylline

Amphotericin B

Co-trimoxazole

Hydralazine HCl

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.

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

  • 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.

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

  • May reduce resting heart rate and produce sinus arrest or SA block in patients with SA node disease (e.g., sick sinus syndrome). (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). (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.

  • 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. (See Cardiac Failure under Cautions.)

Advice to Patients

  • Risk of precipitating or worsening cardiovascular disorders.

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

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

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

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 2021, Selected Revisions October 29, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

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