Verapamil hydrochloride is a nondihydropyridine calcium-channel blocking agent (calcium-channel blocker).117, 118, 302, 352, 382, 602
Verapamil is used for rapid conversion to sinus rhythm of paroxysmal supraventricular tachycardias (PSVT), including tachycardia associated with Wolff-Parkinson-White or Lown-Ganong-Levine syndrome; the drug also is used for control of rapid ventricular rate in nonpreexcited atrial flutter or fibrillation.382, 700, 1307 In general, IV verapamil is recommended for acute treatment, while oral verapamil is recommended for ongoing management of these arrhythmias.118, 382, 700, 1307
Paroxysmal Supraventricular Tachycardia
IV verapamil is used for rapid conversion of PSVT that is uncontrolled or unconverted by vagal maneuvers, including atrioventricular (AV) nodal reentrant tachycardias and PSVT associated with accessory bypass tracts (e.g., Wolff-Parkinson-White or Lown-Ganong-Levine syndrome).382, 700 In about 60-80% of patients with PSVT, rapid (usually within 10 minutes after administration) conversion to sinus rhythm is achieved with IV verapamil.382 Verapamil is also used orally for prophylaxis of repetitive PSVT and for the ongoing management of arrhythmia.118, 171, 181, 182, 183, 184, 185, 186, 187, 188, 700
The American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) guideline for the management of adult patients with supraventricular tachycardia recommends the use of vagal maneuvers, adenosine, IV beta-adrenergic blockers, or IV nondihydropyridine calcium-channel blockers for acute treatment.700 Vagal maneuvers and/or IV adenosine are considered first-line interventions for the acute treatment of patients with SVT and should be attempted prior to other therapies when clinically indicated; if such measures are ineffective or not feasible, an IV nondihydropyridine calcium-channel blocker (i.e., verapamil or diltiazem) or IV beta-adrenergic blocker (e.g., esmolol, metoprolol) may be considered.700 Nondihydropyridine calcium-channel blockers (i.e., diltiazem or verapamil) should only be used in hemodynamically stable patients who do not have impaired ventricular function.700 Oral nondihydropyridine calcium-channel blockers (i.e., diltiazem, verapamil) are recommended for the ongoing management of these arrhythmias.700 While trials comparing IV diltiazem and verapamil have not been performed, experts state that diltiazem may be associated with fewer adverse events (e.g., hypotension).1313, 1314
Although controlled studies have not been conducted to date, IV verapamil also has been used in the management of PSVT in neonates and children.382
IV verapamil is used for temporary control of rapid ventricular rate in atrial flutter or fibrillation.382 Drugs that block AV nodal conduction (e.g., diltiazem, verapamil) should not be used when atrial flutter or fibrillation is associated with an accessory bypass tract (e.g., Wolff-Parkinson-White or Lown-Ganong-Levine syndrome) or with preexcited ventricular complexes or wide QRS complexes, since ventricular tachyarrythmias, including ventricular fibrillation, and cardiac arrest may be precipitated.382, 1307 Although approximately 70% of patients with atrial flutter and/or fibrillation respond to IV verapamil with a reduction in ventricular rate of at least 20%, the drug alone rarely (about 10%, but similar to placebo) converts atrial flutter or fibrillation to normal sinus rhythm.382
Oral verapamil is used in conjunction with digoxin 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 Verapamil also has been used alone†172, 173, 174, 176, 177, 178 to control ventricular rate in patients with chronic atrial fibrillation and/or flutter and a left ventricular ejection fraction greater than 40%.1307 The drug should not be used when these arrhythmias are associated with an accessory bypass tract.118 A limited number of patients with permanent atrial fibrillation requiring rate control were evaluated in a prospective, randomized, cross-over trial.1307, 1308 The 24-hour mean heart rate (measured using Holter monitoring) was 96 beats/minute at baseline (no treatment), and 75, 81, 82, or 84 beats/minute after 3 weeks of treatment with diltiazem 360 mg/day, verapamil 240 mg/day, metoprolol 100 mg/day, or carvedilol 25 mg/day, respectively.1308 All drugs reduced heart rate compared to baseline; diltiazem reduced heart rate significantly more than with any other drug.1307, 1308 There was no difference in all-hospitalization and all-cause mortality among patients receiving monotherapy for rate-control with beta-adrenergic blockers, nondihydropyridine calcium-channel blockers or digoxin in the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial.1307
Cardioversion has been used safely and effectively following IV or oral verapamil administration.118, 382
The 2023 American College of Cardiology/American Heart Association/American College of Clinical Pharmacy/Heart Rhythm Society (ACC/AHA/ACCP/HRS) guideline for the management of adults with atrial fibrillation recommends nondihydropyridine calcium-channel blockers (e.g., diltiazem, verapamil) or beta-adrenergic blockers for acute and long-term ventricular rate control in patients with nonpreexcited atrial fibrillation or flutter.700, 1307 In patients with atrial fibrillation with rapid ventricular response who are hemodynamically stable, IV beta-adrenergic blockers or nondihydropyridine calcium-channel blockers (i.e., diltiazem, verapamil) are recommended for acute rate control.1307 Beta-adrenergic blockers or nondihydropyridine calcium-channel blockers (i.e., diltiazem, verapamil) are also recommended for long-term rate control in patients with nonpreexcited atrial fibrillation.1307 In such patients with comorbid left ventricular ejection fraction (LVEF) <40%, nondihydropyridine calcium-channel blockers should not be administered.1307 Cardioversion is indicated in hemodynamically unstable patients.1307 There are limited data comparing various rate control agents; selection of specific agents should consider patient-specific characteristics (e.g., reduced ejection fraction heart failure, reactive airway disease) and response.1307
Although controlled studies have not been conducted to date, IV verapamil also has been used in the management of atrial fibrillation or flutter in neonates and children.382
IV verapamil may be used for the acute treatment of patients with hemodynamically stable focal atrial tachycardia† (i.e., regular SVT arising from a localized atrial site), and oral verapamil may be used for ongoing management.700
While evidence is more limited, IV verapamil also has been used in patients with multifocal atrial tachycardia† (i.e., rapid, irregular rhythm with at least 3 distinct P-wave morphologies) to control ventricular rate and convert to normal sinus rhythm.255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 700 However, such arrhythmia is commonly associated with an underlying condition (e.g., pulmonary, coronary, or valvular heart disease) and is generally not responsive to antiarrhythmic therapy.700 Antiarrhythmic drug therapy usually is reserved for patients who do not respond to initial attempts at correcting or managing potential precipitating factors (e.g., exacerbation of chronic obstructive pulmonary disease or congestive heart failure, electrolyte and/or ventilatory disturbances, infection, theophylline toxicity).255, 259, 264, 700 Therapy with verapamil has been associated with slowing of atrial261 and ventricular rates255, 256, 257, 259, 260, 261, 263 and conversion to sinus rhythm255, 256, 257, 259, 260, 261 in some patients with this arrhythmia.255, 256, 259, 700 Therefore, some clinicians suggest that IV verapamil may be useful for the acute treatment of patients with multifocal atrial tachycardia who do not have ventricular dysfunction, sinus node dysfunction, or AV block.700 Verapamil also may be useful orally for chronic suppression of recurrent symptomatic multifocal atrial tachycardia.256, 257, 261, 265, 700
Verapamil may be used for the treatment of junctional tachycardia† (i.e., nonreentrant SVT originating from the AV junction), a rapid, occasionally irregular, narrow-complex tachycardia.700β-Adrenergic blocking agents generally are used for acute termination and/or ongoing management of junctional tachycardia; limited evidence suggest there may be a role for verapamil when β-blocking agents (particularly propranolol) are ineffective.700
Verapamil is used in the management of angina, including chronic stable angina, unstable angina, and angina due to coronary artery spasm (e.g., Prinzmetal variant angina).118, 1303, 1321, 1322, 1323 Only the conventional (immediate-release) tablets of verapamil are FDA-labeled for use in the treatment of angina.118
Various placebo-controlled or active-controlled crossover trials have evaluated the effectiveness of verapamil in patients with angina.1321, 1322, 1323 Compared with patients receiving a placebo, nitroglycerin consumption and anginal frequency were reduced in verapamil- and nifedipine-treated patients with stable angina in one study.1321 In another crossover trial in patients with chronic stable angina, exercise time increased by 40 and 66% in the propranolol- and verapamil-treated groups, respectively, compared to placebo-treated groups.1322 More patients were free of angina during the verapamil compared to propranolol treatment period.1322 In a third crossover trial comparing verapamil, propranolol, isosorbide dinitrate, and placebo, both verapamil 120 mg and propranolol 100 mg administered 3 times daily reduced daily anginal attacks, reduced nitroglycerin consumption, and prolonged exercise time; however, isosorbide dinitrate was no more effective than placebo.1323
The 2023 American Heart Association/American College of Cardiology (AHA/ACC) clinical practice guideline for the management of patients with chronic coronary disease addresses the treatment of patients with stable angina symptoms (or ischemic equivalents).1303 The practice guideline recommends the use of beta-adrenergic blocking agents, calcium-channel blocking agents, or long-acting nitrates for relief of angina or equivalent symptoms in patients with chronic coronary disease.1303 The goal of therapy is to maximize relief of symptoms of angina without exacerbating comorbidities or adverse effects.1303
Selection of drug therapy should be individualized and should consider comorbid conditions, which may justify the use of one agent over another.1303 Calcium-channel blockers (used alone or in combination with nitrates) are considered first-line for the management of vasospastic angina.1303 In patients with microvascular angina (nonobstructive coronary artery disease), calcium-channel blockers may be used second-line when beta-adrenergic blockers are not tolerated or are ineffective.1303 Nondihydropyridine calcium-channel blockers (e.g., diltiazem, verapamil) should not be used in patients with significant left ventricular dysfunction.1303 Due to an increased potential for synergistic induction or exacerbation of bradycardia and left ventricular dysfunction, nondihydropyridine calcium-channel blockers should be used with caution in patients receiving beta-adrenergic blockers.1303 In patients with angina refractory to a single agent, symptom control may be improved by the addition of a second agent (e.g., addition of a long-acting nitrate to a calcium-channel or beta-adrenergic blocking agent).1303
Verapamil is used alone or in combination with other classes of antihypertensive agents in the management of hypertension.117, 118, 281, 302, 352, 603, 1200, 1324 Various oral preparations (conventional tablets, extended-release capsules or tablets, and controlled-onset extended-release pellet filled capsules) are available for this use.60, 61, 117, 118, 302, 602, 1324 Verapamil is also commercially available in fixed combination with trandolapril for use in patients for whom treatment with both drugs is appropriate.352
The effectiveness of immediate- and extended-release verapamil preparations in adult patients has been established in placebo- and active-controlled trials of patients with mild to moderate hypertension.1324
Efficacy of verapamil hydrochloride extended-release capsules for the treatment of hypertension was established in 2 placebo-controlled, double-blind studies.602 Patients received either placebo or verapamil hydrochloride (100 mg, 200 mg, 300 mg, or 400 mg as the extended-release capsules) once daily in the evening, and blood pressure changes were measured with 36-hour ambulatory blood pressure monitoring (ABPM).602 Placebo-subtracted net decreases in diastolic blood pressure at trough (averaged over 6-10 pm) were dose-related, and ranged from 3.8-10 mm Hg after 8 weeks of therapy with verapamil hydrochloride doses of 200 mg, 300 mg, or 400 mg.602 The 100-mg dose was effective at reducing diastolic blood pressure when measured manually at trough and peak, but not when measured by ABPM.602
In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the long-term cardiovascular morbidity and mortality benefit of a long-acting dihydropyridine calcium-channel blocker (amlodipine), a thiazide-like diuretic (chlorthalidone), and an ACE inhibitor (lisinopril) were compared in a broad population of patients with hypertension at risk for coronary heart disease.390, 391, 397, 398, 399, 400 Although these antihypertensive agents were comparably effective in providing important cardiovascular benefit, apparent differences in certain secondary outcomes were observed.390, 391 Patients receiving the ACE inhibitor experienced higher risks of stroke, combined cardiovascular disease, GI bleeding, and angioedema, while those receiving the calcium-channel blocker were at higher risk of developing heart failure.399, 400 The ALLHAT investigators suggested that the observed differences in cardiovascular outcome may be attributable, at least in part, to the greater antihypertensive effect of the calcium-channel blocker compared with that of the ACE inhibitor, especially in women and black patients.399, 400
Verapamil/Trandolapril Fixed-combination Therapy
Efficacy of the fixed combination of trandolapril and verapamil hydrochloride extended-release tablets (trandolapril/verapamil) was established in controlled clinical trials in patients receiving trandolapril/verapamil hydrochloride 2/180 mg or 4/240 mg once daily.352 Placebo-corrected seated systolic and diastolic blood pressures at trough (24 hours after dosing) were reduced by about 7-12 and 6-8 mm Hg, respectively, with the combination therapy.352 Blood pressure reductions were significantly greater for the trandolapril/verapamil hydrochloride 4/240 mg combination than for either of the individual components administered alone.352 Clinical trials with trandolapril/verapamil evaluated only once-daily dosing.352
The antihypertensive effect or the adverse effects of adding 4 mg once daily of trandolapril to extended-release verapamil hydrochloride (120 mg twice daily) have not been studied, nor have the effects of adding 180 mg of verapamil hydrochloride extended-release tablets daily to 1 mg of trandolapril twice daily been evaluated.352 Over the dosage range of extended-release verapamil hydrochloride 120-240 mg once daily and trandolapril 0.5-8 mg once daily, the effects of the fixed combination increase with increasing doses of either component.352
The principal goal of preventing and treating hypertension is to reduce the risk of cardiovascular and renal morbidity and mortality, including target organ damage.1200 The relationship between blood pressure and cardiovascular disease is continuous, consistent, and independent of other risk factors.1200, 1300 The higher the blood pressure, the more likely the development of coronary artery disease, heart failure, stroke, and chronic kidney disease across all ages and ethnic groups.1200, 1300 Each 20-mm Hg increment in systolic blood pressure or 10-mm Hg increment in diastolic blood pressure has been shown to double the risk of death from stroke, heart disease, or other vascular disease.266, 1200, 1300
Accurate blood pressure measurement in the office or clinic is essential for proper diagnosis and management of hypertension.1200, 1300, 1302 Out-of-office blood pressure measurements are recommended to confirm the diagnosis of hypertension.1200 Blood pressure categories range from normal to different grades/stages of hypertension and are intended to align therapeutic approaches with blood pressure levels.1300, 1302 According to most major guidelines, hypertension is diagnosed when systolic blood pressure is ≥140 mm Hg and/or diastolic blood pressure is ≥90 mm Hg as measured in the office or clinic.1300, 1302 Some guidelines consider a systolic blood pressure of 130-139 mm Hg and/or a diastolic blood pressure of 80-89 mm Hg to be stage 1 hypertension,1200 whereas other guidelines consider this a high-normal blood pressure; however, treatment recommendations are generally the same (nonpharmacologic therapy with consideration of pharmacologic therapy based on cardiovascular risk).1200, 1300, 1302
Comprehensive guidelines for the management of hypertension have been published by various authoritative groups.501, 1200, 1300, 1301, 1302 The first such guideline was published by the National Heart Lung and Blood Institute (NHLBI) in 1977, followed by a series of Joint National Committee (JNC) guidelines with JNC8 being the last iteration of these guidelines in 2014.501, 1200 The American College of Cardiology (ACC), American Heart Association (AHA), and other experts, including the International Society of Hypertension (ISH), have published more recent clinical practice guidelines for the treatment of hypertension.1200, 1300, 1302 These guidelines all state that lifestyle/behavioral modifications (e.g., weight reduction in patients who are overweight or obese, dietary changes, sodium reduction, potassium supplementation, increased physical activity, moderation of alcohol intake, smoking cessation) are essential in the management of hypertension and should be implemented as first-line therapy to lower blood pressure and reduce total cardiovascular risk.1200, 1300, 1302 The decision whether to initiate antihypertensive drug therapy should be based on the office blood pressure level while also considering cardiovascular risk factors.1200, 1219, 1300, 1302 Most guidelines agree that antihypertensive drug treatment should be offered in addition to lifestyle modifications to patients with grade 2 (blood pressure 160-179/100-109 mm Hg) or grade 3 (systolic blood pressure ≥180/110 mm Hg) hypertension; however, there is some controversy regarding whether patients with grade 1 hypertension (blood pressure 140-159/90-99) should be treated with antihypertensive drug therapy.1200, 1300, 1302 Some guidelines recommend immediate drug treatment in patients with grade 1 hypertension (blood pressure 140-159/90-99) who have high cardiovascular risk or comorbid conditions (cardiovascular disease, chronic kidney disease, diabetes mellitus or hypertension-mediated organ damage) and a trial of lifestyle intervention first in those with low to moderate cardiovascular risk who do not have these comorbid conditions,1302 whereas other guidelines recommend that all hypertensive patients, including those with grade 1 hypertension, receive blood pressure-lowering treatment, irrespective of their cardiovascular risk.1300 In some guidelines, drug treatment is recommended in patients with blood pressure in the high-normal range (≥130/80 mm Hg) who have cardiovascular disease.1200, 1210, 1300
Current evidence-based practice guidelines for the management of hypertension in adults generally recommend the use of drugs from 4 classes of antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, and thiazide or thiazide-like diuretics); data from clinical outcome trials indicate that lowering blood pressure with any of these drug classes can reduce the complications of hypertension and provide similar cardiovascular risk reduction benefits. 501, 503, 1200, 1300, 1302 However, recommendations for initial drug selection and use in specific patient populations may vary across these guidelines.501, 503, 1200 This variability is due, in part, to differences in the guideline development process and the types of studies included in the evidence reviews (e.g., randomized controlled studies only versus a range of studies with different study designs).501, 503, 1200 Ultimately, choice of antihypertensive therapy should be individualized, considering the clinical characteristics of the patient (e.g., age, ethnicity/race, comorbid conditions, cardiovascular risk factors) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, costs).501, 503, 510, 1200, 1300, 1302 Calcium-channel blockers may be particularly useful in the management of hypertension in black patients; these patients tend to have a greater blood pressure response to calcium-channel blockers and thiazide diuretics than to other antihypertensive drug classes (e.g., ACE inhibitors, angiotensin II receptor antagonists).69, 70, 109, 110, 501, 1200 Use of a calcium-channel blocker also may be beneficial in patients with certain coexisting conditions such as ischemic heart disease (e.g., angina) and in geriatric patients, including those with isolated systolic hypertension.71, 72, 73, 74, 510, 1200 Other antihypertensive drugs such as beta blockers, direct vasodilators, alpha-1 blockers, loop diuretics, and aldosterone antagonists are available, but generally recommended as second-line agents or only in specific clinical situations.1200
Because most patients with hypertension will require at least 2 antihypertensive drugs to achieve adequate blood pressure control, use of single pill combinations are generally recommended when available.1302 Drug regimens with complementary activity, where a second antihypertensive agent is used to block compensatory responses to the first agent or affect a different pressor mechanism, can result in additive blood pressure lowering and are preferred.1200 Drug combinations that have similar mechanisms of action or clinical effects (e.g., the combination of an ACE inhibitor and an angiotensin II receptor antagonist) generally should be avoided.1200 Antihypertensive drug dosages should be adjusted and/or other agents substituted or added until goal blood pressure is achieved.1200 After initiation of antihypertensive drug therapy, a blood pressure goal of less than 130/80 mm Hg within 3 months is generally recommended if tolerated, but should be individualized.1200, 1300, 1301 While there is evidence from a randomized controlled study (SPRINT) demonstrating that intensive systolic blood pressure lowering (to <120 mm Hg) may be beneficial in patients with increased risk of cardiovascular disease, the study excluded patients with diabetes mellitus or prior stroke, and those younger than 50 years of age, which may decrease the generalizability of these findings.1210, 1219
Specific guidelines for the management of hypertension in pregnancy have been published by experts such as AHA and the American College of Obstetrics and Gynecologists (ACOG).1305, 1306 First-line oral antihypertensive drugs generally recommended in pregnant patients include labetalol, nifedipine (extended-release), or methyldopa.1200, 1302, 1305 Renin-angiotensin system (RAS) blockers (e.g., ACE inhibitors, angiotensin II receptor blockers, direct renin inhibitors) are contraindicated during pregnancy due to adverse fetal and neonatal outcomes.1200, 1300, 1302, 1305
Although verapamil is not FDA-labeled for use in pediatric patients for the treatment of hypertension, the American Academy of Pediatrics (AAP) has published a clinical practice guideline for the management of high blood pressure in children and adolescents†.1150 The guideline recommends calcium-channel blockers (e.g., nifedipine, amlodipine), ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics for the initial management of hypertension in children requiring drug therapy.1150
Verapamil has been used in the management ofhypertrophic cardiomyopathy (HCM)†.1315 Expert guidelines recommend nonvasodilating beta-adrenergic blockers, titrated to effectiveness (i.e., suppression of resting heart rate) or maximally tolerated doses, to provide relief of symptoms in patients with obstructive HCM and symptoms attributable to left ventricular outflow tract obstruction (e.g., effort-related dyspnea or chest pain and occasionally other exertional symptoms such as syncope or near syncope that interfere with everyday activity or quality of life).1315 In such patients not responding to or intolerant of beta-adrenergic blocker therapy, a nondihydropyridine calcium-channel blocker (i.e., diltiazem, verapamil) is recommended.1315 Based on limited data, nondihydropyridine calcium-channel blockers (i.e., diltiazem, verapamil) may provide relief of symptoms in patients with obstructive HCM; however, the negative inotropic and negative chronotropic effects of such drugs may be limiting.1315 Nondihydropyridine calcium-channel blockers or beta-adrenergic blockers are also recommended in patients with nonobstructive HCM with preserved ejection fraction and symptoms of exertional angina or dyspnea.1315
Verapamil has been used in the management of radial artery spasm†, a complication of transradial artery access (TRA) for percutaneous coronary angiography.1318, 1319 The American Heart Association (AHA) recommends the use of intra-arterial (IA)† calcium channel blockers (i.e., verapamil 2.5-5 mg, diltiazem 2.5-5 mg, nicardipine 250-500 mcg) or nitroglycerin 100-200 mcg to reduce radial artery spasm.1318 The drug should be administered after sheath insertion, and possibly with each catheter exchange or before sheath removal.1318, 1319 A low rate of radial artery spasm (RAS) was observed in a prospective single-blinded randomized clinical trial comparing IA nicardipine (400 mcg) and verapamil (5 mg) during TRA.1319 No significant difference in RAS between the groups was observed; however, patients in the nicardipine group reported less pain and/or discomfort based on a visual analogue scale.1319 In another randomized trial (SPASM3), patients receiving IA verapamil 2.5 mg or isosorbide dinitrate 1 mg compared to diltiazem 5 mg before transradial coronary intervention experienced a lower incidence (16.2, 17.2, and 26.6%, respectively) of radial artery spasm.1320
Verapamil has been used in the management of acute aortic syndromes (AAS).1336 The American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend IV antihypertensive therapy for the management of AAS, including, but not limited to, aortic dissection.1336 IV beta-adrenergic blockers are recommended first-line for initial blood pressure and heart rate management in patients with AAS.1336 IV nondihydropyridine calcium channel blockers (i.e., diltiazem, verapamil) are recommended for heart rate control in patients with AAS who have contraindications to or intolerance to IV beta-adrenergic blockers.1336
Verapamil has been used as a preventative treatment in cluster headache†; some experts consider it the medication of choice.1317 In limited trials, primarily open-label in patients with episodic or chronic cluster headache, verapamil reduced headache frequency by at least 50%, and some patients achieved complete relief.1317
Verapamil has been used in the management of thyrotoxicosis†.1316 Expert guidelines for the management of hyperthyroidism recommend diltiazem or verapamil in patients unable to tolerate or who are not candidates for beta-adrenergic blocking agents (e.g., bronchospastic asthma) for heart rate control, especially elderly patients and thyrotoxic patients with resting heart rates > 90 beats per minute or coexistent cardiovascular disease, with symptomatic thyrotoxicosis.1316
Dispensing and Administration Precautions
Verapamil hydrochloride is administered orally or by direct IV injection depending on the indication.117, 118, 302, 352, 382, 602 The drug has also been administered by IV infusion† and by intra-arterial injection†, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170 but safety and efficacy of these methods of administration have not been established.
Verapamil hydrochloride is administered orally as conventional tablets, extended-release tablets, extended-release pellet filled capsules, or controlled-onset extended-release pellet filled capsules (e.g., Verelan® PM).60, 61, 117, 118, 302, 602 Directions for administration (e.g., dosing frequency, administration with or without food, potential for opening capsules and mixing with food) may vary by manufacturer and formulation; the manufacturer's information for a specific preparation should be consulted for detailed information.117, 118, 302, 602
Conventional (immediate-release) tablets: Administer 3 times daily for the treatment of hypertension and angina.118 Administer 3 or 4 times daily for the treatment of arrhythmias.118 Store the tablets at 20-25°C in a tight, light-resistant container.118
Extended-release tablets: Administer once daily in the morning with food.117 When the dosage exceeds 240 mg daily, administer tablets twice daily in the morning and evening (i.e., 180 mg twice daily, or 240 mg in the morning and 120 mg in the evening).117 Store the extended-release tablets at 20-25°C (excursions permitted to 15-30°C) in a tight, light-resistant container.117 Keep tablets in the original/pharmacy container; store in a dry place and protect from light and moisture.117
Extended-release pellet filled capsules: Administer once daily in the morning; do not crush or chew the capsules.302 Alternatively, the entire contents of a capsule may be sprinkled on a small amount of applesauce immediately prior to administration.302 The applesauce should not be hot, and should be soft enough to be swallowed without chewing.302 Swallow the applesauce mixture immediately without chewing and drink a glass of cool water to ensure complete administration of the pellets.302 Do not store the applesauce mixture for future use.302 Store the pellet filled capsules at 20-25°C (brief excursions above 25°C are not detrimental, but should be avoided) in a tight, light-resistant container.302 Protect from excessive heat and moisture.302
Controlled-onset extended-release pellet filled capsules: Administer once daily at bedtime; do not crush or chew the capsules.602 Alternatively, the entire contents of a capsule may be sprinkled on one tablespoonful of applesauce immediately prior to administration.602 The applesauce should not be hot, and should be soft enough to be swallowed without chewing.602 Swallow the mixture without chewing and drink a glass of cool water to ensure complete administration of the pellets.602 Do not store the applesauce mixture for future use.602 Absorption of the pellets sprinkled onto other foods has not been tested.602 Store the extended-release capsules at 25°C (excursions permitted to 15-30°C) in a tight, light-resistant container; protect from moisture.602
Trandolapril and verapamil hydrochloride extended-release fixed combination tablets: Administer once daily with food.352 Although trandolapril tablets and/or verapamil extended-release capsules or tablets may be administered once or twice daily, verapamil in fixed-combination with trandolapril was only administered once daily in clinical trials.352 Store the fixed-combination tablets at 20-25°C in a tight container.352
Verapamil hydrochloride is administered by direct IV injection in the management of supraventricular tachyarrhythmias.382
Verapamil must be given slowly under continuous ECG and blood pressure monitoring as a direct injection over a period of not less than 2 minutes or, in geriatric patients, of not less than 3 minutes.382 Solutions of the drug should be inspected visually for particulate matter prior to IV administration whenever solution and container permit.382
Verapamil hydrochloride injection should be stored at 20-25°C in its original package and protected from light.382
Verapamil hydrochloride is physically and chemically stable for at least 24 hours at 25°C in most common infusion solutions when protected from light.237, 238, 382 Dilution of the drug in sodium lactate injection in PVC containers is not recommended.382 In solutions with a pH greater than 6, the drug will precipitate.382 Admixing the drug with albumin, amphotericin B, hydralazine hydrochloride, or trimethoprim with sulfamethoxazole should be avoided.239, 382
Dosage of verapamil hydrochloride is expressed in terms of the hydrochloride salt.117, 118, 302, 352, 382, 602
For the management of supraventricular tachycardias (SVT) in adults, the usual initial IV dose of verapamil hydrochloride recommended by the manufacturer is 5-10 mg (0.075-0.15 mg/kg) over at least 2 minutes.382, 700, 1307 Slower injection rates (over at least 3 minutes) should be used in geriatric patients in order to minimize the risk of adverse effects.382 If the response to the initial IV dose is inadequate, a second IV dose of 10 mg (0.15 mg/kg) may be given 30 minutes after the initial dose.382, 1307 An optimal interval for subsequent IV doses has not been determined and should be individualized for each patient.382
For the management of SVT in infants younger than 1 year of age, the usual initial IV dose of verapamil hydrochloride recommended by the manufacturer is 0.75-2 mg (0.1-0.2 mg/kg) administered over at least 2 minutes under continuous ECG monitoring.382 In pediatric patients 1-15 years of age, the usual initial IV dose is 2-5 mg (0.1-0.3 mg/kg), but should not exceed 5 mg.382 The initial pediatric dose may be repeated once after 30 minutes if an adequate response is not achieved.382 In pediatric patients 1-15 years of age, the repeat dose should not exceed 10 mg.382 Controlled studies with IV administration of verapamil have not been conducted.382 An optimal interval for subsequent IV doses has not been determined and should be individualized for each patient.382
The usual oral dosage of verapamil hydrochloride for the prevention of recurrent or ongoing paroxysmal supraventricular tachycardias (PSVT) in adults is 240-480 mg daily given in 3 or 4 divided doses as conventional tablets.118 Some experts recommend an initial dosage of 120 mg daily and a maximum maintenance dosage of 480 mg daily, administered in divided doses (with conventional tablets) or as a single dose with a long-acting preparation†.700
To control ventricular rate in digitalized adults with chronic atrial flutter and/or fibrillation, the usual adult oral dosage of verapamil hydrochloride is 240-320 mg daily given in 3 or 4 divided doses as conventional tablets.118 Some experts recommend a daily dose of 180-480 mg administered as a single dose with a long-acting preparation†.1307 Maximum antiarrhythmic effects are generally apparent within 48 hours after initiating a given verapamil dosage.118
For the management of vasospastic (Prinzmetal variant) angina or unstable or chronic stable angina, the usual adult oral dosage of verapamil hydrochloride (as conventional tablets) is 80-120 mg 3 times daily.118 Lower dosages (e.g., 40 mg 3 times daily) may be necessary in patients who may have an increased response to the drug (e.g., decreased hepatic function, elderly).118 Upward titration should be based on therapeutic efficacy and safety evaluated approximately eight hours after dosing.118 Dosage of the drug may be gradually increased at weekly intervals or, in patients with unstable angina, at daily intervals until optimum control of angina is obtained.118 Maximum response may be delayed since the half-life of the drug increases during chronic dosing.118 The manufacturer of the conventional tablets states that the effectiveness and safety of dosages exceeding 480 mg/day have not been established; therefore, the recommended daily dosage should not be exceeded.118
For the management of hypertension in adults, verapamil hydrochloride conventional tablets, extended-release tablets, or extended-release pellet filled capsules, or controlled-onset extended-release pellet filled capsules may be used.117, 118, 302, 602
The hypotensive effect of verapamil is usually evident within the first week of therapy.117, 118, 302, 602 The need for upward titration of dosage with the conventional tablets should be based on therapeutic efficacy assessed at the end of the dosing interval.118 The need for upward titration of dosage with the extended-release capsules or tablets should be based on efficacy and safety evaluated weekly at approximately 24 hours after a dose.117, 302, 602 When verapamil hydrochloride is administered at bedtime as extended-release capsules, blood pressure determinations the following morning or early afternoon are necessary to determine maximum effect.602
Verapamil Therapy (Extended-release Formulations)
For the management of hypertension in adults, the usual dosage of verapamil as extended-release pellet filled capsules is 240 mg once daily in the morning;302 when given as extended-release tablets, the usual initial dosage is 180 mg once daily in the morning.117 In patients who may have an increased response to the drug, such as geriatric patients and those of small stature, it may be preferable to initially administer 120 mg once daily in the morning as sustained-release capsules or extended-release tablets.117, 302
If an adequate response is not obtained with an initial verapamil hydrochloride dosage of 120 mg once daily in the morning (as extended-release pellet filled capsules), the dosage may be adjusted upward as follows according to the patient's blood pressure response:302
If an adequate response is not obtained with an initial dosage of 180 mg once daily in the morning as extended-release tablets, the dosage may be adjusted upward as follows according to the patient's blood pressure response:117
Some experts recommend a usual dosage range of 120-360 mg given as a single dose or in 2 divided doses daily as the extended-release capsules or tablets.1200
The usual manufacturer-recommended initial adult dosage of verapamil hydrochloride controlled-onset, extended-release pellet filled capsules (e.g., Verelan® PM) is 200 mg daily at bedtime.602 Dosage may be increased to 300 mg daily at bedtime; if an adequate response is not achieved, dosage may be further increased to 400 mg (two 200-mg capsules) daily at bedtime.602 In patients who may have an increased response to the drug (e.g., elderly, low weight, those with impaired renal or hepatic function), an initial dosage of 100 mg daily may be warranted in rare instances.602
Verapamil Therapy (Conventional Tablets)
If a conventional (immediate-release) preparation is used for the management of hypertension in adults, the usual initial oral dosage of verapamil hydrochloride as monotherapy is 80 mg 3 times daily.118 In patients who may have an increased response to the drug, such as geriatric patients and those of small stature, it may be preferable to initially administer 40 mg 3 times daily.118 Oral dosages up to 480 mg daily have been used in some adults,118, 199, 200, 201, 214, 215, 216, 230 but there is no evidence that dosages exceeding 360 mg daily as conventional tablets provide any additional benefit in the management of hypertension.118 Some experts recommend a usual dosage range of 120-360 mg daily (given in 3 divided doses) as conventional tablets.1200 When switching from conventional verapamil hydrochloride tablets to extended-release capsules or tablets, the total daily dose may remain the same.117, 302
Trandolapril/Verapamil Hydrochloride Extended-release Fixed-combination Therapy
When combination therapy is required for the management of hypertension in adults, the commercially available preparation containing trandolapril in fixed combination with verapamil hydrochloride should not be used for initial therapy.352 To minimize dose-independent hazards, it is usually appropriate to begin therapy with trandolapril and verapamil hydrochloride extended-release tablets only after a patient has either failed to achieve the desired antihypertensive effect with one or the other monotherapy at its respective maximally recommended dose and shortest dosing interval, or the dose of one or the other monotherapy cannot be increased further because of dose-limiting side effects.352 For the treatment of hypertension, the recommended usual dosage range of trandolapril and verapamil hydrochloride extended-release tablets is 1-4 mg and 120-480 mg per day, respectively.352 Although trandolapril tablets and/or verapamil extended-release capsules or tablets may be administered once or twice daily, verapamil in fixed-combination with trandolapril was only administered once daily in clinical trials.352 For patients receiving verapamil hydrochloride (up to 240 mg) and trandolapril (up to 8 mg) in separate tablets once daily, replacement with the fixed combination can be attempted using tablets containing the same component doses.352
The usual oral daily doses of verapamil hydrochloride may need to be reduced by 70% in adults with severe hepatic dysfunction.117, 118, 302, 602 Monitor patients for abnormal PR interval prolongation or other signs of excessive pharmacologic effects (e.g., hypotension, bradycardia).117, 118, 302, 602
Hypertension: The manufacturer of verapamil hydrochloride controlled-onset extended-release capsules (e.g., Verelan® PM) states that an initial dosage of 100 mg daily at bedtime rarely may be necessary in patients with impaired hepatic function.602
Angina: The manufacturers of verapamil hydrochloride conventional tablets suggest an initial dosage of 40 mg 3 times daily in patients who may have an increased response (e.g., decreased hepatic function).118
Repeated IV injections of verapamil hydrochloride in patients with impaired hepatic and/or renal function may lead to accumulation and an excessive pharmacologic effect of the drug.382 The manufacturer states that such use should generally be avoided.382 If repeated injections are necessary, closely monitor for PR interval prolongation and blood pressure changes; repeat doses should be smaller.382
The manufacturer of the verapamil hydrochloride controlled-onset extended-release capsules states that an initial dosage of 100 mg daily at bedtime rarely may be necessary in patients with impaired renal function.602 Monitor patients for abnormal PR interval prolongation or other signs of excessive pharmacologic effects (e.g., hypotension, bradycardia).117, 118, 302, 602
Repeated IV injections of verapamil hydrochloride in patients with impaired hepatic and/or renal function may lead to accumulation and an excessive pharmacologic effect of the drug.382 The manufacturer states such use should generally be avoided.382 If repeated injections are necessary, closely monitor for PR interval and blood pressure changes; repeat doses should be smaller.382
Neither verapamil nor norverapamil (the active metabolite) appear to be removed appreciably by hemodialysis; therefore, supplemental doses in patients undergoing hemodialysis are not necessary.117, 118, 281, 290
In general, dose selection for an geriatric patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.117, 118, 302, 602
Hypertension: The manufacturer of the verapamil hydrochloride controlled-onset extended-release capsules states that an initial dosage of 100 mg daily at bedtime rarely may be necessary in elderly patients.602 The manufacturers of the extended-release pellet filled capsules and the extended-release tablets suggest an initial dosage of 120 mg once daily in the morning in patients who may have an increased response (e.g., elderly).117, 302 The manufacturers of conventional verapamil hydrochloride tablets suggest an initial dosage of 40 mg 3 times daily in patients who may have an increased response (e.g., elderly).118
Angina: The manufacturers of verapamil hydrochloride conventional tablets suggest an initial dosage of 40 mg 3 times daily in patients who may have an increased response (e.g., elderly).118
Supraventricular arrhythmias: Slower injection rates (over at least 3 minutes) should be used in geriatric patients in order to minimize the risk of adverse effects.382
The manufacturer of verapamil hydrochloride controlled-onset extended-release capsules states that an initial dosage of 100 mg daily at bedtime rarely may be necessary in patients with low body weight.602 The manufacturers of the extended-release pellet filled capsules and extended-release tablets state that an initial dosage of 120 mg once daily in the morning may be warranted in patients who may have an increased response (e.g., those of small stature).117, 302 The manufacturers of conventional tablets suggest an initial dosage of 40 mg 3 times daily in patients who may have an increased response (e.g., those of small stature).118
Congestive heart failure or pulmonary edema, resulting from verapamil's negative inotropic action, occurs in less than 2% of patients receiving the drug orally.117, 118, 302, 602 Patients with milder ventricular dysfunction should, if possible, be controlled with optimum doses of a cardiac glycoside (e.g., digoxin) and/or diuretics before initiating verapamil therapy.117, 118, 302, 602
Verapamil generally should not be used in patients with severe left ventricular dysfunction (i.e., pulmonary wedge pressure greater than 20 mm Hg, left ventricular ejection fraction less than 30%), unless the heart failure is caused by a supraventricular tachycardia amenable to verapamil, nor should the drug be used in patients with moderate to severe symptoms of cardiac failure.117, 118, 302, 382, 602 Verapamil should also be avoided in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker.117, 118, 302, 602
Adverse effects attributed to the vasodilating action of verapamil on vascular smooth muscle include dizziness or symptomatic hypotension, which occur in less than 2.5% of patients receiving the drug orally.117, 118, 302, 602 Decreases in blood pressure to lower than normal are unusual in hypertensive patients receiving the drug.117, 118, 302, 602 Tilt-table testing (60 degrees) was not able to induce orthostatic hypotension. 117, 118, 302, 602
Systolic and diastolic blood pressures less than 90 and 60 mm Hg, respectively, occur in 5-10% of patients receiving IV verapamil.382 Blood pressures falling below baseline levels are usually transient and asymptomatic but may result in dizziness.382 Hypotension rarely may require treatment with an IV calcium salt or vasopressor.382 Monitor blood pressure during IV verapamil therapy.382
Increases in serum concentrations of AST (SGOT) and ALT (SGPT), with or without concomitant increases in alkaline phosphatase and bilirubin, have been reported rarely with oral verapamil.117, 118, 302, 602 These increases are occasionally transient and may resolve despite continued verapamil therapy.117, 118, 302, 602 However, hepatocellular injury, which recurred during rechallenge, has occurred in several patients and may be accompanied by clinical symptoms of hepatotoxicity, including malaise, fever, and/or right upper quadrant pain.117, 118, 302, 602 Periodic monitoring of liver function is recommended during chronic verapamil therapy.117, 118, 302, 602
In patients with atrial fibrillation and/or flutter and an accessory AV pathway (e.g., Wolff-Parkinson-White or Lown-Ganong-Levine syndrome), increased anterograde conduction across aberrant pathways that bypass the AV node may result in a verapamil-induced increase in ventricular rate, including ventricular fibrillation, following IV verapamil administration.117, 118, 302, 382, 602 Ventricular fibrillation with loss of consciousness and atrial fibrillation with markedly increased ventricular rate and resultant profound hypotension and syncope have occurred within minutes after IV administration of verapamil in patients with an accessory AV pathway.108 The risk of these effects occurring when the drug is used orally in patients with atrial fibrillation and/or flutter and an accessory AV pathway has not been established, but a similar risk may be associated with oral use of the drug.117, 118, 302, 602 Because of the risk of potentially fatal adverse effects, verapamil (parenterally or orally) is contraindicated in these patients.117, 118, 302, 382, 602
Cardiac Conduction Abnormalities
Adverse effects attributed to verapamil's action on the cardiac conduction system include bradycardia, first-, second-, and third-degree AV block, and, in extreme cases, asystole.117, 118, 302, 382, 602 First-degree AV block may be asymptomatic; bradycardia may be transient.117, 118, 302, 602 Prolongation of the PR interval is correlated with plasma verapamil concentrations, especially during initial titration of therapy with the drug.117, 118, 302, 602 Higher degrees of AV block were observed infrequently (0.8%).117, 118, 302, 602 During clinical trials, bradycardia associated with sick sinus syndrome and the total incidence of bradycardia (ventricular rates less than 60 bpm) occurred in 0.3 and 1.2%, respectively.382 Asystole has occurred with IV verapamil but AV nodal or normal sinus rhythm usually has returned within a few seconds except in patients with sick sinus syndrome (SA nodal disease).382
Conduction disturbances, including marked first-degree block or progression to second- or third-degree block, generally respond to discontinuance of IV verapamil, reduction of oral verapamil dosage, or, in the case of rapid ventricular rate due to anterograde conduction in atrial flutter/fibrillation with Wolff-Parkinson-White or Lown-Ganong-Levine syndrome, to cardioversion; severe AV block may rarely require discontinuance of the drug and initiation of appropriate treatment (e.g., IV atropine, isoproterenol, norepinephrine, calcium), depending on the clinical situation.117, 118, 302, 382, 602
Verapamil should be used with caution in patients with hypertrophic cardiomyopathy since serious and sometimes fatal adverse cardiovascular effects (e.g., pulmonary edema and/or severe hypotension) have occurred in such patients during verapamil therapy.117, 118, 302, 602 In 120 patients with hypertrophic cardiomyopathy, most of them refractory or intolerant to propranolol, a variety of serious adverse effects were seen; patients were receiving verapamil at doses up to 720 mg/day.117, 118, 302, 602 Of the 8 patients who died, severe left ventricular outflow obstruction, a past history of left ventricular dysfunction, abnormally high (greater than 20 mm Hg) pulmonary wedge pressure, or a marked left ventricular outflow obstruction were present.117, 118, 302, 602 Concomitant administration of quinidine preceded the severe hypotension in 3 of the 8 patients (2 of whom developed pulmonary edema).117, 118, 302, 602 It must be appreciated that this group of patients had a serious disease with a high mortality rate.117, 118, 302, 602
In patients with hypertrophic cardiomyopathy receiving the drug orally, the incidence of these adverse effects may be increased; in one study, 11% of these patients had bradycardia, 4% had second-degree AV block, and 2% had sinus arrest.117, 118, 302, 602 Most adverse effects responded well to dose reduction, and only rarely did verapamil use have to be discontinued.117, 118, 302, 602
Attenuated Neuromuscular Transmission
It has been reported that verapamil decreases neuromuscular transmission in patients with Duchenne muscular dystrophy, prolongs recovery from the neuromuscular blocking agent vecuronium, and causes a worsening of myasthenia gravis.117, 118, 302, 602 In patients with attenuated neuromuscular transmission, it may be necessary to decrease the dosage of verapamil.117, 118, 302, 602 Respiratory muscle failure may be precipitated by IV verapamil in patients with Duchenne muscular dystrophy.382
Increased Intracranial Pressure
Caution should also be exercised and appropriate monitoring performed when IV verapamil is used in patients with supratentorial tumors who are undergoing anesthesia induction, since increased intracranial pressure can occur.382
Ventricular premature beats (VPBs) may be present following intravenous verapamil administration as well as during cardioversion, other pharmacologic therapy, and during spontaneous conversion of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm.382 Following IV verapamil, VPBs that present on conversion of PSVT to sinus rhythm or marked reduction in ventricular rate are considered to be benign and appear to have no clinical significance.382
When verapamil is used in fixed combination with trandolapril, consider the cautions, precautions, contraindications, boxed warnings, and drug interactions associated with trandolapril.352
There are no adequate and controlled studies to date using verapamil in pregnant women, and the drug should be used during pregnancy only when the potential benefit justifies the potential risk to the fetus117, 118, 302, 382, 602 Verapamil crosses the placenta and is present in umbilical vein blood at delivery.117, 118, 302, 602 Although the effects of verapamil on the mother and fetus during labor and delivery have not been fully determined, the drug has been used short-term without prolonging the duration of labor or increasing the need for forceps delivery or other obstetric intervention and without apparent adverse fetal effect in women who received verapamil as therapy for adverse cardiac effects induced by beta-adrenergic agonists that were used in the management of premature labor.117, 118, 302, 382, 602
Reproduction studies in rabbits and rats using oral verapamil dosages up to 1.5 (15 mg/kg daily) and 6 (60 mg/kg daily) times the usual human oral dosage, respectively, have not revealed evidence of teratogenicity.117, 118, 302, 382, 602 However, in rats, this dosage has been shown to be embryocidal and was associated with retarded fetal growth and development, probably as a result of adverse maternal effects as evidenced by reduced maternal weight gain; this dosage has been shown to cause hypotension in rats.117, 118, 302, 382, 602
Verapamil is distributed into milk.103, 117, 118, 122, 123, 124, 302, 382, 602 In case studies where verapamil concentration in human milk was calculated, the nursing infant doses ranged from less than 0.01-0.1% of the mother's verapamil dose; this exposure should be considered when verapamil is administered to a nursing woman.602 Because of the potential for serious adverse effects of verapamil in nursing infants, the manufacturers recommend that nursing be discontinued during therapy with the drug.117, 118, 302, 382, 602
Females and Males of Reproductive Potential
Reproduction studies in female rats using oral verapamil hydrochloride dosages up to 5.5 times the recommended maximum human dosage have not revealed evidence of impaired fertility.117, 118, 302, 602 The effects of verapamil on male fertility have not been determined,117, 118, 131, 302, 602 but the drug has increased human sperm motility in vitro.131
Controlled studies with verapamil in children have not been performed to date, but experience using IV verapamil in more than 250 children (about 50% were younger than 12 months of age and 25% were neonates) indicates that the drug produces effects similar to those in adults.382 However, severe hemodynamic effects, some of them fatal, have occurred rarely following IV administration of verapamil in neonates and infants.382 Therefore, the manufacturer states that IV verapamil should be used with caution in neonates and infants.382 Safety and efficacy of oral verapamil in children younger than 18 years of age have not been established.117, 118, 302, 602
While clinical experience to date has not revealed age-related differences in response to verapamil, clinical studies evaluating verapamil have not included sufficient numbers of adults 65 years of age or older to determine whether geriatric patients respond differently than younger adults; greater sensitivity cannot be ruled out.302, 602 Aging may affect the pharmacokinetics of verapamil given to patients with hypertension; the elimination half-life may be prolonged, and an increased response to the drug may occur.117, 118, 302, 602 The manufacturers of verapamil state that dosage for geriatric patients should be selected carefully, usually starting at the low end of the dosing range, because these individuals frequently have decreased hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.302, 602 To minimize the risk of adverse effects, IV verapamil should be administered over at least 3 minutes in older patients.382
Verapamil is highly metabolized by the liver; severe liver dysfunction prolongs the elimination half-life of immediate-release verapamil to about 14-16 hours.117, 118, 302, 602 The manufacturers recommend caution and an approximately 70% dose reduction in patients with impaired hepatic function.117, 118, 302, 602 Careful monitoring for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effects should be performed.117, 118, 302, 602
In patients with hepatic and renal failure, duration of action may be prolonged following a single IV verapamil dose.382 Repeated injections of the drug in such patients may lead to accumulation and an excessive pharmacologic effect of the drug.382 The manufacturer states there is no experience to guide use of multiple doses in such patients; use should generally be avoided.382 Blood pressure and PR interval should be closely monitored and smaller repeat doses should be utilized if repeated injections are essential.382
About 70% of an administered dose of verapamil is excreted as metabolites in the urine; verapamil is not removed by hemodialysis.117, 118, 302, 602 The manufacturer states verapamil should be administered cautiously to patients with impaired renal function until further data are available.117, 118, 302, 382, 602 Carefully monitor such patients for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effects.117, 118, 302, 602
In patients with hepatic and renal failure, duration of action may be prolonged following a single IV verapamil dose.382 Repeated injections of the drug in such patients may lead to accumulation and an excessive pharmacologic effect of the drug.382 The manufacturer states there is no experience to guide use of multiple doses in such patients; use should generally be avoided.382 Blood pressure and PR interval should be closely monitored and smaller repeat doses should be utilized if repeated injections are essential.382
The most common adverse effects reported with oral verapamil are constipation, dizziness, nausea, hypotension, headache, and edema.117, 118, 302, 602
The most common adverse effects reported with IV verapamil include symptomatic hypotension, bradycardia, severe tachycardia, dizziness, headache, nausea, and abdominal discomfort.382
In vitro studies indicate that verapamil is metabolized by cytochrome P-450 (CYP) isoenzyme 3A4, 1A2, 2C8, 2C9, and 2C18. 117, 118, 302, 602, 1310 Verapamil also inhibits CYP3A4.1310
When used in fixed combination with trandolapril, the drug interactions associated with each drug must be considered.352
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Concomitant use of verapamil with CYP3A4 inhibitors or inducers may increase or decrease plasma concentrations of verapamil, respectively.117, 118, 302, 602, 1310 Clinically significant drug interactions with CYP3A4 inhibitors (e.g., erythromycin, ritonavir) have been reported, resulting from increased verapamil plasma concentrations.117, 118, 302, 602, 1310 Inducers of CYP3A4 (e.g., rifampin) have caused decreased verapamil plasma concentrations.117, 118, 302, 602, 1310 Concomitant use of verapamil with CYP3A4 substrates such as certain HMG-CoA reductase inhibitors (e.g., atorvastatin, lovastatin, simvastatin) can result in increased plasma concentrations of the substrate and has been associated with myotoxicity (including rhabdomyolysis), a concentration-dependent side effect of statins.117, 118, 302, 602, 1310, 1311
Verapamil is highly protein bound and should be used with caution in patients receiving other highly protein-bound drugs.382
Verapamil may inhibit ethanol elimination, resulting in elevated blood alcohol concentrations and prolonged intoxicating effects.117, 118, 302, 602 Following oral administration of a single dose of alcohol (e.g., 0.8 g/kg of body weight) to healthy men receiving verapamil (80 mg 3 times daily for 5 days) or placebo, mean peak blood alcohol concentrations increased by 17% and the area under the blood alcohol concentration-time curve (AUC0-12) increased by 30%.385
The manufacturers state that dosages of each drug should be titrated carefully when a calcium slow-channel blocker such as verapamil is used concomitantly with inhalation anesthetics that depress cardiovascular activity since potentiation of this depression may occur. 117, 118, 302, 602
Verapamil can increase doxorubicin levels.602 One manufacturer states that verapamil absorption may be reduced by the cyclophosphamide, vincristine, procarbazine, prednisone (COPP) and the vindesine, doxorubicin, cisplatin (VAC) cytotoxic drug regimens.602 Concomitant administration of R -verapamil can decrease the clearance of paclitaxel.602
Coadministration of verapamil with aspirin has resulted in increased bleeding times compared with administration of aspirin alone in a few reported cases. 118, 302, 602
Beta-adrenergic Blocking Agents
Concomitant use of nondihydropyridine calcium-channel blockers (e.g., verapamil, diltiazem) and beta-adrenergic blocking agents can have additive negative effects on myocardial contractility, heart rate, and AV conduction. 117, 118, 302, 602
The manufacturer states controlled studies in small numbers of patients suggest that the concomitant use of immediate-release verapamil and oral beta-adrenergic blocking agents (e.g., propranolol) may be beneficial in certain patients with chronic stable angina or hypertension, but available information is not sufficient to predict with confidence the effects of concurrent treatment in patients with left ventricular dysfunction or cardiac conduction abnormalities.118 Combined therapy should usually be avoided in patients with AV conduction abnormalities and those with depressed left ventricular function.118
The combination of sustained-release verapamil and beta-adrenergic blocking agents has not been studied; however, excessive bradycardia and AV block, including complete heart block, when the combination has been used for the treatment of hypertension has been reported. 117, 302, 602 The manufacturers state the risks of combined therapy may outweigh the potential benefits in patients with hypertension. 117, 302, 602 Verapamil should be used cautiously with a beta-adrenergic blocking agent for the management of hypertension and only with close monitoring. 117, 302, 602
In rare instances, including when patients with severe cardiomyopathy, congestive heart failure, or recent myocardial infarction were given IV beta-adrenergic blocking agents concomitantly with IV verapamil, serious adverse effects have occurred.382 Concomitant use of verapamil with beta-adrenergic blockers may result in an exaggerated hypotensive response.382 IV verapamil is contraindicated in patients currently receiving, or who have recently received IV beta-adrenergic blocker therapy (i.e., within a few hours of IV verapamil therapy), due to the risk of severe hypotension and the depressant effect on myocardial contractility and AV conduction.382
Severe bradycardia (e.g., 36 bpm), which was associated with a wandering atrial pacemaker in one patient, has been reported when oral verapamil and ophthalmic timolol were used concomitantly. 117, 118, 242, 302, 602
Verapamil may decrease metoprolol clearance. 117, 118, 141, 142, 302, 602 A variable effect has been seen when verapamil and atenolol were administered concomitantly. 117, 118, 141, 142, 302, 318, 602
Verapamil also may decrease oral clearance of propranolol; minimal increases in plasma propranolol concentrations have been reported in some individuals receiving verapamil concomitantly. 117, 118, 302, 314, 316, 602
Verapamil may increase serum cyclosporine or tacrolimus concentrations.117, 118, 294, 295, 302, 382, 602, 1310
Concomitant use of verapamil and carbamazepine may result in increased plasma carbamazepine concentrations and adverse effects such as diplopia, headache, ataxia, or dizziness.104, 106, 117, 118, 302, 382, 602 In several patients receiving 1-2 g of carbamazepine daily, initiation of 360 mg of verapamil hydrochloride daily resulted in development of neurologic manifestations (e.g., diplopia, dizziness, ataxia, nystagmus) of carbamazepine toxicity within 36-96 hours.104, 106 Plasma total and unbound carbamazepine concentrations increased by a mean of 46 and 33%, respectively, but returned to baseline values within 1 week after discontinuance of verapamil; manifestations of toxicity also resolved during this period.104 The ratio of plasma carbamazepine 10,11-epoxide to unchanged drug decreased during verapamil therapy but returned toward pretreatment levels following discontinuance of verapamil.104
Variable results on verapamil clearance have been obtained in acute studies of healthy volunteers receiving cimetidine; clearance of verapamil was either reduced or unchanged.117, 118, 302, 382, 602 The interaction between cimetidine and chronically administered verapamil has not been studied.117, 118, 302, 382, 602
Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil.117, 118, 302, 602 Monitor heart rate in patients receiving concomitant verapamil and clonidine.117, 118, 302, 602
Oral verapamil may increase serum digoxin concentrations by 50-75% during the first week of verapamil therapy.117, 118, 302, 602 This effect may be more substantial in patients with underlying hepatic disease (e.g., cirrhosis).117, 118, 302, 602 Verapamil may reduce total body clearance and extrarenal clearance of digitoxin by 27% and 29%, respectively.117, 118, 302, 602 When verapamil is administered to a patient receiving digoxin, dosage of the glycoside generally should be reduced and the patient should be reassessed to avoid over- or under-digitalization.117, 118 Whenever cardiac glycoside toxicity is suspected, dosage of digoxin should be further reduced and/or temporarily withheld.117, 118, 302, 602 If verapamil is discontinued in a patient stabilized on digoxin, the patient should be reassessed to avoid under-digitalization.117, 118, 1310 When verapamil (preparation unspecified) and digoxin were used concomitantly in clinical trials to control ventricular response in patients with atrial fibrillation or atrial flutter, ventricular rates below 50 bpm at rest and asymptomatic hypotension occurred in 15 and 5% of patients, respectively.302, 602
Verapamil hydrochloride injection has been used concomitantly with digitalis preparations without the occurrence of serious adverse effects; patients should be monitored for AV block or excessive bradycardia.382
Pending further accumulation of data on the safety of combined therapy, disopyramide should not be administered within 48 hours before or 24 hours after verapamil administration.117, 118, 302, 382, 602, 1310
Concomitant administration of verapamil and efavirenz, a CYP3A4 inducer, may decrease verapamil exposure.1312 Experts recommend verapamil dosage titration based on clinical response.1312
Decreased verapamil exposure is possible when administered with etravirine, a CYP3A4 inducer.1312 Experts recommend verapamil dosage titration based on clinical response.1312
In a study of healthy individuals, concomitant administration of verapamil and flecainide showed possible additive effects on myocardial contractility, AV conduction, and repolarization.117, 118, 302, 382, 602 Concomitant use of flecainide and verapamil may result in additive negative inotropic effect and prolongation of AV conduction.117, 118, 302, 382, 602
In a small number of healthy individuals, grapefruit juice increased S -verapamil AUC and peak plasma concentrations by 36 and 57%, respectively; smaller increases were observed with R -verapamil.302, 602 No significant pharmacokinetic differences in the active metabolite norverapamil were observed.302, 602 No clinical consequences due to this increased plasma concentration are expected.302, 602
Concomitant use of verapamil and atazanavir or cobicistat- or ritonavir-boosted atazanavir may result in increased verapamil exposure.1312 Concomitant use of verapamil and cobicistat- or ritonavir-boosted darunavir may result in increased verapamil exposure.1312 Experts recommend verapamil dose titration and close monitoring, including ECG monitoring.1312
Concomitant use of verapamil and HMG-CoA reductase inhibitors metabolized by CYP3A4 (e.g., atorvastatin, lovastatin, simvastatin) can increase statin exposure; the risk of myopathy, including rhabdomyolysis, may be increased.117, 118, 302, 602, 1310 When a statin is required in a patient receiving verapamil, a non-CYP3A4-metabolized statin (e.g., pravastatin) should be used although experts state these combination therapies may be considered in appropriate patients when the potential for benefits outweighs potential risks.1310, 1311 Lower starting and maintenance doses of other CYP3A4 substrates (e.g., atorvastatin) may be required as verapamil may increase the plasma concentration of these drugs.117, 118, 302, 602
Experts state that coadministration of verapamil with lovastatin results in moderate increases in lovastatin exposure.1311 The manufacturer of lovastatin states that dosage of lovastatin should not exceed 20 mg daily in patients taking verapamil.603
Co-administration of multiple doses of 10 mg of verapamil hydrochloride with 80 mg simvastatin resulted in increased exposure to simvastatin by 2.5-fold compared with administration of simvastatin alone.117, 118, 302, 602 Limit simvastatin dosage to 10 mg daily when used concomitantly with verapamil.117, 118, 302, 602
Verapamil may be additive with or potentiate the hypotensive actions of hypotensive agents (e.g., diuretics, angiotensin-converting enzyme inhibitors, vasodilators, beta-adrenergic blockers).117, 118, 302, 602 Appropriately monitor patients when these drugs are used concomitantly.117, 118, 302, 602 An excessive reduction in blood pressure may occur in patients receiving verapamil concomitantly with drugs that attenuate alpha-adrenergic response (e.g., prazosin).117, 118, 302, 602 In healthy normotensive individuals, 160 mg of oral verapamil hydrochloride substantially enhanced the hypotensive effect of 1 mg of oral prazosin.140
Concurrent use of verapamil increases exposure to ivabradine; such use may exacerbate bradycardia and conduction disturbances.117, 302, 382, 602 Avoid coadministration of verapamil and ivabradine.117, 302, 382, 602
Serum lithium concentrations may decrease, increase, or remain unchanged during concomitant use of verapamil.117, 118, 132, 302, 382, 602 Increased lithium sensitivity, including neurotoxicity, has been reported.117, 118, 302, 382, 602 Carefully monitor patients receiving both verapamil and lithium.117, 118, 302, 382, 602
Mammalian target of rapamycin inhibitors (mTOR)
In a small number of healthy individuals, when sirolimus and verapamil were coadministered, sirolimus peak concentrations (whole blood) and AUC increased by 130% and 120%, respectively; S -verapamil peak plasma concentrations and AUC were both increased by 50%.117, 302, 602 Co‑administration of verapamil with everolimus in a small number of healthy individuals increased the peak plasma concentration and AUC of everolimus by 130 and 250%, respectively.117, 302, 602 When mTOR inhibitors (e.g., sirolimus, temsirolimus, everolimus) and verapamil are used concomitantly, consider appropriate dose reductions for both drugs.117, 302, 602
Clinical studies and animal data suggest that verapamil may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing).117, 118, 302, 382, 602 It may be necessary to decrease the dosage of verapamil and/or the neuromuscular blocking agent when the drugs are used concomitantly.117, 118, 302, 382, 602
Verapamil has been given concomitantly with short- and long-acting nitrates without any undesirable drug interactions.117, 118, 302, 602
Phenobarbital therapy may increase verapamil clearance.117, 118 In healthy individuals, phenobarbital increased the clearance of total and unbound verapamil, possibly via induction of hepatic cytochrome P-450 microsomal metabolism.303, 304
Verapamil hydrochloride injection has been administered to a small number of patients receiving oral procainamide without the occurrence of serious adverse effects.382
A substantial hypotensive effect has occurred in a small number of patients with hypertrophic cardiomyopathy when verapamil was used concurrently with quinidine; pending further accumulation of data on the safety of combined therapy, concomitant use of verapamil and quinidine in such patients should probably be avoided117, 118, 153, 302, 602 Excessive hypotension has also been reported following an IV dose of verapamil in several other patients who were receiving quinidine therapy concomitantly382 but did not have hypertrophic cardiomyopathy.154 There is in vitro evidence that verapamil and quinidine have additive adrenergic-blocking activity at α1- and α2-receptors.154 The manufacturer states such combination should be used with caution.382 Verapamil has counteracted the effects of quinidine on AV conduction.117, 118, 302, 602 IV verapamil has been administered to a small number of patients receiving oral quinidine without serious adverse effects.382 There is also evidence that verapamil may increase plasma quinidine concentrations during concomitant use.117, 118, 302, 602
Rifampin may substantially reduce the oral bioavailability of verapamil.117, 118, 134, 135, 302, 382, 602, 1310 In a patient receiving 600 mg of rifampin daily and requiring a verapamil dosage of 1920 mg daily, verapamil steady-state trough serum concentrations were 123 ng/mL; 9 days after discontinuance of rifampin, trough serum verapamil concentrations increased almost fourfold.135
Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving verapamil and concurrent telithromycin.117, 118, 302, 602
Concomitant use of verapamil in individuals receiving theophylline has resulted in decreased clearance of theophylline, elevated serum theophylline concentrations, and a prolonged serum half-life of the bronchodilator.117, 118, 302, 602
Verapamil hydrochloride is a phenylalkylamine-derivative calcium-channel blocker.1310 Because most currently available calcium-channel blockers are dihydropyridines (e.g., amlodipine, nicardipine), verapamil, like diltiazem, has been referred to as a nondihydropyridine calcium-channel blocker.1310 Verapamil hydrochloride is commercially available as a racemic mixture; available dosage forms include tablets, extended-release tablets, extended-release and controlled extended-release capsules (containing pellets), and injection for IV use.117, 118, 302, 382, 602
Verapamil has pharmacologic actions similar to those of other calcium-channel blockers (e.g., diltiazem, nifedipine), however vascular-cardiac selectivity ratios differ.602, 1310 The principal physiologic action of verapamil is to inhibit the transmembrane influx of extracellular calcium ions across the membranes of myocardial cells and vascular smooth muscle cells.118, 382 By inhibiting calcium influx, verapamil inhibits the contractile processes of cardiac and vascular smooth muscle, thereby dilating the main coronary and systemic arteries.118 In patients with Prinzmetal variant angina (vasospastic angina), inhibition of spontaneous and ergonovine-induced coronary artery spasm by verapamil results in increased myocardial oxygen delivery.118 Dilation of systemic arteries by verapamil results in a decrease in total peripheral resistance, systemic blood pressure, and afterload of the heart.118 Decreases in peripheral vascular resistance usually occur without orthostatic decreases in blood pressure or reflex tachycardia.118 The reduction in afterload, seen at rest and with exercise, and its resultant decrease in oxygen consumption are thought to be responsible for the effects of verapamil in patients with unstable and chronic stable angina.118 Verapamil has substantial inhibitory effects on the cardiac conduction system and is considered a Vaughan Williams class IV antiarrhythmic agent.604 Verapamil also slows conduction and prolongs refractoriness in the atrioventricular (AV) node; this usually also results in PR-interval prolongation on ECG, which is correlated with plasma verapamil concentrations (especially during initial titration of verapamil therapy), and may rarely cause second- or third-degree AV block (even in patients without preexisting conduction defects).118, 604 Although verapamil rarely produces clinically important changes in the rate of sinoatrial (SA) node discharge or recovery time, the drug may reduce the resting heart rate and produce sinus arrest or SA block in patients with SA node disease (e.g., sick sinus syndrome).118 Verapamil reduces afterload and myocardial contractility.118 Even in patients with c
The hypotensive effect of verapamil is usually evident within the first week of therapy.118 Maximum antiarrhythmic effects are generally apparent within 48 hours after initiating a given verapamil dosage.118 After a single IV injection of verapamil, hemodynamic effects peak within 3-5 minutes and usually persist for 30-60 minutes, but may persist for as long as 6 hours.382, 1313, 1314 Conversion to sinus rhythm is achieved with IV verapamil usually within 10 minutes after administration.382 Slowing of the ventricular rate in patients with atrial fibrillation or flutter generally persists for 30-60 minutes following a single IV injection.382
Cardiac disease, the negative inotropic effect of verapamil is offset by reduced afterload, and cardiac index usually is not reduced except in patients with severe left ventricular dysfunction.118, 382
Approximately 90% of an oral dose of verapamil hydrochloride is absorbed from the GI tract following oral administration of conventional tablets of the drug.118 Only about 20-35% of an oral dose reaches systemic circulation as unchanged drug following administration of conventional tablets since verapamil is rapidly metabolized on first pass through the liver.118 The manufacturers state that oral bioavailability of extended-release capsules or tablets of the drug is similar to that of the conventional tablets when the drug is administered under fasting conditions.117, 302 Oral bioavailability of the drug may be substantially increased in patients with hepatic dysfunction (e.g., in those with hepatic cirrhosis).127, 128, 129
In healthy adults, peak plasma concentrations are reached within 1-2 hours after oral administration of conventional tablets of the drug and within 7-9 or 5-8 hours after extended-release capsules or tablets, respectively.117, 118, 302 Following oral administration of a single 240-mg extended-release capsule or tablet under fasting conditions, mean peak plasma verapamil concentrations of about 77,302 or 150-165 ng/mL,117, 119 respectively, were achieved.119, 120 Food decreases the rate and extent of absorption of extended-release verapamil tablets but produces smaller differences between peak and trough plasma concentrations of the drug;117 food does not appear to substantially affect the absorption of conventional tablets,121 extended-release capsules,302 or controlled-onset, extended-release capsules602 of the drug. When the extended-release or the controlled-onset, extended-release pellet filled capsules were administered by opening the capsule and sprinkling the pellets onto one tablespoonful of applesauce, the rate and extent of verapamil absorption were found to be bioequivalent to the same dose when administered as an intact capsule; similar results were observed with norverapamil, the active metabolite.302, 602
The commercially available controlled-onset, extended-release capsules of verapamil hydrochloride (e.g., Verelan® PM) contain the drug in an oral diffusion delivery system formulation that also is designed to initiate delivery of the drug 4-5 hours after ingestion.602 The diffusion delivery system consists of controlled-release coated pellets enclosed in a hard gelatin capsule.602 The nonenteric controlled-release coating contains water-soluble and water-insoluble polymers.602 When exposed to water in the GI tract, the soluble polymer on individual pellets slowly dissolves, allowing the drug to diffuse through the resultant pores,602 while the insoluble polymer continues to act as a barrier maintaining controlled release of the drug into the GI tract.602 The rate of verapamil delivery in the GI tract is independent of posture, pH, and presence of food in the GI tract.602 The peak plasma concentration is reached within about 11 hours after administration of controlled-onset, extended-release pellet filled capsules.602 However, administration of the extended-release capsules in the morning, instead of at bedtime, increased the extent of absorption of verapamil and/or decreased the metabolism to norverapamil.602
The commercially available fixed combination preparation containing trandolapril and verapamil hydrochloride extended-release tablets (verapamil/trandolapril) is formulated such that trandolapril is released immediately and the verapamil component is extended-release.352 Peak plasma concentrations of trandolapril and verapamil are reached in 0.5-2 and 4-15 hours, respectively.352 Verapamil bioavailability following administration of verapamil/trandolapril fixed-combination tablets with a high-fat meal is reduced; time to peak verapamil and norverapamil concentrations are delayed by approximately 7 hours.352
Approximately 90% of verapamil is bound to plasma proteins.118 Verapamil and norverapamil distribute into cerebrospinal fluid.115 Verapamil crosses the placenta and is present in umbilical vein blood at delivery.118 The drug is distributed into milk.103, 117, 118, 122, 123, 124 In case studies where verapamil concentration in human milk was calculated, the nursing infant doses ranged from less than 0.01-0.1% of the mother's verapamil dose.602
Plasma concentrations of verapamil appear to decline in a biphasic or triphasic manner following IV administration of the drug.382 After IV infusion or administration of a single oral dose, verapamil has a plasma half-life of 2-8 hours.118, 382 After 1-2 days of oral administration of the drug, plasma half-life may increase to 4.5-12 hours.602 Clearance is decreased 30% and plasma half-life of the drug also is increased to 14-16 hours in patients with hepatic cirrhosis.118 Plasma elimination half-life also appears to be increased and clearance is decreased in geriatric patients.118, 126
Verapamil is rapidly and almost completely metabolized in the liver to at least 13 metabolites.118, 602 Only norverapamil is present in plasma in more than trace amounts.118, 602 Norverapamil, an active (approximately 20% of the cardiovascular activity of verapamil) metabolite, achieves plasma concentrations approximately equal to those of verapamil within 4-6 hours of administration.117 Food decreases the rate and extent of drug reaching systemic circulation as norverapamil following oral administration of extended-release verapamil tablets.117 Approximately 70 and 16% of an oral or IV dose are excreted as metabolites in urine and feces, respectively, within 5 days.118 Only 3-4% of a dose is excreted in urine as unchanged drug.118 Neither verapamil nor norverapamil appear to be removed appreciably by hemodialysis.117, 118, 281, 290
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules, controlled-onset extended-release pellet-filled | 100 mg* | ||
Verelan® PM | Lannett | |||
200 mg* | Verapamil Hydrochloride Extended-Release Capsules (PM) | |||
Verelan® PM | Lannett | |||
300 mg* | Verapamil Hydrochloride Extended-Release Capsules (PM) | |||
Verelan® PM | Lannett | |||
Capsules, extended-release pellet-filled | 120 mg* | Verapamil Hydrochloride Extended-Release Capsules | ||
Verelan® | Lannett | |||
180 mg* | Verapamil Hydrochloride Extended-Release Capsules | |||
Verelan® | Lannett | |||
240 mg* | Verapamil Hydrochloride Extended-Release Capsules | |||
Verelan® | Lannett | |||
360 mg | Verapamil Hydrochloride Extended-Release Capsules | |||
Verelan® | Lannett | |||
Tablets, extended-release, film-coated | 120 mg* | Verapamil Hydrochloride Extended-Release Tablets | ||
180 mg* | Verapamil Hydrochloride Extended-Release Tablets | |||
240 mg* | Verapamil Hydrochloride Extended-Release Tablets | |||
Tablets, film-coated | 40 mg* | Verapamil Hydrochloride Tablets | ||
80 mg* | Verapamil Hydrochloride Tablets | |||
120 mg* | Verapamil Hydrochloride Tablets | |||
Parenteral | Injection, for IV use | 2.5 mg/mL* |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, extended-release, film-coated | Trandolapril 1 mg and Verapamil 240 mg* | Trandolapril and Verapamil Hydrochloride Extended-release Tablets | |
Trandolapril 2 mg and Verapamil 180 mg* | Trandolapril and Verapamil Hydrochloride Extended-release Tablets | |||
Trandolapril 2 mg and Verapamil 240 mg* | Trandolapril and Verapamil Hydrochloride Extended-release Tablets | |||
Trandolapril 4 mg and Verapamil 240 mg* | Trandolapril and Verapamil Hydrochloride Extended-release Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
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