Verapamil Hydrochloride

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

Introduction

Calcium-channel blocking agent; nondihydropyridine.^{353 401}

Uses for Verapamil Hydrochloride

Supraventricular Tachyarrhythmias

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

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

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

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

Angina

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

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

Hypertension

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

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

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

Hypertrophic Cardiomyopathy

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

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

AMI

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

Bipolar Disorder

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

Verapamil Hydrochloride Dosage and Administration

General

• 
  

  Individualize dosage according to patient response.^b

  
  

Hypertension

• 
  

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

  
  


• 
  

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

  
  

Supraventricular Tachyarrhythmias

• 
  

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

  
  

Administration

Administer orally or by direct IV injection.^{b 401}

Oral Administration

Extended-release Capsules (Verelan)

Administer orally once daily³⁰² without regard to meals.^b

Swallow capsules whole; do not chew or divide.³⁰²

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

Controlled Extended-release Capsules (Verelan PM)

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

Conventional Tablets (Calan)

Administer orally 2–4 times daily^{118 199 214 215 222 392} without regard to meals.^b

Extended-release Tablets (Calan SR, Isoptin SR)

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

Extended-release tablets are scored^{117 207} and may be halved without affecting oral bioavailability.^b

Extended-release Core Tablets (Covera-HS)

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

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

IV Administration

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

Monitor BP and ECG continuously during IV therapy.³⁸²

Rate of Administration

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

Dosage

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

Pediatric Patients

Supraventricular Tachyarrhythmias

See Pediatric Use under Cautions.

Conversion of PSVT to Sinus Rhythm

IV

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

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

Ventricular Rate Control in Atrial Fibrillation or Flutter

IV

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

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

Adults

Supraventricular Tachyarrhythmias

PSVT Prophylaxis

Oral

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

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

IV

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

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

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

Ventricular Rate Control in Atrial Fibrillation or Flutter

Oral

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

IV

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

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

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

Angina

Oral

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

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

Hypertension

Monotherapy

Oral

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

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

Table 1. Recommended Dosages for Management of Hypertension

Formulation	Initial Dosage	Dosage Titration Regimen
Controlled extended-release capsules (Verelan PM)
200 mg once daily at bedtime376	Manufacturer states that dosage may be increased to 300 mg once daily and then to 400 mg once daily, if required376	JNC 7 recommends usual range of 120–360 mg once daily392
Extended-release capsules (Verelan)
120 mg once daily in the morning302	Manufacturer states that dosage may be increased to 180 mg once daily and then to 240 mg once daily, with subsequent increases in 120-mg increments to 480 mg once daily, if required302	120–240 mg once dailyb
Conventional tablets (Calan)
80 mg 3 times daily118		JNC 7 recommends usual range of 80–320 mg daily, given in 2 divided doses392
Extended-release tablets (CalanSR, Isoptin SR)
180 mg once daily in the morning117	Increase dosage to 240 mg each morning117 Subsequently, increase dosage to 360 mg daily, given in 2 divided doses (either 180 mg in the morning + 180 mg in the evening or 240 mg in the morning + 120 mg in the evening)117 Manufacturer states that dosage may be increased to 240 mg every 12 hours, if required117	JNC 7 recommends usual range of 120–360 mg daily, given in 1 or 2 divided doses392
Extended-release core tablets (Covera-HS)
180 mg once daily at bedtime362	Manufacturer states that dosage may be increased to 240 mg once daily, with subsequent increases to 360 mg once daily and then to 480 mg once daily, if required362	JNC 7 recommends usual range of 120–360 mg once daily392

Combination Therapy

Oral

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

Special Populations

Hepatic Impairment

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

Angina

Oral

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

Hypertension

Oral

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

Renal Impairment

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

Hypertension

Oral

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

Geriatric Patients

Supraventricular Tachyarrhythmias

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

Angina

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

Hypertension

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

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

Formulation	Initial Dosage
Extended-release capsules (Verelan)	120 mg once daily in the morning302
Controlled extended-release capsules (Verelan PM)	100 mg daily at bedtime may rarely be necessary376
Conventional tablets (Calan)	40 mg 3 times daily118 119 214 215 222
Extended-release tablets (CalanSR, Isoptin)	120 mg once daily in the morning117 207

Small-stature Patients

Hypertension

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

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

Formulation	Initial Dosage
Extended-release capsules (Verelan)	120 mg once daily in the morning302
Controlled extended-release capsules (Verelan PM)	100 mg daily at bedtime may rarely be necessary376
Conventional tablets (Calan)	40 mg 3 times daily118
Extended-release tablets (CalanSR, Isoptin)	120 mg once daily in the morning117 207

Cautions for Verapamil Hydrochloride

Contraindications

• 
  

  Severe left ventricular dysfunction^b (unless CHF is secondary to a supraventricular tachycardia amenable to verapamil therapy).³⁸²

  
  


• 
  

  Severe hypotension (SBP <90 mm Hg) or cardiogenic shock.^{118 b}

  
  


• 
  

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

  
  


• 
  

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

  
  


• 
  

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

  
  


• 
  

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

  
  


• 
  

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

  
  


• 
  

  Known hypersensitivity to verapamil or any ingredient in the formulation.^{118 382 b}

  
  

Warnings/Precautions

Warnings

Cardiac Failure

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

Avoid use in patients with severe left ventricular dysfunction (e.g., pulmonary wedge pressure >20 mm Hg, ejection fraction <30%),^{117 118 207} unless the heart failure is caused by a supraventricular tachycardia amenable to verapamil therapy^{382 b} or in patients with moderate to severe symptoms of cardiac failure.

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

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

Wide-complex Ventricular Tachycardia

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

Hypotension

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

Hepatic Effects

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

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

Accessory Bypass Tract

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

Extreme Bradycardia/Asystole

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

AV Block

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

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

Hypertrophic Cardiomyopathy

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

Duchenne’s Muscular Dystrophy

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

Increased Intracranial Pressure

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

General Precautions

GI Effects

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

Use of Fixed Combinations

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

Specific Populations

Pregnancy

Category C.^{117 118}

Lactation

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

Pediatric Use

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

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

Geriatric Use

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

Hepatic Impairment

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

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

Renal Impairment

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

Common Adverse Effects

Constipation,^{207 362} dizziness,^{207 362 382} nausea,^{207 362 382} hypotension,^{207 362 382} headache.^{207 362 382}

Interactions for Verapamil Hydrochloride

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

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inducers: Possible decreased plasma verapamil concentrations.^c

CYP3A4 inhibitors: Possible increased plasma verapamil concentrations.^c

Protein-bound Drugs

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

Specific Drugs and Foods

Drug or Food	Interaction	Comment
ACE inhibitors	Additive hypotensive effectsb	Usually used to therapeutic advantage; monitor BPb
α-Adrenergic blocking agents (e.g., prazosin)	Increased hypotensive effect, possibly excessive in some patients118
β-Adrenergic blocking agents (see entries for atenolol, metoprolol, and propranolol)	Additive negative effects on myocardial contractility, heart rate, and AV conduction356 357 Excessive bradycardia and AV block, including complete heart block, reported in hypertensive patientsb	Use with caution for oral management of hypertension; monitor closelyb Concomitant use of IV verapamil and an IV β-adrenergic blocking agent within a few hours of each other is contraindicatedb
Alcohol	Inhibition of ethanol elimination, resulting in increased blood ethanol concentrations and prolonged intoxicating effects362 385 c
Antineoplastic agents	Increased serum concentrations and efficacy of doxorubicin376 Decreased verapamil absorption when used with COPP (cyclophosphamide, vincristine, procarbazine, prednisone) or VAC (vindesine, doxorubicin, cisplatin) regimen376 Decreased paclitaxel clearance (interaction with R-verapamil)376
Anesthetics, inhalation	Potentiation of cardiovascular depressionb	Titrate dosages carefullyb
Aspirin	Increased bleeding timesc
Atenolol (see entry for β-Adrenergic blocking agents)	Pharmacokinetic interaction unlikely141 142
Carbamazepine	Increased plasma carbamazepine concentrations and subsequent toxicity104 105 106	Reduce carbamazepine dosage by 40–50% after initiating verapamil therapy104 105 Monitor for carbamazepine toxicity (e.g., diplopia, headache, ataxia, dizziness)104 105 362
Cimetidine	Variable effects on verapamil clearance and oral bioavailability reported109 110 111 112 113 114 117 118 207 362	Monitor for changes in verapamil's therapeutic and toxic effects if cimetidine is added to or eliminated from regimen109 110 362
Cyclosporine	Increased blood cyclosporine concentrations117 118 294 295 296	Monitor for cyclosporine toxicity294 296
Dantrolene	Cardiovascular collapse following concomitant use of IV verapamil and IV dantrolene in animalsb	Clinical relevance to humans unknownb
Digoxin	Increased serum digoxin concentrations and digoxin toxicity207 244 b	Monitor serum digoxin concentrations carefully and reduce digoxin dosage as necessary;b observe closely for digoxin toxicityb
Disopyramide	Possible additive effects and impairment of left ventricular functionb	Discontinue disopyramide 48 hours prior to initiating verapamil; do not reinstitute until 24 hours after verapamil has been discontinuedb
Diuretics	Additive hypotensive effectsb	Usually used to therapeutic advantage; monitor BPb
Erythromycin	Increased plasma verapamil concentrationsc
Flecainide	Possible additive effects on myocardial contractility, AV conduction, and repolarization;117 118 241 possible additive negative inotropic effect and prolongation of AV conduction362	Avoid concomitant use unless potential benefits outweigh risks292 293
Grapefruit juice	Increased plasma verapamil concentrationsc	Not considered clinically importantc
Lithium	Possible increased, decreased, or unchanged serum lithium concentrations;117 118 132 133 207 241 362 possible increased sensitivity to lithium’s neurotoxic effects207	Monitor for lithium toxicity;207 monitor serum lithium concentrations; adjust dosage as necessary117 118 132 133 207 241 362
Metoprolol (see entry for β-Adrenergic blocking agents)	Increased oral bioavailability of metoprolol117 118 141 142 143 207	Avoid concomitant use, if possible;141 142 if used concomitantly, adjust metoprolol dosage and monitor patient closely142 Concomitant use of IV verapamil and IV metoprolol within a few hours of each other is contraindicatedb
Neuromuscular blocking agents	Potentiation of neuromuscular blockadeb	Monitor neuromuscular function; decrease dosage of verapamil and/or neuromuscular blocking agent as necessaryb
Nitrates	Possible additive beneficial effects; undesirable interactions unlikely376
Phenobarbital	Increased clearance of total and unbound verapamil,207 302 303 305 possibly via induction of hepatic metabolism303 304	Adjust verapamil dosage as necessary305
Propranolol (see entry for β-Adrenergic blocking agents)	Increased incidence of CHF, arrhythmia, and severe hypotension, particularly if IV route or high propranolol dosages are used or if patient has moderately severe or severe CHF, severe cardiomyopathy, or recent MIb	Use with caution for oral management of hypertension; monitor closelyb Concomitant use of IV verapamil and IV propranolol within a few hours of each other is contraindicatedb
Quinidine	Additive adrenergic blocking activity at α1- and α2-receptors154 Hypotensive effect in patients with hypertrophic cardiomyopathy117 118 153 207 Verapamil counteracts the effects of quinidine on AV conduction362 Possible increased plasma quinidine concentrations117 118 155 207	Avoid concomitant use in patients with hypertrophic cardiomyopathyb
Rifampin	Decreased oral bioavailability of verapamil117 118 134 135 136 137 138 207	Monitor closely if rifampin is added to or eliminated from regimen; adjust verapamil dosage as necessary134 135 136 137 138
Ritonavir	Increased plasma verapamil concentrationsc
Theophylline	Decreased clearance, elevated serum concentrations, and prolonged serum half-life of theophylline117 310 311 312 313	Monitor for theophylline toxicity312 313
Timolol, ophthalmic	Severe bradycardia 207 242 243 (associated with wandering atrial pacemaker 207 242 and transient asystole) reported243	Use with caution243
Vasodilators	Additive hypotensive effectsb	Usually used to therapeutic advantage; monitor BPb

Verapamil Hydrochloride Pharmacokinetics

Absorption

Bioavailability

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

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

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

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

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

Onset

Antihypertensive effect evident within 1 week.¹¹⁸

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

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

Duration

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

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

Food

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

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

Plasma Concentrations

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

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

Special Populations