Product Name
:
VERACARD
Chemical Name
:
Verapamil HCl
Therapeutic Category
:
Cardiovascular drugs
Pharmacologic Category
:
Antiarrhythmic Agent, Class IV - Calcium Channel Blocker - Calcium Channel Blocker, Nondihydropyridine
Pharmaceutical Form
:
Ampoule
Composition
:
Verapamil HCl 5mg
Dosing
 
Dosing: Adult
Supraventricular Tachycardia
IV:
Initial dose: 5 to 10 mg (0.075 to 0.15 mg/kg) given as an IV bolus over at least 2 minutes
Repeat dose: 10 mg (0.15 mg/kg) 30 minutes after the first dose if the initial response is not adequate

An optimal interval for subsequent doses has not been determined and must be individualized for each patient.

ACLS guidelines:
Initial dose: 2.5 to 5 mg
If no response in 15 to 30 minutes and no side effects seen: 5 to 10 mg every 15 to 30 minutes to a maximum total dose of 20 mg

Alternative ACLS dosing regimen:
Initial dose: 5 mg
If no response in 15 minutes and no side effects seen: 5 mg every 15 minutes up to a total dose of 30 mg

Dosing: Pediatric
Usual Pediatric Dose for Supraventricular Tachycardia
IV:

Less than 1 year: Generally not recommended due to potential risk of severe apnea, bradycardia, hypotensive reactions, and cardiac arrest; IV calcium should be available at bedside

Initial dose: 0.1 to 0.2 mg/kg/dose (usual single dose range: 0.75 to 2 mg/dose) should be administered as an IV bolus over at least 2 minutes under continuous ECG monitoring

Repeat dose: 0.1 to 0.2 mg/kg/dose (usual single dose range: 0.75 to 2 mg/dose) 30 minutes after the first dose if the initial response is not adequate (under continuous ECG monitoring)

An optimal interval for subsequent doses has not been determined and must be individualized for each patient.

1 to 15 years:
Initial dose: 0.1 to 0.3 mg/kg/dose (usual single dose range: 2 to 5 mg/dose) should be administered as an IV bolus over at least 2 minutes; doses of 5 mg should not be exceeded

Repeat dose: 0.1 to 0.3 mg/kg/dose (usual single dose range: 2 to 5 mg/dose) 30 minutes after the first dose if the initial response is not adequate; doses of 10 mg should not be exceeded

An optimal interval for subsequent doses has not been determined and must be individualized for each patient.

Dosing: Renal Impairment

IV: In general, multiple doses in patients with renal failure should be avoided. If repeated injections are essential, smaller repeat doses are recommended.

Dosing: Hepatic Impairment
IV: In general, multiple doses in patients with hepatic failure should be avoided. If repeated injections are essential, smaller repeat doses are recommended.
Use
 
I.V.: Supraventricular tachyarrhythmia (PSVT, atrial fibrillation/flutter [rate control])
Adverse Reactions
 
>10%:
Central nervous system: Headache (1% to 12%)
Gastrointestinal: Gingival hyperplasia (≤19%), constipation (7% to 12%)
1% to 10%:
Cardiovascular: Peripheral edema (1% to 4%), hypotension (3%), CHF/pulmonary edema (2%), AV block (1% to 2%), bradycardia (HR <50 bpm: 1%), flushing (1%)
Central nervous system: Fatigue (2% to 5%), dizziness (1% to 5%), lethargy (3%), pain (2%), sleep disturbance (1%)
Dermatologic: Rash (1% to 2%)
Gastrointestinal: Dyspepsia (3%), nausea (1% to 3%), diarrhea (2%)
Hepatic: Liver enzymes increased (1%)
Neuromuscular & skeletal: Myalgia (1%), paresthesia (1%)
Respiratory: Dyspnea (1%)
Miscellaneous: Flu-like syndrome (4%)
I.V.: <1% (Limited to important or life-threatening): Bronchi/laryngeal spasm, depression, diaphoresis, itching, muscle fatigue, respiratory failure, rotary nystagmus, seizure, sleepiness, urticaria, vertigo
Postmarketing and/or case reports: Asystole, eosinophilia, EPS, exfoliative dermatitis, GI obstruction, hair color change, paralytic ileus, Parkinsonian syndrome, pulseless electrical activity, shock, ventricular fibrillation
Contraindications
 
Hypersensitivity to verapamil or any component of the formulation; severe left ventricular dysfunction; hypotension (systolic pressure <90 mm Hg) or cardiogenic shock; sick sinus syndrome (except in patients with a functioning artificial ventricular pacemaker); second- or third-degree AV block (except in patients with a functioning artificial ventricular pacemaker); atrial flutter or fibrillation and an accessory bypass tract (Wolff-Parkinson-White [WPW] syndrome, Lown-Ganong-Levine syndrome)
I.V.: Additional Contraindications include concurrent use of I.V. beta-blocking agents; ventricular tachycardia
Warnings / Precautions Drug
 
Concerns related to adverse effects:
• Conduction abnormalities: Can cause first-degree AV block or sinus bradycardia; other conduction abnormalities are rare. Use is contraindicated in patients with sick sinus syndrome, second- or third-degree AV block (except in patients with a functioning artificial pacemaker), or an accessory bypass tract (eg, WPW syndrome).
• Hypotension/syncope: Symptomatic hypotension with or without syncope can rarely occur; blood pressure must be lowered at a rate appropriate for the patient's clinical condition.
• Increased hepatic enzymes: Rare increases in liver function tests have been observed.
Disease-related concerns:
• Arrhythmia: Considered contraindicated in patients with wide complex tachycardias unless known to be supraventricular in origin; severe hypotension likely to occur upon administration (ACLS, 2010).
• Attenuated neuromuscular transmission: Decreased neuromuscular transmission has been reported with verapamil; use with caution in patients with attenuated neuromuscular transmission (Duchenne's muscular dystrophy, myasthenia gravis); dosage reduction may be required.
• Heart failure: Avoid use in heart failure; can exacerbate condition. Use is contraindicated in severe left ventricular dysfunction.
• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage reduction may be required; monitor hemodynamics and possibly ECG if severe impairment.
• Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use with caution in patients with HCM with outflow tract obstruction (especially those with resting outflow obstruction and severe limiting symptoms); may be used in patients who cannot tolerate beta-blockade (Maron, 2003; Nishimura, 2004).
• Renal impairment: Use with caution; monitor hemodynamics and possibly ECG if severe impairment, particularly if concomitant hepatic impairment.
Concurrent drug therapy issues:
• Agents with SA/AV nodal-blocking properties: Use caution when using verapamil together with a beta-blocker. Administration of I.V. verapamil and an I.V. beta-blocker within a few hours of each other may result in asystole and should be avoided; simultaneous administration is contraindicated. Use with other agents known to reduce SA node function and/or AV nodal conduction (eg, digoxin) or reduce sympathetic outflow (eg, clonidine) may increase the risk of serious bradycardia.
• Digoxin: Verapamil significantly increases digoxin serum concentrations; adjust digoxin dose.
• Neuromuscular-blocking agents: May prolong recovery from nondepolarizing neuromuscular-blocking agents.
Special populations:
• Pediatrics: I.V. use for SVT for is not recommended in infants; use with caution in children as myocardial depression/hypotension may occur.
Dosage form specific issues:
• Extended-release delivery system (Covera-HS®): Use with caution in patients with severe GI narrowing. In patients with extremely short GI transit times (eg, <7 hours), dosage adjustment may be required; inadequate pharmacokinetic data.
Metabolism/Transport Effects
Substrate of CYP1A2 (minor), CYP2B6 (minor), CYP2C9 (minor), CYP2C18 (minor), CYP2E1 (minor), CYP3A4 (major), P-glycoprotein; Inhibits CYP1A2 (weak), CYP2C9 (weak), CYP2D6 (weak), CYP3A4 (moderate), P-glycoprotein.
Interactions
 
Alcohol (Ethyl): Verapamil may increase the serum concentration of Alcohol (Ethyl). Risk C: Monitor therapy
Aliskiren: Verapamil may increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Amiodarone: Calcium Channel Blockers (Nondihydropyridine) may enhance the bradycardic effect of Amiodarone. Sinus arrest has been reported. Risk D: Consider therapy modification
Anilidopiperidine Opioids: May enhance the bradycardic effect of Calcium Channel Blockers (Nondihydropyridine). Anilidopiperidine Opioids may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Atorvastatin: Verapamil may increase the serum concentration of Atorvastatin. Atorvastatin may increase the serum concentration of Verapamil. Management: Consider using lower atorvastatin doses when used together with verapamil. Risk D: Consider therapy modification
Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Risk C: Monitor therapy
Benzodiazepines (metabolized by oxidation): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Beta-Blockers: Calcium Channel Blockers (Nondihydropyridine) may enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Budesonide (Systemic, Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Management: Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Monitor patients closely for signs/symptoms of corticosteroid excess. Risk D: Consider therapy modification
BusPIRone: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of BusPIRone. Risk D: Consider therapy modification
Calcium Channel Blockers (Dihydropyridine): May enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
CarBAMazepine: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of CarBAMazepine. CarBAMazepine may increase the metabolism of Calcium Channel Blockers (Nondihydropyridine). Risk D: Consider therapy modification
Cardiac Glycosides: Calcium Channel Blockers (Nondihydropyridine) may enhance the AV-blocking effect of Cardiac Glycosides. Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Cardiac Glycosides. Risk D: Consider therapy modification
Cimetidine: May decrease the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
Corticosteroids (Systemic): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
CycloSPORINE: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of CycloSPORINE. CycloSPORINE may decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Risk D: Consider therapy modification
CycloSPORINE (Systemic): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
Cyproterone: May decrease the serum concentration of CYP2E1 Substrates. Risk C: Monitor therapy
Dabigatran Etexilate: Verapamil may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Canadian (but not U.S.) dabigatran prescribing information recommends limiting dose to 150 mg/day following orthopedic surgery (OS), dosing 2 hours prior to verapamil, and avoiding initiation of verapamil in patients receiving dabigatran following OS. Risk D: Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. According to Canadian labeling, dabigatran dose for prevention of venous thromboembolism post hip or knee replacement should be reduced to 150 mg/day in patients receiving amiodarone, verapamil, or quinidine. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Disopyramide: Verapamil may enhance the adverse/toxic effect of Disopyramide. Of particular concern is the potential for profound depression of myocardial contractility. Risk X: Avoid combination
Dofetilide: Verapamil may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Dronedarone: Calcium Channel Blockers (Nondihydropyridine) may enhance the AV-blocking effect of Dronedarone. Other electrophysiologic effects of Dronedarone may also be increased. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Dronedarone. Dronedarone may increase the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Management: Use lower starting doses of the nondihydropyridine calcium channel blockers (i.e., verapamil, diltiazem), and only consider increasing calcium channel blocker dose after obtaining ECG-based evidence that the combination is being well-tolerated. Risk D: Consider therapy modification
Eletriptan: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Eletriptan. Risk C: Monitor therapy
Eplerenone: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Eplerenone. Risk C: Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Risk D: Consider therapy modification
Fexofenadine: Verapamil may increase the bioavailability of Fexofenadine. Risk C: Monitor therapy
Fingolimod: Verapamil may enhance the bradycardic effect of Fingolimod. Risk C: Monitor therapy
Flecainide: Verapamil may enhance the adverse/toxic effect of Flecainide. In particular, this combination may significantly impair myocardial contractility and AV nodal conduction. Risk C: Monitor therapy
Fluconazole: May decrease the metabolism of Calcium Channel Blockers. Risk C: Monitor therapy
Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Risk D: Consider therapy modification
Grapefruit Juice: May increase the serum concentration of Verapamil. Risk C: Monitor therapy
Halofantrine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Lithium: Calcium Channel Blockers (Nondihydropyridine) may enhance the neurotoxic effect of Lithium. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Lithium. Decreased or unaltered lithium concentrations have also been reported with this combination. Risk C: Monitor therapy
Lovastatin: Verapamil may increase the serum concentration of Lovastatin. Management: Avoid concurrent use of verapamil with lovastatin when possible. If used together, use lower lovastatin doses (max of 40 mg/day for adults). Risk D: Consider therapy modification
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Risk D: Consider therapy modification
Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Monitor for increased therapeutic effects of calcium channel blockers if an interacting macrolide antibiotic is initiated, or decreased effects if a macrolide is discontinued. Exceptions: Azithromycin; Azithromycin (Systemic); Fidaxomicin (Systemic); Spiramycin. Risk D: Consider therapy modification
Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
MAO Inhibitors: May enhance the hypotensive effect of Antihypertensives. MAO Inhibitors may enhance the orthostatic hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Midodrine: Calcium Channel Blockers (Nondihydropyridine) may enhance the bradycardic effect of Midodrine. Risk C: Monitor therapy
Nafcillin: May increase the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nitroprusside: Calcium Channel Blockers may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: P-glycoprotein/ABCB1 Substrates may increase the serum concentration of P-glycoprotein/ABCB1 Inhibitors. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-glycoprotein/ABCB1 Substrates: May increase the serum concentration of P-glycoprotein/ABCB1 Inhibitors. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Phenytoin: Calcium Channel Blockers may increase the serum concentration of Phenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Risk D: Consider therapy modification
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Protease Inhibitors: May decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Increased serum concentrations of the calcium channel blocker may increase risk of AV nodal blockade. Management: Avoid concurrent use when possible. If this combination is used, monitor for evidence of toxicity. The manufacturer of atazanavir recommends a 50% dose reduction for diltiazem be considered. Use of ritonavir with bepridil is contraindicated. Risk D: Consider therapy modification
QuiNIDine: May enhance the hypotensive effect of Verapamil. Verapamil may increase the serum concentration of QuiNIDine. Risk C: Monitor therapy
Ranolazine: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Ranolazine. Management: Limit ranolazine dose to a maximum of 500 mg twice daily when used with diltiazem or verapamil. Risk D: Consider therapy modification
Red Yeast Rice: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin (and possibly other related compounds) may be increased. Risk C: Monitor therapy
Rifamycin Derivatives: May increase the metabolism of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some U.S. and Canadian calcium channel blockers contraindicate use with rifampin however recommendations vary. Consult appropriate labeling. Risk D: Consider therapy modification
RisperiDONE: Verapamil may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Rivaroxaban: Verapamil may increase the serum concentration of Rivaroxaban. Risk C: Monitor therapy
Rivaroxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rivaroxaban. Risk C: Monitor therapy
Salicylates: Calcium Channel Blockers (Nondihydropyridine) may enhance the anticoagulant effect of Salicylates. Risk C: Monitor therapy
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk X: Avoid combination
Simvastatin: Verapamil may increase the serum concentration of Simvastatin. Management: Avoid concurrent use of verapamil with simvastatin when possible. If used together, limit adult maximum simvastatin dose to 10 mg/day, and avoid Simcor (simvastatin/niacin) because fixed simvastatin doses in the product exceed this maximum. Risk D: Consider therapy modification
Tacrolimus: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Tacrolimus. Risk C: Monitor therapy
Tacrolimus (Systemic): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Tacrolimus (Systemic). Risk C: Monitor therapy
Tacrolimus (Topical): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Tacrolimus (Topical). Risk C: Monitor therapy
Telithromycin: May enhance the hypotensive effect of Verapamil. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid or limit ethanol (may increase ethanol levels).
Food: Grapefruit juice may increase the serum concentration of verapamil; use with caution and monitor for increased verapamil effects.
Herb/Nutraceutical: St John's wort may decrease levels. Avoid herbs with hypertensive properties (bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng [American], kola, licorice); may diminish the antihypertensive effect of verapamil. Avoid herbs with hypotensive properties (black cohosh, California poppy, coleus, golden seal, hawthorn, mistletoe, periwinkle, quinine, shepherd's purse); may enhance the hypotensive effect of verapamil.
Pregnancy
 
C
Pregnancy Implications
In some animal reproduction studies verapamil has been shown to cause fetal harm; adverse maternal effects were also observed. Verapamil crosses the placenta. Although verapamil is not considered a major human teratogen, use during pregnancy may cause adverse fetal effects (bradycardia, heart block, hypotension).
Lactation
 
Enters breast milk/not recommended (AAP considers “compatible”; AAP 2001 update pending)
Breast-Feeding Considerations
Crosses into breast milk; manufacturer recommends to discontinue breast-feeding while taking verapamil.
Mechanism of Action
 
Inhibits calcium ion from entering the “slow channels” or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization; produces relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina; slows automaticity and conduction of AV node.
Pharmacodynamics / Kinetics
 
Onset of action: Peak effect: I.V.: 1-5 minutes
Duration: I.V.: 10-20 minutes
Distribution: Vd: 3.89 L/kg (Storstein, 1984)
Protein binding: ~90%
Metabolism: Hepatic (extensive first-pass effect) via multiple CYP isoenzymes; primary metabolite is norverapamil (20% pharmacologic activity of verapamil)
Half-life elimination: Infants: 4.4-6.9 hours; Adults: Single dose: 3-7 hours, Multiple doses: 4.5-12 hours; severe hepatic impairment: 14-16 hours
Excretion: Urine (70% as metabolites, 3% to 4% as unchanged drug); feces (16%)