Table 2132.

ANTIARRHYTHMIC DRUGS (VAUGHAN WILLIAMS CLASSIFICATION)

DRUG
Class Ia

DOSAGE

TARGET LEVELS

SELECTED ADVERSE EFFECTS

COMMENTS

Uses: APB and VPB suppression, SVT and VT suppression, AF or atrial flutter, and VF suppression Drug should be used cautiously in patients with impaired LV function. Dosage should be decreased in patients with renal insufficiency. Adverse effects may contribute to nonadherence. If QRS interval widens (> 50% if initially < 120 msec or > 25% if initially > 120 msec) or if QTc interval is prolonged > 550 msec, infusion rate or dosage should be decreased or drug stopped. IV form is not available in the US. Sustained-release preparations obviate the need for frequent dosing. If QRS interval widens (> 50% if initially < 120 msec or > 25% if initially >120 msec) or if QTc interval is prolonged > 550 msec, infusion rate or dosage should be decreased or drug stopped. If QRS interval widens (> 50% if initially < 120 msec or > 25% if initially > 120 msec) or if QTc interval is prolonged > 550 msec, infusion rate or dosage should be decreased or drug stopped. To reduce toxicity risk, clinicians should reduce dosage or infusion rate to 2 mg/min after 24 h.

Disopyramide IV: Initially, 27.5 g/mL Anticholinergic 1.5 mg/kg over effects (urinary re> 5 min foltention, glaucoma, lowed by an dry mouth, blurred infusion of vision, intestinal 0.4 mg/kg/h upset), hypoglyceOral immediatemia, torsades de release: 100 or pointes VT; nega150 mg q 6 h tive inotropic effects Oral controlled(which may worsen release: 200 or heart failure or 300 mg q 12 h hypotension)

Procainamide

IV: 1015 mg/ kg bolus at 2550 mg/ min, followed by a constant IV infusion of 14 mg/min Oral: 250625 mg (rarely, up to 1 g) q 3 or 4h Oral: 200400 mg q 46 h

48 g/mL

Quinidine

26 g/mL

Hypotension (with IV infusion), serologic abnormalities (especially ANA) in almost 100% taking drug for > 12 mo, drug-induced lupus (arthralgia, fever, pleural effusions) in 1520%, agranulocytosis in < 1%, torsades de pointes VT Diarrhea, colic, flatulence, fever, thrombocytopenia, liver function abnormalities, torsades de pointes VT; overall adverse effect rate of 30%

Class Ib

Uses: Suppression of ventricular arrhythmias (VPB, VT, VF) IV: 100 mg over 25 g/L 2 min, followed by continuous infusion of 4 mg/min Tremor, seizures; if administration is too rapid, drowsiness, delirium, paresthesias;

Lidocaine

Table 2132. ANTIARRHYTHMIC DRUGS (VAUGHAN WILLIAMS CLASSIFICATION) (Continued )

DRUG DOSAGE TARGET LEVELS SELECTED ADVERSE EFFECTS COMMENTS

Lidocaine (contd)

Mexiletine

(2 mg/min in possibly increased patients > 65); risk of bradyar5 min after first rhythmias after dose, a 2nd acute MI 50-mg bolus is given Oral immediate- 0.52 g/mL Nausea, vomiting, tremor, seizures release: 100 250 mg q 8 h Oral slowrelease: 360 mg q 12 h IV: 2 mg/kg at 25 mg/min, followed by 250mg infusion over 1 h, 250-mg infusion over next 2 h, and maintenance infusion of 0.5 mg/min

Extensive first-pass hepatic metabolism occurs.

Oral slow-release and IV forms are not available in the US.

Class Ic

Flecainide

Propafenone

Uses: APB and VPB suppression, SVT and VT suppression, AF or atrial flutter, and VF suppression Oral: 100 mg 0.21 g/mL Occasionally, IV form is not available q 8 or 12 h blurred vision and in US. IV: 12 mg/kg paresthesias If QRS complex widens over 10 min (> 50% if initially < 120 msec and > 25% if initially > 120 msec), dose must be decreased or drug stopped. 0.11.0 g/ -blocking activity, Pharmacokinetics are Oral: Initially, mL 150 mg tid, possible worsening nonlinear; increases titrated up to of reactive airway in dose should not 150300 mg tid disorders; occaexceed 50% of IV: 2-mg/kg sionally GI upset previous dose. bolus, followed Bioavailability and by 2 mg/min protein binding infusion vary; drug has saturable first-pass metabolism. IV form is not available in the US. Uses: Supraventricular tachyarrhythmias (APB, ST, SVT, AF, atrial flutter) and ventricular arrhythmias (often in a supportive role) Oral: 50100 mg once/day Oral: Initially, 6.25 mg bid, followed by titration to 25 mg bid -Blocker levels not measured; dose adjusted to reduce heart rate by > 25% Typically for -blockers are contrain-blockers, GI disdicated in patients with turbances, insomnia, bronchospastic airway nightmares, lethargy, disorders. erectile dysfunction, possible AV block in patients with AV node dysfunction
Table continues on the following page.

Class II

(-blockers) Atenolol Carvedilol

Table 2132. ANTIARRHYTHMIC DRUGS (VAUGHAN WILLIAMS CLASSIFICATION) (Continued )

DRUG
Class II

DOSAGE

TARGET LEVELS

SELECTED ADVERSE EFFECTS

COMMENTS

(-blockers) (contd) Acebutolol Betaxolol Bisoprolol Esmolol Metoprolol Oral: 200 mg bid Oral: 20 mg once/day Oral: 510 mg once/day IV: 50200 g/ kg/min Oral: 50100 mg bid IV: 5 mg q 5 min up to 15 mg Oral: 6080 mg once/day Oral: 1030 mg tid or qid IV: 13 mg (may repeat once after 5 min if needed) Oral: 1020 mg bid Uses: Any tachyarrhythmia except torsades de pointes VT

Nadolol Propranolol

Timolol
Class III

(membranestabilizing drugs) Amiodarone

Oral: 6001200 12.5 g/mL Pulmonary fibrosis (in Drug has noncompetitive mg/day for up to 5% of patients -blocking, Ca channel blocking, and Na chan710 days, then treated for > 5 yr), 400 mg/day which may be fatal; nel blocking effects, with a long delay in for 3 wk, folQTc prolongation; onset of action. lowed by a torsades de pointes maintenance VT (rare); bradycar- By prolonging refractoriness, drug may cause dose (ideally, dia; gray or blue 200 mg/day) discoloration of sun- homogeneous conditions of repolarization exposed skin; sun IV: 150450 mg throughout the heart. sensitivity; hepatic over 16 h (deabnormalities; peri- IV form can be used for pending on urconversion. pheral neuropathy; gency), folcorneal microdeposlowed by a its (in almost all maintenance treated patients), usudose of 0.52.0 ally without serious mg/min visual effects and reversed by stopping the drug; changes in thyroid function; slow clearance possibly prolonging adverse effects
Table continues on the following page.

Table 2132. ANTIARRHYTHMIC DRUGS (VAUGHAN WILLIAMS CLASSIFICATION) (Continued )

DRUG DOSAGE TARGET LEVELS SELECTED ADVERSE EFFECTS COMMENTS

Azimilide Bretylium*

Dofetilide

Ibutilide

Sotalol

Oral: 100200 mg once/day IV: Initially, 5 mg/kg, followed by 12 mg/min as a constant infusion IM: Initially, 510 mg/kg, which may be repeated to a total dose of 30 mg/kg IM maintenance dose of 5 mg/ kg q 68 h IV: 2.54 g/mL Oral: 500 g bid if CrCl > 60 mL/min; 250 g bid if CrCl is 4060 mL/min; 125 g bid if CrCl is 2040 mL/min IV: For patients 60 kg, 1 mg infusion or, for patients < 60 kg, 0.01 mg/kg over 10 min, with dose repeated after 10 min if the first infusion is unsuccessful Oral: 80160 mg q 12 h IV: 10 mg over 12 min

2001000 ng/mL 0.82.4 g/ mL

Torsades de pointes VT Hypotension

Drug has class II properties. Effects may be delayed 1020 min.

N/A

Torsades de pointes VT

Drug is contraindicated if QTc > 440 msec or if CrCl < 20 mL/min.

N/A

Torsades de pointes VT (in 2%)

Drug is used to terminate AF (success rate, about 40%) and atrial flutter (success rate, about 65%).

0.54 g/mL Similar to class II; possible depressed left ventricular function and torsades de pointes VT

Racemic [D-L] form has class II (-blocking) properties, [D] form does not. Both forms have class III activity. Only racemic sotalol is available for clinical use. Drug should not be used in patients with renal insufficiency.

Table continues on the following page.

Table 2132. ANTIARRHYTHMIC DRUGS (VAUGHAN WILLIAMS CLASSIFICATION) (Continued )

DRUG
Class IV

DOSAGE

TARGET LEVELS

SELECTED ADVERSE EFFECTS

COMMENTS

(Ca channel blockers) Diltiazem

Uses: Termination of SVT and slowing of rapid AF or atrial flutter 0.10.4 g/ Oral slowmL release (diltiazem CD): 120 mg to 360 mg once/day IV: 515 mg/h for up to 24 h Oral: 40120 mg N/A tid or, for sustained-release form, 180 mg once/day to 240 mg bid IV: 515 mg over 10 min Oral prophylaxis: 40120 mg tid 6 mg rapid IV bolus, repeated twice at 12 mg if needed; flush bolus with additional 20 mL saline IV loading dose: 0.5 mg Oral maintenance dose: 0.1250.25 mg/day N/A

Possible precipitation of VF in patients with VT, negative inotropy

IV form is most commonly used to slow ventricular response rate to AF or atrial flutter.

Verapamil

Possible precipitation of VF in patients with VT, negative inotropy

IV form is used to terminate narrowcomplex tachycardias involving the AV node (success rate, almost 100% with 510 mg IV over 10 min).

Other antiarrhythmics

Adenosine

Transient dyspnea, chest discomfort, and flushing (in 3060%), transient bronchospasm

Digoxin

0.81.6 g/ mL

Anorexia, nausea, vomiting, and often serious arrhythmias (VPBs, VT, APBs, atrial tachycardia, 2nd-degree or 3rd-degree AV block, combinations of these arrhythmias)

Drug slows or blocks AV nodal conduction. Duration of action is extremely short. Contraindications include asthma and high-grade heart block. Dipyridamole potentiates effects. Contraindications include antegrade conduction over an accessory AV connection pathway (manifest Wolff-ParkinsonWhite syndrome) because if AF occurs, ventricular responses may be excessive (digoxin shortens refractory periods of the accessory connection).

*Availability uncertain. AF = atrial fibrillation; ANA = antinuclear antibody; APB = atrial premature beat; AV = atrioventricular; CrCl = creatinine clearance; LV = left ventricular; QTc = QT interval corrected for heart rate; SVT = supraventricular tachycardia; VF = ventricular fibrillation; VPB = ventricular premature beat; VT = ventricular tachycardia.
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