0%. about 70% of patients with atrial flutter and/or fibrillation with a fast ventricular rate respond with a decrease in heart rate of at least 20%. conversion of atrial flutter or fibrillation to sinus rhythm is uncommon (about 10%) after verapamil hydrochloride and may reflect the spontaneous conversion rate, since the conversion rate after placebo was similar. the effect of a single injection lasts for 30–60 minutes when conversion to sinus rhythm does not occur. because a small fraction (<1.0%) of patients treated with verapamil hydrochloride respond with life-threatening adverse responses (rapid ventricular rate in atrial flutter/fibrillation with an accessory bypass tract, marked hypotension, or extreme bradycardia/asystole—see contraindications and warnings ), the initial use of intravenous verapamil hydrochloride should, if possible, be in a treatment setting with monitoring and resuscitation facilities, including dc-cardioversion capability (see suggested treatment of acute cardiovascular adverse reactions ) . as familiarity with the patient’s response is gained, an office setting may be acceptable. cardioversion has been used safely and effectively after intravenous verapamil.

extreme cases, asystole. this is more likely to occur in patients with a sick sinus syndrome (sa nodal disease), which is more common in older patients. bradycardia associated with sick sinus syndrome was reported in 0.3% of the patients treated in controlled double-blind trials in the u.s. the total incidence of bradycardia (ventricular rate less than 60 beats/min) was 1.2% in these studies. asystole in patients other than those with sick sinus syndrome is usually of short duration (few seconds or less), with spontaneous return to av nodal or normal sinus rhythm. if this does not occur promptly, appropriate treatment should be initiated immediately. (see adverse reactions including suggested treatment of adverse reactions.) heart failure: when heart failure is not severe or rate related, it should be controlled with digitalis glycosides and diuretics, as appropriate, before verapamil is used. in patients with moderately severe to severe cardiac dysfunction (pulmonary wedge pressure above 20 mm hg, ejection fraction less than 30%), acute worsening of heart failure may be seen. concomitant antiarrhythmic therapy: digitalis: intravenous verapamil has been used concomitantly with digitalis preparations without the occurrence of serious adverse effects. however, since both drugs slow av conduction, patients should be monitored for av block or excessive bradycardia. procainamide: intravenous verapamil has been administered to a small number of patients receiving oral procainamide without the occurrence of serious adverse effects. quinidine: intravenous verapamil has been administered to a small number of patients receiving oral quinidine without the occurrence of serious adverse effects. however a few cases of hypotension have been reported in patients taking oral quinidine who received intravenous verapamil. caution should therefore be used when employing this combination of drugs. beta-adrenergic blocking drugs: intravenous verapamil has been administered to patients receiving oral beta blockers without the development of serious adverse effects. however, since both drugs may depress myocardial contractility or av conduction, the possibility of detrimental interactions should be considered. the concomitant administration of intravenous beta blockers and intravenous verapamil has resulted in serious adverse reactions (see contraindications ), especially in patients with severe cardiomyopathy, congestive heart failure, or recent myocardial infarction. disopyramide: until data on possible interactions between verapamil and disopyramide are obtained, disopyramide should not be administered within 48 hours before or 24 hours after verapamil administration. heart block: verapamil prolongs av conduction time. while high-degree av block has not been observed in controlled clinical trials in the u.s., a low percentage (less than 0.5%) has been reported in the world literature. development of second- or third-degree av block or unifascicular, bifascicular, or trifascicular bundle branch block requires reduction in subsequent doses or discontinuation of verapamil and institution of appropriate therapy, if needed. (see adverse reactions and concomitant antiarrhythmic therapy .) hepatic and renal failure: significant hepatic and renal failure should not increase the effects of a single intravenous dose of verapamil but may prolong its duration. repeated injections of intravenous verapamil in such patients may lead to accumulation and an excessive pharmacologic effect of the drug. there is no experience to guide use of multiple doses in such patients, and this generally should be avoided. if repeated injections are essential, blood pressure and pr interval should be closely monitored and smaller repeat doses should be utilized. data on the clearance of verapamil by dialysis are not yet available. premature ventricular contractions: during conversion to normal sinus rhythm or marked reduction in ventricular rate, a few benign complexes of unusual appearance (sometimes resembling premature ventricular contractions) may be seen after treatment with verapamil. similar complexes are seen during spontaneous conversion of supraventricular tachycardia and after dc-cardioversion or other pharmacologic therapy. these complexes appear to have no clinical significance. duchenne’s muscular dystrophy: intravenous verapamil can precipitate respiratory muscle failure in these patients and should, therefore, be used with caution. increased intracranial pressure: intravenous verapamil has been seen to increase intracranial pressure in patients with supratentorial tumors at the time of anesthesia induction. caution should be taken and appropriate monitoring performed.

first dose if the initial response is not adequate. 1-15 years: 0.1-0.3 mg/kg body weight (usual single dose range: 2-5 mg) 30 minutes after the first dose if the initial response is not adequate. do not exceed 10 mg as a single dose. note: parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. use only if solution is clear and vial seal is intact. unused amount of solution should be discarded immediately following withdrawal of any portion of contents. for stability reasons this product is not recommended for dilution with sodium lactate injection usp in polyvinyl chloride bags. admixing intravenous verapamil with albumin, amphotericin b, hydralazine hcl, and trimethoprim with sulfamethoxazole should be avoided. verapamil will precipitate in any solution with a ph above 6.0.

fective treatment supportive treatment 1. symptomatic hypotenstion requiring treatment dopamine hcl iv calcium chloride iv norepinephrine bitartrate iv metaraminol bitartrate iv isoproterenol hcl iv intravenous fluids trendelenburg position 2. bradycardia, av block, asystole isoproterenol hcl iv calcium chloride iv norepinephrine bitartrate iv atropine sulfate iv cardiac pacing intravenous fluids (slow drip) 3. rapid ventricular rate (due to antegrade con- duction in flutter/fibrilla- tion with wpw or lgl syndromes) dc-cardioversion (high energy may be required) procainamide iv lidocaine hcl iv intravenous fluids (slow drip) *actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician.

conduction across accessory bypass tracts. verapamil does not alter the normal atrial action potential or intraventricular conduction time but depresses amplitude, velocity of depolarization, and conduction in depressed atrial fibers. in the isolated rabbit heart, concentrations of verapamil that markedly affect sa nodal fibers or fibers in the upper and middle regions of the av node have very little effect on fibers in the lower av node (nh region) and no effect on atrial action potentials or his bundle fibers. verapamil does not induce peripheral arterial spasm. verapamil has a local anesthetic action that is 1.6 times that of procaine on an equimolar basis. it is not known whether this action is important at the doses used in man. verapamil does not alter total serum calcium levels. hemodynamics: verapamil reduces afterload and myocardial contractility. in most patients, including those with organic cardiac disease, the negative inotropic action of verapamil is countered by reduction of afterload, and cardiac index is usually not reduced, but in patients with moderately severe to severe cardiac dysfunction (pulmonary wedge pressure above 20 mm hg, ejection fraction less than 30%), acute worsening of heart failure may be seen. peak therapeutic effects occur within 3 to 5 minutes after a bolus injection. the commonly used intravenous doses of 5-10 mg verapamil produce transient, usually asymptomatic, reduction in normal systemic arterial pressure, systemic vascular resistance and contractility; left ventricular filling pressure is slightly increased. pharmacokinetics: intravenously administered verapamil has been shown to be rapidly metabolized. following intravenous infusion in man, verapamil is eliminated bi-exponentially, with a rapid early distribution phase (half-life about 4 minutes) and a slower terminal elimination phase (half-life 2-5 hours). in healthy men, orally administered verapamil undergoes extensive metabolism in the liver, with 12 metabolites having been identified, most in only trace amounts. the major metabolites have been identified as various n- and o-dealkylated products of verapamil. approximately 70% of an administered dose is excreted in the urine and 16% or more in the feces within 5 days. about 3% to 4% is excreted as unchanged drug.