Prescription Drug Name:
Verapamil Hydrochloride Tablets, USP 40 mg and 120 mg
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
• HCl M.W. = 491.08
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
INDICATIONS AND USAGE
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
displayName: WARNINGS SECTION
FDA Article Code: 34071-1
Verapamil has a negative inotropic effect, which in most patients is compensated by its afterload reduction (decreased systemic vascular resistance) properties without a net impairment of ventricular performance. In clinical experience with 4,954 patients, 87 (1.8%) developed congestive heart failure or pulmonary edema. Verapamil should be avoided in patients with severe left ventricular dysfunction (e.g., ejection fraction less than 30%) or moderate to severe symptoms of cardiac failure and in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker (see
Occasionally, the pharmacologic action of verapamil may produce a decrease in blood pressure below normal levels, which may result in dizziness or symptomatic hypotension. The incidence of hypotension observed in 4,954 patients enrolled in clinical trials was 2.5%. In hypertensive patients, decreases in blood pressure below normal are unusual. Tilt-table testing (60 degrees) was not able to induce orthostatic hypotension.
Elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have been reported. Such elevations have sometimes been transient and may disappear even with continued verapamil treatment. Several cases of hepatocellular injury related to verapamil have been proven by rechallenge; half of these had clinical symptoms (malaise, fever, and/or right upper quadrant pain), in addition to elevation of SGOT, SGPT, and alkaline phosphatase. Periodic monitoring of liver function in patients receiving verapamil is therefore prudent.
Some patients with paroxysmal and/or chronic atrial fibrillation or atrial flutter and a coexisting accessory AV pathway have developed increased antegrade conduction across the accessory pathway bypassing the AV node, producing a very rapid ventricular response or ventricular fibrillation after receiving intravenous verapamil (or digitalis). Although a risk of this occurring with oral verapamil has not been established, such patients receiving oral verapamil may be at risk and its use in these patients is contraindicated (see
The effect of verapamil on AV conduction and the SA node may cause asymptomatic first-degree AV block and transient bradycardia, sometimes accompanied by nodal escape rhythms. PR-interval prolongation is correlated with verapamil plasma concentrations especially during the early titration phase of therapy. Higher degrees of AV block, however, were infrequently (0.8%) observed. Marked first-degree block or progressive development to second-or third-degree AV block requires a reduction in dosage or, in rare instances, discontinuation of verapamil HCl and institution of appropriate therapy, depending on the clinical situation.
In 120 patients with hypertrophic cardiomyopathy (most of them refractory or intolerant to propranolol) who received therapy with verapamil at doses up to 720 mg/day, a variety of serious adverse effects were seen. Three patients died in pulmonary edema; all had severe left ventricular outflow obstruction and a past history of left ventricular dysfunction. Eight other patients had pulmonary edema and/or severe hypotension; abnormally high (greater than 20 mm Hg) pulmonary wedge pressure and a marked left ventricular outflow obstruction were present in most of these patients. Concomitant administration of quinidine (see
ANIMAL PHARMACOLOGY & OR TOXICOLOGY
displayName: ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION
FDA Article Code: 34091-9
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
|Dizziness||3.30%||Bradycardia (HR <50/min)||1.40%|
|Nausea||2.70%||AV block total (1°, 2°, 3°)||1.20%|
|Hypotension||2.50%||2° and 3°||0.80%|
|CHF, Pulmonary edema||1.80%|
Elevated liver enzymes (see
angina pectoris, atrioventricular dissociation, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope.
: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia.
ecchymosis or bruising.
cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, paresthesia, psychotic symptoms, shakiness, somnolence, extrapyramidal symptoms.
arthralgia and rash, exanthema, hair loss, hyperkeratosis, macules, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme.
blurred vision, tinnitus.
gynecomastia, galactorrhea/hyperprolactinemia, increased urination, spotty menstruation, impotence.
The frequency of cardiovascular adverse reactions that require therapy is rare; hence, experience with their treatment is limited. Whenever severe hypotension or complete AV block occurs following oral administration of verapamil, the appropriate emergency measures should be applied immediately; e.g., intravenously administered norepinephrine bitartrate, atropine sulfate, isoproterenol HCl (all in the usual doses), or calcium gluconate (10% solution). In patients with hypertrophic cardiomyopathy (IHSS), alpha¬;;;adrenergic agents (phenylephrine HCl, metaraminol bitartrate, or methoxamine HCl) should be used to maintain blood pressure, and isoproterenol and norepinephrine should be avoided. If further support is necessary, dopamine HCl or dobutamine HCl may be administered. Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician.
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
DOSAGE AND ADMINISTRATION
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
Clinical trials show that the usual dose is 80 mg to 120 mg three times a day. However, 40 mg three times a day may be warranted in patients who may have an increased response to verapamil (e.g., decreased hepatic function, elderly, etc). Upward titration should be based on therapeutic efficacy and safety evaluated approximately eight hours after dosing. Dosage may be increased at daily (e.g., patients with unstable angina) or weekly intervals until optimum clinical response is obtained.
The dosage in digitalized patients with chronic atrial fibrillation (see
Dose should be individualized by titration. The usual initial monotherapy dose in clinical trials was 80 mg three times a day (240 mg/ day). Daily dosages of 360 and 480 mg have been used but there is no evidence that dosages beyond 360 mg provided added effect. Consideration should be given to beginning titration at 40 mg three times per day in patients who might respond to lower doses, such as the elderly or people of small stature. The antihypertensive effects of verapamil hydrochloride are evident within the first week of therapy. Upward titration should be based on therapeutic efficacy, assessed at the end of the dosing interval.
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4