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Verelan
Overview
What is Verelan?
Verelan (verapamil hydrochloride
capsules) is a calcium ion influx inhibitor (slow channel blocker or calcium ion
antagonist). Verelan is available for oral administration as a 360 mg hard
gelatin capsule (lavender cap/yellow body), a 240 mg hard gelatin capsule (dark
blue cap/yellow body), a 180 mg hard gelatin capsule (light grey cap/yellow
body), and a 120 mg hard gelatin capsule (yellow cap/yellow body). These pellet
filled capsules provide a sustained-release of the drug in the gastrointestinal
tract.
The structural formula of verapamil HCl is given below:
Chemical name: Benzeneacetonitrile,
α-[3-[[2-(3,4-dimethoxyphenyl)-ethyl]methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl),
monohydrochloride.
Verapamil HCl is an almost white, crystalline powder, practically free of
odor, with a bitter taste. It is soluble in water, chloroform and methanol.
Verapamil HCl is not structurally related to other cardioactive drugs.
In addition to verapamil HCl the Verelan capsule contains the following
inactive ingredients: fumaric acid, talc, sugar spheres, povidone, shellac,
gelatin, FD&C red #40, yellow iron oxide, titanium dioxide, methylparaben,
propylparaben, silicon dioxide, and sodium lauryl sulfate. In addition, the
Verelan 240 mg and 360 mg capsules contain FD&C blue #1 and D&C red #28;
and the Verelan 180 mg capsule contains black iron oxide.
What does Verelan look like?
What are the available doses of Verelan?
Sorry No records found.
What should I talk to my health care provider before I take Verelan?
Sorry No records found
How should I use Verelan?
Verelan (verapamil HCl) is indicated for the management of essential
hypertension.
The dose of Verelan should be individualized by titration. The
usual daily dose of sustained-release verapamil, Verelan, in clinical trials has
been 240 mg given by mouth once daily in the morning. However, initial doses of
120 mg a day may be warranted in patients who may have an increased response to
verapamil (e.g., elderly, small people, etc.). Upward titration should be based
on therapeutic efficacy and safety evaluated approximately 24 hours after
dosing. The antihypertensive effects of Verelan are evident within the first
week of therapy.
If adequate response is not obtained with 120 mg of Verelan, the dose may be
titrated upward in the following manner:
(a) 180 mg in the morning.
(b) 240 mg in the morning.
(c) 360 mg in the morning.
(d) 480 mg in the morning.
Verelan sustained-release capsules are for once-a-day administration. When
switching from immediate-release verapamil to Verelan capsules, the same total
daily dose of Verelan capsules can be used.
As with immediate-release verapamil, dosages of Verelan capsules should be
individualized and titration may be needed in some patients.
Verelan pellet filled capsules may also be administered by
carefully opening the capsule and sprinkling the pellets on a spoonful of
applesauce. The applesauce should be swallowed immediately without chewing and
followed with a glass of cool water to ensure complete swallowing of the
pellets. The applesauce used should not be hot, and it should be soft enough to
be swallowed without chewing. Any pellet/applesauce mixture should be used
immediately and not stored for future use. Subdividing the contents of a Verelan
capsule is not recommended.
What interacts with Verelan?
- Verapamil HCl is contraindicated in:
- Severe left ventricular dysfunction. (See )
- Hypotension (less than 90 mm Hg systolic pressure) 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).
- Patients with atrial flutter or atrial fibrillation and an accessory bypass tract (e.g., Wolff-Parkinson-White, Lown-Ganong-Levine syndromes). (See )
- Patients with known hypersensitivity to Verapamil hydrochloride.
What are the warnings of Verelan?
Azathioprine has been reported to cause temporary depression in spermatogenesis and reduction in sperm viability and sperm count in mice at doses 10 times the human therapeutic dose; a reduced percentage of fertile matings occurred when animals received 5 mg/kg.
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
) Patients with
milder ventricular dysfunction should, if possible, be controlled with optimum
doses of digitalis and/or diuretics before verapamil treatment (note
interactions with digoxin under: ).
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 in the face of
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 elevations 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 flutter or
atrial fibrillation 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 )
Treatment is usually DC-cardioversion. Cardioversion has been used safely and
effectively after oral verapamil.
The effect of verapamil on AV conduction and the SA node may lead
to 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 upon 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 (over 20
mm Hg) capillary wedge pressure and a marked left ventricular outflow
obstruction were present in most of these patients. Concomitant administration
of quinidine (see )
preceded the severe hypotension in 3 of the 8 patients (2 of whom developed
pulmonary edema). Sinus bradycardia occurred in 11% of the patients,
second-degree AV block in 4% and sinus arrest in 2%. It must be appreciated that
this group of patients had a serious disease with a high mortality rate. Most
adverse effects responded well to dose reduction and only rarely did verapamil
have to be discontinued.
What are the precautions of Verelan?
THE CONTENTS OF THE Verelan CAPSULE SHOULD NOT
BE CRUSHED OR CHEWED. Verelan CAPSULES ARE TO BE SWALLOWED WHOLE OR THE ENTIRE
CONTENTS OF THE CAPSULE SPRINKLED ONTO APPLESAUCE
Since verapamil is highly metabolized by the liver, it should be
administered cautiously to patients with impaired hepatic function. Severe liver
dysfunction prolongs the elimination half-life of immediate-release verapamil to
about 14 to 16 hours; hence, approximately 30% of the dose given to patients
with normal liver function should be administered to these patients. Careful
monitoring for abnormal prolongation of the PR interval or other signs of
excessive pharmacologic effects (see ) should be carried out.
It has been reported that verapamil decreases neuromuscular
transmission in patients with Duchenne's muscular dystrophy, and that verapamil
prolongs recovery from the neuromuscular blocking agent vecuronium and causes a
worsening of myasthenia gravis. It may be necessary to decrease the dosage of
verapamil when it is administered to patients with attenuated neuromuscular
transmission.
About 70% of an administered dose of verapamil is excreted as
metabolites in the urine. Until further data are available, verapamil should be
administered cautiously to patients with impaired renal function. These patients
should be carefully monitored for abnormal prolongation of the PR interval or
other signs of overdosage. (See )
When the sprinkle method of administration is prescribed, details
of the proper technique should be explained to the patient. (See .)
In vitro
Concomitant therapy with beta-adrenergic blockers and verapamil
may result in additive negative effects on heart rate, atrioventricular
conduction, and/or cardiac contractility. The combination of sustained-release
verapamil and beta-adrenergic blocking agents has not been studied. However,
there have been reports of excess bradycardia and AV block, including complete
heart block, when the combination has been used for the treatment of
hypertension.
For hypertensive patients, the risk of combined therapy may outweigh the
potential benefits. The combination should be used only with caution and close
monitoring.
Asymptomatic bradycardia (36 beats/min) with a wandering atrial pacemaker has
been observed in a patient receiving concomitant timolol (a beta-adrenergic
blocker) eyedrops and oral verapamil.
A decrease in metoprolol clearance has been reported when verapamil and
metoprolol were administered together. A similar effect has not been observed
when verapamil and atenolol are given together.
Sinus bradycardia resulting in hospitalization and pacemaker
insertion has been reported in association with the use of clonidine
concurrently with verapamil. Monitor heart rate in patients receiving
concomitant verapamil and clonidine.
Consider reducing digoxin dose when verapamil and digoxin are to
be given together. Monitor digoxin level periodically during therapy. Chronic
verapamil treatment can increase serum digoxin levels by 50% to 75% during the
first week of therapy, and this can result in digitalis toxicity. In patients
with hepatic cirrhosis the influence of verapamil on digoxin pharmacokinetics is
magnified. Verapamil may reduce total body clearance and extrarenal clearance of
digoxin by 27% and 29%, respectively. If digoxin toxicity is suspected, suspend
or discontinue digoxin therapy.
In previous clinical trials with other verapamil formulations related to the
control of ventricular response in patients taking digoxin who had atrial
fibrillation or atrial flutter, ventricular rates below 50/min at rest occurred
in 15% of patients, and asymptomatic hypotension occurred in 5% of
patients.
Verapamil administered concomitantly with oral antihypertensive
agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics,
beta blockers) will usually have an additive effect on lowering blood pressure.
Patients receiving these combinations should be appropriately monitored.
Concomitant use of agents that attenuate alpha-adrenergic function with
verapamil may result in reduction in blood pressure that is excessive in some
patients. Such an effect was observed in one study following the concomitant
administration of verapamil and prazosin.
Until data on possible interactions between verapamil and
disopyramide phosphate are obtained, disopyramide should not be administered
within 48 hours before or 24 hours after verapamil administration.
A study in healthy volunteers showed that the concomitant
administration of flecainide and verapamil may have additive effects on
myocardial contractility, AV conduction, and repolarization. Concomitant therapy
with flecainide and verapamil may result in additive negative inotropic effect
and prolongation of atrioventricular conduction.
In a small number of patients with hypertrophic cardiomyopathy
(IHSS), concomitant use of verapamil and quinidine resulted in significant
hypotension. Until further data are obtained, combined therapy of verapamil and
quinidine in patients with hypertrophic cardiomyopathy should probably be
avoided.
The electrophysiological effects of quinidine and verapamil on AV conduction
were studied in 8 patients. Verapamil significantly counteracted the effects of
quinidine on AV conduction. There has been a report of increased quinidine
levels during verapamil therapy.
Verapamil has been given concomitantly with short- and
long-acting nitrates without any undesirable drug interactions. The
pharmacologic profile of both drugs and the clinical experience suggest
beneficial interactions.
Verapamil has been found to significantly inhibit ethanol
elimination resulting in elevated blood ethanol concentrations that may prolong
the intoxicating effects of alcohol. (See
In a few reported cases, coadministration of verapamil with
aspirin has led to increased bleeding times greater than observed with aspirin
alone.
The interaction between cimetidine and chronically administered
verapamil has not been studied. Variable results on clearance have been obtained
in acute studies of healthy volunteers; clearance of verapamil was either
reduced or unchanged.
Grapefruit juice may significantly increase concentrations of
verapamil. Grapefruit juice given to nine healthy volunteers increased S- and R-
verapamil AUC by 36% and 28%, respectively. Steady
state C and C of S-verapamil
increased by 57% and 16.7%, respectively with grapefruit juice compared to
control. Similarly, C and C
of R-verapamil increased by 40% and 13%, respectively. Grapefruit juice did not
affect half-life, nor was there a significant change in AUC ratio R/S compared to control. Grapefruit juice did not
cause a significant difference in the PK of norverapamil. This increase in
verapamil plasma concentration is not expected to have any clinical
consequences.
Pharmacokinetic and pharmacodynamic interactions between oral
verapamil and lithium have been reported. The former may result in a lowering of
serum lithium levels in patients receiving chronic stable oral lithium therapy.
The latter may result in an increased sensitivity to the effects of lithium.
Patients receiving both drugs must be monitored carefully.
Verapamil therapy may increase carbamazepine concentrations
during combined therapy. This may produce carbamazepine side effects such as
diplopia, headache, ataxia, or dizziness.
Therapy with rifampin may markedly reduce oral verapamil
bioavailability.
Phenobarbital therapy may increase verapamil clearance.
Verapamil therapy may increase serum levels of
cyclosporine.
Animal experiments have shown that inhalation anesthetics depress
cardiovascular activity by decreasing the inward movement of calcium ions. When
used concomitantly, inhalation anesthetics and calcium antagonists, such as
verapamil, should be titrated carefully to avoid excessive cardiovascular
depression.
Clinical data and animal studies suggest that verapamil may
potentiate the activity of neuromuscular blocking agents (curare-like and
depolarizing). It may be necessary to decrease the dose of verapamil and/or the
dose of the neuromuscular blocking agent when the drugs are used
concomitantly.
An 18-month toxicity study in rats, at a low multiple (6 fold) of
the maximum recommended human dose, and not the maximum tolerated dose, did not
suggest a tumorigenic potential. There was no evidence of a carcinogenic
potential of verapamil administered in the diet of rats for two years at doses
of 10, 35 and 120 mg/kg per day or approximately 1x, 3.5x and 12x, respectively,
the maximum recommended human daily dose (480 mg per day or 9.6 mg/kg/day).
Verapamil was not mutagenic in the Ames test in 5 test strains at 3 mg per
plate, with or without metabolic activation.
Studies in female rats at daily dietary doses up to 5.5 times (55 mg/kg/day)
the maximum recommended human dose did not show impaired fertility. Effects on
male fertility have not been determined.
Reproduction studies have been performed in rabbits and rats at
oral doses up to 1.5 (15 mg/kg/day) and 6 (60 mg/kg/day) times the maximum
recommended human daily dose, respectively, and have revealed no evidence of
teratogenicity. In the rat, however, this multiple of the human dose was
embryocidal and retarded fetal growth and development, probably because of
adverse maternal effects reflected in reduced weight gains of the dams. This
oral dose has also been shown to cause hypotension in rats. There are no
adequate and well-controlled studies in pregnant women. Because animal
reproduction studies are not always predictive of human response, this drug
should be used during pregnancy only if clearly needed. Verapamil crosses the
placental barrier and can be detected in umbilical vein blood at delivery.
It is not known whether the use of verapamil during labor or
delivery has immediate or delayed adverse effects on the fetus, or whether it
prolongs the duration of labor or increases the need for forceps delivery or
other obstetric intervention. Such adverse experiences have not been reported in
the literature, despite a long history of use of verapamil HCl in Europe in the
treatment of cardiac side effects of beta-adrenergic agonist agents used to
treat premature labor.
Verapamil is excreted in human milk. Because of the potential for
adverse reactions in nursing infants from verapamil, nursing should be
discontinued while verapamil is administered.
Safety and efficacy of verapamil in children below the age of 18
years have not been established.
Clinical studies of verapamil did not include sufficient numbers
of subjects aged 65 and over to determine whether they respond differently from
younger subjects. Other reported clinical experience has not identified
differences in responses between the elderly and younger patients. In general,
dose selection for an elderly patient should be cautious, usually starting at
the low end of the dosing range, reflecting the greater frequency of decreased
hepatic, renal, or cardiac function, and of concomitant disease or other drug
therapy.
Aging may affect the pharmacokinetics of verapamil. Elimination half-life may
be prolonged in the elderly (see ).
Verapamil is highly metabolized by the liver, and about 70% of the
administered dose is excreted as metabolites in the urine. Clinical
circumstances, some of which may be more common in the elderly, such as hepatic
or renal impairment, should be considered (see ). In general, lower initial doses of
Verelan may be warranted in the elderly (see ).
In chronic animal toxicology studies verapamil caused lenticular
and/or suture line changes at 30 mg/kg/day or greater and frank cataracts at
62.5 mg/kg/day or greater in the beagle dog but not the rat. Development of
cataracts due to verapamil has not been reported in man.
What are the side effects of Verelan?
Serious adverse reactions are uncommon when verapamil HCl therapy
is initiated with upward dose titration within the recommended single and total
daily dose. See for
discussion of heart failure, hypotension, elevated liver enzymes, AV block, and
rapid ventricular response. Reversible (upon discontinuation of verapamil)
non-obstructive, paralytic ileus has been infrequently reported in association
with the use of verapamil.
In clinical trials involving 285 hypertensive patients on Verelan for greater
than 1 week the following adverse reactions were reported in greater than 1.0%
of the patients:
In clinical trials of other formulations of verapamil HCl (N=4,954) the
following reactions have occurred at rates greater than 1.0%:
In clinical trials related to the control of ventricular response in
digitalized patients who had atrial fibrillation or atrial flutter, ventricular
rate below 50/min at rest occurred in 15% of patients and asymptomatic
hypotension occurred in 5% of patients.
The following reactions, reported in 1.0% or less of patients, occurred under
conditions (open trials, marketing experience) where a causal relationship is
uncertain; they are listed to alert the physician to a possible
relationship:
Cardiovascular:
Digestive System:
Hemic and Lymphatic:
Nervous System:
Respiratory:
Skin:
Special Senses:
Urogenital:
The frequency of cardiovascular adverse reactions which 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 isoproterenol HCl, levarterenol bitartrate,
atropine (all in the usual doses), or calcium gluconate (10% solution). In
patients with hypertrophic cardiomyopathy (IHSS), alpha-adrenergic agents
(phenylephrine, metaraminol bitartrate or methoxamine) should be used to
maintain blood pressure, and isoproterenol and levarterenol should be avoided.
If further support is necessary, inotropic agents (dopamine or dobutamine) may
be administered. Actual treatment and dosage should depend on the severity and
the clinical situation and the judgment and experience of the treating
physician.
| Constipation | 7.4% |
| Headache | 5.3% |
| Dizziness | 4.2% |
| Lethargy | 3.2% |
| Dyspepsia | 2.5% |
| Rash | 1.4% |
| Ankle Edema | 1.4% |
| Sleep Disturbance | 1.4% |
| Myalgia | 1.1% |
| Constipation | 7.3% |
| CHF/Pulmonary Edema | 1.8% |
| Dizziness | 3.3% |
| Fatigue | 1.7% |
| Nausea | 2.7% |
| Bradycardia (HR less than 50/min) | 1.4% |
| Hypotension | 2.5% |
| AV block-total 1°, 2°, 3° | 1.2% |
| 2° and 3° | 0.8% |
| Edema | 1.9% |
| Headache | 2.2% |
| Flushing | 0.6% |
| Rash | 1.2% |
What should I look out for while using Verelan?
Verapamil HCl is contraindicated in:
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
) Patients with
milder ventricular dysfunction should, if possible, be controlled with optimum
doses of digitalis and/or diuretics before verapamil treatment (note
interactions with digoxin under: ).
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 in the face of
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 elevations 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 flutter or
atrial fibrillation 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 )
Treatment is usually DC-cardioversion. Cardioversion has been used safely and
effectively after oral verapamil.
The effect of verapamil on AV conduction and the SA node may lead
to 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 upon 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 (over 20
mm Hg) capillary wedge pressure and a marked left ventricular outflow
obstruction were present in most of these patients. Concomitant administration
of quinidine (see )
preceded the severe hypotension in 3 of the 8 patients (2 of whom developed
pulmonary edema). Sinus bradycardia occurred in 11% of the patients,
second-degree AV block in 4% and sinus arrest in 2%. It must be appreciated that
this group of patients had a serious disease with a high mortality rate. Most
adverse effects responded well to dose reduction and only rarely did verapamil
have to be discontinued.
What might happen if I take too much Verelan?
There is no specific antidote for verapamil overdosage; treatment
should be supportive. Delayed pharmacodynamic consequences may occur with
sustained-release formulations, and patients should be observed for at least 48
hours, preferably under continuous hospital care. Reported effects include
hypotension, bradycardia, cardiac conduction defects, arrhythmias,
hyperglycemia, and decreased mental status. In addition, there have been
literature reports of non-cardiogenic pulmonary edema in patients taking large
overdoses of verapamil (up to approximately 9g).
In acute overdosage, gastrointestinal decontamination with cathartics and
whole bowel irrigation should be considered. Calcium, inotropes (i.e.,
isoproterenol, dopamine, and glucagon), atropine, vasopressors (i.e.,
norepinephrine, and epinephrine), and cardiac pacing have been used with
variable results to reverse hypotension and myocardial depression. In a few
reported cases, overdose with calcium channel blockers that was initially
refractory to atropine became more responsive to this treatment when the
patients received large doses (close to 1g/hour for more than 24 hours) of
calcium chloride. Calcium chloride is preferred to calcium gluconate since it
provides 3 times more calcium per volume. Asystole should be handled by the
usual measures including cardiopulmonary resuscitation. Verapamil cannot be
removed by hemodialysis.
How should I store and handle Verelan?
Store at 20°-25°C (68°-77°F) (see USP Controlled Room Temperature). PROTECT FROM LIGHT. KEEP TIGHTLY CLOSED. Sarafem is a registered trademark of Eli Lilly and Company. Verelan (verapamil hydrochloride) sustained-release pellet filled capsules are supplied in four dosage strengths:Store at controlled room temperature 20°-25°C (68°-77°F). [See USP]. Avoid excessive heat. Brief digressions above 25°C, while not detrimental, should be avoided. Protect from moisture. Dispense in tight, light-resistant container as defined in USP.Call your doctor for medical advice about side effects. You may report side effects to UCB, Inc. at 1-800-477-7877 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.RonlyVerelan (verapamil hydrochloride) sustained-release pellet filled capsules are supplied in four dosage strengths:Store at controlled room temperature 20°-25°C (68°-77°F). [See USP]. Avoid excessive heat. Brief digressions above 25°C, while not detrimental, should be avoided. Protect from moisture. Dispense in tight, light-resistant container as defined in USP.Call your doctor for medical advice about side effects. You may report side effects to UCB, Inc. at 1-800-477-7877 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.RonlyVerelan (verapamil hydrochloride) sustained-release pellet filled capsules are supplied in four dosage strengths:Store at controlled room temperature 20°-25°C (68°-77°F). [See USP]. Avoid excessive heat. Brief digressions above 25°C, while not detrimental, should be avoided. Protect from moisture. Dispense in tight, light-resistant container as defined in USP.Call your doctor for medical advice about side effects. You may report side effects to UCB, Inc. at 1-800-477-7877 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.RonlyVerelan (verapamil hydrochloride) sustained-release pellet filled capsules are supplied in four dosage strengths:Store at controlled room temperature 20°-25°C (68°-77°F). [See USP]. Avoid excessive heat. Brief digressions above 25°C, while not detrimental, should be avoided. Protect from moisture. Dispense in tight, light-resistant container as defined in USP.Call your doctor for medical advice about side effects. You may report side effects to UCB, Inc. at 1-800-477-7877 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.RonlyVerelan (verapamil hydrochloride) sustained-release pellet filled capsules are supplied in four dosage strengths:Store at controlled room temperature 20°-25°C (68°-77°F). [See USP]. Avoid excessive heat. Brief digressions above 25°C, while not detrimental, should be avoided. Protect from moisture. Dispense in tight, light-resistant container as defined in USP.Call your doctor for medical advice about side effects. You may report side effects to UCB, Inc. at 1-800-477-7877 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.Ronly
Clinical Information
Chemical Structure
No Image foundClinical Pharmacology
Verelan is a calcium ion influx inhibitor (slow channel blocker
or calcium ion antagonist) which exerts its pharmacologic effects by modulating
the influx of ionic calcium across the cell membrane of the arterial smooth
muscle as well as in conductile and contractile myocardial cells.
Normal sinus rhythm is usually not affected by verapamil HCl. However in
patients with sick sinus syndrome, verapamil HCl may interfere with sinus node
impulse generation and may induce sinus arrest or sinoatrial block.
Atrioventricular block can occur in patients without preexisting conduction
defects. (See ) Verapamil
HCl does not alter the normal atrial action potential or intraventricular
conduction time, but depresses amplitude, velocity of depolarization and
conduction in depressed atrial fibers. Verapamil HCl may shorten the antegrade
effective refractory period of accessory bypass tracts. Acceleration of
ventricular rate and/or ventricular fibrillation has been reported in patients
with atrial flutter or atrial fibrillation and a coexisting accessory AV pathway
following administration of verapamil. (See )
Verapamil HCl 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 HCl exerts antihypertensive effects by decreasing
systemic vascular resistance, usually without orthostatic decreases in blood
pressure or reflex tachycardia; bradycardia (rate less than 50 beats/minute is
uncommon). Verapamil HCl regularly reduces arterial pressure at rest and at a
given level of exercise by dilating peripheral arterioles and reducing the total
peripheral resistance (afterload) against which the heart works.
With the immediate release formulations, more than 90% of the
orally administered dose is absorbed, and peak plasma concentrations of
verapamil are observed 1 to 2 hours after dosing. Because of rapid
biotransformation of verapamil during its first pass through the portal
circulation, the absolute bioavailability ranges from 20% to 35%. Chronic oral
administration of the highest recommended dose (120 mg every 6 hours) resulted
in plasma verapamil levels ranging from 125 to 400 ng/mL with higher values
reported occasionally. A nonlinear correlation between the verapamil HCl dose
administered and verapamil plasma levels does exist.
During initial dose titration with verapamil a relationship exists between
verapamil plasma concentrations and the prolongation of the PR interval.
However, during chronic administration this relationship may disappear. The
quantitative relationship between plasma verapamil concentrations and blood
pressure reduction has not been fully characterized.
In a multiple dose pharmacokinetic study, peak concentrations for a single
daily dose of Verelan 240 mg were approximately 65% of those obtained with an 80
mg t.i.d. dose of the conventional immediate-release tablets, and the 24 hour
post-dose concentrations were approximately 30% higher. At a total daily dose of
240 mg, Verelan was shown to have a similar extent of verapamil bioavailability
based on the AUC-24 as that obtained with the conventional immediate-release
tablets. In this same study Verelan doses of 120 mg, 240 mg and 360 mg once
daily were compared after multiple doses. The ratios of the verapamil and
norverapamil AUCs for the Verelan 120 mg, 240 mg and 360 mg once daily doses are
1 (565 ng∙hr/mL):3 (1660 ng∙hr/mL):5 (2729 ng∙hr/mL) and 1 (621 ng∙hr/mL):3
(1614 ng∙ hr/mL):4 (2535 ng∙hr/mL) respectively, indicating that the AUC
increased non-proportionately with increasing doses.
Food does not affect the extent or rate of the absorption of verapamil from
the controlled release Verelan capsule. The Verelan 240 mg capsule when
administered with food had a C of 77 ng/mL which
occurred 9.0 hours after dosing, and an AUC(O-inf) of 1387 ng∙hr/mL. Verelan 240
mg under fasting conditions had a C of 77 ng/mL which
occurred 9.8 hours after dosing, and an AUC(O-inf) of 1541 ng∙hr/mL.
The bioequivalence of Verelan 240 mg, administered as the pellets sprinkled
on applesauce and as the intact capsule, was demonstrated in a single-dose,
cross-over study in 32 healthy adults. Comparative ratios (sprinkled/intact) of
verapamil were 0.95, 1.02, and 1.01 for C, T, and AUC(O-inf) respectively. When the contents of the
Verelan capsule were administered by sprinkling onto one
tablespoonful of applesauce, the rate and extent of verapamil absorption were
found to be bioequivalent to the same dose when administered as an intact
capsule. Similar results were observed with norverapamil.
The time to reach maximum verapamil concentrations (Tmax) with Verelan has
been found to be approximately 7-9 hours in each of the single dose (fasting),
single dose (fed), the multiple dose (steady state) studies and dose
proportionality pharmacokinetic studies. Similarly the apparent half-life (t1/2)
has been found to be approximately 12 hours independent of dose. Aging may
affect the pharmacokinetics of verapamil. Elimination half-life may be prolonged
in the elderly.
In healthy man, orally administered verapamil HCl undergoes extensive
metabolism in the liver. Twelve metabolites have been identified in plasma; all
except norverapamil are present in trace amounts only. Norverapamil can reach
steady-state plasma concentrations approximately equal to those of verapamil
itself. The biologic activity of norverapamil appears to be approximately 20%
that of verapamil.
Approximately 70% of an administered dose of verapamil HCl is excreted as
metabolites in the urine and 16% or more in the feces within 5 days. About 3% to
4% is excreted in the urine as unchanged drug. Approximately 90% is bound to
plasma proteins. In patients with hepatic insufficiency, metabolism is delayed
and elimination half-life prolonged up to 14 to 16 hours (see ), the volume of distribution
is increased and plasma clearance reduced to about 30% of normal. Verapamil
clearance values suggest that patients with liver dysfunction may attain
therapeutic verapamil plasma concentrations with one-third of the oral daily
dose required for patients with normal liver function.
After four weeks of oral dosing (120 mg q.i.d.), verapamil and norverapamil
levels were noted in the cerebrospinal fluid with estimated partition
coefficient of 0.06 for verapamil and 0.04 for norverapamil.
In 10 healthy males, administration of oral verapamil (80 mg every 8 hours
for 6 days) and a single oral dose of ethanol (0.8 g/kg), resulted in a 17%
increase in mean peak ethanol concentrations (106.45 ± 21.40 to 124.23 ± 24.74
mg/dL) compared with placebo. (See )
The area under the blood ethanol concentration versus time curve (AUC over 12
hours) increased by 30% (365.67 ± 93.52 to 475.07 ± 97.24 mg∙hr/dL). Verapamil
AUCs were positively correlated (r = 0.71) to increased ethanol blood AUC
values.
The pharmacokinetics of verapamil GITS were studied after 5
consecutive nights of dosing 180 mg in 30 healthy young (19-43 years) versus 30
healthy elderly (65-80years) male and female subjects. Older subjects had
significantly higher mean verapamil C , C and AUC compared to younger
subjects. Older subjects had mean AUCs that were approximately 1.7-2.0 times
higher than those of younger subjects as well as a longer average verapamil
t (approximately 20 hr vs. 13 hr).
Verapamil HCl reduces afterload and myocardial contractility.
Improved left ventricular diastolic function in patients with IHSS and those
with coronary heart disease has also been observed with verapamil HCl therapy.
In most patients, including those with organic cardiac disease, the negative
inotropic action of verapamil HCl is countered by reduction of afterload and
cardiac index is usually not reduced. In patients with severe left ventricular
dysfunction however, (e.g., pulmonary wedge pressure above 20 mm Hg or ejection
fraction lower than 30%), or in patients on beta-adrenergic blocking agents or
other cardiodepressant drugs, deterioration of ventricular function may occur.
(See )
Verapamil HCl does not induce broncho-constriction and hence,
does not impair ventilatory function.
Non-Clinical Toxicology
Verapamil HCl is contraindicated in: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 ) Patients with milder ventricular dysfunction should, if possible, be controlled with optimum doses of digitalis and/or diuretics before verapamil treatment (note interactions with digoxin under: ).
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 in the face of 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 elevations 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 flutter or atrial fibrillation 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 )
Treatment is usually DC-cardioversion. Cardioversion has been used safely and effectively after oral verapamil.
The effect of verapamil on AV conduction and the SA node may lead to 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 upon 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 (over 20 mm Hg) capillary wedge pressure and a marked left ventricular outflow obstruction were present in most of these patients. Concomitant administration of quinidine (see ) preceded the severe hypotension in 3 of the 8 patients (2 of whom developed pulmonary edema). Sinus bradycardia occurred in 11% of the patients, second-degree AV block in 4% and sinus arrest in 2%. It must be appreciated that this group of patients had a serious disease with a high mortality rate. Most adverse effects responded well to dose reduction and only rarely did verapamil have to be discontinued.
THE CONTENTS OF THE Verelan CAPSULE SHOULD NOT BE CRUSHED OR CHEWED. Verelan CAPSULES ARE TO BE SWALLOWED WHOLE OR THE ENTIRE CONTENTS OF THE CAPSULE SPRINKLED ONTO APPLESAUCE
Since verapamil is highly metabolized by the liver, it should be administered cautiously to patients with impaired hepatic function. Severe liver dysfunction prolongs the elimination half-life of immediate-release verapamil to about 14 to 16 hours; hence, approximately 30% of the dose given to patients with normal liver function should be administered to these patients. Careful monitoring for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effects (see ) should be carried out.
It has been reported that verapamil decreases neuromuscular transmission in patients with Duchenne's muscular dystrophy, and that verapamil prolongs recovery from the neuromuscular blocking agent vecuronium and causes a worsening of myasthenia gravis. It may be necessary to decrease the dosage of verapamil when it is administered to patients with attenuated neuromuscular transmission.
About 70% of an administered dose of verapamil is excreted as metabolites in the urine. Until further data are available, verapamil should be administered cautiously to patients with impaired renal function. These patients should be carefully monitored for abnormal prolongation of the PR interval or other signs of overdosage. (See )
When the sprinkle method of administration is prescribed, details of the proper technique should be explained to the patient. (See .)
In vitro
Concomitant therapy with beta-adrenergic blockers and verapamil may result in additive negative effects on heart rate, atrioventricular conduction, and/or cardiac contractility. The combination of sustained-release verapamil and beta-adrenergic blocking agents has not been studied. However, there have been reports of excess bradycardia and AV block, including complete heart block, when the combination has been used for the treatment of hypertension.
For hypertensive patients, the risk of combined therapy may outweigh the potential benefits. The combination should be used only with caution and close monitoring.
Asymptomatic bradycardia (36 beats/min) with a wandering atrial pacemaker has been observed in a patient receiving concomitant timolol (a beta-adrenergic blocker) eyedrops and oral verapamil.
A decrease in metoprolol clearance has been reported when verapamil and metoprolol were administered together. A similar effect has not been observed when verapamil and atenolol are given together.
Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and clonidine.
Consider reducing digoxin dose when verapamil and digoxin are to be given together. Monitor digoxin level periodically during therapy. Chronic verapamil treatment can increase serum digoxin levels by 50% to 75% during the first week of therapy, and this can result in digitalis toxicity. In patients with hepatic cirrhosis the influence of verapamil on digoxin pharmacokinetics is magnified. Verapamil may reduce total body clearance and extrarenal clearance of digoxin by 27% and 29%, respectively. If digoxin toxicity is suspected, suspend or discontinue digoxin therapy.
In previous clinical trials with other verapamil formulations related to the control of ventricular response in patients taking digoxin who had atrial fibrillation or atrial flutter, ventricular rates below 50/min at rest occurred in 15% of patients, and asymptomatic hypotension occurred in 5% of patients.
Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. Patients receiving these combinations should be appropriately monitored. Concomitant use of agents that attenuate alpha-adrenergic function with verapamil may result in reduction in blood pressure that is excessive in some patients. Such an effect was observed in one study following the concomitant administration of verapamil and prazosin.
Until data on possible interactions between verapamil and disopyramide phosphate are obtained, disopyramide should not be administered within 48 hours before or 24 hours after verapamil administration.
A study in healthy volunteers showed that the concomitant administration of flecainide and verapamil may have additive effects on myocardial contractility, AV conduction, and repolarization. Concomitant therapy with flecainide and verapamil may result in additive negative inotropic effect and prolongation of atrioventricular conduction.
In a small number of patients with hypertrophic cardiomyopathy (IHSS), concomitant use of verapamil and quinidine resulted in significant hypotension. Until further data are obtained, combined therapy of verapamil and quinidine in patients with hypertrophic cardiomyopathy should probably be avoided.
The electrophysiological effects of quinidine and verapamil on AV conduction were studied in 8 patients. Verapamil significantly counteracted the effects of quinidine on AV conduction. There has been a report of increased quinidine levels during verapamil therapy.
Verapamil has been given concomitantly with short- and long-acting nitrates without any undesirable drug interactions. The pharmacologic profile of both drugs and the clinical experience suggest beneficial interactions.
Verapamil has been found to significantly inhibit ethanol elimination resulting in elevated blood ethanol concentrations that may prolong the intoxicating effects of alcohol. (See
In a few reported cases, coadministration of verapamil with aspirin has led to increased bleeding times greater than observed with aspirin alone.
The interaction between cimetidine and chronically administered verapamil has not been studied. Variable results on clearance have been obtained in acute studies of healthy volunteers; clearance of verapamil was either reduced or unchanged.
Grapefruit juice may significantly increase concentrations of verapamil. Grapefruit juice given to nine healthy volunteers increased S- and R- verapamil AUC by 36% and 28%, respectively. Steady state C and C of S-verapamil increased by 57% and 16.7%, respectively with grapefruit juice compared to control. Similarly, C and C of R-verapamil increased by 40% and 13%, respectively. Grapefruit juice did not affect half-life, nor was there a significant change in AUC ratio R/S compared to control. Grapefruit juice did not cause a significant difference in the PK of norverapamil. This increase in verapamil plasma concentration is not expected to have any clinical consequences.
Pharmacokinetic and pharmacodynamic interactions between oral verapamil and lithium have been reported. The former may result in a lowering of serum lithium levels in patients receiving chronic stable oral lithium therapy. The latter may result in an increased sensitivity to the effects of lithium. Patients receiving both drugs must be monitored carefully.
Verapamil therapy may increase carbamazepine concentrations during combined therapy. This may produce carbamazepine side effects such as diplopia, headache, ataxia, or dizziness.
Therapy with rifampin may markedly reduce oral verapamil bioavailability.
Phenobarbital therapy may increase verapamil clearance.
Verapamil therapy may increase serum levels of cyclosporine.
Animal experiments have shown that inhalation anesthetics depress cardiovascular activity by decreasing the inward movement of calcium ions. When used concomitantly, inhalation anesthetics and calcium antagonists, such as verapamil, should be titrated carefully to avoid excessive cardiovascular depression.
Clinical data and animal studies suggest that verapamil may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing). It may be necessary to decrease the dose of verapamil and/or the dose of the neuromuscular blocking agent when the drugs are used concomitantly.
An 18-month toxicity study in rats, at a low multiple (6 fold) of the maximum recommended human dose, and not the maximum tolerated dose, did not suggest a tumorigenic potential. There was no evidence of a carcinogenic potential of verapamil administered in the diet of rats for two years at doses of 10, 35 and 120 mg/kg per day or approximately 1x, 3.5x and 12x, respectively, the maximum recommended human daily dose (480 mg per day or 9.6 mg/kg/day).
Verapamil was not mutagenic in the Ames test in 5 test strains at 3 mg per plate, with or without metabolic activation.
Studies in female rats at daily dietary doses up to 5.5 times (55 mg/kg/day) the maximum recommended human dose did not show impaired fertility. Effects on male fertility have not been determined.
Reproduction studies have been performed in rabbits and rats at oral doses up to 1.5 (15 mg/kg/day) and 6 (60 mg/kg/day) times the maximum recommended human daily dose, respectively, and have revealed no evidence of teratogenicity. In the rat, however, this multiple of the human dose was embryocidal and retarded fetal growth and development, probably because of adverse maternal effects reflected in reduced weight gains of the dams. This oral dose has also been shown to cause hypotension in rats. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Verapamil crosses the placental barrier and can be detected in umbilical vein blood at delivery.
It is not known whether the use of verapamil during labor or delivery has immediate or delayed adverse effects on the fetus, or whether it prolongs the duration of labor or increases the need for forceps delivery or other obstetric intervention. Such adverse experiences have not been reported in the literature, despite a long history of use of verapamil HCl in Europe in the treatment of cardiac side effects of beta-adrenergic agonist agents used to treat premature labor.
Verapamil is excreted in human milk. Because of the potential for adverse reactions in nursing infants from verapamil, nursing should be discontinued while verapamil is administered.
Safety and efficacy of verapamil in children below the age of 18 years have not been established.
Clinical studies of verapamil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Aging may affect the pharmacokinetics of verapamil. Elimination half-life may be prolonged in the elderly (see ).
Verapamil is highly metabolized by the liver, and about 70% of the administered dose is excreted as metabolites in the urine. Clinical circumstances, some of which may be more common in the elderly, such as hepatic or renal impairment, should be considered (see ). In general, lower initial doses of Verelan may be warranted in the elderly (see ).
In chronic animal toxicology studies verapamil caused lenticular and/or suture line changes at 30 mg/kg/day or greater and frank cataracts at 62.5 mg/kg/day or greater in the beagle dog but not the rat. Development of cataracts due to verapamil has not been reported in man.
Serious adverse reactions are uncommon when verapamil HCl therapy is initiated with upward dose titration within the recommended single and total daily dose. See for discussion of heart failure, hypotension, elevated liver enzymes, AV block, and rapid ventricular response. Reversible (upon discontinuation of verapamil) non-obstructive, paralytic ileus has been infrequently reported in association with the use of verapamil.
In clinical trials involving 285 hypertensive patients on Verelan for greater than 1 week the following adverse reactions were reported in greater than 1.0% of the patients:
In clinical trials of other formulations of verapamil HCl (N=4,954) the following reactions have occurred at rates greater than 1.0%:
In clinical trials related to the control of ventricular response in digitalized patients who had atrial fibrillation or atrial flutter, ventricular rate below 50/min at rest occurred in 15% of patients and asymptomatic hypotension occurred in 5% of patients.
The following reactions, reported in 1.0% or less of patients, occurred under conditions (open trials, marketing experience) where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship:
Cardiovascular:
Digestive System:
Hemic and Lymphatic:
Nervous System:
Respiratory:
Skin:
Special Senses:
Urogenital:
The frequency of cardiovascular adverse reactions which 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 isoproterenol HCl, levarterenol bitartrate, atropine (all in the usual doses), or calcium gluconate (10% solution). In patients with hypertrophic cardiomyopathy (IHSS), alpha-adrenergic agents (phenylephrine, metaraminol bitartrate or methoxamine) should be used to maintain blood pressure, and isoproterenol and levarterenol should be avoided. If further support is necessary, inotropic agents (dopamine or dobutamine) may be administered. Actual treatment and dosage should depend on the severity and the clinical situation and the judgment and experience of the treating physician.
Reference
This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"
While we update our database periodically, we cannot guarantee it is always updated to the latest version.
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Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72Tips
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