Isoptin SR (Verapamil HCl)

ISOPTIN® SR

Knoll

Verapamil HCl

Antihypertensive Agent

Action And Clinical Pharmacology: Verapamil is a calcium ion influx inhibitor (calcium entry blocker or calcium ion antagonist) that exerts its pharmacological effects by modulating the influx of ionic calcium across the cell membrane of the arterial smooth muscle as well as in conducting and contractile myocardial cells.

Verapamil exerts antihypertensive effects by inducing vasodilation and reducing peripheral vascular resistance usually without reflex tachycardia. Verapamil does not blunt hemodynamic response to isometric or dynamic exercise.

Verapamil depresses AV nodal conduction and prolongs functional refractory periods. Verapamil does not alter the normal atrial action potential or intraventricular conduction time, but depresses amplitude, velocity of depolarization and conduction in depressed atrial fibres.

Verapamil may shorten the antegrade effective refractory period of the accessory bypass tract. 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 Warnings, Conduction Disturbance). Verapamil has a local anesthetic action that is 1.6 times that of procaine on an equimolar basis.

Verapamil is a potent smooth muscle relaxant with vasodilatory properties, as well as a depressant of myocardial contractility, and these effects are largely independent of autonomic influences.

Compared to baseline, verapamil does not affect electrolytes, glucose, and creatinine. The hypotensive effect of verapamil is not blunted by an increase in sodium intake.

In hypertensive normolipidemic patients, verapamil had no effects on plasma lipoprotein fractions.

Pharmacodynamics: In a study in 5 healthy males, the S enantiomer was found to be 8 to 20 times more active than the R enantiomer in slowing AV conduction. In another study using septal strips isolated from the left ventricle of 5 patients with mitral disease, the S enantiomer was 8 times more potent than the R enantiomer in reducing myocardial contractility.

Pharmacokinetics: Isoptin SR is a racemic mixture consisting of equal portions of the R enantiomer and the S enantiomer. More than 90% of the orally administered dose of Isoptin SR is absorbed. Upon oral administration, there is rapid stereoselective biotransformation during the first pass of verapamil through the portal circulation. The systemic concentrations of R and S enantiomers are dependent upon the route and the rate of administration and the rate and extent of release from the dosage forms.

The following bioavailability information was obtained from healthy volunteers and not from the populations most likely to be treated with verapamil.

In a study in 5 healthy volunteers with oral immediate-release verapamil, the systemic bioavailability varied from 33 to 65% for the R enantiomer and from 13 to 34% for the S enantiomer. The S enantiomer is pharmacologically more active than the R enantiomer (see Pharmacodynamics).

There is a nonlinear correlation between the verapamil dose administered and verapamil plasma levels. In early dose titration with verapamil, a relationship exists between total verapamil (R and S combined) plasma concentration and prolongation of the PR interval. The mean elimination half-life in single-dose studies of immediate release verapamil ranged from 2.8 to 7.4 hours. In these same studies, after steady-state was reached, the half-life increased to a range from 4.5 to 12 hours (after less than 10 consecutive doses given 6 hours apart). Half-life of verapamil may increase during titration. Aging decreases the clearance and elimination of verapamil.

In a randomized, multiple-dose study in 44 healthy young subjects, administration of Isoptin SR 240 mg with food produced peak plasma concentrations at approximately 8 hours postdose of 188 and 76 ng/mL and AUC’s (0 to 24 hours) of 2 553 and 1 046 ngh/mL for the R and S enantiomers, respectively. Similar results were demonstrated for plasma norverapamil.

In healthy men, orally administered verapamil undergoes extensive metabolism by the cytochrome P450 system in the liver. The particular isoenzymes involved are CYP3A4, CYP1A2, and CYP2C family. Thirteen metabolites have been identified in urine. Norverapamil can reach steady-state plasma concentrations approximately equal to those of verapamil itself. The cardiovascular activity of norverapamil appears to be approximately 20% that of verapamil. Approximately 70% of an administered dose 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. R-verapamil is 94% bound to plasma albumin, while S-verapamil is 88% bound. In addition, R-verapamil is 92% and S-verapamil 86% bound to alpha-1 acid glycoprotein. The degree of biotransformation during the first pass of verapamil may vary according to the status of the liver in different patient populations. In patients with hepatic insufficiency, metabolism is delayed and elimination half-life prolonged up to 14 to 16 hours (see Warnings, Hepatic Insufficiency and Dosage).

Verapamil crosses the placental barrier and can be detected in umbilical vein blood at delivery. Verapamil is excreted in human milk.

A study was conducted in which 240 mg single oral doses of Isoptin Standard Release (fasting) and Isoptin Sustained Release (fed) tablets were given to 12 young, healthy males (19 to 37 years old) in a randomized, crossover (7-day washout) study. Serial blood samples for drug determination were taken over a 48 hour period. The pharmacokinetic data from this study is summarized.

Indications And Clinical Uses: In the treatment of mild to moderate essential hypertension. Verapamil should normally be used in those patients in whom treatment with diuretics or beta-blockers has been associated with unacceptable adverse effects.

Verapamil can be tried as an initial agent in those patients in whom the use of diuretics and/or beta-blockers is contraindicated or in patients with medical conditions in which these drugs frequently cause serious adverse effects.

Concomitant use of verapamil with a diuretic or an angiotensin converting enzyme inhibitor has been shown to be compatible and to have additive blood pressure lowering effects.

Verapamil should not be used concurrently with beta adrenoreceptor blockers in the treatment of hypertension (see Precautions, Drug Interactions).

Safety of concurrent use of verapamil with other antihypertensive agents has not been established and such use cannot be recommended at this time.

Contra-Indications: Complicated myocardial infarction (patients who have ventricular failure manifested by pulmonary congestion). Severe congestive heart failure and/or severe left ventricular dysfunction (i.e. ejection fraction).

Manufacturers’ Warnings In Clinical States: General: In patients with angina or arrhythmias using antihypertensive drugs, the additional hypotensive effect of verapamil should be taken into consideration.

Heart Failure: Because of the drug’s negative inotropic effect, verapamil should not be used in patients with poorly compensated congestive heart failure, unless the failure is complicated by or caused by a dysrhythmia. If verapamil is used in such patients, they must be digitalized prior to treatment.

It has been reported that digoxin plasma levels may increase with chronic verapamil administration (see Precautions, Drug Interactions, Digoxin). The use of verapamil in the treatment of hypertension is not recommended in patients with heart failure caused by systolic dysfunction.

Hypotension: Hypotensive symptoms of lethargy and weakness with faintness have been reported following single oral doses and even after some months of treatment. In some patients it may be necessary to reduce the dose.

Conduction Disturbance: Verapamil slows conduction across the AV node and rarely may produce second or third degree AV block, bradycardia and in extreme cases, asystole.

Verapamil causes dose-related suppression of the SA node. In some patients, sinus bradycardia may occur, especially in patients with a sick sinus syndrome (SA nodal disease), which is more common in older patients (see Contraindications).

Bradycardia: The total incidence of bradycardia (ventricular rate less than 50 beats/min) was 1.4% in controlled 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 Overdose: Symptoms and Treatment).

Accessory Bypass Tract (Wolff-Parkinson-White or Lown-Ganong-Levine): Verapamil may result in significant acceleration of ventricular response during atrial fibrillation or atrial flutter in the Wolff-Parkinson-White (WPW) or Lown-Ganong-Levine syndromes after receiving i.v. verapamil. 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 Contraindications).

Concomitant Use with Beta-blockers: Generally, oral verapamil should not be given to patients receiving beta-blockers since the depressant effects on myocardial contractility, heart rate and AV conduction may be additive. However, in exceptional cases when in the opinion of the physician concomitant use in angina and arrhythmias is considered essential, such use should be instituted gradually under careful supervision. If combined therapy is used, close surveillance of vital signs and clinical status should be carried out and the need for continued concomitant treatment periodically assessed.

Verapamil gives no protection against the dangers of abrupt beta-blocker withdrawal and such withdrawal should be done by the gradual reduction of the dose of beta-blocker. Then verapamil may be started with the usual dose.

Patients with Hypertrophic Cardiomyopathy: In 120 patients with hypertrophic cardiomyopathy who received therapy with verapamil at doses up to 720 mg/day, a variety of serious adverse effects was 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 Precautions, Drug Interactions) 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, but in some cases, verapamil use had to be discontinued.

Elevated Liver Enzymes: Elevation of transaminase with and without concomitant elevations in alkaline phosphatase and bilirubin have been reported. Several published cases of hepatocellular injury produced by verapamil have been proven by rechallenge. Clinical symptoms of malaise, fever, and/or right upper quadrant pain, in addition to elevation of AST, ALT and alkaline phosphatase have been reported. Periodic monitoring of liver function in patients receiving verapamil is therefore prudent.

Hepatic Insufficiency: Because verapamil is extensively metabolized by the liver, it should be administered cautiously to patients with impaired hepatic function, since the elimination half-life of verapamil in these patients is prolonged 4-fold (from 3.7 to 14.2 hours). A decreased dosage should be used in patients with hepatic insufficiency and careful monitoring for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effect should be carried out (see Pharmacology, Pharmacokinetics and Dosage).

Renal Insufficiency: About 70% of an administered dose of verapamil is excreted as metabolites in the urine. In one study in healthy volunteers, the total body clearance after i.v. administration of verapamil was 12.08 mL/min/kg, while in patients with advanced renal disease it was reduced to 5.33 mL/min/kg. This pharmacokinetic finding suggests that renal clearance of verapamil in patients with renal disease is decreased. In 2 studies with oral verapamil no difference in pharmacokinetics could be demonstrated. Therefore, until further data are available, verapamil should be used with caution in patients with impaired renal function. These patients should be carefully monitored for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effect (see Dosage).

Precautions: Atypical lens changes and cataracts were observed in beagle dog studies at high doses. This has been concluded to be species-specific for the beagle dog. (These ophthalmological changes were not seen in a second study). No similar changes have been observed in long-term prospective human ophthalmological trials.

Verapamil does not alter total serum calcium levels. However, one report suggested that calcium levels above the normal range may decrease the therapeutic effect of verapamil.

Patients with Attenuated (Decreased) Neuromuscular Transmission: 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. It may be necessary to decrease the dosage of verapamil when it is administered to patients with attenuated neuromuscular transmission.

Geriatrics: Caution should be exercised when verapamil is administered to elderly patients (³65 years) especially those prone to developing hypotension or those with a history of cerebrovascular insufficiency (see Dosage and Pharmacology, Pharmacokinetics). The incidence of adverse reactions is approximately 4% higher in the elderly. The adverse reactions occurring more frequently include dizziness and constipation. Serious adverse events associated with heart block have occurred in the elderly.

Pregnancy: Teratology and 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 human oral daily dose, respectively, and have revealed no evidence of teratogenicity or impaired fertility. In 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 studies in pregnant women. However, verapamil crosses the placental barrier and can be detected in umbilical vein blood at delivery. Verapamil is not recommended for use in pregnant women unless the potential benefits outweigh potential risks to mother and fetus.

Labor and 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 inceases the need for forceps delivery or other obstetric intervention.

Lactation: 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.

Children: The safety and dosage regimen of verapamil in children has not yet been established.

Drug Interactions: As with all drugs, care should be exercised when treating patients with multiple medications. Calcium channel blockers undergo biotransformation by the cytochrome P450 system. Coadministration of verapamil with other drugs which follow the same route of biotransformation may result in altered bioavailability of verapamil or these drugs. Dosages of similarly metabolized drugs, particularly those of low therapeutic ratio, and especially in patients with renal and/or hepatic impairment, may require adjustment when starting or stopping concomitantly administered verapamil to maintain optimum therapeutic blood levels.

Drugs known to be inhibitors of the cytochrome P450 system include: azole antifungals, cimetidine, cyclosporine, erythromycin, quinidine, terfenadine, warfarin.

Drugs known to be inducers of the cytochrome P450 system include: phenobarbital, phenytoin, rifampin.

Drugs known to be biotransformed via P450 include: benzodiazepines, flecainide, imipramine, propafenone, theophylline.

Alcohol: Verapamil may increase blood alcohol concentrations and prolong its effects.

Antineoplastic Agents: Verapamil inhibits P-glycoprotein mediated transport of antineoplastic agents out of tumor cells, resulting in their decreased metabolic clearance. Dosage adjustments of antineoplastic agents should be considered when verapamil is administered concomitantly.

Antihypertensive Agents: Verapamil administered concomitantly with antihypertensive agents such as vasodilators, ACE inhibitors, and diuretics may have an additive effect on lowering blood pressure. In patients with angina or arrhythmias using antihypertensive drugs, this additional hypotensive effect should be taken into consideration. Verapamil should not be combined with beta-blockers for the treatment of hypertension. Concomitant use of verapamil and alpha-adrenoceptor blockers may result in excessive fall in blood pressure in some patients as observed in one study following the concomitant administration of verapamil and prazosin.

ASA: Potential adverse reactions in terms of bleeding due to synergistic antiplatelet effects of the two agents should be taken into consideration in patients taking ASA and verapamil concomitantly.

Beta-Adrenergic Blockers: The concomitant administration of verapamil with beta-blockers can result in severe adverse effects (see Warnings).

Carbamazepine: The concomitant oral administration of verapamil and carbamazepine may potentiate the effects of carbamazepine neurotoxicity. Symptoms include nausea, diplopia, headache, ataxia or dizziness.

Cimetidine: Two clinical trials have shown a lack of significant verapamil interaction with cimetidine. A third study showed cimetidine reduced verapamil clearance and increased elimination half-life.

Cyclosporine: Verapamil therapy may increase serum levels of cyclosporine.

Digoxin: Verapamil treatment increases 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 kinetics is magnified. Verapamil may reduce total body clearance and extrarenal clearance of digitoxin by 27 and 29% respectively. Maintenance and digitalization doses should be reduced when verapamil is administered and the patient should be reassessed to avoid over- or underdigitalization. Whenever overdigitalization is suspected, the daily dose of digitalis should be reduced or temporarily discontinued. On discontinuation of verapamil use, the patient should be reassessed to avoid underdigitalization.

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.

Flecainide: 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.

Inhalation Anesthetics: When used concomitantly, inhalation anesthetics and calcium antagonists, such as verapamil, should be titrated carefully because additive hemodynamic depressive effects have been observed.

Lithium: Increased sensitivity to the effects of lithium (neurotoxicity) has been reported during concomitant verapamil-lithium therapy with either no change or an increase in serum lithium levels. However, the addition of verapamil has also resulted in the lowering of serum lithium levels in patients receiving chronic stable oral lithium. Patients receiving both drugs must be monitored carefully.

Neuromuscular Blocking Agents: 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.

Nitrates, Diuretics: No cardiovascular adverse effects have been attributed to any interaction between these agents and verapamil.

Phenobarbital: Phenobarbital therapy may increase verapamil clearance.

Quinidine: In a small number of patients with hypertrophic cardiomyopathy, 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 electrophysiologic 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.

Rifampin: Therapy with rifampin may markedly reduce oral verapamil bioavailability.

Sulfinpyrazone: Increased clearance and decreased bioavailability of verapamil may occur.

Theophylline: Verapamil may inhibit the clearance and increase the plasma levels of theophylline.

Adverse Reactions: In 4 826 patients treated with Isoptin immediate release tablets for arrhythmias, angina or hypertension, the overall adverse reaction rate in these patients was 37.1% and the dropout rate was 10.2%. The majority of these patients were seriously ill and treated under emergency drug regulations.

In controlled pivotal studies with 128 patients treated with Isoptin SR tablets for hypertension the overall adverse reaction rate was 21.7% and the dropout rate was 3.9%.

The most common adverse reactions were: constipation (7.3%), dizziness (3.2%), and nausea (2.7%). In hypertension studies, constipation occurred in 18.5% of patients on Isoptin and 4.7% of patients on Isoptin SR.

The most serious adverse reactions reported with verapamil are heart failure (1.8%), hypotension (2.5%), AV block (1.2%) and rapid ventricular response (see Warnings).

The following adverse reactions divided by body system have been reported in clinical trials or marketing experience. When incidences are shown, they are calculated based on the 4 954 (4 826+128) patient base.

Cardiovascular: hypotension 2.5%; edema 2.1%; CHF/pulmonary edema 1.9%; bradycardia 1.4%; AV block, total (1 2 3 1.2%, 2and 30.8%.

CNS: dizziness 3.2%, headache 2.2%, fatigue 1.7%.

Gastrointestinal: constipation 7.3%, nausea 2.7%.

The following reactions were reported in 1% or less of patients: Cardiovascular: flushing, angina pectoris, atrioventricular dissociation, chest pain, claudication, myocardial infarction, palpitations, purpura, syncope, severe tachycardia, developing or worsening of heart failure, development of rhythm disturbances, ventricular dysrhythmias, painful coldness and numbness of extremities.

CNS: cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, paresthesia, psychotic symptoms, shakiness, somnolence, excitation, depression, rotary nystagmus, vertigo, tremor, extrapyramidal disorders, muscle fatigue, hyperkinesis.

Gastrointestinal: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia, vomiting.

Respiratory: dyspnea, bronchospasm.

Urogenital: gynecomastia, increased frequency of urination, spotty menstruation, oligomenorrhea, impotence.

Hematologic and Lymphatic: ecchymosis or bruising.

Skin: arthralgia and rash, exanthema, hair loss, hyperkeratosis, macules, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme, pruritus.

Special Senses: blurred vision, diplopia.

Hepatotoxicity with elevated enzymes (AST, ALT, alkaline phosphatase) and bilirubin levels, jaundice and associated symptoms of hepatitis with cholestasis have been reported (see Warnings).

Isolated cases of angioedema have been reported. Angioedema may be accompanied by breathing difficulty.

In clinical trials related to the control of ventricular response in digitalized patients who had atrial fibrillation or flutter, ventricular rates below 50 at rest occurred in 15% of patients and asymptomatic hypotension occurred in 5% of patients.

Symptoms And Treatment Of Overdose: Symptoms: Based on reports of intentional overdosage of verapamil, the following symptoms have been observed. Hypotension occurs, varying from transient to severe. Conduction disturbances seen included: prolongation of AV conduction time, AV dissociation, nodal rhythm, ventricular fibrillation and ventricular asystole. tag_Treatment

Treatment: Treatment of overdosage should be supportive. Gastric lavage should be undertaken, even later than 12 hours after ingestion, if no gastrointestinal motility is present. Beta-adrenergic stimulation or parenteral administration of calcium solutions may increase calcium ion influx across the slow channel.

These pharmacologic interventions have been effectively used in treatment of overdosage with verapamil. Clinically significant hypotensive reactions should be treated with vasopressor agents. AV block is treated with atropine and cardiac pacing. Asystole should be handled by the usual Advanced Cardiac Life Support measures including the use of vasopressor agents, e.g. isoproterenol HCl. Verapamil is not removed by hemodialysis.

In case of overdosage with large amounts of Isoptin SR, it should be noted that the release of the active drug and the absorption in the intestine may take more than 48 hours. Depending on the time of ingestion, incompletely dissolved tablets may be present along the entire length of the gastrointestinal tract which function as active drug depots. Extensive elimination measures are indicated, such as induced vomiting, removal of the contents of the stomach and the small intestine under endoscopy, intestinal lavage and high enemas.

Suggested Treatment of Acute Cardiovascular Adverse Reactions: Actual treatment and dosage should depend on the severity of the clinical situation and the judgement of the treating physician. Patients with hypertrophic cardiomyopathy treated with verapamil should not be administered positive inotropic agents.

Dosage And Administration: Crushing or chewing Isoptin SR tablets is not recommended since the sustained-release effect will be altered by damage to the tablet structure. The Isoptin SR 240 mg tablet may be split in half.

Mild to Moderate Essential Hypertension: Isoptin SR tablets should be taken with food (see Pharmacology, Pharmacokinetics, Influence of Food). The dosage should be individualized by titration depending on patient tolerance and responsiveness to verapamil. Titration should be based on therapeutic efficacy and safety, evaluated weekly and approximately 24 hours after the previous dose.

The usual initial adult dose is 180 to 240 mg/day. If required, the dose may be increased up to 240 mg twice a day. A maximum daily dose of 480 mg should not be exceeded.

The antihypertensive effects of Isoptin SR are evident within the first week of therapy. Optimal doses are usually lower in patients also receiving diuretics since additive antihypertensive effects can be expected.

Geriatrics: Lower dosages of Isoptin SR i.e. 120 mg a day, may be warranted in elderly patients (i.e., 65 years and older) (see Precautions, Geriatrics). The dosage should be carefully and gradually adjusted depending on patient tolerability and response.

Impaired Liver and Renal Function: Isoptin SR should be administered cautiously to patients with liver or renal function impairment. The dosage should be carefully and gradually adjusted depending on patient tolerance and response. These patients should be monitored carefully for abnormal prolongation of the PR interval or other signs of overdosage. Isoptin SR should not be used in severe hepatic dysfunction (see Warnings, Hepatic Insufficiency).

Switching from Isoptin to Isoptin SR: When switching from Isoptin to Isoptin SR the total daily dose in mg may remain the same.

Special Note to Pharmacists: The Isoptin SR 240 mg tablet may be split in half. Crushing Isoptin SR tablets is not recommended since the sustained-release effect will be altered by damage to the tablet structure. Use of Isoptin SR 120 mg is recommended.

Availability And Storage: 120 mg: Each off-white, biconvex, round, film-coated tablet, with SR 120 embossed on one side, KNOLL on the other side, contains: verapamil HCl 120 mg. Nonmedicinal ingredients: cellulose, hydroxypropyl methylcellulose, magnesium stearate, polyethylene glycol, povidone, sodium alginate, talc, titanium dioxide and wax. Bottles of 100.

180 mg: Each light-pink, football-shaped, film coated tablet with KNOLL on one side and SR, scored, 180 on the other, contains: verapamil HCl 180 mg. Nonmedicinal ingredients: cellulose, hydroxypropyl methylcellulose, magnesium stearate, polyethylene glycol, povidone, red iron oxide, sodium alginate, talc, titanium dioxide and wax. Bottles of 100.

240 mg: Each light-green, scored, capsule-shaped, film-coated tablet, with 2 triangles embossed on one side, contains: verapamil HCl 240 mg. Nonmedicinal ingredients: cellulose, hydroxypropyl methylcellulose, indigotine lake, magnesium stearate, polyethylene glycol, povidone, quinoline yellow lake, sodium alginate, talc, titanium dioxide and wax. Bottles of 100 and 500. (Shown in Product Recognition Section)

ISOPTIN® SR Knoll Verapamil HCl Antihypertensive Agent

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Hypertension

General Illness Information Common Name: High Blood Pressure Medical Term: Hypertension. Description: Hypertension is defined as a sustained elevated blood pressure (systolic blood pressure of…

High Blood Pressure

General Illness Information Common Name: High Blood Pressure Medical Term: Hypertension. Description: Hypertension is defined as a sustained elevated blood pressure (systolic blood pressure of…