Verelan Pm 200mg Information
Verelan pm 200mg (Verapamil hydrochloride) Indications And Usage
Verelan PM (verapamil hydrochloride extended-release capsules) for oral use is indicated for the management of essential hypertension.
Verelan pm 200mg (Verapamil hydrochloride) Dosage And Administration
THE CONTENTS OF THE Verelan PM CAPSULE SHOULD NOT BE CRUSHED OR CHEWED. Verelan PM CAPSULES ARE TO BE SWALLOWED WHOLE OR THE ENTIRE CONTENTS OF THE CAPSULE SPRINKLED ONTO APPLESAUCE.
Administer Verelan PM once daily at bedtime. Clinical trials studied doses of 100 mg, 200 mg, 300 mg and 400 mg. The usual daily dose of extended-release Verelan PM in clinical trials has been 200 mg given by mouth once daily at bedtime. In rare instances, initial doses of 100 mg a day may be warranted in patients who have an increased response to verapamil [e.g. patients with impaired renal function, impaired hepatic function, elderly, low-weight patients, etc. (see )]. Base upward titration on therapeutic efficacy and safety evaluated approximately 24 hours after dosing. The antihypertensive effects of Verelan PM are evident within the first week of therapy.
If an adequate response is not obtained with 200 mg of Verelan PM, the dose may be titrated upward in the following manner:
a) 300 mg each evening b) 400 mg each evening (2 × 200 mg)
When Verelan PM is administered at bedtime, office evaluation of blood pressure during morning and early afternoon hours is essentially a measure of peak effect. The usual evaluation of trough effect, which sometimes might be needed to evaluate the appropriateness of any given dose of Verelan PM, would be just prior to bedtime.
Verelan pm 200mg (Verapamil hydrochloride) Dosage Forms And Strengths
Extended-release capsules controlled onset: 100 mg, 200 mg, 300 mg.
100 mg: white opaque cap imprinted SCHWARZ/4085 and amethyst body imprinted 100 mg.
200 mg: amethyst opaque cap imprinted SCHWARZ/4086 and amethyst body imprinted 200 mg.
300 mg: lavender opaque cap imprinted SCHWARZ/4087 and amethyst body imprinted 300 mg.
Verelan pm 200mg (Verapamil hydrochloride) Contraindications
Verapamil is contraindicated in:
Verelan pm 200mg (Verapamil hydrochloride) Warnings And Precautions
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.
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 in previous verapamil clinical trials [see ].
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 and institution of appropriate therapy depending upon the clinical situation.
Verelan pm 200mg (Verapamil hydrochloride) Adverse Reactions
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
Serious adverse reactions are uncommon when verapamil 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.
The following reactions () to orally administered Verelan PM occurred at rates of 2.0% or greater or occurred at lower rates but appeared to be drug-related in clinical trials in hypertension.
In previous experience with other formulations of verapamil (N=4,954) the following reactions () have occurred at rates greater than 1.0% or occurred at lower rates but appeared clearly drug related in clinical trials in 4,954 patients.
In clinical trials related to the control of ventricular response in patients taking digoxin 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 with orally administered verapamil in 2.0% or less of patients, occurred under conditions (open verapamil trials, postmarketing experience [reactions added since the initial US approval of Verelan PM in 1998 are marked with an asterisk]) where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship:
Cardiovascular:
Hemic and Lymphatic:
Nervous System:
Respiratory:
Skin:
Special Senses:
Urogenital:
Other:
Verelan pm 200mg (Verapamil hydrochloride) Drug Interactions
In vitro
The use of HMG-CoA reductase inhibitors that are CYP3A4 substrates in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis.
Co-administration of multiple doses of 10 mg of verapamil with 80 mg simvastatin resulted in exposure to simvastatin 2.5-fold that following simvastatin alone. Limit the dose of simvastatin in patients on verapamil to 10 mg daily. Limit the daily dose of lovastatin to 40 mg. Lower starting and maintenance doses of other CYP3A4 substrates (e.g., atorvastatin) may be required as verapamil may increase the plasma concentration of these drugs.
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 extended-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 and propranolol clearance has been observed when either drug is administered concomitantly with verapamil. A variable effect has been seen when verapamil and atenolol were given together.
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 extra-renal 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.
In a small number of patients with hypertrophic cardiomyopathy, concomitant use of verapamil and quinidine resulted in significant hypotension. Until further data are obtained, avoid combined therapy of verapamil and quinidine in patients with hypertrophic cardiomyopathy.
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.
Verelan pm 200mg (Verapamil hydrochloride) Use In Specific Populations
Clinical studies of Verelan PM were not adequate to determine if subjects aged 65 or over respond differently from younger patients. Other reported clinical experience has not identified differences in response between the elderly and younger patients; however, greater sensitivity to Verelan PM by some older individuals cannot be ruled out.
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 PM may be warranted in the elderly [see ].
Verelan pm 200mg (Verapamil hydrochloride) Overdosage
There is no specific antidote for verapamil overdosage; treatment is supportive. Delayed pharmacodynamic consequences may occur with sustained-release formulations, and observe patients 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 noncardiogenic pulmonary edema in patients taking large overdoses of verapamil (up to approximately 9 g).
In acute overdosage, consider gastrointestinal decontamination with cathartics and whole bowel irrigation. Calcium, inotropes (i.e., isoproterenol HCl, dopamine HCl, and glucagon), atropine sulfate, 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 1 gram/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.
Verelan pm 200mg (Verapamil hydrochloride) Description
Verelan PM (verapamil hydrochloride) is a calcium ion influx inhibitor (slow channel blocker or calcium ion antagonist). Verelan PM is available for oral administration as a 100 mg hard gelatin capsule (white opaque cap/amethyst body), a 200 mg hard gelatin capsule (amethyst opaque cap/amethyst body), and as a 300 mg hard gelatin capsule (lavender opaque cap/amethyst body). Verapamil is administered as a racemic mixture of the R and S enantiomers.
The structural formulae of the verapamil HCl enantiomers are:
CHNO•HCl M.W.=491.07
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 PM capsule contains the following inactive ingredients: D&C Red #28, FD & C Blue #1, FD&C red #40, fumaric acid, gelatin, povidone, shellac, silicon dioxide, sodium lauryl sulfate, starch, sugar spheres, talc, and titanium dioxide.
Verelan pm 200mg (Verapamil hydrochloride) Clinical Pharmacology
Verapamil is a calcium ion influx inhibitor (L-type calcium channel blocker or calcium channel antagonist). Verapamil exerts its pharmacologic effects by selectively inhibiting the transmembrane influx of ionic calcium into arterial smooth muscle as well as in conductile and contractile myocardial cells without altering serum calcium concentrations. Verapamil binding is voltage-dependent with affinity increasing as the vascular smooth muscle membrane potential is reduced. In addition, verapamil binding is frequency dependent and apparent affinity increases with increased frequency of depolarizing stimulus.
The L-type calcium channel is an oligomeric structure consisting of five putative subunits designated alpha-1, alpha-2, beta, tau, and epsilon. Biochemical evidence points to separate binding sites for 1,4-dihydropyridines, phenylalkylamines, and the benzothiazepines (all located on the alpha-1 subunit). Although they share a similar mechanism of action, calcium channel blockers represent three heterogeneous categories of drugs with differing vascular-cardiac selectivity ratios.
Verelan pm 200mg (Verapamil hydrochloride) Nonclinical Toxicology
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/day or approximately 1.3, 4.4 and 15 times, respectively, the maximum recommended human daily dose (400 mg/day or 8 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 6.9 times (55 mg/kg/day) the maximum recommended human dose did not show impaired fertility. Effects on male fertility have not been determined.
Verelan pm 200mg (Verapamil hydrochloride) Clinical Studies
Verelan PM was evaluated in two placebo-controlled, parallel design, double-blind studies of patients with mild to moderate hypertension. In the clinical trials, 413 evaluable patients were randomized to either placebo, 100 mg, 200 mg, 300 mg, or 400 mg and treated for up to 8 weeks. Verelan PM or placebo was given once daily between 9 pm and 11 pm (nighttime) and blood pressure changes were measured with 36-hour ambulatory blood pressure monitoring (ABPM). The results of these studies demonstrate that Verelan PM, at 200, 300 and 400 mg, is a consistently and significantly more effective antihypertensive agent than placebo in reducing ambulatory blood pressures. Over this dose range, the placebo-subtracted net decreases in diastolic BP at trough (averaged over 6-10 pm) were dose-related, and ranged from 3.8 to 10.0 mm Hg after 8 weeks of therapy. Although Verelan PM 100 mg was not effective in reducing diastolic BP at trough when measured by ABPM, efficacy was demonstrated in reducing diastolic BP when measured manually at trough and peak and, from 6 am to 12 noon and over 24 hours when measured by ABPM [see for titration schedule)].
There were no apparent treatment differences between patient subgroups of different age (older or younger than 65 years), sex and race. For severity of hypertension, "moderate" hypertensives (mean daytime diastolic BP ≥ 105 mm Hg and ≤ 114 mm Hg) appeared to respond better than "mild" hypertensives (mean daytime diastolic BP ≥ 90 mm Hg and ≤ 104 mm Hg). However, sample size for the subgroup comparisons were limited.
Verelan pm 200mg (Verapamil hydrochloride) How Supplied/storage And Handling
Verelan PM (verapamil hydrochloride) extended-release pellet filled capsules are supplied in three dosage strengths:
Verelan pm 200mg (Verapamil hydrochloride)
Verelan pm 200mg (Verapamil hydrochloride)
Verelan pm 200mg (Verapamil hydrochloride)
Verelan pm 200mg (Verapamil hydrochloride)
