Product Elements:
Loperamide hydrochloride loperamide hydrochloride loperamide hydrochloride loperamide gelatin ferrosoferric oxide ferric oxide red ferric oxide yellow lactose monohydrate starch, corn magnesium stearate shellac dimethicone titanium dioxide teva;0311 light and dark brown
Boxed Warning:
Boxed warning warning: torsades de pointes and sudden death ⢠cases of torsades de pointes, cardiac arrest, and death have been reported with the use of a higher than recommended dosages of loperamide hydrochloride (see warnings and overdosage). ⢠loperamide hydrochloride is contraindicated in pediatric patients less than 2 years of age (see contraindications). ⢠avoid loperamide hydrochloride dosages higher than recommended in adults and pediatric patients 2 years of age and older due to the risk of serious cardiac adverse reactions (see dosage and administration).
Indications and Usage:
Indications and usage loperamide hydrochloride capsules are indicated for the control and symptomatic relief of acute nonspecific diarrhea in patients 2 years of age and older and of chronic diarrhea in adults associated with inflammatory bowel disease. loperamide hydrochloride is also indicated for reducing the volume of discharge from iloestomies.
Warnings:
Warnings cardiac adverse reactions, including torsades de pointes and sudden death cases of prolongation of the qt/qtc interval, torsades de pointes, other ventricular arrhythmias, cardiac arrest, some resulting in death, have been reported in adults with use of higher than recommended dosages of loperamide hydrochloride. cases include patients who were abusing or misusing loperamide hydrochloride (see overdosage and drug abuse and dependence). cases of syncope and ventricular tachycardia have been reported in adult patients receiving the recommended dosage of loperamide hydrochloride capsules. some of these patients were taking other drugs or had other risk factors that may have increased their risk of cardiac adverse reactions. additionally, postmarketing cases of cardiac arrest, syncope, and respiratory depression have been reported in pediatric patients less than 2 years of age. loperamide hydrochloride is contraindicated in pediatric patients less than 2 years of age due to the ri
Read more...sks of respiratory depression and serious cardiac adverse reactions. avoid loperamide hydrochloride dosages higher than recommended in adults and pediatric patients 2 years of age and older due to the risk of serious cardiac adverse reactions (see dosage and administration, overdosage) avoid loperamide hydrochloride in: ⢠combination with others drugs or herbal products that are known to prolong the qt interval, including class 1a (e.g., quinidine, procainamide) or class iii (e.g., amiodarone, sotalol) antiarrhythmics, antipsychotics (e.g., chlorpromazine, haloperidol, thioridazine, ziprasidone), antibiotics (e.g., moxifloxacin), or any other drug known to prolong the qt interval (e.g., pentamidine, levomethadyl acetate, methadone) ⢠patients with risk factors for qt prolongation, including patients with congenital long qt syndrome, with a history of cardiac arrhythmias or other cardiac conditions, elderly patients and those with electrolyte abnormalities. fluid and electrolyte depletion often occur in patients who have diarrhea. in such cases, administration of appropriate fluid and electrolytes is very important. the use of loperamide hydrochloride does not preclude the need for appropriate fluid and electrolyte therapy. in general, loperamide hydrochloride should not be used when inhibition of peristalsis is to be avoided due to the possible risk of significant sequelae including ileus, megacolon and toxic megacolon. loperamide hydrochloride must be discontinued promptly when constipation, abdominal distention or ileus develop. treatment of diarrhea with loperamide hydrochloride is only symptomatic. whenever an underlying etiology can be determined, specific treatment should be given when appropriate (or when indicated). patients with aids treated with loperamide hydrochloride for diarrhea should have therapy stopped at the earliest signs of abdominal distention. there have been isolated reports of toxic megacolon in aids patients with infectious colitis from both viral and bacterial pathogens treated with loperamide hydrochloride. {ref edms-psdb-2564186, p. 12} variability in pediatric response loperamide hydrochloride should be used with special caution in young children because of the greater variability of response in this age group. dehydration, particularly in younger children, may further influence the variability of response to loperamide hydrochloride. loperamide hydrochloride is contraindicated in pediatric patients less than 2 years of age due to the risks of respiratory depression and serious cardiac adverse reactions.
Dosage and Administration:
Dosage and administration loperamide hydrochloride capsules are contraindicated in pediatric patients less than 2 years of age due to the risks of respiratory depression and serious cardiac adverse reactions (see contraindications). avoid loperamide hydrochloride dosages higher than recommended in adult or pediatric patients 2 years of age and older due to the risk of serious cardiac adverse reactions (see warnings, overdosage). (1 capsule = 2 mg) patients should receive appropriate fluid and electrolyte replacement as needed. acute diarrhea adults and pediatric patients 13 years and older: the recommended initial dose is 4 mg (two capsules) followed by 2 mg (one capsule) after each unformed stool. the maximum daily dose is 16 mg (eight capsules). clinical improvement is usually observed within 48 hours. pediatric patients 2 to 12 years of age: in pediatric patients 2 to 5 years of age (20 kg or less), the non-prescription liquid formulation (loperamide hydrochloride oral solution 1 mg
Read more.../5 ml) should be used; for ages 6 to 12, either loperamide hydrochloride capsules or loperamide hydrochloride oral solution may be used. for pediatric patients 2 to 12 years of age, the following schedule for capsules or liquid will usually fulfill initial dosage requirements. recommended first day dosage schedule two to five years (13 to 20 kg): 1 mg three times daily (3 mg total daily dosage) six to eight years (20 to 30 kg): 2 mg twice daily (4 mg total daily dosage) eight to twelve years (greater than 30 kg): 2 mg three times daily (6 mg total daily dosage) recommended subsequent daily dosage following the first treatment day, it is recommended that subsequent loperamide hydrochloride doses (1 mg/10 kg body weight) be administered only after a loose stool. the total daily dosage should not exceed recommended dosages for the first day. chronic diarrhea children although loperamide hydrochloride has been studied in a limited number of children with chronic diarrhea; the therapeutic dose for the treatment of chronic diarrhea in a pediatric population has not been established. adults the recommended initial dose is 4 mg (two capsules) followed by 2 mg (one capsule) after each unformed stool until diarrhea is controlled, after which the dosage of loperamide hydrochloride capsules should be reduced to meet individual requirements. when the optimal daily dosage has been established, this amount may then be administered as a single dose or in divided doses. the average daily maintenance dosage in clinical trials was 4 to 8 mg (two to four capsules per day). the maximum daily dosage is 16 mg (eight capsules per day). if clinical improvement is not observed after treatment with 16 mg per day for at least 10 days, symptoms are unlikely to be controlled by further administration. loperamide hydrochloride capsules administration may be continued if diarrhea cannot be adequately controlled with diet or specific treatment. children under 2 years there have been rare reports of paralytic ileus associated with abdominal distention. most of these reports occurred in the setting of acute dysentery, overdose, and with very young children less than two years of age. elderly no formal pharmacokinetic studies were conducted in elderly subjects. however, there were no major differences reported in the drug disposition in elderly patients with diarrhea relative to young patients. no dosage adjustment is required for the elderly. in general, elderly patients may be more susceptible to drug-associated effects of the qt interval. avoid loperamide hydrochloride in elderly patients taking drugs that can result in prolongation of the qt interval (for example, class ia or iii antiarrhythmics) or in patients with risk factors for torsade de pointes (see warnings). renal impairment no pharmacokinetic data are available in patients with renal impairment. since the metabolites and the unchanged drug are mainly excreted in the feces, no dosage adjustment is required for patients with renal impairment (see precautions). hepatic impairment although no pharmacokinetic data are available in patients with hepatic impairment, loperamide hydrochloride should be used with caution in such patients because of reduced first pass metabolism (see precautions).
Contraindications:
Contraindications loperamide hydrochloride capsules are contraindicated in: ⢠pediatric patients less than 2 years of age due to the risks of respiratory depression and serious cardiac adverse reactions (see warnings). ⢠patients with a known hypersensitivity to loperamide hydrochloride or to any of the excipients. ⢠patients with abdominal pain in the absence of diarrhea. ⢠patients with acute dysentery, which is characterized by blood in stools and high fever. ⢠patients with acute ulcerative colitis. ⢠patients with bacterial enterocolitis caused by invasive organisms including salmonella, shigella, and campylobacter. ⢠patients with pseudomembranous colitis associated with the use of broad-spectrum antibiotics.
Adverse Reactions:
Adverse reactions clinical trial data the adverse effects reported during clinical investigations of loperamide hydrochloride are difficult to distinguish from symptoms associated with the diarrheal syndrome. adverse experiences recorded during clinical studies with loperamide hydrochloride were generally of a minor and self-limiting nature. they were more commonly observed during the treatment of chronic diarrhea. the adverse events reported are summarized irrespective of the causality assessment of the investigators. 1) adverse events from 4 placebo-controlled studies in patients with acute diarrhea the adverse events with an incidence of 1.0% or greater, which were reported at least as often in patients on loperamide hydrochloride as on placebo, are presented in the table below. acute diarrhea loperamide hydrochloride placebo no. of treated patients 231 236 gastrointestinal ae% constipation 2.6% 0.8% the adverse events with an incidence of 1.0% or greater, which were more frequently
Read more... reported in patients on placebo than on loperamide hydrochloride were: dry mouth, flatulence, abdominal cramp and colic. 2) adverse events from 20 placebo-controlled studies in patients with chronic diarrhea the adverse events with an incidence of 1.0% or greater, which were reported at least as often in patients on loperamide hydrochloride as on placebo, are presented below in the table below. chronic diarrhea loperamide hydrochloride placebo no. of treated patients 285 277 gastrointestinal ae% constipation 5.3% 0% central and peripheral nervous system ae% dizziness 1.4% 0.7% the adverse events with an incidence of 1.0% or greater, which were more frequently reported in patients on placebo than on loperamide hydrochloride were: nausea, vomiting, headache, meteorism, abdominal pain, abdominal cramp and colic. 3) adverse events from seventy-six controlled and uncontrolled studies in patients with acute or chronic diarrhea the adverse events with an incidence of 1.0% or greater in patients from all studies are given in the table below. * all patients in all studies, including those in which it was not specified if the adverse events occurred in patients with acute or chronic diarrhea. acute diarrhea chronic diarrhea all studies* no. of treated patients 1913 1371 3740 gastrointestinal ae% nausea 0.7% 3.2% 1.8% constipation 1.6% 1.9% 1.7% abdominal cramps 0.5% 3.0% 1.4% postmarketing experience the following adverse events have been reported: cardiac disorders qt/qtc-interval prolongation, torsades de pointes, other ventricular arrhythmias, cardiac arrest, syncope, and death (see warnings, overdosage). skin and subcutaneous tissue disorders rash, pruritus, urticaria, angioedema, and extremely rare cases of bullous eruption including erythema multiforme, stevens-johnson syndrome and toxic epidermal necrolysis have been reported with use of loperamide hydrochloride. immune system disorders isolated occurrences of allergic reactions and in some cases severe hypersensitivity reactions including anaphylactic shock and anaphylactoid reactions have been reported with the use of loperamide hydrochloride. gastrointestinal disorders dry mouth, abdominal pain, distention or discomfort, nausea, vomiting, flatulence, dyspepsia, constipation, paralytic ileus, megacolon, including toxic megacolon (see contraindications and warnings). renal and urinary disorders urinary retention. nervous system disorders drowsiness, dizziness. general disorders and administrative site conditions tiredness. a number of the adverse events reported during the clinical investigations and postmarketing experience with loperamide are frequent symptoms of the underlying diarrheal syndrome (abdominal pain/discomfort, nausea, vomiting, dry mouth, tiredness, drowsiness, dizziness, constipation, and flatulence). these symptoms are often difficult to distinguish from undesirable drug effects.
Overdosage:
Overdosage the use of higher than recommended loperamide hydrochloride doses may result in life-threatening cardiac, cns and respiratory adverse reactions. if over-exposure occurs, call your poison control center at 1-800-222-1222 for current information on the management of poisoning or overdosage. cardiac effects symptoms cases of overdosage with loperamide (chronic ingestion of doses ranging from 70 mg to 1600 mg daily; 4 to 100 times the recommended dose) have resulted in life-threatening cardiac adverse reactions, including qt/qtc and qrs interval prolongation, torsades de pointes, brugada syndrome and other ventricular arrhythmias, syncope, cardiac arrest, and death. cases include patients who were abusing (using supratherapeutic doses in place of opioids to induce euphoria) or misusing (taking higher than recommended doses to control diarrhea or to prevent opioid withdrawal) loperamide. the following are representative cases that included cardiac adverse reactions: ⢠25 year old abused loperamide and presented to the hospital on multiple occasions with symptoms of syncope, nausea, vomiting, bradycardia, hypotensive shock. the patient also experienced ventricular tachycardia, a prolonged qtc of 527 ms and qrs interval of 170 ms, frequent premature ventricular contractions, and subsequent cardiac arrest and death (elevated loperamide blood concentration of 32 ng/ml). ⢠54 year old misused loperamide (up to144 mg per day) as a self-treatment for chronic diarrhea for over 2 years. signs of cardiac toxicity included syncope, prolonged qt of 500 ms, sinus arrest with junctional escape rhythm, and polymorphic ventricular tachycardia, which required cardioversion and implantable cardioverter-defibrillator (icd) management. ⢠26 year old, with prior opioid abuse, presented to the hospital with recurrent syncope and developed tdp requiring electrical cardioversion. an ecg revealed a sinus rhythm with a heart rate of 85 bpm and a markedly prolonged qtc interval of greater than 700 ms. the patient reported ingesting 100 to 250 mg of loperamide with 400 mg of cimetidine daily for several months to simulate the euphoric sensation associated with opioids. management consider loperamide as a possible cause of cardiac arrhythmias in patients who may have a history of opioid abuse or recent ingestion of unknown drugs and in the differential diagnosis of unstable arrhythmias, prolonged qtc or qrs intervals, and torsades de pointes. if loperamide-induced cardiac toxicity is suspected, promptly discontinue the drug and initiate therapy to manage and prevent cardiac arrhythmias and serious outcomes. in many cases of loperamide overdosage, anti-arrhythmic medications (e.g., magnesium sulfate) were ineffective in resolving the arrhythmias and preventing further episodes of torsades de pointes. electrical cardioversion and overdrive pacing, and isoproterenol continuous infusion were reported to manage qtc prolongation in the setting of overdose. laboratory testing loperamide serum concentrations are not widely available or clinically useful to guide patient management. cns and respiratory depression symptoms cases of loperamide overdose (including relative overdose due to hepatic dysfunction), may cause opioid toxic effects including cns depression (e.g., altered mental status, stupor, coordination disorders, somnolence, miosis, muscular hypertonia, respiratory depression), hypotension, urinary retention, and paralytic ileus. pediatric patients may be more sensitive to cns effects, including respiratory depression, than adults. management loperamide non-cardiac arrhythmia overdosages should be treated as opioid overdosages. naloxone may reverse the opioid-related toxicity, including cns and respiratory depression, and hypotension, associated with loperamide overdosage. in adults and pediatric patients, naloxone may be administered intravenously. appropriate doses of naloxone, via intranasal, intramuscular, intraosseus, or subcutaneous administration may be necessary if the intravenous route is not available. if the desired degree of opioid-related toxicity counteraction and improvement are not obtained, naloxone may be repeated at two- to three-minute intervals. if no response in opioid-related effects is observed after naloxone has been administered, then diagnosis of opioid-induced toxicity should be questioned. refer to the naloxone prescribing information for complete information on initial and subsequent dosages. for patients whose adverse reactions are responsive to naloxone, monitor vital signs, neurologic and cardiopulmonary status for recurrence of opioid overdose symptoms for at least 24 hours after the last dose of naloxone, due to the prolonged intestinal retention of loperamide and the short duration (one to three hours) of naloxone. patients with severe cns or respiratory depression, and those who require multiple doses of naloxone to reverse symptoms, should be admitted to the hospital and may require intensive care. laboratory testing standard drug screens for opioids do not include an assay for loperamide; such testing for opioids will yield negative results even in the presence of loperamide.
Description:
Description loperamide hydrochloride is a white to slightly yellow powder and is freely soluble in methanol, isopropyl alcohol, chloroform and slightly soluble in water. loperamide hydrochloride, 4-(p-chlorophenyl)-4-hydroxy-n,n-dimethyl-α,α-diphenyl-1-piperidinebutyramide monohydrochloride, is a synthetic antidiarrheal for oral use. its structural formula is: [structural formula for loperaminde hydrochloride] c29h33cln2o2â¢hcl m.w. 513.51 loperamide hydrochloride is available in 2 mg capsules. each capsule, for oral administration, contains 2 mg loperamide hydrochloride. loperamide hydrochloride capsules usp also contain the inactive ingredients: dimethylpolysiloxane, gelatin, iron oxide black, iron oxide red, iron oxide yellow, lactose monohydrate, pregelatinized corn starch, magnesium stearate, shellac, and titanium dioxide.
Clinical Pharmacology:
Clinical pharmacology in vitro and animal studies show that loperamide hydrochloride acts by slowing intestinal motility and by affecting water and electrolyte movement through the bowel. loperamide binds to the opiate receptor in the gut wall. consequently, it inhibits the release of acetylcholine and prostaglandins, thereby reducing peristalsis, and increasing intestinal transit time. loperamide increases the tone of the anal sphincter, thereby reducing incontinence and urgency. in man, loperamide hydrochloride prolongs the transit time of the intestinal contents. it reduces the daily fecal volume, increases the viscosity and bulk density, and diminishes the loss of fluid and electrolytes. tolerance to the antidiarrheal effect has not been observed. clinical studies have indicated that the apparent elimination half-life of loperamide hydrochloride in man is 10.8 hours with a range of 9.1 to 14.4 hours. plasma levels of unchanged drug remain below 2 nanograms per ml after the intake o
Read more...f a 2 mg loperamide hydrochloride capsule. plasma levels are highest approximately five hours after administration of the capsule and 2.5 hours after the liquid. the peak plasma levels of loperamide were similar for both formulations. elimination of loperamide mainly occurs by oxidative n-demethylation. cytochrome p450 (cyp450) isozymes, cyp2c8 and cyp3a4, are thought to play an important role in loperamide n-demethylation process since quercetin (cyp2c8 inhibitor) and ketoconazole (cyp3a4 inhibitor) significantly inhibited the n-demethylation process in vitro by 40% and 90%, respectively. in addition, cyp2b6 and cyp2d6 appear to play a minor role in loperamide n-demethylation. concomitant use of loperamide hydrochloride with inhibitors of cyp3a4 (e.g., itraconazole) or cyp2c8 (e.g., gemfibrozil) or inhibitors of p-glycoprotein (e.g., quinidine, ritonavir) can increase exposure to loperamide (see precautions, drug interactions). excretion of the unchanged loperamide and its metabolites mainly occurs through the feces. in those patients in whom biochemical and hematological parameters were monitored during clinical trials, no trends toward abnormality during loperamide hydrochloride therapy were noted. similarly, urinalyses, ekg and clinical ophthalmological examinations did not show trends toward abnormality.
How Supplied:
How supplied loperamide hydrochloride capsules usp, 2 mg are available as: a light brown opaque body and dark brown opaque capsule, imprinted "teva" on the cap and "0311" on the body and packaged in bottles of 100 (ndc 0093-0311-01) and 500 (ndc 0093-0311-05). store at 20° to 25°c (68° to 77°f) [see usp controlled room temperature]. dispense in a well-closed container, as defined in the usp, with a child-resistant closure (as required). keep this and all medications out of the reach of children. manufactured in czech republic by: teva czech industries, s.r.o. opava-komarov, czech republic manufactured for: teva pharmaceuticals usa, inc. north wales, pa 19454 rev. p 10/2016
Package Label Principal Display Panel:
Package/label display panel 67296-0346