loperamide hydrochloride 2 MG Oral Tablet

INDICATIONS & USAGE Loperamide Hydrochloride Capsules (loperamide hydrochloride) is 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 Capsules is also indicated for reducing the volume of discharge from ileostomies.

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 capsules 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 and 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 years to 12 Years of Age : In pediatric patients 2 years to 5 years of age (20 kg or less), the non-prescription liquid formulation of loperamide (1 mg/5 mL) should be used; for ages 6 to 12, either loperamide hydrochloride capsules or non-prescription liquid formulation of loperamide may be used. For pediatric patients 2 years 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 kg to 20 kg): 1 mg three times daily (3 mg total daily dosage) Six to eight years (20 kg 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 capsules 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 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 mg 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. 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 dose 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 capsules 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 Torsades 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 The pharmacokinetics of loperamide have not been studied in patients with hepatic impairment. Use loperamide hydrochloride capsules with caution in such patients because the systemic exposure may be increased due to reduced metabolism (see PRECAUTIONS ).

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 doses per day of loperamide hydrochloride capsules. 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 capsules are contraindicated in pediatric patients less than 2 years of age due to the risks of respiratory depression and serious cardiac adverse reactions. Avoid loperamide hydrochloride capsules 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 and OVERDOSAGE ). Avoid loperamide hydrochloride capsules 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. Dehydration 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 capsules does not preclude the need for appropriate fluid and electrolyte therapy. Gastrointestinal Disorders In general, loperamide hydrochloride capsules 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 capsules must be discontinued promptly when constipation, abdominal distention or ileus develop. Treatment of diarrhea with loperamide hydrochloride capsules 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 capsules 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. Variability in Pediatric Response Loperamide hydrochloride capsules should be used with special caution in pediatric patients because of the greater variability of response in this age group. Dehydration, particularly in pediatric patients less than 6 years of age, may further influence the variability of response to loperamide hydrochloride capsules. 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.

CONTRAINDICATIONS Loperamide hydrochloride capsules are contraindicated in patients with a known hypersensitivity to loperamide hydrochloride or to any of the excipients. Loperamide hydrochloride is contraindicated in patients with abdominal pain in the absence of diarrhea. Loperamide hydrochloride is not recommended in infants below 24 months of age. Loperamide hydrochloride should not be used as the primary therapy: in patients with acute dysentery, which is characterized by blood in stools and high fever, in patients with acute ulcerative colitis, in patients with bacterial enterocolitis caused by invasive organisms including Salmonella, Shigella, and Campylobacter, in patients with pseudomembranous colitis associated with the use of broad-spectrum antibiotics.

CLINICAL PHARMACOLOGY Mechanism of Action In vitro and animal studies show that Loperamide Hydrochloride Capsules (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 propulsive peristalsis, and increasing intestinal transit time. Loperamide increases the tone of the anal sphincter, thereby reducing incontinence and urgency. Pharmacodynamics Loperamide prolongs the transit time of the intestinal contents. It reduces 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. Pharmacokinetics Absorption Plasma concentrations of unchanged drug remain below 2 ng/mL after the intake of a 2 mg capsule of Loperamide Hydrochloride Capsules. Plasma loperamide concentrations are highest approximately 5 hours after administration of the capsule and 2.5 hours after the liquid. The peak plasma concentrations of loperamide were similar for both formulations. Distribution Based on literature information, the plasma protein binding of loperamide is about 95%. Loperamide is a P-glycoprotein substrate. Elimination The apparent elimination half-life of loperamide is 10.8 hours with a range of 9.1 to 14.4 hours. Elimination of loperamide mainly occurs by oxidative N-demethylation. Metabolism In vitro loperamide is metabolized mainly by cytochrome P450 (CYP450) isozymes, CYP2C8 and CYP3A4, to form- N-demethyl loperamide. In an in vitro study quercetin (CYP2C8 inhibitor) and ketoconazole (CYP3A4 inhibitor) significantly inhibited the N-demethylation process 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 Capsules 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 Excretion of the unchanged loperamide and its metabolites mainly occurs through the feces.