LOPERAMIDE HYDROCHLORIDE
Brand names: Loperamide Hydrochloride, LOPERAMIDE HYDROCHLORIDE, Anti-Diarrheal, anti diarrheal, MEDIQUE Diamode, anti-diarrheal, basic care loperamide hydrochloride, Loperamide hydrochloride, Up and Up anti diarrheal, Good Sense anti diarrheal, CareOne Diarrhea Control, Imodium A-D, AMAZON BASIC CARE LOPERAMIDE HYDROCHLORIDE, topcare anti diarrheal, ANTI-DIARRHEAL, dg health anti diarrheal, Handy Solutions Anti-Diarrheal, WELMATE Anti Diarrheal Loperamide HCl Softgels, Lil Drug Store Anti-Diarrheal, berkley and jensen anti diarrheal, WELMATE Anti Diarrheal Loperamide HCl
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 dosage of loperamide hydrochloride capsules (see WARNINGS and OVERDOSAGE ). ● Loperamide hydrochloride capsules are contraindicated in pediatric patients less than 2 years of age (see CONTRAINDICATIONS ). ● 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 ).
Warnings
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 Capsules (see WARNINGS and OVERDOSAGE). Loperamide Hydrochloride Capsules is contraindicated in pediatric patients less than 2 years of age (see CONTRAINDICATIONS). 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).
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 is 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, 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, 2 mg 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 is contraindicated in pediatric patients less than 2 years of age due to the risks of respiratory depression and serious cardiac adverse reactions.
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 (e.g., Clostridium difficle ) associated with the use of broad-spectrum antibiotics.
Overdose
OVERDOSAGE The use of higher than recommended loperamide hydrochloride capsules 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 hydrochloride (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 hydrochloride (up to 144 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 Torsades de Pointes 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 mg to 250 mg of loperamide hydrochloride 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.
Drug interactions
Drug Interactions Effects of Other Drugs on Loperamide 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. The increased systemic exposure to loperamide may increase a risk for cardiac adverse reactions especially in patients who are taking multiple CYP enzyme inhibitors, or in patients with underlying cardiac conditions (see WARNINGS ). Monitor patients for cardiac adverse reactions. CYP3A4 Inhibitors Itraconazole Concomitant administration of multiple doses of 100 mg itraconazole twice daily, an inhibitor of both CYP3A4 and P-glycoprotein, with a single 4 mg dose of loperamide hydrochloride increased the peak plasma concentration and the systemic exposure to loperamide by 2.9-fold and 3.8-fold, respectively. CYP2C8 Inhibitors Gemfibrozil When a single 4 mg dose of loperamide hydrochloride was coadministered with 600 mg gemfibrozil, a strong inhibitor of CYP2C8, on day 3 of a 5-day treatment with gemfibrozil twice daily, the mean peak plasma concentration and the systemic exposure to loperamide was increased by 1.6-fold and 2.2-fold, respectively. CYP3A4 and CYP2C8 Inhibitors When multiple doses of both 100 mg itraconazole and 600 mg gemfibrozil twice daily were administered with a single 4 mg dose of loperamide hydrochloride, the mean peak plasma concentration and the systemic exposure to loperamide was increased by 4.2-fold and 12.6-fold, respectively. P-glycoprotein Inhibitors Concomitant administration of a 16 mg single dose of loperamide hydrochloride with a 600 mg single dose of quinidine or ritonavir, both of which are P-glycoprotein inhibitors, resulted in a 2- to 3-fold increase in loperamide plasma concentrations. Due to the potential for enhanced CNS adverse reactions when loperamide is coadministered with quinidine and with ritonavir, caution should be exercised when loperamide hydrochloride capsules are administered at the recommended dosages (2 mg, up to 16 mg maximum daily dose) with P-glycoprotein inhibitors. Effects of Loperamide on Other Drugs Saquinavir When a single 16 mg dose of loperamide hydrochloride is coadministered with a 600 mg single dose of saquinavir, loperamide decreased saquinavir exposure by 54%, which may be of clinical relevance due to reduction of therapeutic efficacy of saquinavir. The effect of saquinavir on loperamide is of less clinical significance. Therefore, when loperamide hydrochloride capsules are given with saquinavir, the therapeutic efficacy of saquinavir should be closely monitored.
Uses
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 forms & strengths
Directions do not use more than directed drink plenty of clear fluids to help prevent dehydration caused by diarrhea Adults and children (12 years and older): Take 2 caplets after the first loose stool followed by 1 caplet after each subsequent loose stool but no more than 4 caplets in 24 hours. Children under 12 years: Do not give to children under 12 years of age.
Ingredients
Active ingredient (in each caplet) Loperamide Hydrochloride 2mg
Inactive ingredients anhydrous lactose, croscarmellose sodium, crospovidone, D&C Yellow # 10, FD&C Blue # 1, hydrogenated vegetable oil, magnesium stearate, powdered cellulose, pregelatinized starch
All identified pills
Side effects
ADVERSE REACTIONS Clinical Trial Experience The adverse effects reported during clinical investigations of Loperamide Hydrochloride Capsules (loperamide hydrochloride) are difficult to distinguish from symptoms associated with the diarrheal syndrome. Adverse experiences recorded during clinical studies with Loperamide Hydrochloride Capsules 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 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% 0.0% 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. Acute Diarrhea Chronic Diarrhea All Studies a No. of treated patients 1913 1371 3740 Gastrointestinal AE% Nausea Constipation Abdominal cramps 0.7% 1.6% 0.5% 3.2% 1.9% 3.0% 1.8% 1.7% 1.4% a. 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. 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, and angioedema and extremely rare cases bullous eruption including erythema multiforme, Stevens-Johnson syndrome and Toxic Epidermal Necrolysis have been reported with use of Loperamide Hydrochloride Capsules. 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 Capsules. Gastrointestinal disorders Dry mouth, abdominal pain, distention or discomfort, nausea, vomiting, flatulence, dyspepsia, constipation, paralytic ileus, megacolon; including toxic megacolon (see CONTRAINDICATIONS, 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 post-marketing 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.