Imodium Information
Imodium (Loperamide hcl) Description
Imodium (Loperamide hcl) ® (loperamide hydrochloride), 4-(p-chlorophenyl)-4-hydroxy-N,N-dimethyl--diphenyl-1-piperidinebutyramide monohydrochloride, is a synthetic antidiarrheal for oral use.
Imodium (Loperamide hcl) ® is available in 2mg capsules.
The inactive ingredients are: Lactose, cornstarch, talc, and magnesium stearate. Imodium (Loperamide hcl) ® capsules contain FD&C Yellow No. 6.
Imodium (Loperamide hcl) Clinical Pharmacology
In man, Imodium (Loperamide hcl) ® 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. Clinical studies have indicated that the apparent elimination half-life of loperamide in man is 10.8 hours with a range of 9.1 - 14.4 hours. Plasma levels of unchanged drug remain below 2 nanograms per mL after the intake of a 2mg capsule of Imodium (Loperamide hcl) ®. 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 by 40% and 90%, respectively. In addition, CYP2B6 and CYP2D6 appear to play a minor role in loperamide N-demethylation. 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 Imodium (Loperamide hcl) ® therapy were noted. Similarly, urinalyses, EKG and clinical ophthalmological examinations did not show trends toward abnormality.
Imodium (Loperamide hcl) Indications And Usage
Imodium (Loperamide hcl) ® (loperamide hydrochloride) is indicated for the control and symptomatic relief of acute nonspecific diarrhea and of chronic diarrhea associated with inflammatory bowel disease. Imodium (Loperamide hcl) ® is also indicated for reducing the volume of discharge from ileostomies.
Imodium (Loperamide hcl) Contraindications
Imodium (Loperamide hcl) is contraindicated in patients with a known hypersensitivity to loperamide hydrochloride or to any of the excipients.
Imodium (Loperamide hcl) is contraindicated in patients with abdominal pain in the absence of diarrhea.
Imodium (Loperamide hcl) is not recommended in infants below 24 months of age.
Imodium (Loperamide hcl) should not be used as the primary therapy:
Imodium (Loperamide hcl) Warnings
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 Imodium (Loperamide hcl) ® does not preclude the need for appropriate fluid and electrolyte therapy.
In general, Imodium (Loperamide hcl) 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. Imodium (Loperamide hcl) must be discontinued promptly when constipation, abdominal distention or ileus develop.
Treatment of diarrhea with Imodium (Loperamide hcl) 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 Imodium (Loperamide hcl) 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.
Imodium (Loperamide hcl) ® 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 Imodium (Loperamide hcl) ®.
Imodium (Loperamide hcl) Precautions
Nonclinical data have shown that loperamide is a P-glycoprotein substrate. Concomitant administration of loperamide (16 mg single dose) with a 600 mg single dose of either quinidine, or ritonavir, both of which are P-glycoprotein inhibitors, resulted in a 2- to 3- fold increase in loperamide plasma levels. Due to the potential for enhanced central effects when loperamide is coadministered with quinidine and with ritonavir, caution should be exercised when loperamide is administered at the recommended dosages (2 mg, up to 16 mg maximum daily dose) with P-glycoprotein inhibitors.
When a single 16-mg dose of loperamide 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 is given with saquinavir, the therapeutic efficacy of saquinavir should be closely monitored.
In an 18-month rat study with oral doses up to 40 mg/kg/day (21 times the maximum human dose of 16 mg/day, based on a body surface area comparison), there was no evidence of carcinogenesis.
Loperamide was not genotoxic in the Ames test, the SOS chromotest in , the dominant lethal test in female mice, or the mouse embryo cell transformation assay.
Fertility and reproductive performance was evaluated in rats using oral doses of 2.5, 10, and 40 mg/kg/day (females only) in a second study. Oral administration of 20 mg/kg/day (approximately 11 times the human dose based on a body surface area comparison) and higher produced strong impairment of female fertility. Treatment of female rats with up to 10 mg/kg/day by mouth (approximately 5 times the human dose based on a body surface area comparison) had no effect on fertility. Treatment of male rats with 40 mg/kg/day by mouth (approximately 21 times the human dose based on a body surface area comparison) produced impairment of male fertility, whereas administration of up to 10 mg/kg/day (approximately 5 times the human dose based on a body surface area comparison) had no effect.
Imodium (Loperamide hcl) Adverse Reactions
The adverse effects reported during clinical investigations of Imodium (Loperamide hcl) ® (loperamide hydrochloride) are difficult to distinguish from symptoms associated with the diarrheal syndrome. Adverse experiences recorded during clinical studies with Imodium (Loperamide hcl) ® 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.
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.
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.
The following adverse events have been reported:
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 Imodium (Loperamide hcl)
Immune system disordersIsolated occurrences of allergic reactions and in some cases severe hypersensitivity reactions including anaphylactic shock and anaphylactoid reactions have been reported with the use of Imodium (Loperamide hcl) .
Gastrointestinal disordersDry mouth, abdominal pain, distention or discomfort, nausea, vomiting, flatulence, dyspepsia, constipation, paralytic ileus, megacolon, including toxic megacolon (see and ).
Renal and urinary disordersUrinary retention
Nervous system disordersDrowsiness, dizziness
General disorders and administrative site conditionsTiredness
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.
Imodium (Loperamide hcl) Overdosage
In cases of overdosage, (including relative overdose due to hepatic dysfunction), urinary retention, paralytic ileus and CNS depression may occur. Children may be more sensitive to CNS effects than adults. Clinical trials have demonstrated that a slurry of activated charcoal administered promptly after ingestion of loperamide hydrochloride can reduce the amount of drug which is absorbed into the systemic circulation by as much as ninefold. If vomiting occurs spontaneously upon ingestion, a slurry of 100 gms of activated charcoal should be administered orally as soon as fluids can be retained.
If vomiting has not occurred, gastric lavage should be performed followed by administration of 100 gms of the activated charcoal slurry through the gastric tube. In the event of overdosage, patients should be monitored for signs of CNS depression for at least 24 hours.
If symptoms of overdose occur, naloxone can be given as an antidote. If responsive to naloxone, vital signs must be monitored carefully for recurrence of symptoms of drug overdose for at least 24 hours after the last dose of naloxone.
In view of the prolonged action of loperamide and the short duration (one to three hours) of naloxone, the patient must be monitored closely and treated repeatedly with naloxone as indicated. Since relatively little drug is excreted in the urine, forced diuresis is not expected to be effective for Imodium (Loperamide hcl) ® (loperamide hydrochloride) overdosage.
In clinical trials an adult who took three 20mg doses within a 24 hour period was nauseated after the second dose and vomited after the third dose. In studies designed to examine the potential for side effects, intentional ingestion of up to 60 mg of loperamide hydrochloride in a single dose to healthy subjects resulted in no significant adverse effects.
Imodium (Loperamide hcl) Dosage And Administration
(1 capsule = 2 mg)Patients should receive appropriate fluid and electrolyte replacement as needed.
Imodium (Loperamide hcl) How Supplied
Capsules - each capsule contains 2 mg of loperamide hydrochloride. The capsules have a light green body and a dark green cap with "JANSSEN" imprinted on one segment and "Imodium (Loperamide hcl) " on the other segment. Imodium (Loperamide hcl) ® capsules are supplied in bottles of 100.
NDC 50458-400-10(100 CAPSULES)
Imodium (Loperamide hcl)
