Loperamide

Revision as of 14:42, 12 December 2014 by Vignesh Ponnusamy (talk | contribs)
Jump to navigation Jump to search

Loperamide
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, M.B.B.S. [2]

Disclaimer

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

Black Box Warning

Title
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content

Overview

Loperamide is a that is FDA approved for the {{{indicationType}}} of . There is a Black Box Warning for this drug as shown here. Common adverse reactions include .

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Condition1
  • Dosing Information
  • Dosage
Condition2
  • Dosing Information
  • Dosage
Condition3
  • Dosing Information
  • Dosage
Condition4
  • Dosing Information
  • Dosage

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Loperamide in adult patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Loperamide in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding FDA-Labeled Use of Loperamide in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Loperamide in pediatric patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Loperamide in pediatric patients.

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

Warnings

Title
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content
  • 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}
  • 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.

Precautions

  • Extremely rare allergic reactions including anaphylaxis and anaphylactic shock have been reported. In acute diarrhea, if clinical improvement is not observed in 48 hours, the administration of loperamide hydrochloride should be discontinued and patients should be advised to consult their physician. 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. Patients with hepatic dysfunction should be monitored closely for signs of CNS toxicity. No pharmacokinetic data are available in patients with renal impairment. Since it has been reported that the majority of the drug is metabolized and metabolites or the unchanged drug is excreted mainly in the feces, dosage adjustments in patients with renal impairment are not required. No formal studies have been conducted to evaluate the pharmacokinetics of loperamide in elderly subjects. However, in two studies that enrolled elderly patients, there were no major differences in the drug disposition in elderly patients with diarrhea relative to young patients.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Loperamide in the drug label.

Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Loperamide in the drug label.

Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous

Drug Interactions

  • 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.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Loperamide in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Loperamide during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Loperamide with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Loperamide with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Loperamide with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Loperamide with respect to specific gender populations.

Race

There is no FDA guidance on the use of Loperamide with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Loperamide in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Loperamide in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Loperamide in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Loperamide in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral
  • Intravenous

Monitoring

There is limited information regarding Monitoring of Loperamide in the drug label.

  • Description

IV Compatibility

There is limited information regarding IV Compatibility of Loperamide in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Description

Management

  • Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Loperamide in the drug label.

Pharmacology

There is limited information regarding Loperamide Pharmacology in the drug label.

Mechanism of Action

  • 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.

Structure

  • 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.
  • C29H33ClN2O2•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.
This image is provided by the National Library of Medicine.

Pharmacodynamics

  • 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.

Pharmacokinetics

  • 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 of 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. 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.

Nonclinical Toxicology

  • 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 E. coli, 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 in one study, and 1, 5, 10, 20, 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 p.o. (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 p.o. (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.

Clinical Studies

There is limited information regarding Clinical Studies of Loperamide in the drug label.

How Supplied

Storage

There is limited information regarding Loperamide Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Loperamide |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Loperamide |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Loperamide in the drug label.

Precautions with Alcohol

  • Alcohol-Loperamide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ Empty citation (help)
  2. ↑ "http://www.ismp.org". External link in |title= (help)


{{#subobject: 

 |Page Name=Loperamide
 |Pill Name=No image.jpg
 |Drug Name=
 |Pill Ingred=|+sep=;
 |Pill Imprint=
 |Pill Dosage=
 |Pill Color=|+sep=;
 |Pill Shape=
 |Pill Size (mm)=
 |Pill Scoring=
 |Pill Image=
 |Drug Author=
 |NDC=

}}


{{#subobject: 

 |Label Page=Loperamide
 |Label Name=Loperamide11.png

}}


{{#subobject: 

 |Label Page=Loperamide
 |Label Name=Loperamide11.png

}}

Retrieved from "https://www.wikidoc.org/index.php?title=Loperamide&oldid=1047504"