1. Indication
Lodegald – lope 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. Lodegald – lope capsules are also indicated for reducing the volume of discharge from ileostomies.
2. Dosage & Administration
Adults:
Acute diarrhea: Initially 4mg, then each time loose stools, take 2mg, up to 5 days.
Usual dose: 6-8mg/day. Maximum dose: 16mg/day.
Chronic diarrhea: Take 4mg, then take 2mg each time with loose stools until the diarrhea stops. Maintenance dose: Take 4 – 8mg/day in small doses (2 times).
Maximum: 16mg/day
Children:
Loperamide is not recommended for routine use in children with acute diarrhea.
Children under 6 years old: Not recommended
Children 6-8 years old: Take 2mg, 2 times / day
Children 8-12 years old: Take 2mg, 3 times a day
Maintenance dose: Take 1 mg / 10kg of body weight, after only 1 bowel movement
3. Contraindication
Lodegald – lope 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.
4. Warnings:
Cardiac Adverse Reactions, Including Torsades de Pointes and Sudden Death
Cases of prolongation of theQT/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. 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.
Lodegald – Lope 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 Lodegald – Lope capsules in:
• combination with others drugs or herbal products that are known to prolong the QT interval, including Class IA (e.g., quinidine, procainamide) or Class Ill (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, Lodegald – Lope 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. Lodegald – Lope must be discontinued promptly when constipation, abdominal distention or ileus develop.
Treatment of diarrhea with Lodegald – Lope 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 Lodegald – Lope 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
Lodegald – Lope 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 Lodegald – Lope. Lodegald – Lope capsules are contraindicated in pediatric patients less than 2 years of age due to the risks of respiratory depression and serious cardiac adverse reactions.
5. Precaution:
General
Allergic Reactions
Extremely rare allergic reactions including anaphylaxis and anaphylactic shock have been reported.
Hepatic Impairment
The effects of hepatic impairment on the pharmacokinetics of loperamide have not been studied. Use Lodegald – Lope with caution in such patients because the systemic exposure to loperamide may be increased due to reduced metabolism.
Monitor patients with hepatic impairment closely for signs of central nervous system (CNS) toxicity.
Renal Impairment
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 are excreted mainly in the feces, dosage adjustments in patients with renal impairment are not required.
Geriatric Use
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.
In general, elderly patients may be more susceptible to drug-associated effects on the QT interval. Avoid Lodegald – Lope in elderly patients taking drugs that can result in prolongation of the QT interval (for example, Class IA or Ill antiarrhythmics) or in patients with risk factors for Torsades de Pointes.
6. Interactions:
Effects of Other Drugs on Loperamide
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. 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. Monitor patients for cardiac adverse reactions.
7. Overdosage:
The use of higher than recommended Lodegald – Lope doses may result in life-
threatening cardiac, CNS and respiratory adverse reactions.
8. Undesirable effects:
The most commonly reported (i.e. incidence) adverse drug reactions (ADRs) in clinical trials with loperamide hydrochoride in acute diarrhoea were: constipation (2.7%), flatulence (1.7%), headache (1.2%) and nausea (1.1 %).
Table 1 displays ADRs that have been reported with the use of loperamide hydrochoride from either clinical trial (acute diarrhoea) or post-marketing experience.
The frequency categories use the following convention: very common (21/10); common (21/100 to < 1/10); uncommon (21/1 ,000 to <1/100); rare (21/10,000 to < 1/1 ,000); and very rare / 10,000).
9. 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.
10. Pharmacokinetics:
Absorption
Lodegald – Lope: 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 Lodegald – Lope 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
Excretion
Excretion of the unchanged loperamide and its metabolites mainly occurs through the feces.
11. Storage:
Store below 30°C in a cool and dry place away from direct sunlight.
12. Shelf life:
03 years since manufacture date.
