Instructions for Lopedium capsules 2 mg No. 10
Composition
active ingredient: loperamide hydrochloride;
1 capsule contains loperamide hydrochloride 2 mg;
excipients: lactose monohydrate, corn starch, talc, magnesium stearate; capsule shell: gelatin, titanium dioxide (E 171), black iron oxide (E 172), yellow iron oxide (E 172), patent blue V (E 131).
Dosage form
The capsules are hard.
Main physicochemical properties: hard gelatin capsules of gray to dark green color, size 3, containing a homogeneous white or almost white powder.
Pharmacotherapeutic group
Means that inhibit peristalsis. ATX code A07D A03.
Pharmacological properties
Pharmacodynamics
Loperamide hydrochloride binds to opiate receptors in the intestinal wall. As a result, the release of acetylcholine and prostaglandins is inhibited, thereby reducing propulsive peristalsis and increasing the transit time of the contents through the digestive tract, as well as the ability of the intestinal wall to absorb fluid. Loperamide hydrochloride increases the tone of the anal sphincter, thereby reducing fecal incontinence and the urge to defecate.
Pharmacokinetics
Absorption: Most of the orally administered loperamide is absorbed from the intestine, but as a result of extensive first-pass metabolism, systemic bioavailability is only approximately 0.3%.
Distribution: Distribution studies of loperamide in rats show a high affinity for the intestinal wall with preferential binding to receptors in the longitudinal muscle layer. Loperamide is 95% protein bound, mainly albumin. Preclinical data have shown that loperamide is a substrate for P-glycoprotein.
Metabolism: Loperamide is almost completely excreted by the liver, where it is mainly metabolized, conjugated and excreted in the bile. Oxidative N-demethylation is the main metabolic pathway of loperamide, this process is mediated mainly by the isoforms CYP3A4 and CYP2C8. Due to the very intense first-pass effect, plasma concentrations of unchanged drug remain very low.
Elimination: The elimination half-life of loperamide in humans is approximately 11 hours with a range of 9–14 hours. Excretion of unchanged loperamide and its metabolites occurs primarily in the feces.
Pediatric Patients: Pharmacokinetic studies of loperamide in pediatric patients have not been conducted. The pharmacokinetic behavior of loperamide and drug interactions with loperamide are expected to be similar to those observed in adults.
Indication
Symptomatic treatment of acute diarrhea in adults and children aged 12 years and over.
Symptomatic treatment of acute episodes of diarrhea due to irritable bowel syndrome in adults aged 18 years and older after initial diagnosis by a physician.
Contraindication
Hypersensitivity to loperamide hydrochloride or to any of the components of the drug.
Children under 12 years old.
acute dysentery, characterized by the presence of blood in the stool and fever; acute ulcerative colitis or pseudomembranous colitis associated with the use of broad-spectrum antibiotics; bacterial enterocolitis caused by microorganisms of the Salmonella, Shigella, Campylobacter families.
Lopedium should not be used if peristalsis should be avoided due to the possible risk of significant complications, including intestinal obstruction, megacolon, and toxic megacolon.
The drug should be discontinued immediately if constipation, bloating, or intestinal obstruction develops.
Interaction with other medicinal products and other types of interactions
Interactions have been reported with drugs with similar pharmacological properties. Drugs with a central nervous system (CNS) depressant effect should not be used in children concomitantly with loperamide.
Preclinical data have shown that loperamide is a substrate for P-glycoprotein. Concomitant administration of loperamide (single dose 16 mg) with P-glycoprotein inhibitors (quinidine, ritonavir) results in a 2- to 3-fold increase in plasma levels of loperamide. The clinical significance of this pharmacokinetic interaction at the recommended therapeutic doses of loperamide (2 to 16 mg) is unknown.
Concomitant administration of loperamide (16 mg single dose) and ketoconazole, a CYP3A4 and P-glycoprotein inhibitor, resulted in a 5-fold increase in loperamide plasma concentrations. This increase was not associated with an increase in pharmacodynamic effects as measured by pupillometry.
Concomitant treatment with oral desmopressin resulted in a three-fold increase in plasma desmopressin concentrations, likely due to slower gastrointestinal motility.
It is expected that drugs with similar pharmacological properties may enhance the effect of loperamide, and drugs that accelerate the passage of contents through the gastrointestinal tract may weaken its effect.
Application features
Treatment of diarrhea is symptomatic. If the etiology of the disease can be determined (or is indicated to be so), then specific treatment should be given if possible.
Patients with diarrhea, especially children, debilitated patients, and the elderly, may develop dehydration and electrolyte imbalances. In such cases, the most important measure is the use of replacement therapy to replenish fluids and electrolytes.
The use of the drug does not replace the administration of an appropriate amount of fluid and restoration of electrolytes.
Because persistent diarrhea may indicate a potentially more serious condition, the drug should not be used for a long time until the cause of the diarrhea has been investigated.
In acute diarrhea, when clinical improvement is not observed within 48 hours, the use of loperamide hydrochloride should be discontinued and a doctor should be consulted.
Loperamide should not be used in situations where peristalsis should be avoided due to the possible risk of serious consequences such as megacolon and toxic megacolon.
Patients with acquired immunodeficiency syndrome (AIDS) who are taking Lopedium® for diarrhea should immediately discontinue treatment at the first sign of abdominal distension. There have been isolated reports of intestinal obstruction with an increased risk of toxic megacolon in AIDS patients with infectious colitis of both viral and bacterial origin, when treated with loperamide hydrochloride.
Abuse of loperamide or its misuse as an opioid substitute has been described in individuals with opioid dependence.
Pharmacokinetic data on the use of the drug in patients with impaired liver function are not available, however, loperamide should be used with caution in such patients due to the slowing of first-pass metabolism and because this may lead to relative overdose, which may cause CNS toxicity.
The drug should be used with caution in patients with exacerbations of ulcerative colitis. Drugs that prolong transit time may lead to the development of toxic megacolon in this group of patients.
Since loperamide is well metabolized and excreted in the feces along with its metabolites, dose adjustment is usually not necessary for patients with renal impairment.
The drug contains lactose, so it should not be prescribed to patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
Loperamide does not exhibit pronounced cardiac complications within the therapeutic concentration range. However, at significantly higher concentrations (up to 47 times), loperamide exhibits cardiac complications: inhibition of potassium (hERG) and sodium currents and arrhythmias in animal models in vivo and in vitro.
Cardiac disorders, including QT prolongation and QRS prolongation, and torsade de pointes have been reported in association with overdose. Fatalities have also been reported. Overdose may precipitate pre-existing Brugada syndrome. Patients should not exceed the recommended dose and/or duration of treatment.
If the drug is taken to control diarrhea attacks due to irritable bowel syndrome, which has been previously diagnosed by a doctor, and clinical improvement is not observed within 48 hours, loperamide hydrochloride should be discontinued and a doctor should be consulted. A doctor should also be consulted if the nature of the symptoms changes or if recurrent diarrhea attacks last for more than two weeks.
For the treatment of acute attacks of diarrhea caused by irritable bowel syndrome, Lopedium should only be taken if a doctor has previously diagnosed this condition.
In the following cases, the drug should not be used without prior consultation with a doctor, even if you know that you have irritable bowel syndrome (IBS):
the patient is 40 years of age or older and it has been some time since the last IBS attack; the patient is 40 years of age or older and the symptoms of IBS are different this time; recent intestinal bleeding; severe constipation; nausea or vomiting; loss of appetite or weight loss; difficult or painful urination; fever; recent travel abroad.
If new symptoms develop, symptoms worsen, or if symptoms do not improve within two weeks, you should consult a doctor.
Ability to influence reaction speed when driving vehicles or other mechanisms
Fatigue, dizziness or drowsiness may occur in diarrhea syndrome when using loperamide hydrochloride. Therefore, it is recommended to take this drug with caution when driving a car or operating machinery.
Use during pregnancy or breastfeeding
Use during pregnancy
Although there is no evidence of teratogenic or embryotoxic properties of loperamide hydrochloride, the expected therapeutic benefit should be weighed against the potential risks before starting loperamide hydrochloride, especially during the first trimester of pregnancy. This medicinal product is not recommended during pregnancy.
Use during breastfeeding
Since small amounts of loperamide may pass into breast milk, taking the drug during breastfeeding is not recommended.
In this regard, pregnant and breastfeeding women should be advised to consult their doctor for appropriate treatment.
Method of administration and doses
Lopedium is not indicated for the initial treatment of severe diarrhea accompanied by a decrease in fluid and electrolyte levels. In children in particular, it is desirable to compensate for this loss by administering parenteral or oral replacement therapy.
Capsules should be taken with liquid.
Symptomatic treatment of acute in adults and children aged 12 years and over.
The initial dose is 2 capsules (4 mg), then 1 capsule (2 mg) after each subsequent loose stool. The usual dose is 3–4 capsules (6–8 mg) per day. The maximum daily dose for acute diarrhea should not exceed 6 capsules (12 mg).
Symptomatic treatment of acute attacks of diarrhea due to irritable bowel syndrome in adults aged 18 years and older after initial diagnosis by a physician.
The initial dose is two capsules (4 mg); then take 1 capsule (2 mg) after each loose stool or as previously recommended by your doctor. The maximum daily dose should not exceed 6 capsules (12 mg).
In acute diarrhea, if clinical improvement is not observed within 48 hours, Lopedium should be discontinued.
Application for the treatment of elderly patients.
No dose adjustment is required for elderly patients.
Use in renal impairment.
No dose adjustment is required for patients with renal impairment.
Use in liver dysfunction.
There are no pharmacokinetic data on the effect of the drug in patients with impaired liver function, however, loperamide should be prescribed with caution to such patients due to the slowing of first-pass metabolism.
Children
The drug should be used in children aged 12 years and older for the symptomatic treatment of acute diarrhea.
Overdose
Symptoms: In case of overdose (including relative overdose due to hepatic dysfunction), CNS depression (stupor, incoordination, drowsiness, miosis, muscle hypertonia, respiratory depression, constipation, urinary retention and a symptom complex similar to intestinal obstruction) may occur. Children and patients with impaired hepatic function may be more sensitive to CNS effects.
Cardiac abnormalities such as QT and QRS prolongation, torsade de pointes, other serious ventricular arrhythmias, cardiac arrest, and syncope have been observed in individuals with overdoses of loperamide hydrochloride. Fatalities have also been reported. Overdose may precipitate pre-existing Brugada syndrome.
Cardiac arrest, syncope, and fatalities have been reported in individuals who have knowingly taken higher doses of loperamide (doses ranging from 40 to 792 mg per day).
Treatment. In case of overdose, the patient should immediately consult a doctor. If symptoms of overdose occur, naloxone can be used as an antidote. Since the duration of action of loperamide is longer than naloxone (1-3 hours), repeated administration of naloxone may be necessary. The patient should be closely monitored for symptoms of possible CNS depression for at least 48 hours.
Adverse reactions
Nervous system: headache, dizziness, drowsiness, stupor, depression or loss of consciousness, hypertension, impaired coordination, tremor.
Gastrointestinal: nausea, constipation, flatulence, abdominal pain, dry mouth, vomiting, dyspepsia, glossalgia, bloating, intestinal obstruction, including paralytic ileus; megacolon, including toxic megacolon, upper abdominal pain.
Renal and urinary disorders: urinary retention.
Skin and subcutaneous tissue disorders: rash; bullous rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme; angioedema, urticaria, pruritus.
Immune system disorders: hypersensitivity reactions, anaphylactic reactions (including anaphylactic shock) and anaphylactoid reactions.
From the organs of vision: miosis.
General disorders: increased fatigue.
Expiration date
5 years.
Storage conditions
Store at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
Vacation category
Without a prescription.
Producer
Salutas Pharma GmbH (bulk production, packaging, batch production). Lek S.A. (packaging, batch production).
Location of the manufacturer and its business address
Otto-von-Gürike-Allee 1, 39179, Barleben, Germany. Domaniewska Street 50 C, Warsaw, 02-672, Poland.
