Instructions Loperamide tablets 0.002 g blister No. 20
Composition
active ingredient: loperamide;
1 tablet contains loperamide hydrochloride 0.002 g;
Excipients: lactose monohydrate, corn starch, magnesium stearate, stearic acid, povidone.
Dosage form
Pills.
Main physicochemical properties: tablets from white to white with a yellowish tint.
Pharmacotherapeutic group
Drugs 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 in the intestine, but as a result of extensive first-pass metabolism, systemic bioavailability is 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 to 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 this 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.
Paediatric population: Pharmacokinetic studies in the paediatric population have not been conducted. The pharmacokinetics 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 over) after initial diagnosis by a physician.
Contraindication
Loperamide is contraindicated:
patients with hypersensitivity to loperamide hydrochloride or to any of the components of the drug;
patients with acute dysentery, characterized by the presence of blood in the stool and elevated body temperature;
patients with acute ulcerative colitis or pseudomembranous colitis associated with the use of broad-spectrum antibiotics;
patients with bacterial enterocolitis caused by microorganisms of the Salmonella, Shigella and Campylobacter families.
Loperamide should not be used at all if peristalsis inhibition is to be avoided due to the 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 with drugs with similar pharmacological properties have been reported. Drugs that depress the central nervous system should not be used concomitantly with Loperamide in children.
Preclinical data have shown that loperamide is a substrate for P-glycoprotein. Concomitant administration of loperamide (16 mg) with P-glycoprotein inhibitors (quinidine, ritonavir) resulted in a 2- to 3-fold increase in plasma loperamide levels. The clinical significance of this pharmacokinetic interaction at recommended doses of loperamide is unknown.
Concomitant administration of loperamide (4 mg single dose) and itraconazole, an inhibitor of CYP3A4 and P-glycoprotein, resulted in a 3- to 4-fold increase in plasma concentrations of loperamide. In the same study, the CYP2C8 inhibitor gemfibrozil increased loperamide exposure by approximately 2-fold. Combined administration of itraconazole and gemfibrozil resulted in a 4-fold increase in maximum plasma concentrations of loperamide and a 13-fold increase in total plasma exposure. This increase was not associated with central nervous system (CNS) effects as measured by psychomotor tests (i.e. subjective drowsiness and digit substitution test).
Concomitant treatment with oral desmopressin resulted in a 3-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 food through the gastrointestinal tract may reduce 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.
Since persistent diarrhea may indicate more serious conditions, 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.
Patients with acquired immunodeficiency syndrome who are taking loperamide for diarrhea should discontinue treatment immediately 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.
Although pharmacokinetic data are not available in patients with hepatic impairment, loperamide should be used with caution in such patients due to decreased first-pass metabolism. This drug should be administered with caution to patients with hepatic impairment as it may result in relative overdose, which may result in central nervous system toxicity.
Drugs that prolong transit time may lead to the development of toxic megacolon in this group of patients.
Since loperamide is well metabolized and unchanged substance or metabolites are excreted in the feces, it is usually not necessary to adjust the dose of loperamide for patients with impaired renal function.
Since the drug contains lactose, it should not be used in patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption syndrome.
Cardiac complications, including QT prolongation and QRS prolongation, torsade de pointes, have been reported in association with overdose. Some cases have been fatal (see section 4.8). Overdose may unmask 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, Loperamide 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 over 40 years old and some time has passed since the last IBS attack;
the patient is 40 years old and older and this time the symptoms of IBS are different;
recent intestinal bleeding;
severe constipation;
nausea or vomiting;
loss of appetite or weight loss;
difficult or painful urination;
fever;
recent trip abroad.
If new symptoms occur, symptoms worsen, or if symptoms do not improve within two weeks, you should consult a doctor.
Use during pregnancy or breastfeeding
This medicine is not recommended during pregnancy. Pregnant and breastfeeding women should consult their doctor for appropriate treatment.
The ability to influence the reaction speed when driving or working with other mechanisms
Increased fatigue, dizziness or drowsiness may occur when using loperamide hydrochloride. Therefore, it is recommended to take this drug with caution when driving a car or operating machinery.
Method of administration and doses
Loperamide is not indicated for the initial treatment of severe diarrhoea with reduced fluid and electrolyte levels. In children in particular, this loss should preferably be compensated for by parenteral or oral replacement therapy.
The initial dose is 2 tablets (4 mg), then 1 tablet (2 mg) after each loose stool. The usual dose is 3-4 tablets (6-8 mg) per day. The maximum daily dose for acute diarrhea should not exceed 6 tablets (12 mg).
Symptomatic treatment of acute attacks of diarrhea caused by irritable bowel syndrome in adults (aged 18 years and over) after initial diagnosis by a physician.
The initial dose is 2 tablets (4 mg); then take 1 tablet (2 mg) after each loose stool or as previously recommended by your doctor. The maximum daily dose should not exceed 6 tablets (12 mg).
In acute diarrhea, if clinical improvement is not observed within 48 hours, Loperamide 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.
Although pharmacokinetic data on the effect of the drug in patients with impaired liver function are lacking, Loperamide should be prescribed with caution to such patients due to the slowing of first-pass metabolism in them (see section "Special warnings and precautions for use").
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 impaired liver function), central nervous system depression (stupor, impaired coordination, drowsiness, miosis, muscle hypertonia, respiratory depression), urinary retention and a complex of symptoms similar to intestinal obstruction may occur.
Children may be more sensitive to effects on the central nervous system.
In patients who have overdosed with loperamide, prolongation of the QT interval and QRS complex, torsade de pointes, other serious ventricular arrhythmias, cardiac arrest, syncope have been observed. Fatal cases have also been recorded (see section "Special instructions"). Overdose may reveal existing Brugada syndrome.
Treatment.
In case of overdose, the patient should seek medical attention immediately. Since the duration of action of Loperamide is longer than that of naloxone (1-3 hours), repeated administration of naloxone may be necessary. The patient should be closely monitored for at least 48 hours to detect possible central nervous system depression.
Side effects
Adults and children aged 12 and over.
Side effects in patients with acute diarrhea.
Side effects that occurred with a frequency of 1% or more:
From the nervous system: headache.
On the part of the digestive tract: constipation, bloating, nausea.
Side effects that occurred with a frequency of less than 1%:
Nervous system: dizziness.
On the part of the digestive tract: dry mouth, flatulence, abdominal pain and discomfort, vomiting, upper abdominal pain, dyspepsia.
Skin and subcutaneous tissue disorders: rash.
Side effects that occurred with a frequency of "unknown":
From the digestive tract: acute pancreatitis.
Post-marketing experience.
The following are the side effects that have been spontaneously reported, by frequency of occurrence:
very common (≥1/10);
common (≥1/100, <1/10);
uncommon (≥1/1000, <1/100);
rarely (≥1/10,000, <1/1,000);
very rare (<1/10,000), including isolated reports.
Immune system disorders: very rarely - hypersensitivity reactions, anaphylactic reactions (including anaphylactic shock) and anaphylactoid reactions.
From the nervous system: very rarely - impaired coordination, loss of consciousness, depression of consciousness, hypertonicity, drowsiness, stupor.
On the part of the organs of vision: very rarely - miosis.
On the part of the digestive tract: very rarely - intestinal obstruction (including paralytic intestinal obstruction), megacolon (including toxic megacolon).
Skin and subcutaneous tissue disorders: very rarely - angioedema, bullous eruptions, including Stevens-Johnson syndrome, erythema multiforme and toxic epidermal necrolysis, urticaria and pruritus.
Renal and urinary disorders: very rarely - urinary retention.
General disorders: very rarely - increased fatigue.
Expiration date
5 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister; 1 or 2, or 50, or 100 blisters in a pack.
Vacation category
Without a prescription - No. 10, No. 20. According to the recipe - No. 500, No. 1000.
Producer
Private Joint-Stock Company "Lekhim-Kharkiv". PrJSC "Technolog".
Location of the manufacturer and address of its place of business
Ukraine, 61115, Kharkiv region, Kharkiv city, Severyna Pototskoho street, building 36.
Ukraine, 20300, Cherkasy region, Uman city, Stara Prorizna Street, building 8.
