Instructions for use Imodium Express orodispersible tablets 2 mg blister No. 6
Composition
active ingredient: loperamide hydrochloride;
1 tablet contains 2 mg of loperamide hydrochloride;
excipients: gelatin, mannitol (E 421), aspartame (E 951), mint flavoring (contains traces of sulfites), sodium bicarbonate.
Dosage form
Orodispersible tablets.
Main physicochemical properties: round lyophilized tablets from white to almost white in color.
Pharmacotherapeutic group
Antidiarrheal drugs; drugs used to treat infectious and inflammatory bowel diseases. Drugs that inhibit peristalsis. Loperamide. ATC code A07D A03.
Pharmacological properties
Pharmacodynamics.
Loperamide binds to opiate receptors in the intestinal wall, reducing propulsive peristalsis, increasing transit time, and improving absorption of water and electrolytes. Loperamide increases the tone of the anal sphincter, which helps reduce fecal incontinence and the urge to defecate.
In a double-blind, randomized clinical trial in 56 patients with acute diarrhea treated with loperamide, the onset of antidiarrheal action was observed within one hour after a single 4 mg dose. Clinical comparisons with other antidiarrheal drugs confirmed the exceptionally rapid onset of action of loperamide.
Pharmacokinetics.
Absorption: Most of loperamide is absorbed from the intestine after oral administration, but as a result of extensive first-pass metabolism, systemic bioavailability is only approximately 0.3%.
Distribution: Distribution studies of loperamide in rats demonstrate a high affinity for the intestinal wall with preferential binding to receptors in the longitudinal muscle layer. Loperamide is 95% bound to plasma proteins, primarily 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, bound and excreted in the bile. Oxidative N-demethylation is the main metabolic pathway of loperamide and is mediated mainly by CYP3A4 and CYP2C8. As a result of this very intense first-pass effect, the concentration of unchanged drug in the blood plasma remains extremely low.
Elimination: The elimination half-life of loperamide in humans is approximately 11 hours (range 9-14 hours). Excretion of unchanged loperamide and its metabolites occurs primarily in the feces.
Preclinical data.
Studies of treatment with loperamide in acute and chronic conditions have not revealed specific toxicity. The results of in vivo and in vitro studies have shown that loperamide is not genotoxic. In reproductive studies in female rats, administration of very high doses of loperamide (40 mg/kg/day, which is 20 times the maximum human exposure level (MHUL)), adjusted for body surface area (mg/m2), impaired fertility and fetal survival. Lower doses (≥ 10 mg/kg/day, which is 5 times the MHUL) did not show any effects on maternal or fetal health and did not affect peri- and postnatal development.
Non-clinical in vitro and in vivo evaluations indicate no significant cardiac effects when loperamide is administered within the therapeutic concentration range and at concentrations significantly exceeding these values (up to 47 times). However, at extremely high concentrations associated with overdose, loperamide has electrophysiological effects on the heart and has shown cardiac effects: inhibition of potassium (hERG) and sodium currents and arrhythmias.
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
Imodium® Express is contraindicated:
patients with known hypersensitivity to loperamide hydrochloride or to any of the components of the drug;
children under 12 years of age;
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.
Imodium® Express should not be used at all if inhibition of peristalsis is to 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
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) resulted in a 2- to 3-fold increase in plasma loperamide levels. The clinical significance of this pharmacokinetic interaction with P-glycoprotein inhibitors when loperamide is used at recommended doses is unknown.
Concomitant administration of loperamide (4 mg single dose) and itraconazole, a CYP3A4 and P-glycoprotein inhibitor, resulted in a 3- to 4-fold increase in loperamide plasma concentrations. 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 loperamide concentrations 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 administration of loperamide (16 mg single dose) and ketoconazole, an inhibitor of CYP3A4 and P-glycoprotein, 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 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 transit 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, then specific treatment should be carried out.
The most important measure in acute diarrhea is to prevent or replace fluid and electrolyte losses. This is especially important in children, debilitated patients, and the elderly with acute diarrhea.
The use of Imodium® Express does not replace the administration of an appropriate amount of fluid and restoration of electrolytes.
Since 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, if clinical improvement is not observed within 48 hours, loperamide hydrochloride should be discontinued and a doctor should be consulted.
Patients with acquired immunodeficiency syndrome who are taking Imodium® Express 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 patients with AIDS who have infectious colitis of both viral and bacterial origin treated with loperamide hydrochloride.
Although pharmacokinetic data are not available in patients with hepatic impairment, Imodium® Express should be used with caution in such patients due to decreased first-pass metabolism. Patients with hepatic impairment should be closely monitored for signs of CNS toxicity.
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.
Cardiac complications, including QT prolongation, QRS prolongation and torsades de pointes, have been reported in association with overdose. Some cases have been fatal (see Overdose section). Overdose may reveal pre-existing Brugada syndrome. Patients should not exceed the recommended dose and/or duration of treatment.
Caution is advised in patients with a history of drug abuse. Abuse and misuse of loperamide have been reported (see Overdose). Loperamide is an opioid with low bioavailability and limited potential to cross the blood-brain barrier at therapeutic doses. However, dependence has been observed with opioids as a class.
For the treatment of acute attacks of diarrhea caused by irritable bowel syndrome, Imodium® Express should only be taken if a doctor has previously diagnosed this syndrome.
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):
age 40 or older and some time has passed since the last IBS attack;
age 40 or 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;
If new symptoms occur, symptoms worsen, or if symptoms do not improve within two weeks, you should consult a doctor.
Important information about excipients
Peppermint flavoring contains sulfites, which may occasionally cause hypersensitivity reactions and bronchospasm. Allergic rhinitis-like reactions, urticaria, and anaphylaxis may occur.
Mannitol (E 421) may have a mild laxative effect.
Aspartame (E 951) is a derivative of phenylalanine, which is dangerous for patients with phenylketonuria.
Use during pregnancy or breastfeeding
Pregnancy
The safety of loperamide hydrochloride during pregnancy has not been established, although animal studies have not shown any evidence of teratogenic or embryotoxic properties of loperamide hydrochloride. As with other drugs, the use of loperamide during pregnancy is not recommended, especially during the first trimester.
Breastfeeding period
Small amounts of loperamide may appear in breast milk. Therefore, loperamide is not recommended for use during breastfeeding.
Pregnant and breastfeeding women should be advised to consult a doctor for appropriate treatment.
Fertility
The effect on human fertility has not been evaluated.
Ability to influence reaction speed when driving vehicles or other mechanisms
Due to the possibility of loss of consciousness, depression of consciousness, fatigue, dizziness or drowsiness in diarrhea syndrome, it is not recommended to drive a car or operate complex machinery while using loperamide hydrochloride (see section "Adverse reactions").
Method of administration and doses
The orodispersible tablet should be placed on the tongue. The tablet will dissolve and should be swallowed with saliva. The orodispersible tablet should not be taken with water.
Symptomatic treatment of acute diarrhea in adults and children aged 12 years and over.
The initial dose is two 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 should not exceed 6 tablets (12 mg). In acute diarrhea, if there is no clinical improvement within 48 hours, the drug should be discontinued.
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.
Adults (ages 18 and over):
The initial dose is 2 tablets (4 mg), then 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).
Elderly patients
Elderly patients do not require dose adjustment.
Kidney dysfunction
No dose adjustment is required for patients with renal impairment.
Liver dysfunction
Although pharmacokinetic data are not available in patients with hepatic impairment, Imodium® Express should be used with caution in such patients due to decreased first-pass metabolism (see section 4.4).
Method of application
Administer orally. Allow the tablet to dissolve on the tongue and swallow the medication.
Children.
The medicine 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), CNS depression (stupor, incoordination, drowsiness, miosis, muscle hypertonia and respiratory depression), constipation, urinary retention and intestinal obstruction are possible. Children and patients with impaired liver function may be more sensitive to CNS effects.
In individuals who have overdosed with loperamide, cardiac complications such as QT prolongation, QRS prolongation, torsades de pointes and other serious ventricular arrhythmias, cardiac arrest and syncope have been observed (see section "Special precautions"). Fatalities have also been reported. Overdose may reveal the presence of Brugada syndrome.
Treatment
In case of overdose, ECG monitoring should be initiated to detect QT prolongation. If CNS symptoms of overdose occur, naloxone can be used as an antidote. Since the duration of action of loperamide is longer than that of naloxone (1-3 hours), repeated administration of naloxone may be necessary. Therefore, patients should be closely monitored for at least the first 48 hours to detect possible CNS depression.
Side effects
Adults and children aged 12 and over
The safety of loperamide hydrochloride was evaluated in 2755 adults and children ≥ 12 years of age who participated in 26 controlled and uncontrolled clinical trials of loperamide hydrochloride for the treatment of acute diarrhea.
The following are adverse reactions that have been reported with loperamide hydrochloride in clinical trials (acute diarrhea) or during post-marketing experience.
Adverse reactions reported spontaneously with frequencies: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and frequency unknown (cannot be estimated from the available data).
Immune system disorders: Rare: hypersensitivity reactionsa, anaphylactic reactions (including anaphylactic shock)a and anaphylactoid reactionsa.
Nervous system disorders: common: headache; uncommon: dizziness, drowsiness; rare: loss of consciousness, stupor, depression of consciousness, hypertension, impaired coordination.
Visual disorders: rarely – miosis.
Gastrointestinal disorders: common: constipation, abdominal distension, nausea; uncommon: abdominal pain and discomfort, dry mouth, upper abdominal pain, vomiting, dyspepsia; rare: intestinal obstruction (including paralytic ileus), megacolon (including toxic megacolonb), glossodynia, abdominal distension; frequency unknown: acute pancreatitis.
Skin and subcutaneous tissue disorders: uncommon - rash; rare - angioedema, bullous eruptions (including Stevens-Johnson syndrome, erythema multiforme and toxic epidermal necrolysis), urticaria and pruritus.
Renal and urinary disorders: rarely - urinary retention.
General disorders: rarely - increased fatigue.
a These adverse reactions are included based on postmarketing reports of loperamide hydrochloride. Since it is not possible to distinguish from postmarketing reports whether adverse reactions occurred in acute or chronic conditions, or in adults or children, the frequency of adverse reactions was estimated based on data from all clinical trials of loperamide hydrochloride, including studies in children ≤ 12 years of age (N = 3683).
b See section “Special application features”.
Adverse reaction reporting
Reporting adverse reactions after registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua/.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 ºС in a place inaccessible to children.
Packaging
6 tablets in a blister, 1 blister in a cardboard box.
Vacation category
Without a prescription.
Producer
Production, primary packaging and quality control of the finished product:
Catalent UK Swindon Zydis Limited,
Secondary packaging, quality control of the finished product, batch release authorization:
JNTL Consumer Health (France) SAS.
Location of the manufacturer and address of its place of business.
Production, primary packaging and quality control of the finished product:
Frankland Road, Blagrove, Swindon, Wiltshire, SN5 8RU, United Kingdom.
Secondary packaging, quality control of the finished product, batch release authorization:
Domaine de Maigremont, Val-de-Reuil, 27100 France.
Applicant
McNeil Products Limited.
Applicant's location
50-100 Holmers Farm Way, High Wycombe, HP12 4EG, England/50-100 Holmers Farm Way, High Wycombe, HP12 4EG, England
Applicant's representative
Johnson & Johnson Ukraine LLC.
Location of the applicant's representative
01010, Kyiv, 32/2 Ostrozkyh Knyaziv St., Ukraine.
+38 (044) 498 0888
+38 (044) 498 7392
