Imodium^® Express (Lyophilized tablets) Instructions for Use

Marketing Authorization Holder

J&JTL, LLC (Russia)

Manufactured By

Catalent UK Swindon Zydis, Ltd. (United Kingdom)

Packaging and Quality Control Release

JNTL CONSUMER HEALTH (France), S.A.S. (France)

Contact Information

JNTL LLC (Russia)

ATC Code

A07DA03 (Loperamide)

Active Substance

Loperamide (Rec.INN registered by WHO)

Dosage Form

Imodium® Express

Lyophilizate tablets 2 mg: 6, 10, 18, or 20 pcs.

Dosage Form, Packaging, and Composition

Lyophilizate tablets white or almost white, round, lyophilized; on one side of the tablet, a central convexity, an uneven rough surface, and uneven thinned edges of the tablet are allowed; on the other side of the tablet – a bevel, roughness of the surface is allowed.

Excipients: gelatin, mannitol, aspartame, mint flavor, sodium bicarbonate.

6 pcs. – blisters (1) – cardboard packs.
6 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

Antidiarrheal drug

Pharmacotherapeutic Group

Antidiarrheal, intestinal anti-inflammatory/antimicrobial agents; agents that reduce gastrointestinal motility

Pharmacological Action

Loperamide, by binding to opioid receptors in the intestinal wall, suppresses the release of acetylcholine and prostaglandins, thereby slowing peristalsis and increasing the transit time of contents through the intestine. It increases the tone of the anal sphincter, thereby reducing fecal incontinence and the urge to defecate.

Clinical study data showed that the antidiarrheal effect occurs within 1 hour after taking a single dose (4 mg).

Pharmacokinetics

Absorption

Most of the loperamide is absorbed in the intestine, but due to active presystemic metabolism, the systemic bioavailability is approximately 0.3%.

Distribution

Preclinical study data indicate that Loperamide is a substrate of P-glycoprotein.

The binding of loperamide to plasma proteins (mainly albumin) is 95%.

Metabolism

Loperamide is predominantly metabolized in the liver, conjugated, and excreted in the bile. Oxidative N-demethylation is the main metabolic pathway of loperamide and is carried out primarily with the participation of the CYP3A4 and CYP2C8 isoenzyme inhibitors. Due to active presystemic metabolism, the concentration of unchanged loperamide in plasma is negligible.

Excretion

In humans, the T_1/2 of loperamide averages 11 hours, ranging from 9 to 14 hours. Unchanged Loperamide and its metabolites are excreted primarily in the feces.

Pharmacokinetics in special patient groups

Pharmacokinetic studies have not been conducted in children. The pharmacokinetics of loperamide and its interaction with other drugs are expected to be similar to those in adults.

Indications

For adults and children aged 6 years and older

• Symptomatic treatment of acute and chronic diarrhea:
  • Allergic, emotional, drug-induced, radiation-induced;
  • Due to changes in diet and food composition, due to impaired metabolism and absorption;
  • Symptomatic treatment of acute episodes of diarrhea associated with irritable bowel syndrome (IBS) in patients over 18 years of age after a physician-established diagnosis;
• As an auxiliary drug for diarrhea of infectious origin;
• For stool regulation in patients with ileostomy.

ICD codes

Dosage Regimen

Orally. The tablet is placed on the tongue, it dissolves within a few seconds, after which it is swallowed with saliva, without drinking water.

Adults

Acute diarrhea: initial dose – 2 tablets (4 mg) for adults and 1 tablet (2 mg) for children, then 1 tablet (2 mg) after each bowel movement in case of loose stools.

Chronic diarrhea: initial dose – 2 tablets (4 mg)/day for adults and 1 tablet (2 mg) for children; then the initial dose should be adjusted so that the frequency of normal stools is 1-2 times/day, which is usually achieved with a maintenance dose of 1 to 6 tablets (2-12 mg)/day.

The maximum daily dose should not exceed 6 tablets (12 mg); the maximum daily dose for children is calculated based on body weight (3 tablets per 20 kg of the child’s body weight), but should not exceed 6 tablets (12 mg).

When stool normalizes or if there is no stool for more than 12 hours, the drug is discontinued.

Symptomatic treatment of acute episodes of diarrhea associated with irritable bowel syndrome (IBS)

Patients aged 18 years and older: initially 2 tablets (4 mg), then 1 tablet (2 mg) after each loose stool or as directed by a physician. The maximum daily dose should not exceed 6 tablets (12 mg).

Special patient groups

When treating elderly patients, dose adjustment is not required.

When treating patients with renal impairment, dose adjustment is not required.

Although pharmacokinetic data in patients with hepatic impairment are lacking, Imodium^® Express should be used with caution in such patients due to slowed presystemic metabolism (see section “Special Precautions”).

Children

The safety and efficacy of Imodium^® Express in children aged 0 to 6 years have not been established. Data are not available.

Children over 6 years of agewith acute and chronic diarrhea are prescribed: initial dose – 1 tablet (2 mg), then 1 tablet (2 mg) after each bowel movement in case of loose stools.

Instructions for use

Since the lyophilizate tablets are quite fragile, to avoid damage, they should not be pushed through the foil.

To remove the tablet from the blister, the following steps must be performed

• Take the foil by the edge and completely remove it from the cell containing the tablet;
• Gently press from below and remove the tablet from the packaging.

Adverse Reactions

Based on clinical studies

Adverse reactions observed in ≥1% of patients taking Imodium^® Express for acute diarrhea headache, constipation, flatulence, nausea, vomiting.

Adverse reactions observed in ≥1% of patients taking Imodium^® Express for chronic diarrhea: dizziness, flatulence, constipation, nausea.

Based on post-marketing studies (spontaneous reports of adverse reactions and clinical or epidemiological studies)

The following adverse reactions were classified as follows: very common (≥1/10), common (≥1/100 but <1/10), uncommon (≥1/1000 but <1/100), rare (≥1/10000 but <1/1000), very rare (<1/10000), frequency not known (cannot be estimated from the available data).

Contraindications

• Hypersensitivity to loperamide or to any of the excipients included in the drug;
• Phenylketonuria;
• First trimester of pregnancy;
• Breastfeeding period.

Imodium^® Express should not be used as primary therapy

• In patients with acute dysentery, characterized by bloody stools and high fever;
• In patients with ulcerative colitis in the acute phase;
• In patients with bacterial enterocolitis caused by pathogenic microorganisms, including Salmonella spp., Shigella spp. and Campylobacter spp.);
• In patients with pseudomembranous colitis associated with the use of broad-spectrum antibiotics.

Imodium^® Express should not be used in cases where slowing of peristalsis is undesirable due to the possible risk of serious complications, including intestinal obstruction, megacolon, and toxic megacolon. Imodium^® Express should be immediately discontinued if constipation, abdominal distension, or intestinal obstruction occurs.

Use in Pregnancy and Lactation

Pregnancy

The drug is not recommended for use during pregnancy.

Breastfeeding period

The drug is contraindicated for use during breastfeeding.

Fertility

The effect on fertility in humans has not been evaluated.

Use in Hepatic Impairment

Caution should be exercised when prescribing the drug to patients with impaired liver function due to slowed presystemic metabolism.

Use in Renal Impairment

When treating patients with renal impairment, dose adjustment is not required.

Pediatric Use

Contraindicated in children under 6 years of age.

Geriatric Use

When treating elderly patients, dose adjustment is not required.

Special Precautions

Treatment of diarrhea with Imodium^® Express is only symptomatic. In cases where the cause of diarrhea can be identified, appropriate therapy should be administered.

In patients with diarrhea, especially children, fluid and electrolyte loss may occur. In such cases, appropriate replacement therapy (fluid and electrolyte replenishment) should be administered.

Since persistent diarrhea may be an indicator of potentially more serious conditions, the drug should not be taken for a long period until the underlying cause of the diarrhea is determined.

In acute diarrhea, if clinical improvement is not observed within 48 hours, administration of Imodium^® Express should be discontinued and a physician should be consulted.

Patients with AIDS taking Imodium^® Express for diarrhea should discontinue the drug at the first signs of abdominal distension, as well as signs of intestinal obstruction. Isolated reports of constipation with an increased risk of toxic megacolon have been received in AIDS patients with infectious colitis of viral and bacterial etiology who were treated with loperamide.

Imodium^® Express should be used with caution in patients with hepatic insufficiency, as this may lead to toxic effects on the CNS due to relative overdose.

Abuse or misuse of loperamide as an opioid substitute has been described in individuals with opioid dependence.

If patients are taking Imodium^® Express to control episodes of diarrhea associated with previously diagnosed irritable bowel syndrome, and clinical improvement is not observed within 48 hours, administration of loperamide hydrochloride should be discontinued and a physician should be consulted. Patients should also consult a physician if their symptom pattern changes or if recurrent episodes of diarrhea last more than 2 weeks.

QT interval prolongation and the development of ventricular arrhythmias, including torsades de pointes, have been reported in connection with loperamide overdose, in some cases with fatal outcome. Overdose may reveal an existing Brugada syndrome. Imodium^® Express should not be used for a long period without medical supervision, and patients should not exceed the recommended dose and/or the recommended duration of treatment.

If patients are taking this drug for the symptomatic treatment of acute episodes of diarrhea associated with irritable bowel syndrome (IBS), additional precautions for use must be observed

• Patients should take the drug to treat IBS symptoms only if this diagnosis has been previously established by a physician;
• Patients aged 40 years and older should consult a physician before using the drug if IBS symptoms have not been present for some time or if the current symptomatic picture differs from previous IBS symptoms;
• Patients should consult a physician before using the drug if they have: intestinal bleeding, severe constipation, nausea or vomiting, loss of appetite or weight loss, difficulty or pain when urinating, high body temperature; if patients have recently traveled abroad.

If symptoms worsen, if new symptoms appear, if the nature of the symptoms changes, or if recurrent episodes of diarrhea last more than 2 weeks, a physician should be consulted immediately.

Excipients

Imodium^® Express lyophilizate tablets contain a source of phenylalanine (aspartame). Use of the drug in patients with phenylketonuria is contraindicated.

Sulfites, which are part of the mint flavor, can cause allergic reactions and bronchospasm, most commonly asthma symptoms in people with concomitant asthma. Reactions similar to allergic rhinitis, urticaria, and anaphylaxis may be observed.

Effect on ability to drive vehicles and operate machinery

During treatment with Imodium^® Express, one should refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions, because the drug may cause dizziness and other side effects that may affect these abilities.

Overdose

Symptoms: in case of overdose (including relative overdose due to impaired liver function), urinary retention, paralytic ileus, constipation, signs of CNS depression (respiratory depression, airway obstruction, vomiting with impaired consciousness, stupor, impaired coordination, drowsiness, miosis, muscle hypertonia) may occur. Children and patients with impaired liver function may be more sensitive to the CNS effects of loperamide than adults.

In individuals who intentionally took an excessive dose (from 40 mg to 240 mg/day) of loperamide hydrochloride, QT interval and QRS complex prolongation and/or serious ventricular arrhythmias, including torsades de pointes; cardiac arrest, syncope (see section “Special Precautions”) were noted. Cases of fatal outcome with intentional overdose have also been described.

Abuse, misuse, and/or overdose with high doses of loperamide may lead to the clinical manifestation of Brugada syndrome.

Treatment: in case of overdose, ECG monitoring should be initiated to detect QT interval prolongation.

If overdose symptoms appear, 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 required. Therefore, the patient’s condition should be carefully monitored for at least 48 hours to timely detect signs of possible CNS depression.

Since the management of overdose is constantly changing, it is recommended to contact a poison control center (if available) for the most current recommendations on the treatment of overdose.

Drug Interactions

According to preclinical studies, Loperamide is a substrate of P-glycoprotein. With simultaneous use of loperamide (single dose of 16 mg) and quinidine or ritonavir, which are P-glycoprotein inhibitors, the plasma concentration of loperamide increased 2-3 times. The clinical significance of the described pharmacokinetic interaction with P-glycoprotein inhibitors when using loperamide at recommended doses is unknown.

Simultaneous use of loperamide (single dose of 4 mg) and itraconazole, an inhibitor of the CYP3A4 isoenzyme and P-glycoprotein, led to a 3-4-fold increase in the plasma concentration of loperamide. In the same study, the use of the CYP2C8 isoenzyme inhibitor, gemfibrozil, led to an approximately 2-fold increase in the plasma concentration of loperamide.

When using the combination of itraconazole and gemfibrozil, the C_max of loperamide in plasma increased 4 times, and the total concentration increased 13 times. This increase was not associated with an effect on the CNS, as assessed by psychomotor tests (i.e., subjective assessment of drowsiness and the digit symbol substitution test).

Simultaneous use of loperamide (single dose of 16 mg) and ketoconazole, a CYP3A4 and P-glycoprotein inhibitor, led to a fivefold increase in the plasma concentration of loperamide. This increase was not associated with an increase in pharmacodynamic action, assessed by pupil size.

With simultaneous oral administration of desmopressin, the plasma concentration of desmopressin increased 3 times, probably due to slowed gastrointestinal motility.

Drugs with similar pharmacological properties are expected to enhance the effect of loperamide, and drugs that increase the transit rate through the gastrointestinal tract may reduce the effect of loperamide.

Storage Conditions

The drug should be stored in the original packaging in a place inaccessible to children at a temperature from 15°C (59°F) to 30°C (86°F).

Shelf Life

The shelf life is 5 years. Do not use after the expiration date printed on the package.

Dispensing Status

The product is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.