Loperamide Grindeks (Capsules) Instructions for Use

Marketing Authorization Holder

Grindeks, JSC (Latvia)

ATC Code

A07DA03 (Loperamide)

Active Substance

Loperamide (Rec.INN registered by WHO)

Dosage Form

Loperamide Grindeks

Capsules 2 mg: 10 or 20 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin, size No. 3, with a pink body and a dark green cap; the capsule contents are a white powder.

Excipients: lactose monohydrate, corn starch, magnesium stearate.

Capsule body composition: titanium dioxide (E171), patent blue V (E131), ponceau 4R (E124), gelatin.
Capsule cap composition: titanium dioxide (E171), quinoline yellow (E104), patent blue V (E131), yellow iron oxide (E172), gelatin.

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

Clinical-Pharmacological Group

Symptomatic antidiarrheal drug

Pharmacotherapeutic Group

Antidiarrheal agent

Pharmacological Action

Loperamide, by binding to opioid receptors in the intestinal wall (stimulation of cholinergic and adrenergic neurons via guanine nucleotides), reduces the tone and motility of the intestinal smooth muscle (by inhibiting the release of acetylcholine and prostaglandins). The drug slows down peristalsis and increases the transit time of intestinal contents. It increases the tone of the anal sphincter, promotes fecal retention, and reduces the urge to defecate. The action of loperamide develops rapidly and lasts for 4 to 6 hours.

Pharmacokinetics

Absorption – 40%. T_max – 2.5 hours after capsule intake. Plasma protein binding (primarily to albumin) – 97%. At recommended doses, it does not cross the blood-brain barrier. It undergoes intensive metabolism via oxidative N-demethylation during the first pass through the liver. The drug is almost completely metabolized in the liver by conjugation. T_1/2 – 9 – 14 hours (average 10.8 hours). It is excreted primarily via the intestines, with a small portion excreted by the kidneys (as conjugated metabolites).

Indications

• Symptomatic treatment of acute (allergic, emotional, drug-induced, radiation-induced) and chronic (in irritable bowel syndrome) diarrhea;
• Regulation of stool in patients with an ileostomy.

As an auxiliary medicinal product:

• Diarrhea of infectious origin.

ICD codes

Dosage Regimen

Capsules are taken orally, without chewing, and washed down with water.

For acute diarrhea the initial dose for adults is 4 mg; then – 2 mg after each bowel movement (in case of loose stools); the maximum daily dose is 16 mg.

For chronic diarrhea the recommended dose for adults is 4 mg/day; the maximum daily dose is 16 mg.

For acute diarrhea in children over 6 years of age, the recommended initial dose of loperamide is 2 mg, then – 2 mg after each bowel movement; the maximum daily dose is 8 mg.

For chronic diarrhea in children over 6 years of age, Loperamide is prescribed at a daily dose of 2 mg.

The drug should be discontinued upon the appearance of normal stools or if no stool has occurred for more than 12 hours. The maximum duration of treatment is 2 days.

Patients with impaired liver function. Although pharmacokinetic data in this patient category are not available, due to the pronounced first-pass effect through the liver, patients with impaired liver function should exercise particular caution when using loperamide (see the Special Precautions section).

Adverse Reactions

Skin and subcutaneous tissue disorders rash, itching, urticaria, angioedema. Very rarely – bullous rash, including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Immune system disorders allergic reactions – urticaria, angioedema; very rarely – severe hypersensitivity reactions, including anaphylactic shock and anaphylactoid reactions.

Gastrointestinal disorders dry mouth, abdominal pain, abdominal bloating or discomfort, nausea, vomiting, flatulence, dyspepsia, constipation; extremely rarely – paralytic ileus, toxic megacolon.

Renal and urinary disorders urinary retention.

Nervous system disorders drowsiness, dizziness.

General disorders fatigue.

Contraindications

• Hypersensitivity,
• Intestinal obstruction;
• Acute ulcerative colitis;
• Diverticulosis;
• Diarrhea associated with pseudomembranous enterocolitis, dysentery, and other gastrointestinal infections;
• Pregnancy (first trimester);
• Lactation period;
• Childhood (under 6 years);
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

With caution hepatic insufficiency.

Use in Pregnancy and Lactation

Contraindicated during pregnancy (in the first trimester) and during lactation.

Use in Hepatic Impairment

Patients with impaired liver function should exercise particular caution when using loperamide.

In patients with impaired liver function, careful monitoring for signs of toxic CNS damage is necessary. These include stupor, drowsiness, miosis, muscle hypertonia, respiratory depression, and impaired coordination of movements.

Pediatric Use

Contraindicated in childhood (under 6 years).

Special Precautions

If there is no effect after 2 days of using loperamide, it is necessary to consult a doctor.

If constipation or abdominal bloating develops during treatment, Loperamide should be discontinued.

In patients with impaired liver function, careful monitoring for signs of toxic CNS damage is necessary. These include stupor, drowsiness, miosis, muscle hypertonia, respiratory depression, and impaired coordination of movements.

During the treatment of diarrhea, it is necessary to replenish fluid and electrolyte losses.

Effect on ability to drive vehicles and operate machinery

During the treatment period, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms CNS depression (stupor, impaired coordination of movements, drowsiness, miosis, muscle hypertonia, respiratory depression), intestinal obstruction.

Treatment antidote – naloxone; given that the duration of action of loperamide is longer than that of naloxone, repeated administration of the latter is possible. Symptomatic treatment, activated charcoal, gastric lavage, artificial ventilation.

Drug Interactions

Loperamide is a substrate of P-glycoprotein. According to preclinical studies, simultaneous administration of loperamide (single dose of 16 mg) with quinidine (single dose of 600 mg) or ritonavir (which are P-glycoprotein inhibitors) caused a 2 to 3-fold increase in plasma levels of loperamide. Due to the possible increased risk of CNS side effects, caution should be exercised when using loperamide concomitantly with the P-glycoprotein inhibitors quinidine and ritonavir.

When loperamide and saquinavir are used together, Loperamide clinically significantly reduces the therapeutic efficacy of saquinavir.

Concomitant use of loperamide with co-trimoxazole increases the bioavailability of loperamide.

Concomitant administration of narcotic (opioid) analgesics and loperamide increases the risk of constipation.

Storage Conditions

Store in a place inaccessible to children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 5 years.

Dispensing Status

Over-the-counter.

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.