Each capsule contains: Loperamide Hydrochloride BP 2 mg.
Pharmacology: Pharmacodynamics: Loperamide is a synthetic derivative of pethidine that inhibits gut motility and may also reduce gastrointestinal secretions. Loperamide binds to the opiate receptor in the gut wall. Consequently, it inhibits the release of acetylcholine and prostaglandins, thereby reducing propulsive peristalsis, and increasing intestinal transit time. Loperamide increases viscosity, increases bulk density, reduces daily fecal volume, and diminishes loss of fluids and electrolytes. Loperamide increases the tone of the anal sphincter, thereby reducing incontinence and urgency. Additionally, loperamide will prolong mouth-to-cecum transit time without affecting gastric emptying.
Pharmacokinetics: Most ingested loperamide is absorbed from the gut, but as a result of significant first-pass metabolism, systemic bioavailability is only approximately 0.3%. Loperamide undergoes significant first-pass metabolism in the liver. Oxidative N-demethylation is the main metabolic pathway for loperamide, and is mediated mainly through CYP3A4 and CYP2C8. Oxidative n-dealkylation may be another pathway. Due to this very high first-pass effect; plasma concentrations of unchanged drug remain extremely low.
Used in the management of acute and chronic diarrheas, and of colostomies and ileostomies.
Adult: Acute diarrhoea: the initial dose is 4 mg; followed by 2 mg after every subsequent loose stool.
Chronic diarrhoea: the initial dose is 4 mg daily; this initial dose should be adjusted until 1-2 solid stools a day are obtained, which is usually achieved with a maintenance dose of 2 mg - 12 mg daily.
The maximum dose for acute and chronic diarrhoea is 16 mg daily for adults.
Paediatric: Acute diarrhoea: Below 6 years old: The use of loperamide in children under 6 years is not recommended.
6 to 8 years old: 4 mg per day in divided doses, 9 to 12 years old: 6 mg per day in divided doses.
Elderly: No dose adjustment is required for the elderly.
Renal impairment: No dose adjustment is required for patients with renal impairment.
Hepatic impairment: Although no pharmacokinetic data are available in patients with hepatic impairment, Loperamide should be used with caution in such patients because of reduced first-pass metabolism.
Symptoms: Common overdose effects: miosis, drowsiness, nausea, vomiting, abdominal pain, and headache. Seizures, dystonic reactions, ileus and pancreatitis have also occurred following overdose.
Treatment: Naloxone is an effective reversal agent. Initial dose of 2.0 mg intravenously; repeat as necessary. Patient should be monitored closely to detect possible CNS depression.
Loperamide HCl is contraindicated in patients with a known hypersensitivity to Loperamide HCI or to any of the excipients. Loperamide HCl should not be used in children under 2 years, Loperamide HCl should not be used as the primary therapy: in patients with acute dysentery, which is characterized by blood in stools and high fever, in patients with acute ulcerative colitis, in patients with bacterial enterocolitis caused by invasive organisms including Salmonella, Shigella, and Campylobacter, in patients with pseudomembranous colitis associated with the use of broad-spectrum antibiotics. Loperamide HCl should not be used when inhibition of peristalsis is to be avoided due to the possible risk of significant sequelae including ileus, megacolon and toxic megacolon. Loperamide HCl be discontinued promptly when constipation, abdominal distension or ileus develop.
Appropriate fluid and electrolyte therapy should be given to protect against dehydration in all cases of diarrhoea.
Skin rash, Erythema multiforme, rash, Stevens-Johnson syndrome, Toxic epidermal necrolysis, urticaria, angioedema.
appendicitis, bowel obstruction, constipation, flatulence, gallstone, gastrointestinal tract finding, indigestion, necrotizing enterocolitis in fetus or newborn, paralytic ileus, toxic megacolon, epigastric pain, nausea, dry mouth, vomiting, abdominal cramps, anorexia.
hypersensitivity reactions including anaphylactic shock and anaphylactoid reactions.
delirium, dizziness, fatigue, irritability, drowsiness, extrapyramidal reactions (acute dystonia, akathisia, pseudo-parkinsonism, tardive dyskinesia).
urinary retention and increased urethral pressure.
Concomitant administration of loperamide with quinidine, or ritonavir, which are both P-glycoprotein inhibitors, resulted in a 2 to 3-fold increase in loperamide plasma levels.
Saquinavir Interaction Effect: decreased saquinavir plasma concentrations, and increased loperamide plasma concentrations co-administration of Loperamide and Saquinavir significantly decreases saquinavir Cmax and AUC, possibly due to impaired absorption of saquinavir caused by the effect of loperamide to the gastrointestinal tract. Due to the possibility of reduced antiviral efficacy of saquinavir, their concomitant use should be avoided, especially for prolonged therapy.
There is also an increase in the exposure of loperamide, although it is unlikely to be clinically significant. The concomitant administration of loperamide and itraconazole, an inhibitor of CYP3A4 and P-glycoprotein, resulted in a 3 to 4-fold increase in loperamide plasma concentrations.
Gemfibrozil increased loperamide by approximately 2-fold. The combination of itraconazole and gemfibrozil resulted in a 4-fold increase in peak plasma levels of loperamide and a 13-fold increase in total plasma exposure.
The concomitant administration of loperamide and ketoconazole, an inhibitor of CYP3A4 and P-glycoprotein, resulted in a 5-fold increase in loperamide plasma concentrations.
Concomitant treatment with oral desmopressin resulted in a 3-fold increase of desmopressin plasma concentrations, presumably due to slower gastrointestinal motility.
St John's Wort Interaction Effect: delirium with symptoms of confusion, agitation, and disorientation.
Valerian Interaction Effect: delirium with symptoms of confusion, agitation, and disorientation.
Co-trimoxazole: Use with co-trimoxazole increases the bioavailability of loperamide apparently by inhibiting its first-pass metabolism. It is expected that drugs with similar pharmacological properties may potentiate loperamide's effect and that drugs that accelerate gastrointestinal transit may decrease its effect.
Store at temperatures not exceeding 30°C.
A07DA03 - loperamide ; Belongs to the class of antipropulsives. Used in the treatment of diarrhea.