Loperamide

Oral
Acute diarrhoea
Adult: As loperamide hydrochloride cap or oral solution/susp: Initially, 4 mg, followed by 2 mg after every subsequent loose stool. Max: 16 mg daily. As loperamide hydrochloride conventional or orodispersible tab: Initially, 4 mg, followed by 2 mg after each loose stool. Usual dose: 6-8 mg daily. Max: 12 mg daily. Discontinue treatment if clinical improvement is not observed within 48 hours. Dosage recommendations may vary among individual products or between countries. Refer to specific product guidelines.
Child: As loperamide hydrochloride cap: 8-17 years Initially, 2 mg, then 2 mg after every subsequent loose stool. Max: Based on individual body weight (6 mg/20 kg) up to 16 mg daily. As loperamide hydrochloride conventional or orodispersible tab: ≥12 years Same as adult dose. As loperamide hydrochloride oral solution/susp: 6-8 years weighing 21.8-27 kg: Initially, 2 mg, followed by 1 mg after every subsequent loose stool. Max: 4 mg daily; 9-11 years weighing 27.2-43 kg: Initially, 2 mg, followed by 1 mg after each loose stool. Max: 6 mg daily. Alternatively, for loperamide hydrochloride oral solution: 4-8 years 1 mg 3 or 4 times daily for up to 3 days; >8-11 years 2 mg 4 times daily for up to 5 days. Discontinue treatment if clinical improvement is not observed within 48 hours. Dosage recommendations may vary among individual products or between countries. Refer to specific product guidelines.

Oral
Chronic diarrhoea
Adult: As loperamide hydrochloride cap: Initially, 4 mg daily; adjusted until 1-2 solid stools a day are obtained, which is usually achieved with maintenance dose of 2-12 mg daily. Max: 16 mg daily. As loperamide hydrochloride oral solution: Initially, 4-8 mg daily in divided doses, may be adjusted depending on response. Doses may be given bid once the maintenance dose is established. Max: 16 mg daily. For cases associated with inflammatory bowel disease: As loperamide hydrochloride cap: Initially, 4 mg, followed by 2 mg after each loose stool until diarrhoea is controlled. Usual maintenance dose: 4-8 mg daily as a single dose or in divided doses. Max: 16 mg daily. If improvement does not occur after therapy with 16 mg daily for at least 10 days, symptoms are unlikely to be controlled by further use. Dosage recommendations may vary among individual products or between countries. Refer to specific product guidelines.

May be taken with or without food.

Acute dysentery (characterised by bloody stools and high fever), acute ulcerative colitis, abdominal pain without diarrhoea, bacterial enterocolitis caused by invasive organisms (e.g. Salmonella, Shigella, Campylobacter), pseudomembranous colitis associated with the use of broad-spectrum antibiotics; conditions wherein inhibition of peristalsis must be avoided (e.g. ileus, megacolon, toxic megacolon, constipation, abdominal distension).

Patient with AIDS, history of drug abuse, risk factors for QT interval prolongation (e.g. congenital long QT syndrome, history of cardiac arrhythmias or other heart conditions, electrolyte abnormalities). Not recommended to be used for prolonged periods until the underlying cause of the diarrhoea has been investigated. Hepatic impairment. Children. Pregnancy and lactation. Patient Counselling This drug may cause dizziness, drowsiness or tiredness, if affected, do not drive or operate machinery. Monitoring Parameters Assess for the cause of diarrhoea prior to treatment. Closely monitor for signs of CNS toxicity, particularly in patients with hepatic impairment.

Significant: Gastrointestinal effects (e.g. constipation, abdominal pain or distension, blood in stool, ileus, toxic megacolon, acute pancreatitis), syncope, ventricular tachycardia. Rarely, anaphylaxis and anaphylactic shock. Eye disorders: Rarely, miosis. General disorders and administration site conditions: Rarely, fatigue. Gastrointestinal disorders: Flatulence, nausea, dry mouth, abdominal cramps or discomfort, vomiting, dyspepsia. Nervous system disorders: Dizziness, headache, somnolence. Rarely, stupor, depressed level of consciousness, coordination abnormality. Renal and urinary disorders: Rarely, urinary retention. Skin and subcutaneous tissue disorders: Rash. Rarely, pruritus, Stevens-Johnsons syndrome, toxic epidermal necrolysis.
Potentially Fatal: Serious CV events (e.g. QT and QRS complex prolongation, torsades de pointes, cardiac arrest), particularly in higher than recommended doses.

Symptoms: CNS depression (e.g. stupor, somnolence, coordination abnormality, miosis, muscular hypertonia, respiratory depression), constipation, urinary retention and ileus. Cardiac events such as syncope, QT interval and QRS complex prolongation, torsades de pointes, other serious ventricular arrhythmias, and cardiac arrest may also occur. Management: Symptomatic and supportive treatment. If vomiting has occurred spontaneously, administer activated charcoal as soon as fluids can be maintained. Perform gastric lavage followed by administration of activated charcoal through the gastric tube in patients who have not vomited. Repeated doses of naloxone may be given as an antidote for CNS depression. Monitor the patient closely for at least 48 hours to detect possible CNS depression.

Concomitant use with inhibitors of P-glycoprotein (e.g. ritonavir, quinidine), CYP3A4 (e.g. ketoconazole, itraconazole), and CYP2C8 (e.g. gemfibrozil) increase loperamide plasma concentrations. May increase the plasma levels of oral desmopressin. Increased risk of serious CV events with agents known to prolong QT interval (e.g. procainamide, amiodarone, haloperidol, moxifloxacin).

Loperamide, an opioid agonist, binds to the opioid receptor directly on the circular and longitudinal muscles in the intestinal wall thereby reducing propulsive peristalsis and prolonging transit time of intestinal contents, and enhancing resorption of water and electrolytes. It also increases the tone of the anal sphincter, thus reducing faecal incontinence and urgency.
Absorption: Absorbed from the gastrointestinal tract. Bioavailability: Approx 0.3%. Time to peak plasma concentration: 2.5 hours (oral solution); approx 5 hours (cap).
Distribution: Enters breast milk (small amounts). Plasma protein binding: 95%, mainly to albumin.
Metabolism: Metabolised in the liver mainly via oxidative N-demethylation primarily by CYP3A4 and CYP2C8 isoenzymes; undergoes extensive first-pass metabolism.
Excretion: Mainly via faeces (as unchanged drug and metabolites); urine (small amounts). Elimination half-life: Approx 11 hours (range: 9-14 hours).

Oral: Store between 20-25°C.

Antidiarrheals

A07DA03 - loperamide ; Belongs to the class of antipropulsives. Used in the treatment of diarrhea.