INFORMATION FOR HEALTH PROFESSIONALS
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Apo-Loperamide 2mg tablets are green, capsule-shaped tablets, identified APO 2 on one side. Each tablet contains 2mg loperamide hydrochloride and typically weighs 435mg.
Loperamide is an antidiarrhoeal agent which 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 the tone of the anal sphincter, thereby reducing incontinence and urgency.
Substances such as serotonin, acetylcholine and other cholinergic agonists are believed to cause diarrhoea by increasing intracellular calcium levels. Intracellular calcium combines with calmodulin to activate adenyl cyclase, which again results in an increase in cellular cyclic nucleotides, hence an increase in chloride permeability. Loperamide inhibits the calcium-calmodulin-mediated increase in enzyme function in vitro at concentrations as low as 4micromoles. This action appears to be separate from the opiate receptor binding properties of loperamide.
Clinical improvement occurs within 1 to 3 hours after administration of the medicine.
Due to its high affinity for the gut wall and its high first-pass metabolism, loperamide hardly reaches the systemic circulation.
Loperamide is easily absorbed from the gut, but it is almost completely extracted and metabolised by the liver where it is conjugated and excreted via the bile. Little of the intact medication reaches the systemic circulation. The peak plasma level of loperamide occurs 4 hours after treatment, but is only about 0.3% of the administered dose.
The half-life of loperamide in man is 10.8 hours with a range of 9-14 hours. Studies on distribution in rats show a high affinity for the gut wall with a preference for binding to receptors of the longitudinal muscle layer. Excretion mainly occurs through the faeces as inactive conjugate.
Apo-Loperamide is indicated for the symptomatic control of acute and chronic diarrhoea. In patients with an ileostomy, colostomy or other intestinal resection it can be used to reduce the number and volume of stools and to harden their consistency.
Adults and children over 12 years:
Acute Diarrhoea: The initial dose is two tablets, followed by one tablet after every subsequent loose stool.
Chronic Diarrhoea: The initial dose is two tablets 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 1-6 tablets daily.
The maximum dose for acute and chronic diarrhoea is 8 tablets daily.
Children aged under 12 years:
Apo-Loperamide is not recommended for children under 12 years of age.
Patients should be advised to drink plenty of clear fluids, water, unsweetened juices or clear soups.
Apo-Loperamide is not recommended in children under the age of 12 years.
Since treatment of diarrhoea with loperamide is only symptomatic, diarrhoea should be treated causally, whenever causal treatment is available.
Apo-Loperamide should not be used as a primary therapy in acute dysentery, which is characterised by blood in the stools and high fever.
Apo-Loperamide should not be used when inhibition of peristalisis is to be avoided and must be discontinued promptly when constipation, abdominal distension or subileus develop.
Apo-Loperamide must not be used in patients with acute ulcerative colitis or pseudomembranous colitis associated with broad-spectrum anitbacterial agents.
Apo-Loperamide is contraindicated in patients with known hypersensitive to the drug.
In patients with diarrhoea, fluid and electrolyte depletion may occur. In such cases, administration of appropriate fluid and electrolyte replacement therapy is the most important measure.
In acute diarrhoea, if clinical improvement is not observed within 48 hours, the administration of Apo-Loperamide should be discontinued and patients should be advised to consult their physician.
Patients with hepatic dysfunction should be monitored closely for signs of CNS toxicity because of the high first-pass metabolism.
The use of Apo-Loperamide is not recommended for children 12 years of age or under except on the advice of a physician. Apo-Loperamide should be used with special caution in young children and those with compromised blood-brain barrier (eg: meningitis) because of the greater variability of response in these groups. Dehydration, particularly in young children, may further influence the variability of response to Apo-Loperamide.
Pregnancy and lactation:
Category B3
Although there are no indications that loperamide possesses teratogenic or embryotoxic properties, the anticipated therapeutic benefits should be weighed against potential hazards before Apo-Lopermide is given during pregnancy, especially during the first trimester. There is little information on the excretion of loperamide in human milk, but as small amounts of the drug were detectable in the milk of a nursing mother, the use of Apo-Loperamide is not recommended in breast-feeding subjects
Effect on ability to drive and operate machinery:
Loperamide does not affect alertness but if tiredness, dizziness or drowsiness are present it is preferable not to drive a car or operate machinery.
In no case in which the dose recommendations and contraindications were followed have any major adverse reactions been observed, even after prolonged administration.
The following adverse effects have been reported:
Hypersensitivity reactions eg: skin rash
Constipation and/or abdominal distension, in very rare cases associated with ileus, particularly in cases in which the prescribing information had not been followed (see dosage, duration of treatment, contraindications).
Several complaints that are usually difficult to distinguish from symptoms associated with the diarrhoeal syndrome, namely: abdominal pain or discomfort, nausea and vomiting, tiredness, drowsiness or dizziness, dry mouth.
Opiate-like effects (CNS) have been observed in young children (under 3 years of age).
Except for agents with similar pharmacological properties, no drug interactions have been reported.
In case of overdosage (including relative overdosage due to hepatic dysfunction), central nervous system depression (stupor, coordination abnormality, somnolence, miosis, muscular hypotonia, respiratory depression) and ileus may occur. Children may be more sensitive to CNS effects than adults.
Clinical trials have demonstrated that a slurry of activated charcoal administered promptly after ingestion of loperamide hydrochloride can reduce the amount of drug which is absorbed into the systemic circulation by as much as ninefold. If vomiting occurs spontaneously upon ingestion, a slurry of 100g of activated charcoal should be administered orally as soon as fluids can be retained. If vomiting has not occurred, gastric lavage should be performed followed by administration of 100g of the activated charcoal slurry through the gastric tube.
In the event of overdosage patients should be monitored for signs of CNS depression for at least 48 hours. If CNS depression is observed, naloxone can be given as an antidote. Since the duration of action of loperamide is longer than that of naloxone (1 to 3 hours) repeated treatment with naloxone may be indicated.
Since relatively little drug is excreted in the urine, forced diuresis is not expected to be effective for Apo-Loperamide overdose.
Store below 25°C. Protect from heat, light and moisture.
Prescription Only Medicine for bottles of 60 and 100 tablets and blister
packs of 30, 60 and 90 tablets.
Pharmacy Only Medicine for blister packs of 15 tablets.
Bottles of 60 and 100 tablets
Blister packs of 15, 30, 60 and 90 tablets
Tablets contain lactose and non-sensitising glutens
Apotex NZ Ltd
32 Hillside Road
Glenfield
Private Bag 102-995
North Shore Mail Centre
Auckland
Tel: (09) 444-2073
Fax: (09) 444-2951
18 October 2001