Kaolin And Morphine Mixture
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Kaolin and Morphine Mixture BP
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 5ml contains:
Kaolin Light (Sterilised) BP 1.000g
Chloroform and Morphine Tincture BP 0.200ml
For excipients see 6.1
3 PHARMACEUTICAL FORM
Oral Suspension
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the symptomatic treatment of chronic diarrhoea.
4.2 Posology and method of administration
Oral administration.
Adults: Two 5ml spoonfuls up to 4 times daily after meals.
Children over 14 years: One 5ml spoonful up to 4 times daily after meals
Children 0-14 years: Not recommended.
4.3 Contraindications
Kaolin and Morphine mixture BP is contra-indicated in respiratory depression, obstructive airways disease, known morphine sensitivity, acute hepatic disease, concurrent administration of monoamine oxidase inhibitors or within two weeks of discontinuation of their use.
It is also contra-indicated in patients with pseudomembranous colitis and diverticular disease and in patients with renal failure and raised intracranial pressure and head injury.
4.4 Special warnings and precautions for use
Excessive sedation may occur in children and in patients with chronic liver disease. Use with caution in colitic attacks as they may possibly increase the risk of toxic megacolon. Prolonged use could possibly aggravate irritable bowel syndrome. Use with caution in the elderly as opioid analgesics may induce faecal impaction, producing incontinence, spurious diarrhoea, abdominal pain, and rarely colonic obstruction. The risk of dependence is greater in prolonged use fore the relief of chronic diarrhoea.
Caution should also be exercised in patients with renal impairment, cardiac arrhythmias, acute attack of asthma, acute abdominal condition, respiratory impairment and drug abuse. May cause drowsiness. If affected do not drive or operate machinery. Avoid alcoholic drink. Do not exceed the recommended dose.
4.5 Interaction with other medicinal products and other forms of interaction
Concurrent administration of Kaolin and Morphine Mixture with antidiarrhoeal and anti-peristaltics such as difenoxin, atropine, kaolin, pectin, belladonna alkaloids opium preparations and loperamide, may increase the risk of severe constipation and central nervous system depression. Concurrent administration of morphine with antihypertensive agents especially ganglionic blockers such as guanethidine, diuretics, hypotension producing medication may potentiate the hypotensive effect and increase risk of orthostatic hypotension. Concomitant administration of this product with other medications with antimuscrinic action may lead to an increased risk of severe constipation and may lead to paralytic ileus and/or urinary retention.
Concurrent administration with metoclopramide may antagonise the effects of metoclopramide on gastrointestinal motility. Concurrent administration with CNS depressants may result in an increase in CNS depression, respiratory depression and hypotensive effects.
Kaolin interacts with linomycin to reduce its absorption.
4.6 Pregnancy and lactation
Morphine traverses the placental barrier, regular use during pregnancy may cause physical dependence in the foetus, leading to withdrawal symptoms. Teratogenic effects have not been demonstrated in humans, however, studies in mice have shown delayed ossification and increased resorption has been reported in rats. Therefore risk benefits must be considered when administering during pregnancy. Morphine is excreted in the breast milk and neonates are more susceptible to its effects, especially the respiratory depressant effects. Therefore, nursing mothers should avoid breastfeeding while using this product.
4.7 Effects on ability to drive and use machines
May cause drowsiness if affected do not drive or operate machinery.
4.8 Undesirable effects
The most common side effects include nausea, vomiting, constipation and drowsiness. Larger doses produce respiratory depression and hypotension.
Development of tolerance, psychological and physical dependence may occur especially if large doses are given. Effects of alcohol may be enhanced.
4.9 Overdose
Symptoms resulting from overdose are cold clammy skin, confusion, convulsions, dizziness, drowsiness, asthenia, hypotension, bradycardia, nervousness, restlessness, pin-point pupils, slow or troubled breathing and unconsciousness.
Treatment entails emptying the stomach via induction of emesis or gastric lavage. Maintenance of a patent airway and institution of assisted or controlled respiration if necessary. Administration of opioid antagonist naloxone 10 mcg/kg of body-weight or 400 mcg-2mg as a single dose preferably intravenous may be required. It must be borne in mind that naloxone may also antagonize the analgesic action of opoid analgesics and may precipitate withdrawal symptoms in physically dependant paitents.
Naloxone dosage should be carefully titrated to avoid causing hypertension and tachycardia.
Initial doses as low as 0.5mcg/kg of body weight have been recommended.
Supportive measures such as intravenous fluids and vasopressor drugs may be required.
Patients should be monitored continuously while administering additional naloxone as needed.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Kaolin is a hydrated aluminium silicate. Light kaolin is an adsorbent and is employed in the symptomatic treatment of diarrhoea. It is administered orally, usually in combination with other anti-diarrhoeal agents. Since it is an adsorbent, it should be remembered that the absorption of other drugs from the gastrointestinal tract may be reduced if administered concomitantly. Morphien, a phenanthrene derivative and the principle alkaloid of opium is an opioid analgesic which acts mainly on the central nervous system and smooth muscle. Morphine generally increases smooth muscle tone, especially intestinal motility and has been used in the symptomatic treatment of diarrhoea.
5.2 Pharmacokinetic properties
Kaolin is not absorbed from the gastro-intestinal tract and nearly the whole of orally administered dose is recovered in the faeces. Morphine salts are well absorbed from the gastro-intestinal tract but have poor oral bioavailability since they undergo extensive first-pass metabolism in the liver and gut. The majority of a dose of morphine is conjugated with glucuronic acid in the liver and gut to produce its major metabolite morphine-3-glucuronide which is inactive and the active metabolite morphine-6-glucuronide. The latter may contribute to the analgesic effect of morphine, especially when repeated doses are given by mouth. Other active metabolites include normorphine, codeine, and morphine ethereal sulphate. Enterohepatic circulation probably occurs. Morphine is distributed throughout the body but mainly in the kidneys, liver, lungs, and spleen, with lower concentrations in the brain and muscles. Morphine crosses the blood-brain barrier less readily than more lipid-soluble drugs such as diamorphine, but it has been detected in the cerebrospinal fluid as have its highly polar metabolites morphine-3-glucuronide and morphine-6-glucuronide. Morphine diffuses across the placenta and traces also appear in milk and sweat. About 35% is protein bound.
Mean plasma elimination half-lives of 1.7 hours for morphine and 2.4 to 6.7 hours for morphine-3-glucuronide have been reported. Up to 10% of a dose of morphine may eventually be excreted, as conjugates, through the bile into the faeces. The remainder is excreted in the urine, mainly as conjugates. About 90% of total morphine is excreted in 24 hours with traces in urine for 48 hours or more.
5.3 Preclinical safety data
None available.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium Bicarbonate BP Potable Water
6.2 Incompatibilities
None.
6.3 Shelf life
36 months unopened.
6.4 Special precautions for storage
Store below 25°C and protect from light and moisture. Keep out of reach of children.
6.5 Nature and contents of container
The product is packed in amber glass bottles of 200ml fitted with ROPP closures.
6.6 Special precautions for disposal
7 MARKETING AUTHORISATION HOLDER
STERLING PHARMACEUTICALS LIMITED
288 UPPER BALSALL HEATH ROAD
BIRMINGHAM
B12 9DR
UNITED KINGDOM
8 MARKETING AUTHORISATION NUMBER(S)
PL 32515/0002
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
Date of grant 15 th January 2001
10 DATE OF REVISION OF THE TEXT
April 2001