KAOLIN AND MORPHINE MIXTURE - summary of medicine characteristics

Kaolin and Morphine Mixture

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Kaolin Light (Grade A1) 1g

Sodium Hydrogen Carbonate Powder 250mg

Morphine Hydrochloride 0.458mg per 5ml dose.

Excipients with known effects

Each 5ml dose contains 0.46%vol ethanol (alcohol)

Each 5ml dose contains 3.2mmol (74mg) sodium

Each 5ml dose contains 0.08g sucrose

Each 5ml dose contains 0.000025mg benzyl alcohol

Each 5ml dose contains 32.5mg sodium methyl hydroxybenzoa­te (E219)

Each 5ml dose contains 3.4mg sodium propyl hydroxybenzoa­te (E217)

Each 5ml dose contains 0.0875mg benzyl benzoate (equivalent to 0.00175% w/v)

Each 5ml dose contains 35mg fructose

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Oral suspension.

A buff coloured suspension which separates on standing to give a buff coloured sediment and a brown supematant liquid.

4.1

Therapeutic Indications

For relief of the symptoms of diarrhoea and upset stomachs in adults and children over 12 years.

4.2 Posology and method of administration

Oral.

Recommended doses:

Adults and children over 12 years: Two 5ml spoonfuls.

Children under 12 years: Not recommended for children under 12 years.

Directions for use: Shake the bottle.

Dosage schedule:

The dose may be repeated 3 times daily or as directed.

4.3 Contra-indications

Kaolin is contraindicated in intestinal obstruction. Whilst this product only contains a small amount of morphine, theoretically it should be contraindicated in the same conditions as other morphine-containing preparations. These conditions include respiratory depression, obstructive airways disease, known morphine sensitivity, acute hepatic disease, acute alcoholism, head injuries, coma, convulsive disorders, where intracranial pressure is raised, and in concurrent administration with monoamine oxidase inhibitors or within 2 weeks of discontinuation of their use.

Hypersensitivity to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

As this product contains sodium hydrogen carbonate, it should not be administered to patients with metabolic or respiratory alkalosis, hypocalcaemia or hypochlorhydria, and should be administered with caution in patients with congestive heart failure, renal impairment, cirrhosis of the liver, hypertension and to patients receiving corticosteroids.

Whilst this product only contains a small amount of morphine, it should (as with other morphine-containing preparations) be used with care in the elderly or debilitated (when the dose should be reduced), in prostatic hypertrophy, in hypotension, in hypothyroidism and where there is reduced respiratory reserve (avoid use during an asthma attack), and should not be given if paralytic ileus is likely to occur.

Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs: Concomitant use of morphine and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe this medicine concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.

The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5).

Oral P2Y12 inhibitor antiplatelet therapy

Within the first day of concomitant P2Y12 inhibitor and morphine treatment, reduced efficacy of P2Y12 inhibitor treatment has been observed (see section 4.5).

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption should not take this medicine. This product contains 70mg fructose in each 10ml dose. The additive effect of concomitantly administered products containing fructose (or sorbitol) and dietary intake of fructose (or sorbitol) should be taken into account.

This medicine contains 0.175mg benzyl benzoate in each 10ml dose, which is equivalent to 0.00175% w/v.

This product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

This medicine contains 38mg ethanol per 10ml dose which is equivalent to 0.38% w/v. The amount in 10ml is equivalent to less than 1ml of beer and 1ml of wine. The small amount of alcohol in this medicine will have no noticeable effects.

This product contains 6.4mmol (or 148mg) of sodium (main component of cooking/table salt) per 10ml dose, equivalent to 7.4% of the WHO recommended maximum daily intake of 2g sodium for an adult.

This product contains 0.05pg benzyl alcohol per 10ml dose, which may cause allergic reactions. High volumes should be used with caution and only if necessary, especially in subjects with liver or kidney impairment because of the risk of accumulation and toxicity (metabolic acidosis). This product contains sodium methyl and sodium propyl parahydroxyben­zoates (E219 and E217 respectively) which may cause allergic reactions (possibly delayed).

The following warnings and precautions appear on the labels:

Do not take more medicine than the label tells you to.

Keep out of the sight and reach of children Do not take with alcoholic or hot drinks.

4.5 Interaction with other medicinal products and other forms of interaction

As kaolin is adsorbent, the absorption of other drugs from the gastro-intestinal tract administered concomitantly may be reduced. Kaolin possibly reduces absorption of aspirin, tetracycline, chloroquine and hydroxychloroquine, and phenothiazines.

Sodium hydrogen carbonate may also reduce or delay absorption of other drugs as a result of its antacid effect.

Morphine, whilst only present in a very low concentration, theoretically may potentiate the effects of tranquillisers such as barbiturates, anaesthetics, anxiolytics and hypnotics, sedatives and alcohol. The reduction in intestinal motility caused by morphine may delay the absorption or antagonise the gastrointestinal effects of other drugs. The effects of domperidone and metoclopramide on gastrointestinal activity are antagonised by opioid analgesics. Metabolism of opioid analgesics is inhibited by cimetidine leading to increased plasma concentration.

Opioid analgesics should be avoided when ciprofloxacin is to be used for antibacterial surgical prophylaxis as concomitant use can lead to decreased plasma concentration of ciprofloxacin. The opioid analgesics enhance effects of sodium oxybate, used to treat symptoms of narcolepsy and concomitant use should be avoided.

Possible CNS excitation or depression (hypertension or hypotension) can occur when opioid analgesics are given with antidepressants such as moclobemide and MAOIs (avoid concomitant use and for 2 weeks after stopping MAOIs). The sedative effects of morphine can possibly be increased when given with tricyclic antidepressants, with anxiolytics or hypnotics, or with sedating antihistamines. Antipsychotic medicines can enhance hypotensive and sedative effects when opioid analgesics are given with antipsychotics.

Morphine also has the following specific interaction information. Morphine possibly increases plasma concentration of the beta-blocker esmolol which may be used as an anti-arrythmic. The plasma concentration of morphine is possibly reduced by the antiviral ritonavir.

Morphine increases the bioavailability of the anticonvulsant medication gabapentin.

Sedative medicines such as benzodiazepines or related drugs: The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dose and duration of concomitant use should be limited (see section 4.4).

A delayed and decreased exposure to oral P2Y12 inhibitor antiplatelet therapy has been observed in patients with acute coronary syndrome treated with morphine. This interaction may be related to reduced gastrointestinal mobility and apply to other opioids. The clinical relevance is unknown, but data indicate the potential for reduced P2Y12 inhibitor efficacy in patients co-administered morphine and a P2Y12 inhibitor (see section 4.4). In patients with acute coronary syndrome, in whom morphine cannot be withheld and fast P2Y12 inhibition is deemed crucial, the use of a parenteral P2Y12 inhibitor may be considered.

4.6 Fertility, pregnancy and lactation

This product should not be used in pregnancy or whilst breastfeeding unless recommended by a doctor.

4.7 Effects on Ability to Drive and Use Machines

Although it is not considered that the product will have any effect, morphine may cause drowsiness, patients should not drive or operate machinery if affected.

4.8 Undesirable effects

The sodium hydrogen carbonate in this product may cause stomach cramps and flatulence. Morphine, whilst only present in a low concentration, may theoretically cause nausea, vomiting, constipation, drowsiness and confusion. Prolonged use may lead to tolerance and dependence.

Although there are qualitative and quantitative differences in side effects for the opioid analgesics, other recognised possible side effects include:

difficulty with micturition; ureteric or biliary spasm; dry mouth; sweating; headache; facial flushing; vertigo; bradycardia, tachycardia or palpitation; postural hypotension; hypothermia; hallucinations, dysphoria or mood changes; miosis; decreased libido or potency; rashes, urticaria, pruritis and opioid-induced hyperalgesia (OIH).

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for “MHRA Yellow Card” in the Google Play or Apple App Store.

4.9 Overdose

In the unlikely event of overdosage with this product, signs of morphine toxicity and overdosage include pin-point pupils, respiratory depression and hypotension. Circulatory failure and deepening coma may occur in more severe cases.

Treatment should consist of naloxone administration, aspiration and gastric lavage with assisted respiration (if necessary), and maintenance of fluid and electrolytes.

Excessive administration of sodium hydrogen carbonate may lead to metabolic alkalosis.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic Properties

A07 DA52 – Antipropulsives

Kaolin is an adsorbent, it adsorbs toxic and other substances from the alimentary tract and increases the bulk of the faeces.

Sodium hydrogen carbonate is an alkalising agent and antacid.

Morphine reduces the peristaltic activity of the intestines.

5.2 Pharmacokinetic Properties

Kaolin is not absorbed following oral administration. It remains unchanged throughout transit of the gastrointesti­nal tract.

Sodium hydrogen carbonate is neutralised in the stomach with the formation of carbon dioxide. Any remaining is absorbed and excreted as bicarbonate and sodium ions in the urine in the absence of a plasma deficit.

Morphine is well absorbed from the gastrointestinal tract but has poor bioavailability due to extensive first pass metabolism in the liver. It is distributed throughout the body but mainly in the kidneys, liver, lungs and spleen, with lower concentrations in the brain and muscles. Morphine diffuses across the placenta and traces appear in milk and sweat. About 35% is protein bound. Conjugation to 3– and 6– glucuronides occurs in the liver and gut. Up to 10% of morphine is excreted as conjugates in the bile and faeces and the remainder is excreted in the urine. About 90% of total morphine is excreted in 24 hours with traces in the urine up to 48 hours or more.

5.3 Preclinical Safety Data

No data of relevance to the prescriber, which is additional to that included in other sections of the SPC.

PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Ethanol (96%)

Peppermint Oil

Anise oil

Saccharin sodium

Sodium methyl hydroxybenzoate (E219)

Sodium propyl hydroxybenzoate (E217)

Treacle black commercial (contains fructose)

Liquorice Flavour (contains E1518 glyceryl triacetate, E1520 propylene glycol, E1505

triethyl citrate & E1529 benzyl alcohol and benzyl benzoate)

Syrup (sucrose)

Purified water

6.2 Incompatibilities

None.

6.3

200ml:

18 months unopened.

6.4

Store below 25°C. Keep tightly closed.

6.5

200ml:

Glass bottle with polypropylene cap.

6.6 Instructions for Use, Handling and Disposal

None.

7. MARKETING AUTHORISATION HOLDER

L.C.M. Ltd.

Linthwaite Laboratories

Huddersfield

HD7 5QH

8. MARKETING AUTHORISATION NUMBER(S)

PL 12965/0021

9. DATE OF FIRST AUTHORISATION/RE­NEWAL OF THE AUTHORISATION

25th October 1993