SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

J Collis Browne’s Tablets

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Morphine hydrochloride    0.35mg/tablet

Light kaolin    750mg/tablet

Calcium carbonate, heavy    200mg/tablet

For the full list of excipients, see section 6.1.

3.    PHARMACEUTICAL FORM

Tablet

Flat, circular, mottled pink tablet with bevelled edges with J Collis Browne compressed into one face.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the symptomatic relief of occasional diarrhoea.

4.2    Posology and method of administration

Oral.

Adults and children over 12 years:

Two or three tablets at once, then two or three tablets every four hours.

Elderly and debilitated patients:

Should be used with caution; a reduced dose is recommended.

Children under 12 years Not recommended.

4.3 Contraindications

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 include acute respiratory depression (avoid during an asthma attack), obstructive airways disease, acute alcoholism, hypercalcaemia, acute hepatic disease, pancreatitis, paralytic ileus or obstructive bowel disorders, acute ulcerative colitis, raised intra-cranial pressure and head injury, pheochromocytoma, coma, convulsive disorders, delayed gastric emptying, acute abdomen; heart failure secondary to chronic lung disease.

Hypersensitivity to any of the ingredients.

Concurrent administration with monoamine oxidase inhibitors (MAOIs) or within 2 weeks of discontinuation of their use.

4.4 Special warnings and precautions for use

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 in debilitated patients, in patients with prostatic hypertrophy, a history of asthma, shock, myasthenia gravis, diseases of the biliary tract, cardiac arrhythmias, severe cor pulmonale, hypothyroidism, hypotension, renal or heptic impairment and where there is reduced respiratory reserve, and should not be given if paralytic ileus is likely to occur. This product should be given with caution to patients with a history of drug dependence.

Calcium salts should generally be avoided in patients with calcium renal calculi or a history of renal calculi.

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

If symptoms persist for more than 48 hours, consult the doctor.

Keep out of sight and reach of children. Do not exceed the stated dose.

Do not take more than 6 doses in 24 hours. In addition to taking these tablets, it is important to replace body fluids lost during diarrhoea.

Not recommended for children under 12 years of age.

4.5 Interaction with other medicinal products and other forms of interaction

The depressant effects of opioid analgesics are enhanced by other CNS depressants such as alcohol, anxiolytics, hypnotics, antidepressants including tricyclic antidepressants, sedating antihistamines, anticoagulants such as warfarin, antiepileptics and antipsychotics.

Possible CNS excitation or depression (hypertension or hypotension) can occur when opioid analgesics are given with antidepressants such as moclobenide and MAOIs (avoid concomitant use and for 2 weeks after stopping MAOIs).

Opioid analgesics can lead to reduced plasma levels of ciprafloxacin when used for surgical prophylaxis, and can enhance the effects of sodium oxybate. Metabolism of opioid analgesics is inhibited by cimetidine leading to increased plasma concentration.

The effects of morphine in reducing gastrointestinal motility may interfere with the absorption of antiarrhythmics such as mexiletine, and may counteract the stimulatory effect of metoclopramide, domperidone and cisapride.

Morphine may increase the plasma concentration of the beta-blocker esmolol, and may increase the bioavailability of the anticonvulsant gabapentin. The plasma concentration of morphine is possibly reduced by the antiviral ritonavir, and the sedative effect of morphine may be increased when given with baclofen.

The absorption of chloroquine, hydroxychloroquine, tetracycline and phenothiazines may be reduced by calcium salts and kaolin. Kaolin may also reduce the absorption of aspirin.

Calcium salts reduce the absorption of ciprofloxacin (and other fluoroquinolone antibiotics), bisphosphonates, fluorides, oral iron, levothyroxine and zinc. There is an increased risk of hypercalcaemia when calcium salts are given with thiazides and related diuretics, and Vitamin D. Calcium-containing products reduce the absorption of numerous drugs including captopril, enalapril, fosinopril, azithromycin, cefaclor, cefpodoxime, isoniazid, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, rifampicin, gabapentin, phenytoin, itraconazole, ketoconazole, fexofenadine, sulpiride, tipranavir, deflazacort, mycophenolate mofetil, rosuvastatin and penicillamine. Calcium-containing products possible reduce the absorption of ACE inhibitors, amprenavir, atazanavir, bile acids, digoxin, dipyridamole and lanzoprazole. Absorption of calcium salts is reduced by corticosteroids.

Kaolin and calcium can affect the absorption of other medicinal products from the gastrointestinal tract, therefore this product should not be taken at the same time as, nor within two to four hours of other medications.

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 considered unlikely with this product, morphine may cause drowsiness and other central nervous system disorders which may have an effect on the ability to drive or operate machinery. If affected, patients should not drive or operate machinery.

This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:

•    The medicine is likely to affect your ability to drive

•    Do not drive until you know how the medicine affects you

•    It is an offence to drive while under the influence of this medicine

•    However, you would not be committing an offence (called “statutory defence”) if:

o The medicine has been prescribed to treat a medical or dental problem and

o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and o It was not affecting your ability to drive safely

4.8 Undesirable effects

Opioid analgesics share many side-effects, although qualitative and quantitative differences exist. Side effects which may occur are nausea, vomiting, dyspepsia, anorexia, constipation, paralytic ileus, abdominal pain, exacerbation of pancreatitis, bronchospasm, inhibition of cough reflex, seizures, syncope, drowsiness, dizziness, confusion, sleep disturbances, difficulty in micturition, ureteric or biliary spasm, urinary retention, dry mouth, sweating, headache, raised intracranial pressure, facial flushing, vertigo, bradycardia, tachycardia, palpitations, oedema, hypertension, postural hypotension, hypothermia, hallucinations, euphoria, dysphoria, mood changes, dependence, miosis, visual disturbances, decreased libido or potency, amenorrhoea, rashes, paraesthesia, contact dermatitis, urticaria, pruritus and opioid-induced hyperalgesia (OIH).

Respiratory depression in sensitive patients, muscle rigidity, rhabdomyolysis and hypotension with larger doses.

Reporting of suspected adverse reactions

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.

4.9 Overdose

Symptoms;

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. Convulsions may occur, especially in infants and children. Muscle rigidity has been reported in high doses. Rhabdomyolysis progressing to renal failure has been reported following overdose of morphine.

High doses or prolonged use may lead to gastric hypersecretion and acid rebound. Calcium carbonate can cause hypercalcaemia, particularly in patients with renal impairment or after high doses. Alkalosis may also occur as a result of the carbonate anion. There have been reports of the milk-alkali syndrome and tissue calcification. Symptoms of hypercalcaemia include anorexia, nausea, vomiting, constipation, abdominal pain, muscle weakness, mental disturbances, polydipsia, polyuria, nephrocalcinosis, renal calculi, and in severe cases, cardiac arrhythmias and coma.

Treatment;

In acute overdosage, gastric lavage and symptomatic treatment as for morphine hydrochloride is recommended, including assisted respiration if necessary. Naloxone may be used to counteract central nervous system depression.

Mild hypercalcaemia is best corrected by increasing oral fluid intake and treating any identified underlying disease. Severe hypercalcaemia requires prompt treatment to reduce plasma calcium concentrations.

5.1 Pharmacodynamic properties

A07X - Other antidiarrhoeals

Light kaolin is absorbent and, when given by mouth, absorbs toxic and other substances from the alimentary tract.

Morphine, among other actions, diminishes propulsive peristalsis in the intestinal tract.

It is an effective agent for treating diarrhoea.

Calcium carbonate is an antacid that also has a constipating effect.

5.2. Pharmacokinetic Properties

No pharmacokinetic studies have been carried out.

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

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Magnesium stearate, sodium polymetaphosphate, sucrose (icing sugar), talc, dispersed pink 11150 (contains E127), liquorice powder 07123937, peppermint flavour extra

6.2.    Incompatibilities

None stated.

6.3.    Shelf Life

Three years unopened.

6.4.    Special Precautions for Storage

None.

6.5.    Nature and Contents of Container

250 micron rigid uPVC 25^ aluminium foil blisters in cardboard cartons in packs of 18 or 36 tablets

6.6.    Instruction for Use/Handling

None stated.

MARKETING AUTHORISATION HOLDER

Thornton & Ross Limited

Linthwaite

Huddersfield

West Yorkshire

HD75QH

United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 00240/0092

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

22/08/2013

10    DATE OF REVISION OF THE TEXT

05/05/2016