SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Galcodine Linctus

Care Codeine 15mg/5ml Oral Solution Sugar Free

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Codeine phosphate 15mg (Per 5ml Dose)

For excipients, see 6.1

3.    PHARMACEUTICAL FORM

Oral Liquid

A viscous orange coloured liquid.

4.1 Therapeutic Indications

Codeine is indicated in adults for the relief of an unproductive dry cough.

4.2    Posology and method of administration

For oral administration.

Adult:

One 5ml spoonful four times daily.

Elderly:

Should be used with caution; a reduced dose can be recommended by a doctor. Paediatric population

Codeine should not be used for the treatment of children under the age of 18 years.

4.3    Contraindications

Suspected opiate abuse, known hypersensitivity to codeine or any of the other ingredients.

Liver or respiratory failure or patients at risk of paralytic ileus.

In patients with raised intracranial pressure or head injury.

In patients for whom it is known they are CYP2D6 ultra-rapid metabolisers. During an acute asthma attack.

Children under 18 years of age.

In women during breastfeeding (see section 4.6)

4.4 Special warnings and precautions for use

This medicine should be used with caution in patients with renal and hepatic impairment (but avoid if severe), patients suffering from asthma or other respiratory disorders, or patients with a history of asthma, hypotension, shock, myasthenia gravis, cardiac arrhythmias, acute abdomen, gallstones, prostatic hypertrophy, urethral stenosis, obstructive or inflammatory bowel disorders, diseases of the biliary tract, and convulsive disorders.

Administration of pethidine and possibly other opioid analgesics to patients taking a monoamine oxidase inhibitor (MAOI) has been associated with very severe and sometimes fatal reactions. If the use of codeine is considered essential then great care should be taken in patients taking MAOIs or within 14 days of stopping MAOIs. (See section 4.5).

Use with caution in the elderly as codeine may contribute to faecal impaction, producing incontinence, spurious diarrhoea, abdominal pain and rarely colonic obstruction. Prolonged use could aggravate irritable bowel syndrome.

A reduced dose is recommended in elderly or debilitated patients, in hepatic and renal impairment (but avoid if severe), in hypothyroidism, and in adrenocortical insufficiency. Repeated use of opioid analgesics is associated with the development of psychological and physical dependence; although this is rarely a problem with therapeutic use, caution is advised if prescribing for patients with a history of drug dependence or in acute alcoholism.

This medicine and other cough suppressants may cause sputum retention and this may be harmful in patients with chronic bronchitis and bronchiectasis.

If symptoms persist consult your doctor.

CYP2D6 metabolism

Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite. If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effects will not be obtained. Estimates indicate that up to 7% of the Caucasian population may have this deficiency. However, if the patient is an extensive or ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at commonly prescribed doses. These patients convert codeine into morphine rapidly resulting in higher than expected serum morphine levels. General symptoms of opioid toxicity include

nausea, vomiting, constipation, lack of appetite and somnolence. In severe cases this may include symptoms of circulatory and respiratory depression.

Estimates of prevalence of ultra-rapid metabolisers in different populations are summarized below:

Population	Prevalence %
Afri can/Ethi opi an	29%
African/Am erican	3.4% to 6.5%
Asian	1.2% to 2%
Caucasian	3.6% to 6.5%
Greek	6.0%
Hungarian	1.9%
Northern European	1%-2%

Precautions/warnings to be declared on labels:

Do not exceed the stated dose.

Keep out of the sight and reach of children.

It contains sodium hydroxybenzoates and sunset yellow dye which may cause allergic reactions (possibly delayed).

This medicine contains small amounts of ethanol (alcohol), less than 100mg per 10ml dose.

4.5 Interaction with other medicinal products and other forms of interaction

Antimuscarinics: codeine phosphate may increase the risk of antimuscarinic side effects such as dry mouth, urine retention and constipation (but this does not generally apply to antimuscarinics taken by inhalation).

Metabolism of codeine is accelerated by rifampicin leading to reduced effect.

As an opioid analgesic, codeine phosphate may potentiate the effects of tranquillisers such as barbiturates, general anaesthetics, anxiolytics and hypnotics, sedatives and alcohol.

Possible CNS excitation or depression (hypertension or hypotension) can occur when opioid analgesics are given with antidepressants such as moclobemide (a reversible MAO-A inhibitor). The sedative effects of codeine 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.

Monoamine oxidase inhibitors: MAOIs taken with pethidine have been associated with severe CNS excitation or depression (including hypertension or hypotension). Although this has not been documented with codeine, it is possible that a similar interaction may occur and therefore the use of codeine should be avoided while the patient is taking MAOIs and for 2 weeks after MAOI discontinuation, including MAO-B inhibitor selegiline. This may also apply to the antibacterial linezolid, which is a reversible, non-selective MAO inhibitor.

Anti-emetics: The reduction in intestinal motility caused by codeine may delay the absorption or antagonise the gastrointestinal effects of other drugs e.g. metoclopramide and domperidone.

Metabolism of opioid analgesics is inhibited by cimetidine leading to increased plasma concentration.

Anti-arrhythmics: May delay the gastro-intestinal absorption of mexiletine or quinidine (which may also reduce the efficacy of codeine).

The opioid analgesics enhance effects of sodium oxybate, used to treat symptoms of narcolepsy and concomitant use should be avoided.

4.6    Fertility, pregnancy and lactation

The product should be avoided during pregnancy unless considered necessary by the physician and should be avoided during the first trimester. Opioid administration in the third trimester may cause respiratory depression in the newborn, withdrawal effects in neonates of dependent mothers, gastric stasis and risk of inhalation pneumonia in the mother during labour.

Codeine should not be used-during breastfeeding (see section 4.3). At normal therapeutic doses codeine and its active metabolite may be present in breast milk at very low doses and is unlikely to adversely affect the breast fed infant. However, if the patient is a ultra-rapid metaboliser of codeine, higher levels of the active metabolite, morphine, may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in the infant, which may be fatal. The infant itself may be a CYP2D6 ultra-rapid metaboliser. In either case on very rare occasions this may result in symptoms of opioid toxicity in the infant. (See also section 4.4).

If symptoms of opioid toxicity develop in either the mother or the infant, then all codeine containing medicines should be stopped and alternative non-opioid analgesics prescribed. In severe cases consideration should be given to prescribing naloxone to reverse these effects.

4.7    Effects on ability to drive and use machines

Using the dose recommended, this medicine is not considered to be a hazard. Nevertheless, use of codeine at higher doses or in more sensitive individuals may cause sedation, dizziness and nausea. Patients should be advised not to drive or operate machinery if affected by dizziness or sedation.

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

The following undesirable effects have been reported following use of codeine phosphate or opioid analgesics and may arise following use of this medicine. The frequency of adverse effects cannot be estimated from available data. Psychiatric disorders: hallucinations, dysphoria, euphoria, mood changes, restlessness, confusion.

Nervous system disorders: dizziness, drowsiness, seizures, addiction, tolerance, dependence, headache, vertigo, malaise, sleep disturbances.

Eye disorders: miosis, visual disturbances.

Cardiac disorders: palpitations, bradychardia, tachycardia.

Vascular disorders: postural hypotension, hypothermia, facial flushing, oedema.

Respiratory, thoracic and mediastinal disorders: respiratory depression. Gastrointestinal disorders: nausea, vomiting, constipation, abdominal pain, anorexia, pancreatitis, dry mouth.

Hepatobiliary disorders: biliary spasm.

Skin and subcutaneous tissue disorders: rashes, urticaria, pruritis, sweating. Musculoskeletal and connective tissue disorders: muscle fasciculation or rigidity.

Renal and urinary disorders: difficulty with micturition, ureteric spasm or retention.

Reproductive system and breast disorders: decreased libido or potency. 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

The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

Symptoms

Central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been coingested, including alcohol, or the overdose is very large. The pupils may be pin-point in size; nausea and vomiting are common. Hypotension and tachycardia are possible but unlikely.

Management

This should include general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable. Consider activated charcoal if an adult presents within one hour of ingestion of more than 350 mg or if more than

2.5 mg/kg (adults and children) has been ingested.

Give naloxone if coma or respiratory depression is present. Naloxone is a competitive antagonist and has a short half-life so large and repeated doses may be required in a seriously poisoned patient. Observe for at least four hours after ingestion, or eight hours if a sustained release preparation has been taken.

5.1    Pharmacodynamic properties

RO5D A04 - Cough suppressants, excl. combinations with expectorants -opium alkaloids and derivatives

Galcodine contains codeine phosphate which is an opiate with analgesic, anti-diarrhoeal and cough suppressant activities.

Codeine is a centrally acting weak analgesic. Codeine exerts its effect through p opioid receptors, although codeine has low affinity for these receptors, and its analgesic effect is due to its conversion to morphine. Codeine, particularly in combination with other analgesics such as paracetamol, has been shown to be effective in acute nociceptive pain.

5.2    Pharmacokinetic properties

None stated.

5.3 Preclinical safety data

None stated

6.1 List of excipients

Citric acid Monohydrate (E330)

Sodium methyl parahydroxybenzoate (E219) Sodium ethyl parahydroxybenzoate (E215) Sodium propyl parahydroxybenzoate Ethanol (96%)

Sunset yellow dye (E110)

Saccharin sodium Carmellose sodium Levomenthol Condensed milk flavour Orange flavour Glycerol (E422)

Purified water

6.2 Incompatibilities

None stated.

6.3 Shelf life

Two years from the date of manufacture.

6.4    Special precautions for storage

Do not store above 25°C

6.5    Nature and contents of container

Amber HDPE 2 litre Winchester with a white tamper evident polyethylene cap.

200ml Amber glass bottle with a white 28mm child-resistant tamper evident cap with EPE/Saranex Liner.

6.6    Instructions for use/handling

None stated.

MARKETING AUTHORISATION HOLDER

Thornton & Ross Ltd. Linthwaite Huddersfield HD75QH United Kingdom

8.    MARKETING AUTHORISATION NUMBER

PL 00240/0099

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10^th March 2005

10    DATE OF REVISION OF THE TEXT

10/11/2014