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Cofsed Linctus

SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Cofsed Linctus

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Active Ingredients:

Per 5ml

Pholcodine    5.0mg

Ephedrine Hydrochloride    8.0mg

Chlorphenamine Maleate    2.0mg

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Liquid medicine

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Indicated for the symptomatic relief of dry or painful cough. It also relieves nasal congestion in colds and hay fever.

4.2    Posology and method of administration

For oral administration

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

Not more than 3 doses should be given in any 24 hours

4.3    Contraindications

Patients with a known hypersensitivity to ephedrine hydrochloride, chlorphenamine maleate, pholcodine or any of the excipients.

In patients currently taking or within 2 weeks of stopping monoamine oxidase inhibitors (MAOIs, see section 4.5). This is relevant for all three active substances.

Epilepsy, prostatic hypertrophy, urinary retention and pyloroduodenal obstruction because of the antihistamine content.

Hepatic disease because of the antihistamine and pholcodine content.

Angle-closure glaucoma and/or raised intraocular pressure because of the antihistamine and ephedrine content.

Chronic bronchitis, chronic obstructive pulmonary disease, bronchiectasis, severe renal impairment and patients in or at risk of developing ventilatory failure because of the pholcodine content.

Hyperthyroidism, phaeochromocytoma, cardiovascular disease including hypertension, in patients receiving anti-hypertensive therapy (e.g. beta-blockers, see section 4.5), or concomitant use of other sympathomimetic decongestants because of the ephedrine content.

Children under 12 years of age.

4.4 Special warnings and precautions for use

Asthmatics and patients with chronic, persistent or productive cough should consult a medical practitioner before using the product.

Use with caution in patients with diabetes mellitus as possible higher incidence of atherosclerotic disease may increase risk, and ephedrine as a sympathomimetic may affect blood glucose levels.

This product contains 7.8g sucrose and 0.17g invert sugar (a mixture of fructose and glucose) per 10ml dose. This should be taken into account in patients with diabetes.

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

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

It contains parahydroxybenzoates which may cause allergic reactions (possibly delayed).

Caution should be exercised in patients taking other sympathomimetic agents, such as amphetamine-like psychostimulants and appetite suppressants. The effects of a single dose of Cofsed Linctus on the blood pressure of these patients should be observed before recommending repeated or unsupervised treatment.

Caution is required in renal impairment and in the elderly.

If any of the following occur, Cofsed Linctus should be stopped

•    Hallucinations

•    Restlessness

•    Sleep disturbances.

Labels state:

Do not exceed the stated dose.

Keep out of the reach and sight of children.

Do not give to children under 12 years.

Do not take with other cough, cold or decongestant medicines.

If symptoms persist consult your doctor.

Consult your doctor before use if you have asthma, a chronic or persistent cough or where a cough is accompanied by excessive secretions.

May cause drowsiness. If affected do not drive or operate machinery. Avoid alcoholic drink.

4.5 Interaction with other medicinal products and other forms of interaction

Chlorphenamine maleate, All interact with monoamine oxidase inhibitors Ephedrine hydrochloride (MAOIs); therefore Cofsed Linctus should not be & Pholcodine    used in patients taking MAOIs or within 14 days of

stopping treatment as there is a risk of serotonin syndrome.

Chlorphenamine maleate Both may enhance the sedative effects of CNS & Pholcodine    depressants including barbiturates, hypnotics, opioid

analgesics, anxiolytic sedatives, antipsychotics and alcohol.

Chlorphenamine maleate Antimuscarinic and sedative effects increased when & Ephedrine    chlorphenamine maleate is given with tricyclic

hydrochloride    antidepressants (and possibly with related

tricyclics).

Tricyclic antidepressants may reduce the effect of sympathomimetics such as ephedrine hydrochloride and increase the risk of arrhythmias.

Chlorphenamine maleate Antiretroviral lopinavir: plasma concentration of

chlorphenamine may be increased.

Antiepileptic phenytoin: plasma concentration of phenytoin may be increased.

Antimuscarinics such as atropine the antimuscarinic effects may be increased.

Histamine the effects of exogenously administered histamine may in theory be antagonised; as an antihistamine chlorphenamine maleate should not be taken for several days before skin tests of allergen extracts.

Betahistine: effects of betahistine may be antagonised.

Ephedrine hydrochloride


Pholcodine


Antihypertensives: may diminish the effects of ephedrine.

Antipsychotics: may antagonise the hypertensive effects of sympathomimetics.

Caffeine: may enhance the side effects of ephedrine.

Theophylline: concomitant use with ephedrine may potentiate the adverse effects.

Anti-arrhythmics - including beta-blockers and quinidine: ephedrine may increase the risk of arrhythmias, and block the hypotensive effects of beta-blockers (see Section 4.3).

Adrenergic neurone blockers such as guanethidine: ephedrine may block the hypotensive effects.

Cardiac glycosides such as digoxin: ephedrine may increase the risk of arrhythmias.

Ergotamine and methysergide: ephedrine may increase the risk of ergotism.

Oxytocin: there is increased risk of hypertension when vasoconstrictor sympathomimetics are given with oxytocin.

Doxapram: there is increased risk of hypertension when sympathomimetics are given with doxapram. Dexamethasone: ephedrine accelerates the metabolism of dexamethasone.

MAO-B inhibitors (such as rasagiline and selegiline): risk of hypertension.

Moclobemide: risk of hypertensive crisis when given with sympathomimetics.

Appetite suppressants and amphetamine-like psychostimulants: risk of hypertension. Antiparkinsonian drugs: Risk of additive cardiovascular toxicity when some sympathomimetics given with drugs such as levodopa and bromocriptine

Interaction with neuromuscular blocking agents (anaphylaxis) has been reported.

The reduction of blood pressure caused by antihypertensives may accentuate the hypotensive effects of pholcodine. Diuretics may have the same effect.

The antibacterial agent furazolidone has a metabolite which is a monoamine oxidase inhibitor and is known to cause a progressive inhibition of monoamine oxidase. Although there are no reports of hypertensive crisis having occurred, the cautions advised for MAOIs regarding use with other drugs are applicable and furazolidone should not be administered concurrently with Cofsed Linctus.

4.6 Fertility, pregnancy and lactation

Not to be used during pregnancy or lactation without prior consultation with a medical practitioner. Use of the product in pregnancy and lactation should be avoided unless the benefit outweighs the risk.

4.7 Effects on ability to drive and use machines

May cause drowsiness or other central nervous system disorders which may have an effect on the ability to drive or operate machinery. This may be potentiated by alcohol or other central sedatives. If affected, patients should not drive or operate machinery.

4.8 Undesirable effects

The following side effects may be associated with the use of Cofsed Linctus (frequencies not known: cannot be estimated from available data)

Blood and lymphatic system disorders

Chlorphenamine maleate: blood disorders

Immune system disorders

Chlorphenamine maleate: anaphylactic reactions, hypersensitivity, angioedema Ephedrine hydrochloride: rash

Pholcodine: rash, hypersensitivity reactions, anaphylaxis

Metabolism and nutrition disorders

Chlorphenamine maleate: anorexia

Ephedrine hydrochloride: anorexia, hyperglycaemia

Psychiatric disorders

Ephedrine hydrochloride: anxiety, insomnia, restlessness, excitability, fear, confusion, irritability, psychotic states

Pholcodine: excitation, confusion

Nervous system disorders

Chlorphenamine maleate: headache, drowsiness, dizziness, extrapyramidal effects, sweating

Ephedrine hydrochloride: headache, sweating, piloerection, increased salivation Pholcodine: drowsiness, dizziness Eye disorders

Chlorphenamine maleate: blurred vision, angle-closure glaucoma Ephedrine hydrochloride: mydriasis

Ear and labyrinth disorders

Chlorphenamine maleate: tinnitus

Cardiac disorders

Chlorphenamine maleate: arrhythmia, palpitations Ephedrine hydrochloride: tachycardia, palpitations, arrhythmias

Vascular disorders

Chlorphenamine maleate: hypotension

Ephedrine hydrochloride: hypertension, cold extremities

Respiratory, thoracic and Mediastinal disorders

Chlorphenamine maleate: thickening of bronchial secretions

Ephedrine hydrochloride: dyspnoea

Gastrointestinal disorders

Chlorphenamine maleate: dry mouth, nausea, vomiting, abdominal pain, diarrhoea, constipation, altered taste and smell

Ephedrine hydrochloride: dry mouth, nausea, vomiting

Pholcodine: nausea, vomiting, constipation Hepatobiliary disorders

Chlorphenamine maleate: liver dysfunction

Skin and subcutaneous tissue disorders

Chlorphenamine maleate: exfoliative dermatitis, rashes, photosensitivity Musculoskeletal and connective tissue disorders

Chlorphenamine maleate: tremor, convulsions, paraesthesias, facial dyskinesias Ephedrine hydrochloride: muscle tremor, weakness

Renal and Urinary disorders:

Chlorphenamine maleate: urinary retention

Ephedrine hydrochloride: difficulty in micturition, urinary retention.

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:

Overdosage with chlorphenamine maleate, a sedating antihistamine, is associated with antimuscarinic, extrapyramidal, and CNS effects. When CNS stimulation predominates over CNS depression, which is more likely in

children or the elderly, it causes ataxia, excitement, tremors, psychoses, hallucinations, and convulsions; hyperpyrexia may also occur. Deepening coma and cardiorespiratory collapse may follow. In adults, CNS depression is more common with drowsiness, coma, and convulsions, progressing to respiratory failure and cardiovascular collapse.

Ephedrine hydrochloride is associated with paranoid psychosis, delusions, and hallucinations.

Pholcodine is thought to be of low toxicity, but the effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs. The symptoms include nausea, drowsiness, restlessness, excitement, ataxia and respiratory depression.

Management:

In the event of gross overdosage with Cofsed Linctus, the stomach should be emptied by aspiration and lavage; 0.02% aqueous solution of potassium permanganate may be employed. A saline purgative such as sodium sulphate, 30g in 250m1 of water, should be given to aid peristalsis. If consciousness is impaired and respiration depressed nalorphine hydrobromide is given intravenously. The circulation should be maintained with infusions of plasma or suitable electrolyte solutions. Assisted respiration may be necessary. For pholcodine, naloxone has been used successfully to reverse central or peripheral opioid effects in children (0.01mg/kg body weight). Other treatment option is activated charcoal (1g/kg body weight) if more than 4mg/kg has been ingested within 1 hour, provided the airway can be protected.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pholcodine has a specific depressant effect on the cough centre in the medulla and a powerful antitussive action. It does not demonstrate the properties of a narcotic analgesic and therefore in use is free from the important associated side effects - respiratory depression and gastro-intestinal effects such as constipation, anorexia or vomiting.

Ephedrine in therapeutic doses produces peripheral vasoconstriction on the blood vessels of the nasal and sinus mucosa. It reduces the swelling associated with inflammation of the mucous membrane lining the nasal passage, clearing the airway and minimising the contribution of the post-nasal drip to the irritation and congestion in the lower respiratory tract.

Chlorphenamine maleate is one of the most potent antihistamines. It is useful in the control of symptoms which are allergic in origin. It has a drying action and renders respiratory tract secretions more viscid. Chlorphenamine also displays a sedative action but much less than diphenhydramine.

5.2 Pharmacokinetic properties

None stated

5.3 Preclinical safety data

None stated

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Ethanol 96%

Aniseed Flavour (545008E)

Glycerol Invert Syrup Menthol

Hydroxybenzoates Quinoline Yellow (E104)

Syrup

Purified water

6.2    Incompatibilities

None stated

6.3    Shelf life

24 months from the date of manufacture

6.4    Special precautions for storage

Protect from light

6.5    Nature and contents of container

Amber glass sirop bottles with 28mm tamper evident child resistant closure with a low density polyethylene plug containing a clear viscous yellow liquid. Pack size: 100ml

6.6    Special precautions for disposal

None stated

7    MARKETING AUTHORISATION HOLDER

Thornton & Ross Ltd Linthwaite Huddersfield HD75QH

United Kingdom

8    MARKETING AUTHORISATION NUMBER

PL 00240/0097

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

30/08/2002

10 DATE OF REVISION OF THE TEXT

09/04/2015