SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Otrivine Mu-Cron

Boots Decongestant with Pain Relief Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Active ingredient    mg/tab

Paracetamol    500.0

Pseudoephedrine hydrochloride    60.0

3    PHARMACEUTICAL FORM

Tablets

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the symptomatic relief of the symptoms of colds and influenza including feverishness, aches and pains, headache, nasal and sinus congestion (blocked nose and sinuses).

For oral administration.

4.2 Posology and method of administration

Adults and children over 12 years

One tablet to be taken three or four times a day, up to a maximum daily dose of 4 tablets (240mg pseudoephedrine and 2g paracetamol).

Elderly

Although no specific studies have been carried out in this age group, there is no need for dosage reduction in the elderly.

Children 6 to 12 years

Half a tablet to be taken four times a day, up to a maximum daily dose of 2 tablets (120mg pseudoephedrine and 1g paracetamol).

This medicine is contraindicated in children under 6 years of age (see section 4.3).

Children of 6-12 years of age: not to be used for more than 5 days without the advice of a doctor. Parents or carers should seek medical attention if the child's condition deteriorates during treatment.

Administration in those with hepatic disorders

Care should be taken in administering this product to patients with severe hepatic impairment.

Administration in those with renal disorders

Care should be taken in administering this product to patients with moderate to severe renal impairment.

Warning: Do not exceed the stated dose.

Keep all medicines out of the sight and reach of children.

4.3 Contraindications

Hypersensitivity to the active substances or any of the excipients.

Severe renal impairment

Cardiovascular disease including hypertension and peripheral vascular disease.

Diabetes mellitus

Phaeochromocytoma

Hyperthyroidism

Closed angle glaucoma or where intraocular pressure is raised Severe liver disease

Concomitant use of other sympathomimetic decongestants Monoamine oxidase inhibitors (MAOIs, or within 14 days of stopping treatment, see section 4.5)

Beta-blockers - (see section 4.5)

Not to be used in children under the age of 6 years

4.4 Special warnings and precautions for use

Caution in moderate to severe renal impairment.

Should be taken with caution by patients with hepatic impairment, prostatic enlargement and alcohol dependence.

If any of the following occur, the product should be stopped:

Hallucinations Restlessness Sleep disturbances

Not to be given to children under 6 years.

Do not take for longer than five days, unless your doctor agrees.

If symptoms persist, consult your doctor.

Do not take with any other decongestant-containing products.

Do not take with any other paracetamol-containing products.

Label

Immediate medical advice should be sought in the event of an overdose, even if you feel well.

Leaflet or combination label/leaflet

Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of delayed, serious liver damage.

4.5 Interaction with other medicinal products and other forms of interaction Pseudoephedrine

MAOIs and/or RIMAs: should not be given to patients treated with MAOIs or within 14 days of stopping treatment: increased risk of hypertensive crisis. Moclobemide: risk of hypertensive crisis.

Antihypertensives (including adrenergic neurone blockers & beta-blockers): this product may block the hypotensive effects.

Cardiac glycosides: increased risk of dysrhythmias.

Ergot alkaloids (ergotamine & methysergide): increased risk of ergotism. Appetite suppressants and amphetamine-like psychostimulants: risk of hypertension.

Oxytocin - risk of hypertension.

Enhances effects of anticholinergic drugs (such as TCAs).

Concomitant use of this medicine with tricyclic antidepressants and sympathomimetic agents such as decongestants may cause a rise in blood pressure.

Paracetamol

Drugs which induce hepatic microsomal enzymes, such as anticonvulsants and oral contraceptive steroids, may increase the rate at which paracetamol is metabolised, leading to a reduced plasma concentration of the drug.

Alcohol may reduce the capacity of the liver to metabolise paracetamol.

Chronic use of paracetamol enhances the effects of anticoagulants.

Concurrent use of paracetamol with NSAIDs may increase the risk of adverse renal effects. The prolonged combined use of these compounds may increase the risk of renal damage.

4.6 Pregnancy and lactation

The safety of this medicine during pregnancy and lactation has not been established but in view of a possible association of foetal abnormalities with first trimester exposure to pseudoephedrine, the use of the product during pregnancy should be avoided. The amounts of paracetamol and pseudoephedrine secreted

into breast milk are considered to be too small to be harmful.

4.7 Effects on ability to drive and use machines

No adverse effects known.

4.8 Undesirable effects Pseudoephedrine

Cardiovascular disorders: Tachycardia, palpitations, other cardiac dysrhythmias.

Gastrointestinal disorders: Nausea and/or vomiting.

General disorders and administration site conditions: Irritability.

Immune system disorders: Hypersensitivity reactions, including crosssensitivity that may occur with other sympathomimetics.

Nervous system disorders: Headache, tremor, anxiety, restlessness, excitability, insomnia, hallucinations (particularly in children) and paranoid delusions.

Psychiatric disorders: Sleep disturbance.

Renal and urinary disorders: Urinary retention.

Skin and subcutaneous tissue disorders: Skin reactions including rash.

Vascular disorders: Hypertension.

Paracetamol

Very rare cases of serious skin reactions have been reported.

Blood and lymphatic system disorders: There have rarely been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

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

Immediate symptoms of overdosage in the first 24 hours include pallor, nausea, vomiting, anorexia, abdominal pain, irritability, restlessness, palpitations, hypertension, difficulty in micturition, thirst and convulsions.

Liver damage may become apparent 12 to 48 hours after ingestion. Though

hepatic enzymes may become elevated and prothrombin time prolonged within 10-12 hours of paracetamol overdosage, clinical symptoms may not be apparent for 1 to 6 days following ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatits have been reported.

In paracetamol overdosage with hepatic damage, paracetamol half life is often prolonged from around 2 hours in normal adults to 4 hours or longer. Liver damage and nephrotoxic effects have been reported after the daily ingestion of excessive amounts of paracetamol.

Liver damage is likely in adults who have taken 10g or more of paracetamol. It is considered that excess quantities of toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.

Immediate treatment is essential in the management of overdosage. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention and any patient who has ingested around 7.5g or more of paracetamol in the preceding 4 hours should undergo gastric lavage and activated charcoal administered to reduce paracetamol absorption As peak plasma concentrations may be delayed by up to 4 hours following overdose, to accurately assess the risk of hepatotoxicity, plasma paracetamol levels should be measured at least 4 hours post-ingestion.

Generally treatment is required if the blood-paracetamol concentration is higher than a line drawn on semi-log/linear paper joining the points 200mg per litre (1.32 mmol/litre) at 4 hours and 30 mg per litre (0.2mmol/litre) at 15 hours following ingestion. Administration of oral methionine or intravenous N-acetylcysteine, which may have a beneficial effect up to at least 48 hours after overdose, may be required. It has been proposed that the threshold for treatment with Nacetylcysteine

should be reduced by 30-50% in patients taking drugs which induce hepatic enzymes, who abuse alcohol long-term or who are chronically malnourished. These patients may be more susceptible to toxic effects of paracetamol.

Symptomatic and supportive measures should be undertaken, particularly with regard to the cardiovascular and respiratory systems. Convulsions should be controlled with intravenous diazepam. Chlorpromazine may be used to control marked excitement and hallucinations. Severe hypertension may need to be treated with an alpha-adrenoreceptor blocking drug, such as phentolamine. A beta-blocker may be required to control cardiac arrhythmias.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Paracetamol is a peripherally acting analgesic with antipyretic activity. Pseudoephedrine is a sympathomimetic agent with direct and indirect effects on adrenergic receptors. It has alpha and beta adrenergic activity and some stimulant effect on the central nervous system. The sympathomimetic effect of pseudoephedrine produces vasoconstriction which in turn relieves nasal congestion.

5.2 Pharmacokinetic properties

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion. Paracetamol is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates, with about 10% as glutathione conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 14 hours. Plasma protein binding is negligible at usual therapeutic concentrations, although this is dose-dependent.

The rate and extent of paracetamol absorption is normal in the elderly but plasma half life is longer and paracetamol clearance lower than in young adults.

In renal impairment though the mean plasma half-life of paracetamol is similar in normal and renally impaired subjects at 2-8 hours, from 8-24 hours paracetamol is eliminated less rapidly. An increase in the interval between doses of paracetamol has been recommended for adults with chronic renal failure.

With severe hepatic impairment the mean plasma half life of paracetamol is significantly prolonged (by approximately 75%). The clinical significance of this is however unclear, as no evidence exists of drug accumulation or hepatotoxicity in patients with liver disease.

Pseudoephedrine is readily and completely absorbed from the gastrointestinal tract. It is resistant to metabolism by monoamine oxidase and is largely excreted in the urine unchanged. It has an elimination half-life of 5 to 8 hours but its urinary elimination and hence half-life is pH dependent. Pseudoephedrine is rapidly distributed throughout the body, its volume of distribution being 2 to 3L/Kg bodyweight.

5.3 Preclinical safety data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Pregelatinised maize starch Microcrystalline cellulose Sodium lauryl sulphate Magnesium stearate Quinoline yellow (E104) Croscarmellose sodium.

6.2 Incompatibilities

None.

6.3 Shelf life

36 months.

6.4 Special precautions for storage

Do not store above 30 oC.

Store in the original package.

6.5 Nature and contents of container

A child-resistant push through pack of opaque 250 micron PVC/40gsm PVdC blisters, heat sealed to 35gsm Glassine paper/9 micron soft temper aluminium foil.

Pack sizes: 6, 12.

6.6 Special precautions for disposal

None.

7 MARKETING AUTHORISATION HOLDER

The Boots Company PLC or The Boots Company PLC - Trading as BCM 1 Thane Road West Nottingham NG2 3AA

8    MARKETING AUTHORISATION NUMBER(S)

PL 00014/0594

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

02/03/2009

DATE OF REVISION OF THE TEXT

24^th June 2015