NAME OF THE MEDICINAL PRODUCT

Galpharm Four In One Flu Relief

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 20ml dose contains:

Paracetamol 1000mg Phenylephrine Hydrochloride 12.18mg Guaifenesin 200mg Cetylpyridinium Chloride 3.0mg

For excipients, see 6.1.

3.    PHARMACEUTICAL FORM

Oral Solution

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the short term symptomatic relief of the symptoms of colds and influenza, including aches and pains, headache, nasal congestion, tickly sore throat and chesty coughs.

4.2    Posology and method of administration

For oral administration.

Adults and children 16 years and over: One 20ml dose (four 5ml spoonfuls) up to 4 times a day as required.

The dose must not be repeated more frequently than every four hours.

Maximum of 4 doses in any 24 hours.

Not recommended for children under 16 years of age.

4.3 Contraindications

Patients with known hypersensitivity to paracetamol, phenylephrine hydrochloride, guaifenesin or cetylpyridinium chloride or any of the other ingredients.

Contra-indicated during pregnancy.

4.4 Special warnings and precautions for use

This product is not suitable for long term use.

Paracetamol should be used with care in patients with severe renal or hepatic impairment. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

Do not take with other cold or decongestant medicines or any other paracetamol-containing products.

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.

Phenylephrine should be used with care in patients with hyperthyroidism, cardiovascular disease, diabetes mellitus, closed angle glaucoma, prostatic enlargement and hypertension.

Do not exceed the stated dose.

If symptoms persist consult your doctor.

Each dose contains Liquid Maltitol and approximately 3g of Sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine. This product may have a mild laxative effect.

This product contains 19% (v/v) ethanol. Each dose contains up to 3g of ethanol (alcohol) equivalent to 32ml of wine or 76ml of beer. Harmful for those suffering from alcoholism. To be taken into account in pregnant or breast feeding women, children and high-risk groups such as patients with liver disease, epilepsy. The amount of alcohol in this medicinal product may alter the effects of other medicines. The amount of alcohol in this medicinal product may impair your ability to drive or use machines.

4.5 Interaction with other medicinal products and other forms of interaction

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone; and absorption reduced by colestyramine. The anti-coagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect. Alcohol may potentiate the hepatotoxicity of paracetamol.

Phenylephrine may reduce the efficacy of beta-blocking drugs and antihypertensive drugs; the product is contra-indicated in such circumstances.

With phenylephrine there is a possibility that an increased risk of arrhythmias may occur in patients receiving cardiac glycosides or tri-cyclic anti-depressants.

Phenylephrine interacts with monoamine oxidase inhibitors; it should not therefore, be taken by patients receiving monoamine oxidase inhibitors or within 14 days of stopping such medication.

Guaifenesin may interfere with diagnostic measurements of urinary 5-hydroxyindoleacetic acid or vanillylmandelic acid.

4.6 Pregnancy and lactation

Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage, but patients should follow the advice of their doctor regarding its use. Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding.

Phenylephrine should not be taken during pregnancy as it has been reported to cause foetal hypoxia. Excretion in breast milk is reported to be minimal.

Guaifenesin is considered safe for use in lactating women and at normal doses in pregnant women.

4.7 Effects on ability to drive and use machines

None.

4.8 Undesirable effects

Undesirable effects with paracetamol are rare, however, hypersensitivity including skin rashes may occur. There have been a few reports of blood dyscrasias including thrombocytopenia and agranulocytosis after regular or excessive ingestion of paracetamol, and of acute pancreatitis after ingestion of above normal dosage.

Undesirable effects are rare with normal doses of phenylephrine, however it can cause the adverse effects typical of sympathomimetics including: hypertension, palpitations (tachycardia), headache, dizziness, vomiting, diarrhoea and insomnia.

Guaifenesin has occasionally been reported to cause gastrointestinal discomfort.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisations 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

Liver damage is possible in adults who have taken 10g or more of paracetamol.

Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).

Risk factors

If the patient

a)    Is on long term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.

OR

b)    Regularly consumes ethanol in excess of recommended amounts.

OR

c)    Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

Symptoms

Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.

Management

Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines, see BNF overdose section.

Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with Nacetylcysteine may be used up to 24 hours after ingestion of paracetamol, however,

the maximum protective effect is obtained up to 8 hours post-ingestion. The

effectiveness of the antidote declines sharply after this time. If required the patient

should be given intravenous N-acetylcysteine, in line with the established dosage

schedule. If vomiting is not a problem, oral methionine may be a suitable alternative

for remote areas, outside hospital. Management of patients who present with serious

hepatic dysfunction beyond 24h from ingestion should be discussed with the NPIS or

a liver unit.

The principal features of phenylephrine overdosage are a rise in blood pressure and associated reflex bradycardia. A severe hypertensive response can be countered by administration of an alpha-antagonist and any reflex bradycardia by atropine (but preferably only after the pressure has been controlled by alpha-adrenergic blockade). Very large doses of guaifenesin may cause nausea and vomiting.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Paracetamol has analgesic and antipyretic actions probably due to the inhibition of prostaglandin biosynthesis. It is effective against pain of mild to moderate severity, but is less successful against chronic pain.

Phenylephrine hydrochloride is a sympathomimetic agent with mainly direct effect on adrenergic receptors. It has predominantly alpha-adrenergic activity and is without

significant stimulating effects on the central nervous system at usual doses. It may be given orally to relieve nasal congestion.

Guaifenesin is an expectorant which reduces the viscosity of tenacious sputum.

Cetylpyridinium Chloride is a cationic disinfectant with properties and uses similar to other cationic surfactants. These surfactants have bactericidal activity against Grampositive and, at higher concentration against some Gram-negative organisms. Cetylpyridinium Chloride may be used in a variety of preparations for the local treatment of minor infections.

5.2 Pharmacokinetic properties

Paracetamol is readily absorbed from the gastrointestinal tract and peak plasma concentrations usually occur 30 minutes to 2 hours after ingestion. Paracetamol is metabolised in the liver and largely excreted in the urine as sulphate and glucuronide conjugates. Less than 5% is excreted unchanged. The elimination half-life varies from about 1 to 4 hours.

Phenylephrine hydrochloride is irregularly absorbed after oral administration and undergoes first-pass metabolism by monoamine oxidase in the gut and liver, resulting in reduced bioavailability. Peak plasma concentrations are achieved in 1 to 2 hours. It is excreted in the urine mainly as the sulphate conjugate, with less than 20% as unchanged drug.

Guaifenesin is rapidly absorbed from the gastrointestinal tract. It is rapidly metabolised by oxidation to ^-(2 methoxy-phenoxy) lactic acid, which is excreted in the urine.

Cetylpyridinium Chloride has only a local effect.

5.3 Preclinical safety data

There are no preclinical safety data on these active ingredients in the literature of relevance to the prescriber or to the recommended dosage and use of the product which are additional to that already included in other sections of the SPC.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sorbitol Solution, Ethanol, Propylene Glycol, Glycerol, Saccharin Sodium, Sodium Cyclamate, Acesulphame Potassium, Sodium Citrate, Anhydrous Citric Acid, Xanthan Gum, Levomenthol, Eucalyptus Oil, Quinoline Yellow (E104), Purified Water.

6.2 Incompatibilities

None.

6.3 Shelf life

2 Years.

6.4    Special precautions for storage

Do not store above 25°C.

Keep the container in the outer carton.

Keep the container tightly closed.

6.5    Nature and contents of container

Amber type III glass bottle and polypropylene child resistant closure with aluminium foil film liner containing 160ml.

Graduated polypropylene measuring cup.

6.6 Special precautions for disposal

Not applicable

7. MARKETING AUTHORISATION HOLDER

Galpharm Healthcare Limited

Wrafton

Braunton

Devon

EX33 2DL

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 16028/0077

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

18/03/2009

DATE OF REVISION OF THE TEXT

17/02/2016