PERRIGO PARACETAMOL/GUAIFENESIN/PHENYLEPHRINE HYDROCHLORIDE 500 MG / 200 MG / 10 MG POWDER FOR ORAL SOLN - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Perrigo Paracetamol/Gu­aifenesin/Phe­nylephrine Hydrochloride 500mg/200mg/10mg powder for oral solution

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Active Ingredient                             ­mg/Sachet

Paracetamol

Guaifenesin

Phenylephrine hydrochloride

Excipient(s) with known effect

Sucrose 2077 mg

Aspartame (E951) 12 mg

Sodium citrate (E331) 500 mg (contains 117.3 mg sodium)

Sodium cyclamate (E952) 100 mg (contains 11.5 mg sodium)

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Powder for oral solution.

Sachets containing the drug product, an off-white powder with a characteristic citrus/menthol o­dour.

The reconstituted solution is opalescent yellow with a characteristic citrus/menthol o­dour.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the short term symptomatic relief of colds and flu including aches and pains, headache, blocked nose and sore throat, chills and fever, and for relief from chesty coughs.

4.2 Posology and method of administration

Posology

Adults, the elderly and children aged 12 years and over:

One sachet every four hours as required. Do not exceed 4 sachets (4 doses) in any 24 hour period.

Do not give to children under 12 years old.

Seek medical advice if symptoms persist for more than 5 days.

Method of administration

For oral use after dissolving the contents of the sachet in a standard mug of hot, but not boiling water (250 ml). Allow to cool to a drinkable temperature. Drink all of the solution within 1^ hours.

4.3 Contraindications

Hypersensitivity to paracetamol, guaifenesin, phenylephrine hydrochloride or to any of the excipients listed in section 6.1

Pregnancy and breastfeeding

Hepatic or severe renal impairment

Heart disease and cardiovascular disorders, including severe haemolytic anaemia

Hypertension

Hyperthyroidism

Diabetes

Phaeochromocytoma

Those taking tricyclic antidepressants (see section 4.5)

Those currently taking other paracetamol-containing products (see section 4.4)

Closed angle glaucoma

Patients taking beta-blocking drugs

Contraindicated in patients currently receiving or within two weeks of stopping therapy with monoamine oxidase inhibitors

Use in patients with glaucoma or urinary retention

Use in patients who are currently receiving other sympathomimetic drugs (such as decongestants, appetite suppressants and amphetamine-like psychostimulants).

4.4 Special warnings and precautions for use

Care is advised in the administration of paracetamol to patients with severe renal or hepatic impairment. The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.

The physician or pharmacist should check that sympathomimetic-containing preparations are not simultaneously administered by several routes i.e. orally and topically (nasal, aural and eye preparations).

Sympathomimetic-containing products should be used with great care in patients suffering from angina.

Medical advice should be sought before taking this product in patients with these conditions:

Prostatic hypertrophy (patients may experience increased difficulty with micturition)

Occlusive vascular disease e.g. Raynaud’s phe­nomenon

Cardiovascular disease

Myasthenia gravis – an autoimmune disorder

Severe gastrointestinal diseases.

This medicine should only be recommended if all symptoms (pain and/or fever, nasal congestion and chesty cough) are present.

Patients suffering from chronic cough or asthma should consult a physician before taking this product.

Do not take with a cough suppressant.

Patients should stop using this product and consult a health care professional if cough lasts for more than 5 days or comes back, or is accompanied by a fever, rash or persistent headache.

Concomitant use with alcohol should be avoided.

This product should not be used by patients taking other sympathomimetics (such as decongestants, appetite suppressants and amphetamine-like psychostimulants).

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

Contains aspartame (E951) a source of phenylalanine. May be harmful for people with phenylketonuria.

This medicinal product contains 129 mg of sodium per dose. To be taken into consideration by patients on a controlled sodium diet.

Concomitant use of other paracetamol-containing products should be avoided. If symptoms persist consult your doctor.

Special label warnings

Contains paracetamol. Do not take with any other paracetamol-containing products.

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

Do not take with other flu, cold or decongestant products.

Special leaflet warnings

Contains paracetamol. 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

PARACETAMOL

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by colestyramine.

The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding, although occasional doses have no significant effect. The hepato-toxicity of paracetamol may be potentiated by excessive intake of alcohol.

Drugs which induce hepatic microsomal enzymes, such as barbiturates, monoamine oxidase inhibitors and tricyclic antidepressants, may increase the hepatotoxicity of paracetamol particularly after overdosage. Contraindicated in patients currently receiving or within two weeks of stopping therapy with monoamine oxidase inhibitors because of a risk of hypertensive crisis.

Regular use of paracetamol probably reduces metabolism of zidovudine (increased risk of neutropenia).

Salicylates/aspirin may prolong the elimination t1/2 of paracetamol.

Pharmacological interactions involving paracetamol with a number of other drugs have been reported. These are considered to be of unlikely clinical significance in acute use at the dosage regimen proposed.

Concomitant paracetamol and NSAID’s treatment increases the risk of renal dysfunction.

Paracetamol may affect phosphotungstate uric acid tests and blood sugar tests.

GUAIFENESIN

If urine is collected within 24 hours of a dose of this product, a metabolite may cause a colour interference with laboratory determinations of 5 hydroxyindo­leacetic acid (5-HIAA) and vanillymandelic acid (VMA).

Guaifenesin potentiates the action of sedatives and muscle relaxants.

PHENYLEPHRINE HYDROCHLORIDE

Phenylephrine should be used with caution in combination with the following drugs as interactions have been reported:

4.6 Fertility, Pregnancy and lactation

Pregnancy

PARACETAMOL

Epidemiological data on the oral administration of therapeutic doses of paracetamol indicate no adverse effects on pregnancy or on the health of the fetus or the newborn. Reproduction studies investigating oral administration did not indicate signs of malformation or fetotoxicity.

GUAIFENESIN

The safety of guaifenesin in pregnancy has not been established. The product should not be used during pregnancy.

PHENYLEPHRINE HYDROCHLORIDE

The safety of the phenylephrine use during pregnancy has not been established.

The product should not be used during pregnancy.

Breast-feeding

PARACETAMOL

Paracetamol is excreted into human milk but not in a clinically significant amount.

No undesirable effects on infants have been reported.

GUAIFENESIN

The safety of guaifenesin in lactation has not been established. The product should not be used during breast-feeding.

PHENYLEPHRINE HYDROCHLORIDE

The safety of the phenylephrine use during breast-feeding has not been established.

Phenylephrine can be excreted in human milk.

The product should not be used during breast-feeding.

Fertility

There is no information available to suggest that the active ingredients have an effect on human fertility.

4.7 Effects on ability to drive and use machines

Perrigo Paracetamol/Gu­aifenesin/Phe­nylephrine Hydrochloride 500mg/200mg/10mg powder for oral solution could have an effect on the ability to drive and use machines as it may cause dizziness.

4.8 Undesirable effects

The frequency of occurrence of undesirable effect is usually classified as follows:

Very common (> 1/10)

Common (> 1/100 to < 1/10)

Uncommon (> 1/1,000 to < 1/100)

Rare (> 1/10,000 to 1/1,000)

Very rare (< 1/10,000)

Not known (incidence cannot be assessed on the basis of the available data).

PARACETAMOL

Adverse events from historical clinical trial data are both infrequent and from limited patient exposure. Events reported from extensive post-marketing experience at therapeutic/la­belled dose and considered attributable are tabulated below by MedDRA System Organ Class. Due to limited clinical trial data, the frequency of these adverse events is unknown (cannot be estimated from available data), but postmarketing experience indicates that adverse reactions to paracetamol are rare (>1/10,000 to <1/1,000) and serious reactions are very rare (<1/10,000).

There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.

Very rare cases of serious skin reactions have been reported.

GUAIFENESIN

The frequency of these events is unknown but considered likely to be rare

PHENYLEPHRINE HYDROCHLORIDE

The following adverse events have been observed in clinical trials with phenylephrine and may therefore represent the most commonly occurring adverse events though actual frequencies are not available.

Adverse reactions identified during post-marketing use are listed below. The frequency of these reactions is unknown but likely to be rare (>1/10,000 to <1/1,000).

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

PARACETAMOL

Liver damage is possible in adults who have taken 10 g or more of paracetamol. Ingestion of 5 g 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 and signs

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 accordance with established treatment guidelines, see British National Formulary (BNF) overdose section.

Treatment with activated charcoal should be considered if the overdose has been taken within one hour. Plasma paracetamol concentration should be measured at four hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine, may be used up to 24 hours after ingestion of paracetamol, however, the maximum protective effect is obtained up to eight 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 24 hours from ingestion should be discussed with the National Poisons Information Service (NPIS) or a liver unit.

GUAIFENESIN

Symptoms and signs

Very large doses of guaifenesin can cause nausea and vomiting.

Treatment

Vomiting should be treated by fluid replacement and monitoring of electrolytes if indicated.

PHENYLEPHRINE HYDROCHLORIDE

Symptoms and signs

Phenylephrine overdosage is likely to result in effects similar to those listed under adverse reactions. Additional symptoms may include hypertension and possibly associated reflex bradycardia. In severe cases confusion, hallucinations, seizures and arrhythmias may occur, however the amount required to produce serious phenylephrine toxicity would be greater than required to cause paracetamol-related toxicity.

Treatment

Clinically appropriate treatment measures should be instituted and may include early gastric lavage and symptomatic and supportive measures. The hypertensive effects may be treated with an alpha-receptor blocking agent (such as phentolamine mesylate 6 – 10 mg) given intravenously, and the bradycardia treated with atropine, preferably only after blood pressure has been controlled.

5.1 Pharmacodynamic properties

Pharmacotherapeutic Group:           Para­cetamol combinations excluding

psycholeptics

ATC code:                      N­02BE51

Mechanism of action

PARACETAMOL

Analgesic:

The mechanism of analgesic action has not been fully determined. Paracetamol may act predominantly by inhibiting a prostaglandin synthesis in the central nervous system (CNS) and to a lesser extent through a peripheral action by blocking painimpulse generation. The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitise pain receptors to mechanical or chemical stimulation.

Antipyretic:

Paracetamol probably produces antipyresis by acting on the hypothalamic heatregulating centre to produce peripheral vasodilation resulting in increased blood flow through the skin, sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the hypothalamus.

GUAIFENESIN

Guaifenesin is a well known expectorant. Such expectorants are known to increase the volume of secretions in the respiratory tract and therefore to facilitate their removal by cilary action and coughing.

PHENYLEPHRINE HYDROCHLORIDE

Sympathomimetic amines, such as phenylephrine, act on alpha-adrenergic receptors of the respiratory tract to produce vasoconstriction, which temporarily reduces the swelling associated with inflammation of the mucous membranes lining the nasal and sinus passages. This allows the free drainage of the sinusoidal fluid from the sinuses.

In addition to reducing mucosal lining swelling, decongestants also suppress the production of mucous, therefore preventing a build up of fluid within the cavities which could otherwise lead to pressure and pain.

5.2 Pharmacokinetic properties

Paracetamol is rapidly and almost completely absorbed from the gastrointesti­nal tract.

Peak plasma concentrations are attained 10–60 minutes following oral dosing.

Paracetamol is primarily metabolised in the liver via three pathways: glucuronidation, sulphation and oxidation. It is excreted in the urine, mainly as the glucuronide and sulphate conjugates. The elimination half-life ranges from 1 to 3 hours.

Guaifenesin is rapidly absorbed from the gastrointestinal tract after oral administration with maximum blood levels occurring within 15 minutes of administration. It is rapidly metabolised in the kidneys by oxidation to P-(2 methyoxy-phenoxy) lactic acid, which is excreted in the urine. The elimination half life is one hour.

Phenylephrine hydrochloride is irregularly absorbed from the gastrointestinal tract and undergoes first-pass metabolism by monoamine oxidase in the gut and liver; orally administered phenylephrine thus has reduced bioavailability. It is excreted in the urine almost entirely as the sulphate conjugate. Peak plasma levels occur between 1 and 2 hours and the plasma half life ranges from 2 to 3 hours.

5.3 Preclinical safety data

Preclinical safety data on these active ingredients in the literature have not revealed any pertinent and conclusive findings which are of relevance to the recommended dosage and use in the product and which have not already been mentioned elsewhere in this Summary.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sucrose

Citric acid E330

Tartaric acid E334

Sodium cyclamate E952

Sodium citrate E331

Acesulfame potassium E950

Aspartame E951

Powdered menthol flavour

Lemon flavour

Lemon juice flavour

Quinoline yellow E104

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

36 months.

Shelf life after reconstitution: 1^ hours.

6.4 Special precautions for storage

Do not store above 30°C.

6.5 Nature and contents of container

Pack sizes:

5 sachets

6 sachets

10 sachets

Not all pack sizes may be marketed.

The sachet laminate comprises either:

Low density polyethylene 30 gm-2/aluminium foil 15 micron/low density polyethylene

12 gm-2/paper 40 gm-2 (outer layer).

or

‘Surlyn’ 25 gm-2 (product contact layer)/aluminium foil 15 microns/low density polyethylene 12 gm-2 / paper 40 – 45 gm-2 (outer layer).

6.6 Special precautions for disposal

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Omega Pharma Limited

32 Vauxhall Bridge Road

London

SW1V 2SA

U.K

8 MARKETING AUTHORISATION NUMBER(S)

PL 02855/0319