SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Galpharm Paracetamol, Guaifenesin, Phenylephrine Hydrochloride 250 mg/100 mg/5 mg hard capsules

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Active Ingredient    mg/Capsule

Paracetamol    250

Guaifenesin    100

Phenylephrine Hydrochloride 5

For full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Capsule, hard (capsule).

Light blue / purple hard gelatin capsules containing the drug product, an off-white powder.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the relief of symptoms associated with colds and flu and the pain and congestion of sinusitis, including aches and pains, headache, blocked nose and sore throat, chills, lowering of temperature, and to loosen stubborn mucous and provide relief from chesty coughs.

4.2 Posology and method of administration

For oral use. Swallow whole with water, do not chew.

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

Two capsules every four hours as required. Do not take more than 8 capsules (4 doses) in any 24 hour period.

Do not give to children under 12 years old.

4.3 Contraindications

Hypersensitivity to paracetamol, guaifenesin or phenylephrine or any of the other ingredients.

Hypertension (high blood pressure), hyperthyroidism, diabetes, serious heart disease, cardiovascular disorders or those patients receiving or within two weeks of stopping therapy with monoamine oxidase inhibitors (see Section 4.5).

Those taking tricyclic anti-depressant drugs (see Section 4.5).

Phaeochromocytoma

Prostatic enlargement or urinary retention

Use in patients with glaucoma, including closed angle glaucoma.

Hepatic and renal impairment

Use in patients who are currently receiving other sympathomimetic drugs (see Section 4.5)

Pregnancy and lactation (see Section 4.6)

Porphyria

4.4 Special warnings and precautions for use

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).

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

Use with caution in patients with circulatory disorders such as Raynaud’s Phenomenom.

Patients with prostatic hypertrophy may have increased difficulty with micturition.

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

Sympathomimetic-containing products may act as cerebral stimulants giving rise to insomnia, nervousness, hyperpyrexia, tremor and epileptiform convulsions.

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

Long term use of the product in not recommended.

Do not take with alcohol.

Special label warnings

Do not take more medicine than the label tells you to. If you do not get better, talk to your doctor.

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

Contains paracetamol. Do not take anything else containing paracetamol while taking this medicine. Talk to a doctor at once if you take too much of this medicine, even if you feel well.

If you are taking medication or are under medical care, consult your doctor before using this medicine. Do not take with any other flu, cold or decongestant products.

Special leaflet warnings

Do not take more medicine than the label tells you to. If you do not get better, talk to your doctor.

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

Contains paracetamol. Do not take anything else containing paracetamol while taking this medicine. Talk to a doctor at once if you take too much of this medicine, even if you feel well. This is because too much paracetamol can cause delayed, serious liver damage.

If you are taking medication or are under medical care, consult your doctor before using this medicine. Do not take with any other flu, cold or decongestant products.

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, occasional doses have no significant effect.

Drugs which induce hepatic microsomal enzymes, such as alcohol, barbiturates, monoamine oxidase inhibitors and tricyclic antidepressants, may increase the hepatoxicity 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.

PHENYLEPHRINE HYDROCHLORIDE

Phenylephrine may adversely interact with other sympathomimetics, vasodilators and beta blockers. Concomitant use of phenylephrine with other sympathomimetic amines can increase the risk of cardiovascular side effects.

Hypertensive interactions occur between sympathomimetic amines such as phenylephrine and monoamine oxidase inhibitors.

Sympathomimetic-containing products should be used with great care in patients receiving phenothiazines or tricylic antidepressants.

Sympathomimetic-containing products should be used in caution in patients receiving digitalis, beta-adrenergic blockers, guanethidine, reserpine, methyldopa or antihypersensitive agents.

Concurrent use with halogenated anaesthetic agents such as chloroform, cyclopropane, halothane, enflurane or isoflurane may provoke or worsen ventricular arrhythmias.

This medicine should not be used with enzyme inducers such as alcohol.

GUAIFENESIN

If urine is collected within 24 hours of a dose of this product a metabolite of guaifenesin may cause a colour interference with laboratory determinations or urinary-5-hyrdoxyindolacetic acid (5-HIAA) and vanillylmandelic acid (VMA).

4.6 Fertility, pregnancy and lactation

Pregnancy

Paracetamol

A large amount of data on pregnant women indicate no malformative nor feto/neonatal toxicity of Paracetamol.

Guaifenesin

There are no or limited amount of data from the use of guaifenesin in pregnant women.

Phenylephrine Hydrochloride

Based on human experience phenylephrine hydrochloride causes congenital malformations when administered during pregnancy. It has also been shown to have possible associations with fetal hypoxia.

Breast-feeding

Paracetamol

Paracetamol / metabolites are excreted in human milk, but at therapeutic doses of the product no effects on the breastfed newborns/infants are anticipated.

Guaifenesin

There are no or limited amount of data from the use of guaifenesin in pregnant women.

Phenylephrine Hydrochloride

There is insufficient information on the excretion of Phenylephrine Hydrochloride/metabolite excreted in human milk.

Fertility

There are no or limited amount of data regarding the use of paracetamol, guaifenesin or phenylephrine hydrochloride and its impact on fertility.

4.7 Effects on ability to drive and use machines

None known.

Undesirable effects

The active ingredients are usually well tolerated in normal use. PARACETAMOL

Blood and lymphatic system disorders Frequency unknown

Agranulocytosis; Blood disorders; Thrombocytopenia

Hepatobiliary disorders Frequency unknown Hepatic function abnormal

Immune system disorders

Frequency unknown

Anaphylactic reaction; Hypersensitivity

Respiratory, thoracic and mediastinal disorders

Frequency unknown

Bronchospasm*

Skin and subcutaneous tissue disorders Frequency unknown

Angioedema; Dermatitis allergic; Rash; Stevens Johnson syndrome *There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.

GUAIFENESIN

Gastrointestinal disorders Frequency unknown

Abdominal discomfort, nausea and vomiting

Immune system disorders Frequency unknown Hypersensitivity

PHENYLEPHRINE HYDROCHLORIDE

Cardiac disorders Frequency unknown

Arrhythmia; Palpitations; Bradycardia, Tachycardia

Eye disorders Frequency unknown

Mydriasis, acute angle closure glaucoma, most likely to occur in those with closed angle glaucoma.

Gastrointestinal disorders Frequency Unknown Nausea, Vomiting; Diarrhoea

General disorders and administration site condition

Frequency unknown

Irritability

Immune system disorders Frequency unknown

Hypersensitivity reactions - including that cross-sensitivity may occur with other sympathomimetics.

Nervous system disorders Frequency unknown Dizziness; Headache; Paraesthesia;

Psychiatric disorders Frequency unknown

Anxiety; Hallucination; Insomnia; Nervousness; Restlessness

Renal and urinary disorders Frequency unknown Dysuria, Urinary retention

Skin and subcutaneous tissue disorders

Frequency unknown

Dermatitis allergic; Rash; Urticaria

Vascular disorders

Frequency unknown

Peripheral coldness; Hypertension

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 carbamazeopine, phenobarbital, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.

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 encephalophathy, 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 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 Services (NPIS) or a liver unit.

GUAIFENESIN

Gastrointestinal discomfort has occasionally been reported with Guaifenesin.

Very large doses of guaifenesin can cause nausea and vomiting. Vomiting should be treated by fluid replacement and monitoring or electrolytes.

PHENYLEPHRINE HRYDROCHLORIDE

Phenylephrine Hydrochloride may elevate blood pressure with headache, vomiting and rarely palpitations, tachycardia or reflex bradycardia, tingling and coolness of the skin. There have been rare reports of allergic reactions.

Symptoms of overdosage include irritability, palpitations, hypertension, difficulty in micturition, nausea, vomiting, thirst and convulsions.

Severe overdosage of phenylephrine may produce hypertension and associated reflex bradycardia, haemodynamic changes and cardiovascular collapse with respiratory depression.

Treatment measures 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 the pressure has been controlled. In severe overdosage gastric lavage and aspiration should be performed. Symptomatic and supportive measures should be undertaken, particularly with regard to 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 requires to control cardiac arrhythmias.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic Group: Other analgesics and antipyretics & other cold combination preparations

ATC Code:

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 pain-impulse 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

Absorption and Fate

Paracetamol is rapidly absorbed from the gastro-intestinal tract with peak plasma concentrations occurring between 10 and 120 minutes after oral administration. It is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1 to 4 hours.

Plasma-protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations.

A minor hydroxylated metabolite which is usually produced in very small amounts by mixed-function oxidases in the liver and which is usually detoxified by conjugation with liver glutathione may accumulate following paracetamol overdose and cause liver damage.

GUAIFENESIN

Guaifenesin is rapidly absorbed after oral administration. It is rapidly metabolised by oxidation to P-(2 methoxy-phenoxy)lactic acid, which is excreted in the urine.

PHENYLEPHRINE HYDROCHLORIDE

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.

5.3 Preclinical safety data

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

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Maize Starch

Croscarmellose Sodium Sodium Laurilsulfate Talc

Magnesium Stearate

Gelatin Capsule:

Gelatin

Titanium Dioxide (E171) Erythrosine (E127) Brilliant Blue FCF (E133)

6.2 Incompatibilities

6.3 Shelf life

36 months.

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

PVC / Child resistant Aluminium foil / paper blister.

PVC/PE/PVDC (product contact) / Child resistant Aluminium foil / paper blister. Pack sizes: 8 and 16 capsules.

6.6 Special precautions for disposal

None.

7 MARKETING AUTHORISATION HOLDER

Wrafton Laboratories Limited (T/A Perrigo)

Braunton Devon EX33 2DL

8    MARKETING AUTHORISATION NUMBER(S)

PL 12063/0125

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

14/04/2015

10    DATE OF REVISION OF THE TEXT

14/04/2015