Document: spc-doc_PL 44673-0019 change

• spc-doc_PL 00079-0657
• spc-doc_PL 44673-0019

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Beechams Max Strength All in One Capsules, hard

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Active Ingredient mg/Capsule

Paracetamol 500 Guaifenesin 100 Phenylephrine hydrochloride 6.1

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Capsule, hard.

Dark blue/dark green 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.

Not to be given to children under 12 years except on medical advice. Do not take continuously for more than 5 days without medical advice.

4.3 Contraindications

Known hypersensitivity to any of the ingredients.

Concomitant use of other sympathomimetic decongestants. Phaeochromocytoma.

Closed angle glaucoma.

Hepatic or severe renal impairment, hypertension, hyperthyroidism, diabetes, heart disease or those taking tricyclic antidepressants or beta-blocking drugs and those patients who are taking or have taken within the last two weeks, monoamine oxidase inhibitors (see section 4.5).

4.4 Special warnings and precautions for use

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

Patients should stop using the 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.

Do not take with a cough suppressant.

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

An enlargement of the prostate gland

Occlusive vascular disease (e.g. Raynaud’s Phenomenon)

This product should not be used by patients taking other sympathomimetics (such as decongestants, appetite suppressants and amphetamine-like psychostimulants) (see section 4.5).

Concomitant use of other paracetamol-containing products should be avoided.

Special label warnings

If you are taking medication or are under medical care, consult your doctor before using this medicine.

Do not exceed the stated dose.

If symptoms persist consult your doctor.

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

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.

Special leaflet 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, because of the risk of delayed, serious liver damage.

4.5 Interaction with other medicinal products and other forms of interaction

Paracetamol

The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding. The hepato-toxicity of paracetamol may be potentiated by excessive intake of alcohol. The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by colestyramine. 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.

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

Monoamine oxidase inhibitors (including moclobemide)	Hypertensive interactions occur between sympathomimetic amines such as phenylephrine and monoamine oxidase inhibitors (see contraindications).
Sympathomimetic amines	Concomitant use of phenylephrine with other sympathomimetic amines can increase the risk of cardiovascular side effects.
Beta-blockers and other antihypertensives (including debrisoquine, guanethidine, reserpine, methyldopa)	Phenylephrine may reduce the efficacy of betablocking drugs and antihypertensive drugs. The risk of hypertension and other cardiovascular side effects may be increased.
Tricyclic antidepressants (e.g. amitriptyline)	May increase the risk of cardiovascular side effects with phenylephrine.

Ergot alkaloids (ergotamine and methylsergide)	Increased risk of ergotism
Digoxin and cardiac glycosides	Increase the risk of irregular heartbeat or heart attack

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).

No significant interactions with other drugs have been noted for guaifenesin.

4.6 Fertility, Pregnancy and lactation

This product should not be used during pregnancy without medical advice.

Human and animal studies with paracetamol have not identified any risk to pregnancy or embryo-foetal development.

No relevant data are available for products containing phenylephrine.

The safety of guaifenesin during pregnancy has not been established.

Lactation

This product should not be used whilst breast feeding without medical advice.

Human studies with paracetamol have not identified any risk to lactation or the breast-fed offspring.

Paracetamol crosses the placental barrier and is excreted in breast milk. Phenylephrine may be excreted in breast milk.

No relevant data available for guaifenesin.

4.7 Effects on ability to drive and use machines

Patients should be advised not to drive or operate machinery if affected by dizziness.

4.8 Undesirable effects

Adverse events from historical clinical trial data are both infrequent and from small patient exposure.

Events reported from extensive post-marketing experience at therapeutic/labelled dose and considered attributable are tabulated below by MedDRA System Organ Class. 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 not known (cannot be estimated from available data), but post-marketing experience indicates that adverse reactions to paracetamol are rare and serious reactions are very rare.

Body System	Undesirable effect
Blood and lymphatic system disorders	Thrombocytopenia Agranulocytosis
	These are not necessarily causally related to paracetamol
Immune system disorders	Anaphylaxis Cutaneous hypersensitivity reactions including skin rashes, angiodema and Stevens Johnson syndrome
Respiratory, thoracic and mediastinal disorders	Bronchospasm in patients sensitive to aspirin and other NSAIDs
Hepatobiliary disorders	Hepatic dysfunction
Gastrointestinal disorders	Acute pancreatitis

The following adverse events have been observed in clinical trials with phenylephrine and may therefore represent the most commonly occurring adverse events.

Body System	Undesirable effect
Psychiatric disorders	Nervousness, irritability, restlessness, and excitability
Nervous system disorders	Headache, dizziness, insomnia
Cardiac disorders	Increased blood pressure
Gastrointestinal disorders	Nausea, Vomiting, diarrhoea

Adverse reactions identified during post-marketing use are listed below. The frequency of these reactions is unknown but likely to be rare.

Eye disorders	Mydriasis, acute angle closure glaucoma, most likely to occur in those with closed angle glaucoma
Cardiac disorders	Tachycardia, palpitations

Skin and subcutaneous disorders	Allergic reactions (e.g. rash, urticaria, allergic dermatitis). Hypersensitivity reactions - including that cross-sensitivity may occur with other sympathomimetics.
Renal and urinary disorders	Dysuria, urinary retention. This is most likely to occur in those with bladder outlet obstruction, such as prostatic hypertrophy.

Guaifenesin

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

Body system	Undesirable effect
Immune system disorders	Allergic reactions, angioedema, anaphylactic reactions
Respiratory, thoracic and mediastinal disorders	Dyspnoea*
Gastrointestinal disorders	Nausea, vomiting, abdominal discomfort,
Skin and subcutaneous disorders	Rash, urticaria

*Dyspnoea has been reported in association with other symptoms of hypersensitivity

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

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

or

Regularly consumes ethanol in excess of recommended amounts.

or

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 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

Very large doses of guaifenesin can cause nausea and vomiting.

Treatment

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

Phenylephrine

Symptoms

Phenylephrine overdosage is likely to result in effects similar to those listed under adverse reactions. Additional symptoms may include irritability, restlessness, hypertension and possibly reflux brachycardia. 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 liver toxicity.

Treatment

Treatment should be as clinically appropriate. Severe hypertension may need to be treated with an alpha blocking drug such as phentolamine.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

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

ATC code: N02BE51

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 heat-regulating 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 ^-(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 Magnesium stearate Talc

Gelatin capsule:

Gelatin

Quinoline yellow E104 Indigo carmine E132 Erythrosine E127 Titanium dioxide E171

6.2 Incompatibilities

None known.

6.3 Shelf life

24 months

6.4 Special precautions for storage

Do not store above 25 °C.

6.5 Nature and contents of container

Child Resistant blister comprising 250 micron PVC lidded with 35 gsm paper/9 micron aluminium foil.

Pack sizes of 8 and 16 capsules are available.

6.6 Special precautions for disposal

None.

7 MARKETING AUTHORISATION HOLDER

GlaxoSmithKline Consumer Healthcare (UK) Trading Limited,

980 Great West Road

Brentford

Middlesex