SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Lemsip Max All in One Cold & Flu Capsules

Lemsip Cough Max for Mucus Cough & Cold 500mg/100mg/6.1mg Capsules

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Each capsule contains paracetamol 500mg, phenylephrine hydrochloride 6.1mg and guaifenesin 100mg

For a full list of excipients, see Section 6.1.

3    PHARMACEUTICAL FORM

Capsule, hard

Capsules with a red cap and green body, printed ‘Lemsip’ on the cap in white ink, containing white, free flowing powder.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the relief of symptoms of cold and influenza, including the relief of aches and pains, sore throat, headache, nasal congestion, lowering of temperature and chesty coughs.

4.2    Posology and method of administration

Adults (over 16 years and over): Two capsules every 4-6 hours to a maximum of four doses in any 24 hours.

Do not exceed eight capsules in any 24 hours.

Children (12-15 years): One capsule every 4-6 hours to a maximum of four doses in any 24 hours.

Do not exceed 4 capsules in any 24 hours.

Swallow whole with water. Do not chew.

Not recommended for children under 12 years of age.

4.3 Contraindications

Hypersensitivity to any of the ingredients. Severe coronary heart disease and cardiovascular disorders. Hypertension. Hyperthyroidism. Contraindicated in patients currently receiving or within two weeks of stopping therapy with monoamine oxidase inhibitors.

4.4 Special warnings and precautions for use

Use with caution in patients with Raynaud's phenomenon or diabetes mellitus. Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease. Do not take with any other paracetamol-containing products.

Phenylephrine should be used with care in patients with closed angle glaucoma and prostatic enlargement

4.5 Interaction with other medicinal products and other forms of interaction

Paracetamol

The rate of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular daily use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

Medicinal products which induce hepatic microsomal enzymes, such as alcohol, barbiturates, monoamine oxidase inhibitors and tricyclic antidepressants, may increase the hepatotoxicity of paracetamol, particularly after overdose.

Phenylephrine Hydrochloride

Monoamine oxidase inhibitors (including moclobemide): hypertensive interactions occur between sympathomimetic amines such as phenylephrine and monoamine oxidase inhibitors (see section 4.3).

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 beta-blockers and antihypertensives. The risk of hypertension and other cardiovascular side effects may be increased (see section 4.3).

Tricyclic antidepressants (e.g. amitriptyline): may increase the risk of cardiovascular side effects with phenylephrine (see section 4.3).

Digoxin and cardiac glycosides: concomitant use of phenylephrine may increase the risk of irregular heartbeat or heart attack.

Guaifenesin

Guaifenesin may increase the rate of absorption of paracetamol. Guaifenesin may interfere with diagnostic measurements of urinary 5-hydroxyindoleactic acid or vanillylmandelic acid.

4.6 Fertility, pregnancy and lactation

Paracetamol

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 breastfeeding.

Phenylephrine hydrochloride

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 phenylephrine, the use of the product during pregnancy should be avoided. In addition, because phenylephrine may reduce placental perfusion, the product should not be used in patients with a history of pre-eclampsia. In view of the lack of data on the use of phenylephrine during lactation, this medicine should not be used during breast feeding.

Guaifenesin:

Has been linked with an increased risk of neural tube defects in a small number of women with febrile illness in the first trimester of pregnancy. The product should be used in pregnancy only if the benefits outweigh this risk. There is no information on use in lactation.

4.7 Effects on ability to drive and use machines

Lemsip Max All in One Cold and Flu Capsules.has no or negligible influence on ability to drive or use machinery.

4.8    Undesirable effects

Paracetamol: Adverse effects of paracetamol are rare, but hypersensitivity including skin rash may occur. There have been reports of blood dyscrasias including thrombocytopenia, leucopenia, pancytopenia, nutropenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

Phenylephrine hydrochloride: High blood pressure with headache, vomiting, Rarely, palpitations. Also, rare reports of allergic reactions and occasionally urinary retention in males.

Guaifenesin: Guaifenesin has occasionally been reported to cause gastrointestinal discomfort, nausea and vomiting, particularly in very high doses. Also, hypersensitivity reactions may occur.

4.9    Overdose

Paracetamol:

There is a risk of poisoning, particularly in elderly subjects, in young children, in patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition. Overdosing may be fatal in these cases. Symptoms generally appear within the first 24 hours and comprise: nausea, vomiting, anorexia, pallor, and abdominal pain.

Overdose of paracetamol in a single administration in adults or in children causes liver cell necrosis likely to induce complete and irreversible necrosis, resulting in hepatocellular insufficiency, metabolic acidosis and encephalopathy which may lead to coma and death. Simultaneously, increased levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin are observed together with increased prothrombin levels that may appear 12 to 48 hours after administration.

Liver damage is likely in adults who have taken more than the recommended amounts 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.

Some patients may be at increased risk of liver damage from paracetamol toxicity

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 N-acetylcysteine 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 24 hours from ingestion should be discussed with the NPIS or a liver unit.

Phenylephrine hydrochloride:    Features of severe overdosage of

phenylephrine include haemodynamic changes and cardiovascular collapse

with respiratory depression. Treatment includes early gastric lavage and symptomatic and supportive measures. Hypertensive effects may be treated with an i.v. alpha-receptor-blocking agent.

Phenylephrine overdose is likely to result in: nervousness, headache, dizziness, insomnia, increased blood pressure, nausea, vomiting, Mydriasis, acute angle closure glaucoma (most likely to occur in those with closed angle glaucoma), tachycardia, palpitations, allergic reactions (e.g. rash, urticaria, allergic dermatitis), dysuria, urinary retention (most likely to occur in those with bladder outlet obstruction, such as prostatic hypertrophy).

Additional symptoms may include hypertension, and possibly 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 that required to cause paracetamol-related liver toxicity.

Guaifenesin:. Very large doses may cause nausea and vomiting. The active substance is, however, rapidly metabolised and excreted in the urine. Patients should be kept under observation and treated symptomatically.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

ATC Code: N02B E51

Paracetamol: Paracetamol has both analgesic and antipyretic activity, which is believed to be mediated principally through its inhibition of prostaglandin synthesis within the central nervous system.

Phenylephrine hydrochloride: Phenylephrine is a post-synaptic alpha-receptor agonist with low cardioselective beta-receptor affinity and minimal central stimulant activity. It is a recognised decongestant and acts by vasoconstriction to reduce oedema and nasal swelling.

Guaifenesin: Guaifenesin is an expectorant which increases the volume and reduces the viscosity of tenacious sputum.

5.2 Pharmacokinetic properties

Paracetamol: Paracetamol is absorbed rapidly and completely from the small intestine, producing peak plasma levels after 15-20 minutes following oral dosing. The systemic availability is subject to first-pass metabolism and varies with dose between 70% and 90%. The drug is rapidly and widely distributed throughout the body and is eliminated from plasma with a T/ of approximately 2 hours. The major metabolites are glucuronide and sulphate conjugates (>80%) which are excreted in urine.

Phenylephrine hydrochloride: Phenylephrine is absorbed from the gastrointestinal tract, but has reduced bioavailability by the oral route due to first-pass metabolism. It retains activity as a nasal decongestant when given orally, the drug distributing through the systemic circulation to the vascular bed of the nasal mucosa. When taken by mouth as a nasal decongestant phenylephrine is usually given at intervals of 4-6 hours.

Guaifenesin: Guaifenesin is absorbed from the gastrointestinal tract. It is metabolised and excreted in the urine.

5.3 Preclinical safety data

There are no findings of relevance to the prescriber other than those already mentioned elsewhere in the SPC

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Capsule contents:

Maize starch Croscarmellose sodium Sodium laurilsulfate Magnesium stearate Talc

Capsule shell:

Gelatin

Titanium dioxide (E171)

Yellow iron oxide (E172)

Red iron oxide (E172)

Brilliant blue - FD&C blue 1 (E133)

Printing ink:

Shellac (E904)

Titanium dioxide (E171)

6.2 Incompatibilities

Not applicable

6.3 Shelf life

3 Years.

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

250 micron opaque uPVC blister with foil/paper laminate, 35 gsm paper/9 micron soft-temper foil and heat-seal coated, contained in an outer cardboard carton.

Pack sizes: 2, 4, 6, 8, 10, 12, 14 and 16.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7    MARKETING AUTHORISATION HOLDER

Reckitt Benckiser Healthcare (UK) Limited, Dansom Lane,

Hull,

HU8 7DS,

East Yorkshire,

UK.

8    MARKETING AUTHORISATION NUMBER(S)

PL 00063/0551.

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10/09/2009

10    DATE OF REVISION OF THE TEXT

28/08/2015