SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Lemsip Max Cold & Flu Lemon.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Active Ingredients	mg/Sachet	Specification
Paracetamol	1000.00	Ph Eur
Phenylephrine hydrochloride*	12.20	Ph Eur
*Equivalent to phenylephrine (base)	10.0 mg.

Excipient(s) with known effect:

Sucrose

Sodium

Aspartame

Lactose

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Oral powder.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

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

4.2 Posology and method of administration

Patients should consult a doctor or pharmacist if symptoms persist for more than 3 days, or worsen.

Posology

Adults and children over 12: Content of one sachet dissolved by stirring in hot water and sweetened to taste.

The dose may be repeated in 4-6 hours as required.

No more than four doses should be taken in 24 hours.

Not to be given to children under 12.

There is no indication that dosage need be modified in the elderly.

Method of Administration

Oral administration after dissolution in water.

4.3    Contraindications

•    Hypersensitivity to paracetamol, phenylephrine or to any of the excipients listed in section 6.1..

•    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 (see section 4.5).

•    Concomitant use of other sympathomimetic decongestants

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.

Patients should be advised not to take other paracetamol -containing products concurrently.

Immediate medical advice should be sought in the event of an overdose, even if the patient feels well because of the risk of delayed serious liver damage (see section 4.9).

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

The product should not be used during pregnancy unless recommended by a healthcare professional (see section 4.6).

Use during breastfeeding should be avoided, unless recommended by a healthcare professional (see section 4.6).

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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

Each sachet contains approximately 2.2 g of carbohydrate. Due to its aspartame content this product should not be given to patients with phenylketonuria.

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 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.

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.

4.6    Pregnancy, Fertility and Lactation Pregnancy

The product should not be used during pregnancy unless recommended by a healthcare professional.

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 preeclampsia.

Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage.

Breast-feeding

The product should be avoided during lactation unless recommended by a healthcare professional. There are limited data on the use of phenylephrine in lactation.

Paracetamol is excreted in breast milk, but not in a clinically significant amount. Available published data do not contraindicate breast feeding.

Fertility

There are no available data regarding the effects of the active ingredients on fertility.

4.7 Effects on ability to drive and use machines

Lemsip Max Cold & Flu Lemon has no or negligible influence on ability to drive or use machinery.

4.8 Undesirable effects

Adverse events which have been associated with paracetamol and phenylephrine hydrochloride are given below, tabulated by system organ class and frequency. Frequencies are defined as: Very common (>1/10); Common (>1/100 and <1/10); Uncommon (>1/1000 and <1/100); Rare (>1/10,000 and <1/1000); Very rare (< 1/10,000); Not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness.

System Organ Class	Frequency	Adverse Events
Blood and Lymphatic System Disorders	Not known	Thrombocytopenia, leucopenia, pancytopenia, neutropenia, agranulocytosis1
Immune System Disorders	Not known	Hypersensitivity
Gastrointestinal Disorders	Not known	Abdominal discomfort, nausea, vomiting
Skin and Subcutaneous Tissue Disorders	Very rare	Cases of serious skin reactions have been reported
	Not known	Skin rash
Renal and Urinary Disorders	Not known	Urinary retention2

Description of Selected Adverse Reactions

¹    There have been reports of blood dyscrasias including thrombocytopenia, leucopenia, pancytopenia, neutropenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

²    Especially in males

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 of 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, phenobarbitone, 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 depleted, e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

Symptoms

Symptoms of paracetamol overdose 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 overdose of phenylephrine include haemodynamic changes and cardiovascular collapse with respiratory depression, seizures and arrhythmias. However, smaller amounts of the paracetamol and phenylephrine hydrochloride combination product would be required to cause paracetamol related liver toxicity than to cause serious phenylephrine-related toxicity. Treatment includes 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, reflex bradycardia, 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, 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.

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

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Analgesics, Anilides;

ATC Code: N02BE51. Paracetamol, combinations excl. psycholeptics

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 sympathomimetic post-synaptic al-adrenergic receptor agonist with low cardioselective beta receptor affinity and minimal central nervous stimulant activity. It is a recognised decongestant and acts by vasoconstriction to reduce oedema and nasal swelling.

5.2. Pharmacokinetic properties

Paracetamol: Paracetamol is absorbed rapidly and completely mainly from the small intestine producing peak plasma levels after 15-20 minutes following oral dosing.

In a study of healthy controls fasted overnight the T_max for an equivalent product compared to two tablets of standard paracetamol was 20 minutes versus 35 minutes (p=0.0865). However, the speed to achieve 10 pg/ml for the product was faster than a standard paracetamol (17 minutes versus 30 minutes).

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 T1_/2 of approximately 2 hours. The major metabolites are glucuronide and sulphate conjugates (>80%) which are excreted in urine.

Phenylephrine: 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 nasal mucosa. When taken by mouth as a nasal decongestant phenylephrine is usually given at intervals of 4 - 6 hours.

5.3 Preclinical safety data

No preclinical findings of relevance have been reported.

6.1    List of excipients

Sodium citrate,

Citric acid,

Curcumin (curcumin (E100), Lactose, Polysorbate 80 (E433) and Silica (E551)). Lemon flavour,

Aspartame,

Saccharin sodium,

Pulverised sucrose,

Caster sugar and Ascorbic acid.

6.2    Incompatibilities

None known.

6.3 Shelf life

Three years.

6.4 Special precautions for storage

Store below 25°C in a dry place.

6.5. Nature and contents of container

Heat-sealed laminate sachet of 40 g/m² Paper/12 g/m² PE extrusion/8 pm Aluminium foil/18 g/m² Surlyn

Pack sizes: 5, 7, 9 and 10 sachets.

6.6 Special precautions for disposal

Oral administration after dissolution in water.

7 MARKETING AUTHORISATION HOLDER

Reckitt Benckiser Healthcare (UK) Limited, Dansom Lane, Hull, HU8 7DS, East Yorkshire.

8    MARKETING AUTHORISATION NUMBER(S)

PL 00063/0069.

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

16/03/2009

10    DATE OF REVISION OF THE TEXT

19/10/2016