NAME OF THE MEDICINAL PRODUCT

Lemsip Max Apple & Cinnamon Flavour Powder for Oral Solution.

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.

Each tablet contains 2.2 g of sucrose.

For a full list of excipients, see 6.1

3    PHARMACEUTICAL FORM

A white to off-white powder for oral solution

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

Oral administration after dissolution in water.

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

The dose may be repeated in 4-6 hours.

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

Not to be given to children under 12 without medical advice. There is no indication that dosage need be modified in the elderly.

4.3    Contraindications

Hypersensitivity to any of the active substances or any other ingredient.

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.

Each sachet contains approximately 2.2 g of carbohydrate. This product contains 2.2 g sucrose per dose (total sugars 2.2 g). Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

This medicinal product contains 5.61 mmol (or 129.0 mg) sodium per dose. To be taken into consideration by patients on a controlled sodium diet.

Due to its aspartame content this product should not be given to patients with phenylketonuria.

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 noncirrhotic alcoholic liver disease. Patients should be advised not to take other paracetamol-containing products concurrently.

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

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.

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.

4.6 Pregnancy and lactation

Due to the vasoconstrictive properties of phenylephrine the product should not be used in patients with a history of pre-eclampsia. Phenylephrine may reduce placental perfusion There is no information on use in lactation.. 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.

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 breastmilk, but not in a clinically significant amount. Available published data do not contraindicate breast feeding.

4.7 Effects on ability to drive and use machines

Lemsip Max Cold & Flu Citrus Fruit.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 a few reports of blood dyscrasias including thrombocytopenia leucopenia, pancytopenia, neutropenia and agranulocytosis, but these were not necessarily causally related to paracetamol. Acute pancreatitis after ingestion of above normal amounts.

Phenylephrine hydrochloride

High blood pressure with headache and vomiting, probably only in overdosage. Rarely palpitations. Also, rare reports of allergic reactions and occasionally urinary retention in males.

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, 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 deplete, e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

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.

Hypertensive effects may be treated with an i.v. alpha-receptor blocking agent.

Phenylephrine Hydrochloride

Features of severe overdose 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.

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. 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: 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

Ascorbic acid,

Sucrose,

Citric acid anhydrous, Sodium citrate,

Apple & Cinnamon Flavour, Aspartame,

Saccharin sodium and Caramel (E150)

6.2 Incompatibilities

None known.

Shelf life

Two years.

6.4    Special precautions for storage

Do not store above 25°C. Store in the original package

6.5    Nature and contents of container

Sachet prepared from paper/PE/aluminium/ionomer laminate.

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 00063/0163.

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

13/02/2009

10    DATE OF REVISION OF THE TEXT

30/08/2016