4.1. Therapeutic indications

For the relief of symptoms of colds 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

Patients should consult a doctor or pharmacist if symptoms persist for more than 5 days, or worsen.

Posology

Adults and children 16 years and over:

Content of one sachet dissolved by stirring in hot water and sweetened to taste.

Dose may be repeated in 4-6 hours as required.

Do not take more than 4 sachets in 24 hours.

Do not give to children under 16 years of age.

Elderly Population: No dosage adjustment is considered necessary in the elderly.

Method of administration

Oral administration after dissolution in water.

4.3. Contraindications

Hypersensitivity to any of the active substances or any of the excipients listed in section 6.1.

Due to the presence of phenylephrine, use of the product is contraindicated in:

• Patients with severe coronary heart disease and cardiovascular disorders

• Patients with hypertension

• Patients with hyperthyroidism

• Patients currently receiving or within two weeks of stopping therapy with monoamine oxidase inhibitors (MAOIs)

• Concomitant use of other sympathomimetic decongestants

• Patients with prostatic enlargement

• Patients with phaeochromocytoma

• Patients with diabetes mellitus

• Patients with closed-angle glaucoma

4.4. Special warnings and precautions for use

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.

Caution is advised if paracetamol is administered concomitantly with flucloxacillin due to increased risk of high anion gap metabolic acidosis (HAGMA), particularly in patients with severe renal impairment, sepsis, malnutrition and other sources of glutathione deficiency (e.g. chronic alcoholism), as well as those using maximum daily doses of paracetamol. Close monitoring, including measurement of urinary 5-oxoproline, is recommended.

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

This product should not be used for persistent or chronic cough such as that occurring with smoking, asthma, chronic bronchitis or emphysema, or for cough associated with excessive phlegm. A persistent cough may be indicative of a serious condition. If cough persists for more than 5 days, is recurrent, or is accompanied by fever, rash, or persistent headache, a physician should be consulted.

Use with caution in patients suffering from porphyria.

Not recommended for concomitant use with a cough suppressant.

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).

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).

Use with care in patients with Raynaud's Phenomenon.

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.

This product also contains 1973.3mg sucrose per dose (total sugars 2g). Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

This product contains 129.0mg (5.61mmol) sodium per dose – to be taken into consideration for patients on a controlled sodium diet.

Contains a source of phenylalanine. May be harmful for people with phenylketonuria.

Keep out of the sight and reach of children.

Do not exceed the stated dose.

If symptoms persist, consult your doctor.

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.

Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis, especially in patients with risks factors (see section 4.4).

Isoniazid: The toxicity of paracetamol may be increased by isoniazid.

Liver enzyme-inducing drugs: Drugs which induce or regulate liver microsomal enzymes, such as anticonvulsants (including phenytoin, barbiturates, carbamazepine) and alcohol, may increase the hepatotoxic potential of paracetamol.

Phenylephrine Hydrochloride

Monoamine oxidase inhibitors (including moclobemide): Do not use in patients taking monoamine oxidase inhibitors (MAOIs) or who have taken MAOIs within the previous 14 days. Hypertensive interactions occur between sympathomimetic amines such as phenylephrine and monoamine oxidase inhibitors (see section 4.3).

Sympathomimetic agents: Concomitant use of phenylephrine hydrochloride with other sympathomimetic agents can increase the risk of hypertension and other cardiovascular side effects.

Oxytocic agents: The vasopressor effect of sympathomimetics such as phenylephrine may be potentiated when used in conjunction with oxytocic drugs such as oxytocin and ergot alkaloids which can increase risk of haemorrhagic stroke.

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

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

4.6. Fertility, pregnancy 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.

There are limited data on the use of guaifenesin in pregnant women. 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.

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.

There is no information on the use of guaifenesin in lactation.

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 All in One 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, guaifenesin and phenylephrine 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, diarrhoea

Skin and Subcutaneous Tissue Disorders

Very rare

Not known

Cases of serious skin reactions have been reported

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 grams 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:

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 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, urticarial and allergic dermatitis), dysuria and 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.

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