4.1. Therapeutic indications

Adults, the elderly and children: For the temporary relief of pain caused by recurrent mouth ulcers and denture irritation.

In children from 5 months of age: For relief of pain and discomfort associated with teething where non-pharmacological treatments have failed to provide sufficient relief.

4.2. Posology and method of administration

Route of administration: oromucosal

Adults and the elderly: Apply to the affected area, a small undiluted amount of Anbesol Liquid, by covering the bottle mouth with a clean fingertip, inverting once and returning the bottle to the upright position. Two applications immediately will normally be sufficient to obtain pain relief. The application may be repeated if necessary after 3 hours.

Babies teething and children: Apply once to the affected area, 0.25 ml of undiluted Anbesol Liquid, by covering the bottle mouth with a clean fingertip, inverting once and returning the bottle to the upright position. The application may be repeated if necessary after 3 hours, up to a maximum of 6 applications in 24 hours.

Treatment should be stopped once symptoms have resolved.

Not to be used for more than 7 days.

Parents or carers should seek medical attention if the child's condition deteriorates during treatment.

In case of vomiting, spitting or accidental ingestion, the dose should not be repeated immediately. One application may be repeated if necessary after 3 hours.

4.3. Contraindications

Hypersensitivity to the active substances, anaesthetics of the amide-type or to any of the excipients listed in section 6.1.

Lidocaine is considered to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in animals.

4.4. Special warnings and precautions for use

Do not use more than one product containing lidocaine at the same time.

Excessive dosage, or short intervals between doses, may result in high plasma levels and serious adverse effects (see Section 4.9). Anbesol should be used with caution in patients with wounds or traumatised mucosa in the region of the proposed application. A damaged mucosa will permit increased systemic absorption resulting in systemic effects, such as convulsions, particularly if excessive quantities are used.

This medicinal product contains chlorocresol which may cause allergic reactions.

A dose of 0.25 ml of this medicine administered to a child 5 months of age weighing 5 kg would result in exposure to 30.2 mg/kg of ethanol which may cause a rise in blood alcohol concentration (BAC) of about 5 mg/100ml.

For comparison, for an adult drinking a glass of wine or 500 ml of beer, the BAC is likely to be about 50 mg/100 ml.

Co-administration with medicines containing e.g. propylene glycol or ethanol may lead to accumulation of ethanol and induce adverse effects, in particular in young children with low or immature metabolic capacity.

4.5. Interaction with other medicinal products and other forms of interaction

Lidocaine should be used with caution in patients receiving other local anaesthetics or agents structurally related to amide-type local anaesthetics, e.g. antiarrhythmic drugs such as mexiletine, since the toxic effects are additive.

In patients taking erythromycin the toxicity of oral lidocaine may be markedly increased.

In patients taking itraconazole, the toxicity of oral lidocaine may be markedly increased.

Antiarrhythmic drugs class III (e.g. amiodarone) may incur additive cardiac effects in combination with lidocaine.

Drugs that reduce the clearance of lidocaine (e.g. cimetidine or beta-blockers) may cause potentially toxic plasma concentrations when lidocaine is given in repeated high doses over a long time period. Such interactions should therefore be of no clinical importance following short-term treatment with topical lidocaine (e.g. Anbesol) at the recommended dose.

Chlorocresol has long been recognised to be incompatible with a range of compounds including calcium chloride, codeine phosphate, diamorphine hydrochloride, papaveretum, quinine hydrochloride, methylcellulose and non-ionic surfactants such as cetomacrogol 1000 and polysorbate 80.

4.6. Fertility, pregnancy and lactation

Pregnancy:

The safety of this medicinal product for use in human pregnancy has not been established. The product is, therefore, not recommended during pregnancy.

Lactation:

Lidocaine enters the mother's milk, but in such small quantities that there is generally no risk of the child being affected at therapeutic dose levels.

Fertility:

No data on human fertility is available.

4.7. Effects on ability to drive and use machines

None known.

4.8. Undesirable effects

Undesirable effects are listed by MedDRA System Organ Classes.

Assessment of undesirable effects is based on the following frequency groupings:

Very common: ≥1/10

Common: ≥1/100 to <1/10

Uncommon: ≥1/1,000 to <1/100

Rare: ≥1/10,000 to <1/1,000

Very rare: <1/10,000

Not known: cannot be estimated from the available data

System Organ Class

Undesirable Effect

Frequency

Immune system disorders

Allergic reactions

Not known

Gastrointestinal disorders

Non-specific ulceration

Not known

Skin and subcutaneous tissue disorders

Dermatitis

Not known

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, or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Lidocaine:

Systemic features:

CNS Symptoms: Increasing restlessness, visual disturbances, agitation, tinnitus, confusion, hallucinations, drowsiness, weakness, shivering, paraesthesia, and muscle twitching lead to convulsions, which are the major feature of toxicity. Coma and apnoea may develop.

Cardiac Symptoms: Possibly transient hypertension and tachycardia followed by arrhythmias (including sinus bradycardia, AV nodal or ventricular arrhythmias, asystole). The incidence of torsade de pointes is less than with other groups of antiarrhythmics. Hypotension may result from depressed myocardial contractility and peripheral vasodilation.

GI Symptoms: Nausea and vomiting.

Allergic reactions occur rarely and may include urticaria, angioedema, contact dermatitis and pruritis. Acute respiratory distress syndrome (ARDS) has been reported in severe allergic reactions.

Rarely methaemoglobinaemia may occur with excessive exposure to some local anaesthetics. This is much more commonly seen with benzocaine and prilocaine (due to its metabolite o-toluidine) than with lidocaine.

Serious toxicity is usually due to inadvertent intravenous overdosage. It is much less likely after oral administration because of extensive first pass metabolism but has been reported after ingestion of large amounts. Lidocaine is readily absorbed across mucous membranes and through damaged skin.

Systemic toxicity and death have been reported in children and adults following ingestion or aspiration of topical solutions or viscous preparations. The effect may also be due to absorption of high concentrations across the buccal mucosa causing systemic toxicity (see Section 4.4).

Potential toxic doses range from 800mg of gargled lidocaine solution (death), 1200mg ingestion (agitation and confusion) and 6g ingestion (death). Toxicity may also arise from rectal or urethral instillation.

Anaphylaxis or an anaphylactoid reaction has been reported following administration of 1% lidocaine solution for topical anaesthesia prior to fiberoptic bronchoscopy.

Signs of serious toxicity may occur at plasma concentrations greater than 5-8 microgram/mL (5-8mg/L).

Following ingestion bioavailability of lidocaine is 30-35% and peak levels occur within 40 minutes. The elimination half-life is about 1-2 hours. Metabolites of lidocaine have longer half-lives than lidocaine itself as well as antiarrhythmic activity.

All patients who have taken a deliberate overdose should be referred for assessment. Children and adults who have ingested 6mg/kg or more lidocaine, or those who are symptomatic, should be referred for medical assessment.

Children and adults who have accidentally ingested less than 6mg/kg lidocaine and who have no new symptoms since the time of ingestion do not need to be referred for medical assessment. Patients should be advised to seek medical attention if symptoms develop.

Chlorocresol:

Systemic features:

Nausea, vomiting, diarrhoea, hypotension, tachycardia, cardiac arrhythmias, metabolic acidosis, pallor, sweating and shock. CNS stimulation is followed by drowsiness, respiratory depression, cyanosis, convulsions, coma, bronchospasm and rapid onset pulmonary oedema and death. Methaemoglobinaemia is recognised. Phenol may also cause renal and hepatic injury.

Chronic exposure is rare but has been associated with nausea, vomiting, diarrhoea, anorexia, weight loss, hypersalivation, headache, fainting, mental disturbances, weakness, muscle aches and pain, mouth sores, renal and hepatic injury.

Exposure by any route can cause irritation, burns and systemic effects.

Ingestion causes irritation of mucous membranes, and of the GI tract. Significant ingestion is said to cause white/brown skin and mucosal burns which may be painless as phenol destroys the nerve endings. Laryngeal oedema can occur, and oesophageal stricture may be a late complication.

Skin contact – even dilute solutions (1%) can cause irritation, dermatitis and burns to the skin following prolonged contact. Often presents as relatively painless white or brown necrotic lesions; the brown colouration may remain after healing.

Management:

1. Wash area with soap and water.

2. Maintain a clear airway and ensure adequate ventilation. Give oxygen if clinically indicated.

3. Observe for at least 4 hours after exposure. Perform 12 lead ECG. Monitor pulse, blood pressure and cardiac rhythm continuously for 4 hours if the ECG is abnormal or the patient is symptomatic. Measure urea and electrolytes, arterial blood gases, liver and renal function in symptomatic cases and monitor in a critical care facility.

4. If cardiotoxicity is unresponsive to the above consider the use of a lipid emulsion. It is thought lipid may reduce free concentrations of active drug and therefore improve myocardial function, although other mechanisms are also postulated.

5. Correct acid base and metabolic disturbances as required.

6. Institute drug treatment of seizures as per local protocol.

Paediatric populations:

Lidocaine:

In children up to 6mg/kg lidocaine (with chlorhexidine in mouth paint) produced only minor symptoms. A 5 month old child had a seizure after ingestion of 100mg (14mg/kg). Severe toxicity in children is unlikely at doses less than 15mg/kg.