This information is intended for use by health professionals

1. Name of the medicinal product

Xylocaine 1% with Adrenaline (Epinephrine) 1:200,000.

2. Qualitative and quantitative composition

Each ml of solution for injection contains lidocaine hydrochloride monohydrate Ph. Eur., equivalent to 10 mg of lidocaine hydrochloride anhydrous (200 mg per 20 ml vial), 5 micrograms of adrenaline (epinephrine) as the acid tartrate (100 micrograms per 20 ml vial).

Excipients with known effect:

Each ml of solution also contains 0.5 mg sodium metabisulphite (E223), 1 mg methyl parahydroxybenzoate (E218) and 2.49 mg of sodium.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Solution for injection

4. Clinical particulars
4.1 Therapeutic indications

Xylocaine 1% with Adrenaline is indicated for regional anaesthesia in adults and children above 1 year of age.

4.2 Posology and method of administration

Adults and children above 12 years of age

The dosage is adjusted according to the response of the patient and the site of administration. The lowest concentration and smallest dose producing the required effect should be given (see section 4.4). The maximum single dose of Xylocaine when given with adrenaline is 500 mg.

The following table is a guide for the more commonly used techniques in the average adult. The figures reflect the expected average dose range needed. Standard textbooks should be consulted for factors affecting specific block techniques and for individual patient requirements.

The clinician's experience and knowledge of the patient's physical status are of importance in calculating the required dose. Elderly or debilitated patients require smaller doses, commensurate with age and physical status.

Type of block

% Conc.

Each dose

Indication

ml

mg

Field Block (e.g. minor nerve blocks and infiltration)

Infiltration

1

up to 15

up to 150

Surgical operations

Intercostals (per nerve)

1

2-5

Max. 15 ml

20-50

Max. 150 mg

Surgical operations

Postoperative pain and fractured ribs

Pudendal

1

10

100

Instrumental delivery

Major Nerve Block

Paracervical (each side)

1

10

100

Surgical operations and dilatation of cervix

Obstetric pain relief

Sciatic

2

15

300

Surgical operations

Paediatric patients 1 to 12 years of age (Xylocaine 1 % with Adrenaline)

Weight-based doses in ml/kg, up to 0.7 ml (7 mg/kg) should be regarded as guidelines for use in paediatric patients. Consider both age and weight for calculation of dosages. In children with a high body weight a gradual reduction of the dosage is often necessary and should be based on the ideal body weight. Standard textbooks should be consulted for factors affecting specific block techniques and for individual patient requirements.

For local anaesthesia only.

Preservative containing solutions should not be used intracisternally, epidurally, intrathecally or by any route giving access to the cerebrospinal fluid, or intra- or retro-bulbary. The volume to be injected in a single dose should not exceed 15 ml, unless otherwise justified.

In general, surgical anaesthesia requires the use of higher concentrations and doses. When a less intense block is required, the use of a lower concentration is indicated. The volume of drug used will affect the extent and spread of anaesthesia.

Care should be taken to prevent acute toxic reactions by avoiding intravascular injection. Careful aspiration before and during the injection is recommended. An accidental intravascular injection may be recognised by a temporary increase in heart rate. The main dose, should be injected slowly, at a rate of 100-200 mg/min, or in incremental doses, while keeping in constant verbal contact with the patient. If toxic symptoms occur, the injection should be stopped immediately.

4.3 Contraindications

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

Hypersensitivity to methyl and/or propyl parahydroxybenzoate (methyl-/propyl paraben), or to their metabolite para amino benzoic acid (PABA). Formulations of lidocaine containing parabens should be avoided in patients allergic to ester local anaesthetics or their metabolite PABA.

The use of a vasoconstrictor is contraindicated for anaesthesia of fingers, toes, tip of nose, ears and penis.

4.4 Special warnings and precautions for use

Regional anaesthetic procedures should always be performed in a properly equipped and staffed area. Equipment and drugs necessary for monitoring and emergency resuscitation should be immediately available. When performing major blocks, or using large doses, an IV cannula should be inserted before the local anaesthetic is injected. Clinicians should have received adequate and appropriate training in the procedure to be performed and should be familiar with the diagnosis and treatment of side effects, systemic toxicity or other complications (see sections 4.8 and 4.9).

Xylocaine with Adrenaline should not be given intravenously.

The effect of local anaesthetics may be reduced if an injection is made into an inflamed or infected area.

Attempts should be made to optimise the patient's condition before major blocks.

Although regional anaesthesia is frequently the optimal anaesthetic technique, some patients require special attention in order to reduce the risk of dangerous side effects:

- Patients with epilepsy.

- Patients with impaired respiratory function.

- Older people and patients in poor general condition.

- Patients with partial or complete heart conduction block - due to the fact that local anaesthetics may depress myocardial conduction.

- Patients with advanced liver disease or severe renal dysfunction.

- Patients treated with anti-arrhythmic drugs class III (e.g. amiodarone) should be under close surveillance and ECG monitoring considered, since cardiac effects may be additive (see section 4.5).

- Patients with acute porphyria. Xylocaine solution for injection is probably porphyrinogenic and should only be prescribed to patients with acute porphyria on strong or urgent indications. Appropriate precautions should be taken for all porphyric patients.

Certain local anaesthetic procedures may be associated with serious adverse reactions, regardless of the local anaesthetic drug used, e.g.:

- Injections in the head and neck regions may be made inadvertently into an artery, causing cerebral symptoms even at low doses.

- Paracervical block can sometimes cause foetal bradycardia/tachycardia, and careful monitoring of the foetal heart rate is necessary.

- There have been post-marketing reports of chondrolysis in patients receiving post-operative intra-articular continuous infusion of local anaesthetics. The majority of reported cases of chondrolysis have involved the shoulder joint. Due to multiple contributing factors and inconsistency in the scientific literature regarding mechanism of action, causality has not been established. Intra-articular continuous infusion is not an approved indication for Xylocaine.

Solutions containing adrenaline should be used with caution in patients with hypertension, cardiac disease, cerebrovascular insufficiency hyperthyroidism, advanced diabetes and any other pathological condition that may be aggravated by the effects of adrenaline.

Xylocaine with adrenaline contains sodium metabisulphite, which may cause allergic reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulphite sensitivity in the general population is unknown and probably low. Sulphite sensitivity is seen more frequently in asthmatic than non-asthmatic people.

For local anaesthesia only.

Preservative containing solutions should not be used intracisternally, epidurally, intrathecally or by any route giving access to the cerebrospinal fluid, or intra- or retro-bulbary. The volume to be injected in a single dose should not exceed 15 ml, unless otherwise justified.

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. certain anti-arrhythmics, such as mexilitine, since the systemic toxic effects are additive. Specific interaction studies with lidocaine and anti-arrhythmic drugs class III (e.g. amiodarone) have not been performed, but caution is advised (see also section 4.4).

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

Solutions containing adrenaline should be used cautiously in patients taking tricyclic antidepressants, monoamine oxidase inhibitors or receiving potent general anaesthetic agents since severe, prolonged hypertension may be the result. In addition, the concurrent use of adrenaline-containing solutions and oxytocic drugs of the ergot type may cause severe, persistent hypertension and possibly cerebrovascular and cardiac accidents. Phenothiazines and butyrophenones may oppose the vasoconstrictor effects of adrenaline giving rise to hypotensive responses and tachycardia.

Solutions containing adrenaline should be used with caution in patients undergoing general anaesthesia with inhalation agents, such as halothane and enflurane, due to the risk of serious cardiac arrhythmias.

Non-cardioselective betablockers such as propranolol enhance the pressor effects of adrenaline, which may lead to severe hypertension and bradycardia.

4.6 Fertility, pregnancy and lactation

Pregnancy

Although there is no evidence from animal studies of harm to the foetus, as with all drugs, Xylocaine should not be given during early pregnancy unless the benefits are considered to outweigh the risks.

The addition of adrenaline may potentially decrease uterine blood flow and contractility, especially after inadvertent injection into maternal blood vessels.

Foetal adverse effects due to local anaesthetics, such as foetal bradycardia, seem to be most apparent in paracervical block anaesthesia. Such effects may be due to high concentrations of anaesthetic reaching the foetus.

Breast-feeding

Lidocaine may enter the mother's milk, but in such small amounts that there is generally no risk of this affecting the neonate. It is not known whether adrenaline enters breast milk or not, but it is unlikely to affect the breast-fed child.

4.7 Effects on ability to drive and use machines

Besides the direct anaesthetic affect, local anaesthetics may have a very mild effect on mental function and co-ordination, even in the absence of overt CNS toxicity, and may temporarily impair locomotion and alertness.

4.8 Undesirable effects

In common with other local anaesthetics, adverse reactions to Xylocaine with Adrenaline are rare and are usually the result of excessively high blood concentrations due to inadvertent intravascular injection, excessive dosage, rapid absorption or occasionally to hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient. In such circumstances systemic effects occur involving the central nervous system and/or the cardiovascular system.

The adverse reaction profile for Xylocaine with adrenaline is similar to those of other amide local anaesthetics. Adverse reactions caused by the drug per se are difficult to distinguish from the physiological effects of the nerve block (e.g. decrease in blood pressure, bradycardia), events caused directly (e.g. nerve trauma) or indirectly by the needle puncture.

Tabulated list of adverse reactions

Frequencies are defined as 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) or not known (cannot be estimated from the available data).

The following table gives a list of the frequencies of undesirable effects:

System Organ Class

Frequency Classification

Adverse Drug Reaction

Immune system disorders

Rare

Allergic reactions, anaphylactic reaction

Nervous system disorders

Common

Paraesthesia, dizziness

Uncommon

Signs and symptoms of CNS toxicity (convulsions, numbness of tongue and paraesthesia circumoral, tinnitus, tremor, dysarthria, hyperacusis, visual disturbances, CNS depression)

Rare

Neuropathy, peripheral nerve injury, arachnoiditis

Eye disorders

Rare

Diplopia

Cardiac disorders

Common

Bradycardia

Rare

Cardiac arrest, cardiac arrhythmias

Vascular disorders

Common

Hypotension, hypertension

Respiratory, thoracic and mediastinal disorders

Rare

Respiratory depression

Gastrointestinal disorders

Common

Nausea, vomiting

4.8.1 Acute systemic toxicity

Systemic toxic reactions primarily involve the central nervous system (CNS) and the cardiovascular system (CVS). Such reactions are caused by high blood concentrations of a local anaesthetic, which may appear due to (accidental) intravascular injection, overdose or exceptionally rapid absorption from highly vascularised areas (see section 4.9). CNS reactions are similar for all amide local anaesthetics, while cardiac reactions are more dependent on the drug, both quantitatively and qualitatively. Signs of toxicity in the central nervous system generally precede cardiovascular toxic effects, unless the patient is receiving a general anaesthetic or is heavily sedated with drugs such as benzodiazepine or barbiturate.

Central nervous system toxicity is a graded response with symptoms and signs of escalating severity. The first symptoms are usually, circumoral paraesthesia, numbness of the tongue, light-headedness, hyperacusis, tinnitus and visual disturbances. Dysarthria, muscular twitching or tremors are more serious and precede the onset of generalised convulsions. These signs must not be mistaken for a neurotic behaviour. Unconsciousness and grand mal convulsions may follow which may last from a few seconds to several minutes. Hypoxia and hypercarbia occur rapidly following convulsions due to the increased muscular activity, together with the interference with respiration and possible loss of functional airways. In severe cases apnoea may occur. Acidosis hyperkalaemia, hypocalcaemia and hypoxia increase and extend the toxic effects of local anaesthetics.

Recovery is due to redistribution of the local anaesthetic drug from the central nervous system and subsequent metabolism and excretion. Recovery may be rapid unless large amounts of the drug have been injected.

Cardiovascular system toxicity may be seen in severe cases and is generally preceded by signs of toxicity in the central nervous system. In patients under heavy sedation or receiving a general anaesthetic, prodromal CNS symptoms may be absent. Hypotension, bradycardia, arrhythmia and even cardiac arrest may occur as a result of high systemic concentrations of local anaesthetics, but in rare cases cardiac arrest has occurred without prodromal CNS effects.

In children, early signs of local anaesthetic toxicity may be difficult to detect in cases where the block is given during general anaesthesia.

4.8.2 Treatment of acute toxicity

If signs of acute systemic toxicity appear, injection of the local anaesthetic should be stopped immediately and CNS symptoms (convulsion, CNS depression) must promptly be treated with appropriate airway/respiratory support and the administration of anticonvulsant drugs.

If circulatory arrest should occur, immediate cardiopulmonary resuscitation should be instituted. Optimal oxygenation and ventilation and circulatory support as well as treatment of acidosis are of vital importance.

If cardiovascular depression occurs (hypotension, bradycardia), appropriate treatment with intravenous fluids, vasopressor, chronotropic and or inotropic agents should be considered. Children should be given doses commensurate with age and weight.

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 website: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Accidental intravascular injections of local anaesthetics may cause immediate (within seconds to a few minutes) systemic toxic reactions. In the event of overdose, systemic toxicity appears later (15–60 minutes after injection) due to the slower increase in local anaesthetic blood concentration (see section 4.8.1 and 4.8.2).

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group (ATC code): N01B B52

Lidocaine is a local anaesthetic of the amide type. At high doses lidocaine has a quinidine like action on the myocardium i.e. cardiac depressant. All local anaesthetics stimulate the CNS and may produce anxiety, restlessness and tremors.

5.2 Pharmacokinetic properties

Lidocaine is readily absorbed from the gastro-intestinal tract, from mucous membranes and through damaged skin. It is rapidly absorbed from injection sites including muscle.

Elimination half-life is 2 hours.

Lidocaine undergoes first pass metabolism in the liver.

Less than 10% of a dose is excreted unchanged via the kidneys.

The speed of onset and duration of action of lidocaine are increased by the addition of a vasoconstrictor and absorption into the site of injection is reduced.

5.3 Preclinical safety data

Lidocaine and adrenaline are well-established active ingredients.

In animal studies, the signs and symptoms of toxicity noted after high doses of lidocaine are the results of the effects on the central nervous and cardiovascular systems. No drug related adverse effects were seen in the reproduction toxicity studies, neither did lidocaine show any mutagenic potential in either in vitro or in vivo mutagenicity tests. Cancer studies have not been performed with lidocaine, due to the area and duration of therapeutic use for this drug.

Genotoxicity tests with lidocaine showed no evidence of mutagenic potential. A metabolite of lidocaine, 2,6-dimethylaniline, showed weak evidence of activity in some genotoxicity tests. The metabolite 2,6-dimethylaniline has been shown to have carcinogenicity potential in preclinical toxicological studies evaluating chronic exposure. Risk assessments comparing the calculated maximum human exposure from intermittent use of lidocaine, with the exposure used in preclinical studies, indicate a wide margin of safety for clinical use.

6. Pharmaceutical particulars
6.1 List of excipients

Sodium chloride, sodium metabisulphite, methylparahydroxybenzoate, sodium hydroxide, hydrochloric acid and water for injections.

6.2 Incompatibilities

Not applicable

6.3 Shelf life

Two years.

Use within 3 days of first opening.

6.4 Special precautions for storage

Store between 2°C and 8°C.

6.5 Nature and contents of container

Multiple dose vial – 20 ml.

6.6 Special precautions for disposal and other handling

No special requirements. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. Marketing authorisation holder

Aspen Pharma Trading Limited,

3016 Lake Drive,

Citywest Business Campus,

Dublin 24, Ireland

8. Marketing authorisation number(s)

PL 39699/0084

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 14/08/1985

Date of last renewal: 21st May 2002

10. Date of revision of the text

31/01/2017