Xylocaine Accordion Gel 2%

1. Name Of The Medicinal Product

Xylocaine Accordion Gel 2%.

2. Qualitative And Quantitative Composition

Each gram of gel contains lidocaine hydrochloride Ph. Eur. corresponding to lidocaine hydrochloride anhydrous 20mg.

3. Pharmaceutical Form

Topical anaesthetic gel.

4. Clinical Particulars

4.1 Therapeutic Indications

Surface anaesthesia and lubrication:

- The male and female urethra during cystoscopy, catheterisation, exploration by sound and other endourethral operations.

- Nasal and pharyngeal cavities in endoscopic procedures such as gastroscopy and bronchoscopy.

- During proctoscopy and rectoscopy.

- Intubation.

Symptomatic treatment of pain in connection with cystitis and urethritis.

4.2 Posology And Method Of Administration

As with any local anaesthetic, reactions and complications are best averted by employing the minimal effective dosage. No more than 4 doses should be given in any 24 hour period. Debilitated, elderly patients and children should be given doses commensurate with their age and physical condition. In children under 12 years of age, the dose should not exceed 6mg/kg.

Urethral anaesthesia

Surface anaesthesia of the male adult urethra: For adequate analgesia in males 20ml ( = 400mg lidocaine hydrochloride) jelly is required. The jelly is instilled slowly until almost half the syringe (10ml = 200mg lidocaine hydrochloride) is emptied. A penile clamp is then applied for several minutes at the corona; then the rest of the jelly is instilled.

When anaesthesia is especially important, e.g. during sounding or cystoscopy, a larger quantity of jelly, for example 30-40ml, may be instilled in 3-4 portions and allowed to work for 10 minutes before insertion of the instrument.

Surface anaesthesia of the female adult urethra: Instil 5-10ml in small portions to fill the whole urethra. In order to obtain adequate anaesthesia, several minutes should be allowed prior to performing urological procedures.

Endoscopy

Instillation of 10-20ml is recommended for adequate analgesia and a small amount should be applied on the instrument for lubrication.

Lubrication for endotracheal intubation

About 5ml applied on the surface of the tube just prior to insertion. Care should be taken to avoid introducing the product into the lumen of the tube.

4.3 Contraindications

Known history of hypersensitivity to local anaesthetics of the amide type or other components of the gel.

4.4 Special Warnings And Precautions For Use

Absorption from wound surfaces and mucous membranes is relatively high, especially in the bronchial tree. Xylocaine Accordion Gel 2% should be used with caution in patients with traumatised mucosa and/or sepsis in the region of the proposed application.

If the dose or site of administration is likely to result in high blood levels, lidocaine, in common with other local anaesthetics, should be used cautiously in patients with epilepsy, impaired cardiac conduction, bradycardia, impaired hepatic function and in severe shock.

The oropharyngeal use of topical anaesthetic agents may interfere with swallowing and thus enhance the danger of aspiration. This is particularly important in children because of their frequency of eating. Numbness of the tongue or buccal mucosa may increase the danger of biting trauma.

When used for endotracheal tube lubrication care should be taken to avoid introduction of the jelly into the lumen of the tube. The jelly may dry on the inner surface leaving residue which tend to clump with flexion, narrowing the lumen. There have been rare reports in which this residue has caused the lumen to occlude.

Care should be taken to avoid instillation of excessive amounts of Xylocaine Accordion Gel 2% into the rectum. This is of particular importance in infants and children. Systemic absorption of lidocaine may occur from the rectum, and large doses may result in CNS side-effects. On rare occasions convulsions have occurred in children.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Lidocaine should be used with caution in patients receiving antiarrhythmic drugs since the toxic effects are additive.

4.6 Pregnancy And Lactation

There is no, or inadequate, evidence of safety of the drug in human pregnancy but it has been in wide use for many years without apparent ill consequence, animal studies having shown no hazard. If drug therapy is needed in pregnancy, this drug can be used if there is no safer alternative.

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

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

In extremely rare cases local anaesthetic preparations have been associated with allergic reactions (in most severe instances anaphylactic shock).

Systemic adverse reactions are rare and may result from high plasma levels due to excessive dosage, rapid absorption or may result from hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient. Such reactions involve the central nervous system and/or the cardiovascular system.

CNS reactions are excitatory and/or depressant and may be characterised by nervousness, dizziness, convulsions, unconsciousness and possibly, respiratory arrest. The excitatory reactions may be very brief or may not occur at all, in which case the first manifestations of toxicity may be drowsiness, merging into unconsciousness and respiratory arrest.

Cardiovascular reactions are depressant and may be characterised by hypotension, myocardial depression, bradycardia and possibly cardiac arrest.

4.9 Overdose

Treatment of a patient with systemic toxicity consists of arresting convulsions and ensuring adequate ventilation with oxygen, if necessary, by assisted or controlled ventilation (respiration). If convulsions occur, they must be treated promptly by intravenous injection of thiopentone 100 or 200mg or diazepam 5 to 10mg. Alternatively succinylcholine 50 to 100mg i.v. may be used providing the clinician is capable of performing endotracheal intubation and managing a fully paralysed patient. If ventricular fibrillation or cardiac arrest occurs effective cardiopulmonary resuscitation must be instituted. Adrenaline in repeated doses and sodium bicarbonate should be given as rapidly as possible.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Xylocaine 2% gel provides prompt and profound anaesthesia of mucous membranes and lubrication which reduces friction. Its water-miscible base, characterized by high viscosity and low surface tension, brings the anaesthetic into intimate and prolonged contact with the tissue, giving effective anaesthesia of long duration (approx. 20-30 min). Anaesthesia usually occurs rapidly (within 5 min, depending upon the area of application).

Lidocaine like other local anaesthetics, causes a reversible blockade of impulse propagation along nerve fibres by preventing the inward movement of sodium ions through the nerve membrane. Local anaesthetics of the amide type are thought to act within the sodium channels of the nerve membrane.

Local anaesthetic drugs may also have similar effects on excitable membranes in the brain and myocardium. If excessive amounts of drug reach the systemic circulation rapidly, symptoms and signs of toxicity will appear, emanating from the central nervous and cardiovascular systems.

Central nervous system toxicity (See "Overdose") usually precedes the cardiovascular effects as it occurs at lower plasma concentrations. Direct effects of local anaesthetics on the heart include slow conduction, negative inotropism and possibly cardiac arrest.

5.2 Pharmacokinetic Properties

Lidocaine is absorbed following topical administration to mucous membranes, its rate and extent of absorption being dependent upon the concentration and total dose administered, the specific site of application, and duration of exposure. In general, the rate of absorption of local anaesthetic agents following topical application is most rapid after intratracheal and bronchial administration. Lidocaine is also well-absorbed from the gastrointestinal tract, although little intact drug appears in the circulation because of biotransformation in the liver.

The plasma protein binding of lidocaine is dependent on the drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4μg of free base per ml, 60 to 80 per cent of lidocaine is protein-bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.

Blood concentrations of lidocaine after instillation into the urethra of doses up to 800mg are of low range and below toxic levels.

Lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion.

Lidocaine is metabolised rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. N-dealkylation, a major pathway of biotransformation yields the metabolites monoethylglycinexylidide and glycinexylidide. The pharmacological and toxicological actions of these metabolites are similar to, but less potent than, those of lidocaine. Approximately 90% of lidocaine administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. The primary metabolite in urine is a conjugate of 4-hydroxy-2, 6-dimethylaniline.

The elimination half-life of lidocaine following an intravenous bolus injection is typically 1.5 to 2.0 hours. Because of the rapid rate at which lidocaine is metabolised, any condition that affects liver function may alter lidocaine kinetics. The half-life may be prolonged two-fold or more in patients with liver dysfunction. Renal dysfunction does not affect lidocaine kinetics but may increase the accumulation of metabolites.

Factors such as acidosis and the use of CNS stimulants and depressants affect the CNS levels of lidocaine required to produce overt systemic effects. Objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6.0µg free base per ml.

5.3 Preclinical Safety Data

Lidocaine hydrochloride is a well established active ingredient.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Hydroxypropyl methylcellulose, sodium hydroxide, hydrochloric acid, purified water.

6.2 Incompatibilities

None.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Store below 25°C.

6.5 Nature And Contents Of Container

Disposable bellows syringes made of polypropylene.

6.6 Special Precautions For Disposal And Other Handling

None stated.

7. Marketing Authorisation Holder

Astra Pharmaceuticals Limited

Home Park

Kings Langley

Hertfordshire

WD4 8DH

8. Marketing Authorisation Number(S)

PL 0017/5037R

9. Date Of First Authorisation/Renewal Of The Authorisation

Granted 29th May 1990 following review

10. Date Of Revision Of The Text

17 May 2000