Consumer medicine information

Lignospan Special

Lidocaine (lignocaine) hydrochloride; Adrenaline (epinephrine)

BRAND INFORMATION

Brand name

Lignospan Special

Active ingredient

Lidocaine (lignocaine) hydrochloride; Adrenaline (epinephrine)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Lignospan Special.

WHAT’S IN YOUR MEDICINE

Active ingredients:

  • Lignocaine hydrochloride 44 mg (2.2 mL Cartridge), 36 mg (1.8 mL Cartridge)
  • Adrenaline (as acid tartrate) 27.5 µg (2.2 mL Cartridge), 22.5 µg (1.8 mL Cartridge)

Other ingredients:

  • Sodium chloride,
  • sodium hydroxide,
  • disodium edetate,
  • potassium metabisulfite,
  • water for injections.

Presentation:
Box of 50 cartridges single use, containing each 2.2 mL or 1.8 mL of solution.

WHAT YOUR MEDICINE IS USED FOR AND HOW IT WORKS

LIGNOSPAN SPECIAL is given by injection to cause loss of feeling before and during dental procedures. It contains two active ingredients: Lignocaine hydrochloride, a local anaesthetic to prevent the pain, and adrenaline tartrate, a vasoconstrictor, which makes it, last longer (Adrenaline narrows the blood vessels at the site of injection, which keeps the anaesthetic where it’s needed for a longer time) and controls bleeding during the surgery.

ADVICE BEFORE USING THE MEDICINAL PRODUCT:

In deciding to use a medicine, the risks of using the medicine must be weighed against the good it will do. This is a decision you and your dentist will make. For local anaesthetics, the following should be considered.

This product should not be used if:

  • You are allergic to:
    - adrenaline
    - lignocaine, procaine or any local anaesthetic
    - sodium metabisulfite or any sulfites
    - any other ingredient included in the product.
    Symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing: swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.
  • You have arterial hypertension (high blood pressure), coronary disease or valvular cardiac disease (heart or circulation problems).
  • You have an over active thyroid gland, whether or not treated for this.
  • You have cerebral arteriosclerosis (hardening in the brain arteries).
  • You have an inflammation (pain, swelling, redness and heat) or sepsis (blood infection) in the region of the proposed injection.

This product should be used with caution if:

  • You have problems with your heart, blood vessels, circulation and heart rhythm.
  • You have epilepsy.
  • You have high blood pressure, asthma, diabetes and thyroid problems.
  • You have hepatic (liver) or renal (kidney) diseases.
  • You have an allergy to Para Amino Benzoic Acid (PABA) derivatives (such as procaine and benzocaine).
  • You have prostatic hypertrophy (enlarged prostate).
  • You are pregnant or breast-feeding.

LIGNOSPAN SPECIAL MAY INTERACT WITH OTHER MEDICINES.

It should not be used if you are taking:

  • Mono Amine Oxidase Inhibitors (MAOI) or tricyclic antidepressants (medicines used to treat depression).
  • Phenothiazines or butyrophenones (medicines used to treat mental illnesses).
  • Vasopressor drugs (medicines used to elevate blood pressure).
  • Ergot type oxytocic drugs (medicines used to induce labour in pregnant women).

It should be used with caution if you are taking:

  • Beta-blockers (medicines used to lower high blood pressure and/or treat heart problems).
  • Guanethidine, a medicine used for pain or in surgery.
  • Hypoglycaemic drugs (medicine used to treat high blood sugar).
  • Anti-arrhythmic drugs and amiodarone (medicines used to treat irregular heartbeats).
  • Anti-epileptic drugs (medicines used to treat epilepsy).
  • Cardiac glycosides (medicines used to treat heart failure).
  • Cimetidine (medicine used to treat reflux and stomach or duodenal ulcers).
  • Halogenated compounds (medicines used in anaesthetics such as chloroform, halothane, or cyclopropane).

These medicines may be affected by LIGNOSPAN SPECIAL, or may affect how well it works. Please make sure that you tell your dentist about all medicines which you are taking, including any that you buy without a prescription from your pharmacy, supermarket or health food shop. Your dentist will advise you what to do if you are taking any of these medicines.

HOW THIS MEDICINE WILL BE USED:

Your dentist will explain to you why you are being treated with LIGNOSPAN SPECIAL and what dose you will be administered. Your dentist will inject LIGNOSPAN SPECIAL into your oral (mouth) cavity. This will result in an area of numbness at the site of injection. One cartridge is usually sufficient but your dentist may give you a greater quantity. He will adjust the dosage according to your age, your health and the dental work to be performed.

IN CASE OF OVERDOSE:

Your dentist will determine the amount of solution, which is needed to provide pain control during your treatment, and it is very unlikely that you would receive too much LIGNOSPAN SPECIAL. However, some persons tolerate lignocaine and adrenaline less well than others and the signs and symptoms of too much of these substances in your blood include: nervousness, dizziness, blurred vision, nausea, trembling, convulsions, slow or irregular heart beat, troubled breathing.

Tell your dentist immediately if you experience any of these symptoms during or shortly after your treatment.

Whenever you are given LIGNOSPAN SPECIAL, equipment will be available to care for you if an overdose happens.

While you are being given LIGNOSPAN SPECIAL

Things you must not do:

  • Do not eat or drink anything hot until the feeling has returned to your mouth. You may burn or bite yourself.

Things to be careful of:

  • Be careful driving or operating machinery until you know how LIGNOSPAN SPECIAL 1/80.000 affects you. You may be drowsy and your reflexes may be slow.
  • Do not drink alcohol immediately before or after you are given LIGNOSPAN SPECIAL.
  • If you drink alcohol while you are being given LIGNOSPAN SPECIAL, your blood pressure may drop making you feel dizzy and faint.
  • Please talk to your dentist or pharmacist about these possibilities if you think they may bother you.

UNWANTED EFFECTS

LIGNOSPAN SPECIAL like most other medicines may cause side effects in some patients.

Although not all of these side effects may occur, if they do occur they may need medical attention. While you are in your dentist office, your dentist will carefully follow the effects of LIGNOSPAN SPECIAL. However, some effects may not be noticed or appear later.

Check with your dentist if any of the following side effects occur:
Common reactions:

  • Infection and pain in the injection site
  • Tingling and numbness of the hand and feet or increased feeling or sensitivity of the skin
  • You are feeling nervous, nauseous or dizzy
  • You have a headache
  • You are trembling, have buzzing in the ears, blurred vision or have any abnormal feeling
  • Your breathing is difficult
  • Your heart is beating slowly or irregularly
  • You have facial swelling or inflammation of gums
  • You may have a loss of sensation and muscle function following the injection of LIGNOSPAN SPECIAL.

Resolution occurs generally within two weeks.

Very rare reactions:
There are some serious unwanted reactions, which may happen if LIGNOSPAN SPECIAL is given intravenously or you are very sensitive to it, it may cause:

  • You have skin rash, hives or itching.
  • Fits.
  • Unconsciousness.
  • Breathing problems.
  • Low blood pressure.
  • Slow heart beat.
  • Collapse.

If you have them, you may have had a serious (allergic) reaction to LIGNOSPAN SPECIAL.

You may need urgent medical attention or hospitalisation.

Tell your dentist if you notice anything else that is making you feel unwell.

Some people may get other side effects while using LIGNOSPAN SPECIAL.

You may be allergic to sulfites and therefore show allergic symptoms to LIGNOSPAN SPECIAL as difficulty breathing or shortness of breath or skin reactions.

If you have problems with your blood vessels or have high blood pressure, you may react exaggeratedly to the adrenaline contained in LIGNOSPAN SPECIAL and develop a small injury at the site of injection.

STORAGE CONDITIONS

It is most unlikely that you will be asked to look after this medicine. Your dentist will keep it below 25°C and protected from light. He will not use this medicine after the expiry date printed on the package.

All medicines must be kept in a safe place out of the reach of children.

FURTHER INFORMATION

Remember this medicine is only for you. Only a dentist can administer this product. This leaflet provides only a summary of the information known about LIGNOSPAN SPECIAL. If you have any questions, want to know more about this medicine, or have some doubts, ask your dentist.

SPONSOR

Specialites Septodont,
14 Cliffbrook Crescent,
EMU PLAINS,
NSW 2750, Australia.

DISTRIBUTOR

Henry Schein Regional Pty Ltd,
3 -11 Primrose Avenue,
Roseberry
NSW 2018 Australia.

DATE OF INFORMATION

June 2003

1.8 mL - AUST R 49327
2.2 mL - AUST R 49328

LIGNOSPAN SPECIAL

(LIGNOCAINE HYDROCHLORIDE 2%, ADRENALINE 1/80.000 INJECTION)
LOCAL AND REGIONAL ANAESTHETIC

Published by MIMS December 2014

BRAND INFORMATION

Brand name

Lignospan Special

Active ingredient

Lidocaine (lignocaine) hydrochloride; Adrenaline (epinephrine)

Schedule

S4

 

1 Name of Medicine

Lidocaine (lignocaine) hydrochloride monohydrate with adrenaline (epinephrine) (as acid tartrate).

2 Qualitative and Quantitative Composition

See Table 1.
For single patient use only. Contains no anti-microbial agent. Discard unused contents after use.
Lignospan Special contains a local anaesthetic of amide type, lidocaine (lignocaine) hydrochloride monohydrate (2%), combined with a vasoconstrictor, adrenaline (epinephrine) as acid tartrate (1/80,000).

3 Pharmaceutical Form

Lignospan Special is an injection, solution - a clear colourless liquid.

4 Clinical Particulars

4.1 Therapeutic Indications

Lidocaine (lignocaine) solutions are indicated for the production of local anaesthesia in routine dental procedures and oral surgery by means of infiltration and nerve block techniques.
Lidocaine (lignocaine) solutions with adrenaline (epinephrine) are recommended for oral surgery requiring prolonged duration of anaesthesia and haemostasis.

4.2 Dose and Method of Administration

The lowest dosage that results in effective anaesthesia for the planned treatment should be used.
The dosage will depend upon the area of the oral cavity to be anaesthetised, the vascularity of the oral tissues and the technique of anaesthesia. Toxic doses vary widely between patients and toxic effects may occur after any local anaesthetic procedure. Careful observation of the patient must be maintained after administration of the local anaesthetic.
For adults, a single cartridge (2.2 mL) is generally sufficient.
Two cartridges (4.4 mL) may be used in case of large interventions.
For adolescents between 14 and 17 years, usual dosage one cartridge (2.2 mL).
Do not exceed 2 cartridges (4.4 mL) in general cases.
For children between 6 and 14, usual dose 3/4 of the cartridge (1.65 mL).
Do not exceed 1 1/2 cartridges (3.3 mL) in usual cases.
For children between 3 and 6, between 1/2 to 1 cartridge (1.1 mL to 2.2 mL).
Do not use on children under three years of age.
The product is injected either locally or in the vicinity of a dental nervous trunk.
The safe dose for people with acute or chronic disease may be substantially less than that for healthy individuals.
Cartridges are for single patient use only. Once opened, use immediately and discard remainder.

4.3 Contraindications

These may be of three types:

a. Contraindications to lidocaine (lignocaine).

Specific allergies to lidocaine (lignocaine) or to other anaesthetics of amide type; allergies of cross type procaine - lidocaine (lignocaine).

b. Contraindications to the vasoconstrictor.

Cerebral arteriosclerosis; arterial hypertension; coronary disease; valvular cardiac disease (particularly sequelae to acute rheumatic fever); thyrotoxicosis, untreated; known sensitivity to sympathomimetic amines.

c. Hypersensitivity to sulfites (potassium metabisulfite is present in the formula as an antioxidant).

Injection by intravenous route; inflammation or sepsis in the region of the proposed injection.
Use of a single cartridge in more than one patient is absolutely contraindicated.

4.4 Special Warnings and Precautions for Use

General precautions.

When any local anaesthetic agent is used, resuscitative equipment and drugs, including oxygen, should be immediately available in order to manage possible adverse reactions involving the cardiovascular, respiratory or central nervous systems. Because of the possibility of hypotension and bradycardia following major blocks, an IV cannula should be inserted before the local anaesthetic is injected. Delay in proper management of dose related toxicity, under ventilation from any cause and/or altered sensitivity may lead to the development of acidosis, cardiac arrest and death.
Injection should always be made slowly with frequent aspirations to avoid inadvertent intravascular injection which can produce cerebral symptoms even at low doses.
Note, however, that the absence of blood in the syringe does not assure that intravascular injection will be avoided. There should be careful monitoring of cardiovascular and respiratory vital signs after each injection.

Use with caution in the following circumstances.

The lowest dosage that results in effective anaesthesia should be used to avoid high plasma levels and serious adverse effects. Repeated doses of lidocaine (lignocaine) may cause significant increases in blood levels with each repeated dose due to slow accumulation of the drug or its metabolites. However, this is unlikely to occur at the doses normally used in dentistry. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients, acutely ill patients and children should be given reduced doses commensurate with their age and physical condition.
Lidocaine (lignocaine) should be used with caution in patients with epilepsy, bradycardia, digitalis intoxication, severe shock or heart block. Lidocaine (lignocaine) should also be used with caution in patients with impaired cardiovascular function as they may be less able to compensate for functional changes associated with prolongation of AV conduction produced by the drug. In patients with Stoke-Adams syndrome or Wolff-Parkinson-White syndrome care should be taken to avoid accidental arterio-venous injection.
Local anaesthetic solutions containing adrenaline (epinephrine) should be used with caution in areas of the body supplied by end arteries or having otherwise compromised blood supply. Patients with peripheral vascular disease and those with hypersensitive vascular disease may exhibit exaggerated vasoconstrictor response. Ischaemic injury or necrosis may result. Preparations containing a vasoconstrictor should be used with caution in patients during or following the administration of potent general anaesthetic agents, since cardiac arrhythmias may occur under such conditions.
Inadvertent intravascular injection of small doses of lidocaine (lignocaine) injected into the head or neck area, including retrobulbar, dental and stellate injection blocks, may produce adverse effects similar to systemic toxicity seen with unintentional intravascular injection of larger doses.
Lidocaine (lignocaine) should be used with caution in persons with known drug sensitivities. Patients allergic to para-aminobenzoic acid derivatives (procaine, benzocaine, etc.) have not shown cross sensitivity to lidocaine (lignocaine).
Solutions containing adrenaline (epinephrine) should be used with extreme caution in patients with severe or untreated hypertension, arteriosclerotic heart disease, heart block, cerebral vascular insufficiency, thyrotoxicosis, advanced diabetes or any other pathological condition that might be aggravated by the effects of adrenaline (epinephrine). Adrenaline (epinephrine) may induce anginal pain in patients suffering from ischaemic heart disease.
The safety and effectiveness of lidocaine (lignocaine) depend on proper dosage, correct technique and adequate precautions. Standard textbooks should be consulted regarding specific techniques and precautions for various anaesthetic procedures.
The patient should be advised to exert caution to avoid inadvertent trauma to the lips, tongue, check mucosa or soft palate when these structures are anaesthetised. Eating and drinking hot liquids should therefore be postponed until normal function returns.
Lidocaine (lignocaine) with adrenaline (epinephrine) solutions contain sodium metabisulfite, a sulfite that may cause allergic type reactions including anaphylactic symptoms and life threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than non-asthmatic people.
Prostatic hypertrophy.

Use in hepatic impairment.

Lidocaine (lignocaine) should be used with caution in patients with hepatic disease, since amide-type local anaesthetics are metabolised by the liver. Patients with hepatic impairment, because of their inability to metabolise or excrete local anaesthetics normally, are at greater risk of developing toxic plasma concentrations.

Use in renal impairment.

Lidocaine (lignocaine) should be used with caution in patients with renal disease, since amide-type local anaesthetics are excreted via kidneys. Patients with renal impairment, because of their inability to metabolise or excrete local anaesthetics normally, are at greater risk of developing toxic plasma concentrations.

Use in the elderly.

Elderly patients should be given reduced doses commensurate with their age and physical condition.

Paediatric use.

Do not use on children under three years of age. Children should be given reduced doses commensurate with their age and physical condition.

Effects on laboratory tests.

The intramuscular injection of lidocaine (lignocaine) may result in an increase in creatine phosphokinase levels. Thus, the use of this enzyme determination without isoenzyme separation, as a diagnostic test for the presence of acute myocardial infarction may be compromised by the intramuscular injection of lidocaine (lignocaine).

4.5 Interactions with Other Medicines and Other Forms of Interactions

The administration of local anaesthetic solutions containing adrenaline (epinephrine) or noradrenaline to patients receiving monoamine oxidase inhibitors, butyrophenones, tricyclic antidepressants or phenothiazines may produce severe prolonged hypotension or hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential. Concurrent administration of vasopressor drugs and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents.
As the Lignospan Special solution contains a vasoconstrictor (adrenaline (epinephrine) 1/80,000), concurrent use of either with a beta-adrenergic blocking agent (propranolol, timolol, etc.) may result in dose dependent hypertension and bradycardia with possible heart block.
The effects of adrenaline (epinephrine) may be potentiated by thyroid hormones.
Lignospan Special should be administered with caution to patients under the following treatments:
Hypoglycaemics: adrenaline (epinephrine) induced hyperglycaemia may lead to loss of blood sugar control in diabetic patients treated with hypoglycaemics.
Anti-arrhythmic agents (e.g. procainamide, mexiletine, disopyramide): lidocaine (lignocaine) may increase their effects.
Skeletal muscle relaxant (suxamethonium), combination with lidocaine (lignocaine) may lead to excessive neuro-muscular block.
Cardiac glycosides (e.g. digoxin): adrenaline (epinephrine) may interact with cardiac glycosides resulting in cardiac arrhythmias.
Adrenergic neuron blocking agents (e.g. guanethidine) since the product contains adrenaline (epinephrine).
Quinidine: combination with adrenaline (epinephrine) may lead to cardiac arrhythmias.
Cimetidine: increased serum levels of lidocaine (lignocaine) have been reported after concurrent cimetidine and lidocaine (lignocaine) administration.
Amiodarone: combination with lidocaine (lignocaine) may reduce the clearance of lidocaine (lignocaine) and seizures, sinus bradycardia and a long sinoatrial arrest have been reported. Patients receiving the combination should be carefully monitored.
Phenytoin and other antiepileptic drugs such as phenobarbitone, primidone and carbamazepine appear to enhance the metabolism of lidocaine (lignocaine) but the significance of this is not known. Phenytoin and lidocaine (lignocaine) have additive cardiac depressant effects.
Lidocaine (lignocaine) decreases the minimum effective concentration of inhalational anaesthetics, e.g. nitrous oxide.
Serious cardiac arrhythmias and acute pulmonary oedema if hypoxia present may occur if preparations containing adrenaline (epinephrine) are employed in patients during or following the administration of chloroform, halothane, cyclopropane, trichlorethylene or other halogenated compounds.
Structurally related local anaesthetics, lidocaine (lignocaine) should be used with caution in patients receiving agents structurally related to local anaesthetics.
Beta-adrenoreceptor antagonists - Propranolol and metoprolol reduce the metabolism of intravenous lidocaine (lignocaine). It is possible that this effect may also occur with other beta-adrenoreceptor antagonists. If these drugs are used concurrently then the patient should be closely observed for the signs of lidocaine (lignocaine) toxicity.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category A)
Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed.
The safe use of lidocaine (lignocaine) during pregnancy has not been established. Lidocaine (lignocaine) has, however, been used extensively for dental procedure during pregnancy with no proven increase in frequency of malformations or of harmful effects to mother or foetus.
 Lidocaine (lignocaine) passes into breast milk.
The amount of lidocaine (lignocaine) appearing in breast milk from a breastfeeding mother receiving parenteral lidocaine (lignocaine) is unlikely to lead to significant accumulation of the parent drug in the breastfed infant.
The remote possibility of an idiosyncratic or allergic reaction in the breastfed infant from lidocaine (lignocaine) remains to be determined.

4.7 Effects on Ability to Drive and Use Machines

Depending on the dosage, or if given inadvertently intravenously, local anaesthetics may have a mild effect on mental function and may temporarily impair locomotion and coordination.

4.8 Adverse Effects (Undesirable Effects)

Common reactions (≥ 1%).

Excluding postprocedural dental pain, local reactions at the injection site are the most common adverse events: infection, gingivitis, pain and oedema. Headache, paresthesia and hyperaesthesia are also reported after use of anaesthetic injections during dental procedures.

Very rare reaction (≤ 1%).

Serious adverse experiences following the administration of lidocaine (lignocaine) are similar in nature to those observed with other amide local anaesthetic agents. These adverse experiences are, in general, dose-related and may result from high plasma levels caused by excessive dosage, rapid absorption, unintended intravascular injection or may result from hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient. Serious adverse experiences are generally systemic in nature. The following types are those most commonly reported:

Central nervous system (very rare).

CNS manifestations are excitatory and/or depressant and may be characterised by light-headedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensations of heat, cold or numbness, agitation, difficulty in swallowing and slurred speech, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest which are less common.
The excitatory manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory arrest.
Drowsiness following the administration of lidocaine (lignocaine) is usually an early sign of a high blood level of the drug and may occur as a consequence of rapid absorption.

Cardiovascular system (very rare).

Cardiovascular manifestations are usually depressant and are characterised by bradycardia, hypotension, and cardiovascular collapse, which may lead to cardiac arrest.
Signs and symptoms of depressed cardiovascular function may commonly result from a vasovagal reaction, particularly if the patient is in an upright position.
Less commonly, they may result from a direct effect of the drug. Failure to recognize the premonitory signs such as sweating, a feeling of faintness, changes in pulse or sensorium may result in progressive cerebral hypoxia and seizure or serious cardiovascular catastrophe. Management consists of placing the patient in the recumbent position and ventilation with oxygen. Supportive treatment of circulatory depression may require the administration of intravenous fluids and, when appropriate, a vasopressor (e.g. ephedrine) as directed by the clinical situation.

Allergic reactions (very rare).

Allergic reactions are characterised by cutaneous lesions, urticaria, oedema or anaphylactoid reactions. Allergic reactions as a result of sensitivity to lidocaine (lignocaine) are extremely rare and, if they occur, should be managed by conventional means. The detection of sensitivity by skin testing is of doubtful value. Caution should be taken in asthmatic patients since Lignospan Special contains metabisulfites.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
The injection of excessive amounts of lidocaine (lignocaine) and adrenaline (epinephrine) injection may, due to the vasoconstrictor, cause ischaemia. This can be followed by reactive hyperaemia resulting in post extraction bleeding.
Most systemic reactions to local anaesthetics are from overdose and in dentistry would most frequently be caused by accidental intravenous injection (for symptoms, see Section 4.8 Adverse Effects (Undesirable Effects)).
If unusual reactions develop resuscitative and/or supportive measures should be started promptly:

For all symptoms.

If acute toxicity occurs the injection should be stopped immediately. A patent airway should be established and maintained, oxygen should be administered, and assisted or controlled ventilation should be provided as required.

Circulatory collapse.

Toxic cardiovascular reactions can include peripheral vasodilation, hypotension, bradycardia and cardiac arrest. Immediately resuscitate with oxygen and commence cardiovascular resuscitation procedures as appropriate, as well as treatment of acidosis are of vital importance.

Convulsions.

If convulsions occur, IV diazepam should be administered incrementally. Sodium thiopentone (5 mg/kg) may be used if diazepam is unavailable or ineffective. If convulsions interfere with breathing and/or are not rapidly controlled by specific anticonvulsant medication, suxamethonium (1-2 mg/kg) may be used to paralyse the patient.
Artificial ventilation must then be instituted.
If not treated immediately, both convulsions and cardiovascular depression may result in hypoxia, acidosis, bradycardia, arrhythmia and cardiac arrest.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Lidocaine (lignocaine) stabilises the neuronal membrane by decreasing its permeability to sodium ions and reversibly blocks the initiation and conduction of nerve impulses thereby producing local anaesthesia.
Local anaesthetics of the amide type are thought to act within sodium channels of the nerve membrane.
The onset - considered as rapid - and duration of anaesthesia (1 to 3 hours) depend on the route of administration and the dosage (volume and concentration) employed.
The addition of adrenaline (epinephrine) reduces the rate of local clearance of lidocaine (lignocaine) from the site of injection, thereby prolonging the duration of action.
Adrenaline (epinephrine) acts on both adrenergic receptors of tissue innervated by sympathetic nerves, except for the sweat glands and arteries of the face. It is the most important alpha receptor activator. Adrenaline (epinephrine) stimulates the heart to increase output, raises the systolic blood pressure, lowers the diastolic blood pressure, relaxes bronchial spasm and mobilises liver glycogen, resulting in hyperglycaemia and possibly glycosuria.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Information derived from diverse formulations, concentrations and usages reveals that lidocaine (lignocaine) is completely absorbed following parenteral administration, its rate of absorption depending, for example, upon various factors such as the site of administration and the presence or absence of a vasoconstrictor agent. The addition of adrenaline (epinephrine) considerably slows the absorption of lidocaine (lignocaine). Peak plasma concentrations are reduced by 50% following subcutaneous injection if adrenaline (epinephrine) in a proportion of 5 microgram/mL is added. Except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration.

Distribution.

The plasma binding of lidocaine (lignocaine) is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentration of 1 to 4 microgram of freebase per mL, 60 to 80 percent of lidocaine (lignocaine) is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.
Lidocaine (lignocaine) crosses the blood brain and placental barriers, presumably by passive diffusion.
Since the degree of plasma protein binding in the foetus is less than that of the mother, although free lidocaine (lignocaine) concentration will be the same, the total plasma concentration will be greater than in the mother.

Metabolism and excretion.

Lidocaine (lignocaine) is metabolised rapidly by the liver. Lidocaine (lignocaine) has a total plasma clearance of 0.95 L/min, a volume of distribution at steady state of 91 L, an elimination half-life of 1.6 hr and an estimated hepatic extraction ratio of 0.65. 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/toxicological actions of these metabolites are similar to, but less potent than those of lidocaine (lignocaine). Approximately 90% of lidocaine (lignocaine) 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.
Studies of lidocaine (lignocaine) metabolism following intravenous bolus injections have shown that the elimination half-life of this agent is typically 1.5 to 2.0 hours. Because of the rapid rate at which lidocaine (lignocaine) is metabolized, any condition that affects liver function may alter lidocaine (lignocaine) kinetics, e.g. acute myocardial infarction and/or congestive heart failure. The half-life may be prolonged two-fold or more in patients with liver dysfunction, possibly because of altered perfusion. Renal dysfunction does not affect lidocaine (lignocaine) kinetics but may increase the accumulation of metabolites (see Section 4.4 Special Warnings and Precautions for Use).

5.3 Preclinical Safety Data

Studies of lidocaine (lignocaine) in animals to evaluate the carcinogenic and mutagenic potential or the effect on fertility have not been conducted.

Genotoxicity.

The genotoxic potential of 2,6-xylidine has been studied with mixed results. Positive results were reported in assays for gene mutations (weakly positive in the Ames test with metabolic activation and the mouse lymphoma assay) and chromosomal damage (chromosomal aberrations in Chinese hamster ovary cells at concentrations at which the drug precipitated from solution). No evidence of genotoxicity was found in in vivo assay for chromosomal damage (micronucleus assay) and DNA damage (unscheduled DNA synthesis). Covalent binding studies of DNA from liver and ethmoid turbinates in rates indicated that 2,6-xylidine may be genotoxic under certain conditions in vivo.

Carcinogenicity.

A two year oral toxicity study of 2,6-xylidine, a metabolite of lidocaine (lignocaine), has shown that in both male and female rats, 2,6-xylidine in daily doses of 900 mg/m2 (150 mg/kg) resulted in carcinomas and adenomas of the nasal cavity. No nasal tumours were observed in the low dose (15 mg/kg or control animals). In addition, the compound also caused subcutaneous fibromas and or fibrosarcomas in male and female rats (significant at 150 mg/kg).

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C - Protect from light.

6.5 Nature and Contents of Container

Box of 50 cartridges single use containing each 2.2 mL or 1.8 mL of solution.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Lidocaine (lignocaine) hydrochloride monohydrate.

Chemical structure.


C14H23ClN2O.H2O.
Mr: 288.8.
2-diethylaminoaceto-2'6'-xylidide hydrochloride monohydrate.

CAS number.

CAS [6108-05-0].
White crystalline powder practically odourless. Lidocaine (lignocaine) hydrochloride monohydrate is very soluble in water, freely soluble in ethanol, and practically insoluble in ether.

Adrenaline (epinephrine) acid tartrate.

Chemical structure.


C13H19NO9.
Mr: 333.3.
(R)-1-(3,4-di-hydroxyphenyl)-2-methylaminoethanol hydrogen tartrate.

CAS number.

CAS [51-42-3].
White to greyish-white or light brownish-grey, odourless, crystalline powder. Adrenaline (epinephrine) acid tartrate 1.8 mg is approximately equivalent to 1 mg of adrenaline (epinephrine).

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine - S4.

Summary Table of Changes