4.1 Therapeutic indications
Lidocaine is a local anaesthetic of the amide group. Lidocaine solution for
injection is indicated for use in infiltration anaesthesia, intravenous regional
anaesthesia and nerve blocks.

The method of administration of lidocaine varies according to the procedure
(infiltration anaesthesia or nerve block)and intravenous regional anaesthesia for
lidocaine supplied in glass vials due to contain Methyl Paraben which is used as
preservative in glass vials.
The dosage should be 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. The maximum dose for healthy adults should not
exceed 200 mg.

Children and elderly or debilitated patients require smaller doses, commensurate
with age and physical status.

Lidocaine should be administered by persons with resuscitative skills and
equipment.
Facilities for resuscitation should be available when administering local
anaesthetics.
As with other local anaesthetics, lidocaine should be used with caution in patients
with epilepsy, myasthenia gravis, impaired cardiac conduction, congestive cardiac
failure, bradycardia or impaired respiratory function, including where agents are
known to interact with lidocaine either to increase its availability or additive
effects e.g. phenytoin or prolong its elimination e.g. hepatic or end renal
insufficiency where the metabolites of Lidocaine may accumulate, or if the dose or
site of administration is likely to produce high blood levels. Lidocaine is
metabolised in the liver and it should be used with caution in patients with
impaired hepatic function.
The effect of local anaesthetics may be reduced if the injection is made into an
inflamed or infected area.

Intramuscular Lidocaine may increase creatinine phosphokinase concentrations
which can interfere with the diagnosis of acute myocardial infarction. Lidocaine
has been shown to be porphyrinogenic in animals and should be avoided in persons
suffering from porphyria.
Hypokalaemia, hypoxia and disorder of acid-base balance should be corrected
before treatment with intravenous lidocaine begins.
Certain local anaesthetic procedures may be associated with serious adverse
reactions, regardless of the local anaesthetic drug used, e.g.:
Central nerve blocks may cause cardiovascular depression, especially in the
presence of hypovolaemia, and therefore epidural anaesthesia should be used with
caution in patients with impaired cardiovascular function.

Retrobulbar injections may rarely reach the cranial subarachnoid space, causing
serious / severe reactions, including cardiovascular collapse, apnoea, convulsions
and temporary blindness.
Retro- and peribulbar injections of local anaesthetics carry a low risk of persistent
ocular muscle dysfunction. The primary causes include trauma and/or local toxic
effects on muscles and/or nerves.
The severity of such tissue reactions is related to the degree of trauma, the
concentration of the local anaesthetic and the duration of exposure of the tissue to
the local anaesthetic. For this reason, as with all local anaesthetics, the lowest
effective concentration and dose of local anaesthetic should be used.
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 (see section 4.6).

Epidural anaesthesia may lead to hypotension and bradycardia. This risk can be
reduced by preloading the circulation with crystalloidal or colloidal solutions.
Hypotension should be treated promptly
Lidocaine Injection is not recommended for use in neonates. The optimum serum
concentration of lidocaine required to avoid toxicity, such as convulsions and
cardiac arrhythmias, in this age group is not known.

Cimetidine and propranolol depress microsomal enzyme activity, thus enhancing
lidocaine toxicity during anti-arrhythmic infusions if concomitantly administered
with these drugs, requiring a reduction in the dosage of lidocaine. Both drugs
decrease hepatic blood flow. Also, cimetidine depresses microsomial activity.
Ranitidine produces a small reduction in Lidocaine clearance. Increase in serum
levels of lidocaine may also occur with anti-viral agents (e.g. amprenavir,
atazanavir, darunavir, lopinavir).
Hypokalaemia caused by diuretics may antagonize the action of lidocaine if
administered concomitantly (see section 4.4).

Lidocaine should be used with caution in patients receiving other local anaesthetics
or agents structurally related to amide-type local anaesthetics (e.g. antiarrhythmics,
such as mexiletine), since the systemic toxic effects are additive.
Specific interaction studies with lidocaine and class III antiarrhythmic drugs (e.g.
amiodarone) have not been performed, but caution is advised.
There may be an increased risk of ventricular arrhythmia in patients treated
concurrently with antipsychotics which prolong or may prolong the QT interval
(e.g. pimozide, sertindole, olanzapine, quetiapine, zotepine), prenylamine,
adrenaline (if accidently injected intravenously)) or 5HT3 antagonists (e.g.
tropisetron, dolasetron).
Concomitant use of quinupristin/dalfopristin may increase lidocaine levels with a
subsequent increased risk of ventricular arrhythmias and therefore should be
avoided.

There may be an increased risk of enhanced and prolonged neuromuscular
blockade in patients treated concurrently with muscle relaxants (e.g.
suxamethonium).
Narcotics are probably proconvulsants and this would support the evidence that
Lidocaine reduces the seizure threshold to fentanyl in man.
Opioid-antiemetic combination sometimes used for sedation in children could
reduce the convulsant threshold to lignocaine and increase the CNS depressant
effect.
While adrenaline (epinephrine) when used in conjunction with lidocaine might
decrease vascular absorption, it greatly increases the danger of ventricular
tachycardia and fibrillation if accidentally injected intravenously.
Cardiovascular collapse has been reported following the use of bupivacaine in

patients on treatment with verapamil and timolol; lidocaine is closely related to
bupivacaine.

Pregnancy
Although animal studies have revealed no evidence of harm to the foetus, lidocaine
should not be administered during early pregnancy unless the benefits are
considered to outweigh the risks.

Lidocaine readily crosses the placental barrier after epidural or intravenous
administration to the mother. The ratio of umbilical to maternal venous
concentration is 0.5 to 0.6. The foetus appears to be capable of metabolising
Lidocaine at term. The elimination half-life in the newborn of the drug received in
utero is about three hours, compared with 100 minutes in the adult. Elevated
lidocaine levels may persist in the newborn for at least 48 hours after delivery.
Foetal bradycardia or tachycardia (see section 4.4), neonatal bradycardia,
hypotonia or respiratory depression may occur.
Lactation
Small amounts of lidocaine are secreted into breast milk and the possibility of an
allergic reaction in the infant, albeit remote, should be borne in mind when using
lidocaine in nursing mothers.

Where outpatient anaesthesia affects areas of the body involved in driving or
operating machinery, patients should be advised to avoid these activities until
normal function is fully restored. Where major motor nerve block occurs e.g.
Brachial plexus, epidural, spinal block. Where there is a loss of sensation resulting
from nerve block to areas of muscle co-ordination or balance. Advice is that for
general anaesthesia as sedative/hypnotic drugs are often used during nerve
blockade.

In common with other local anaesthetics, adverse reactions to lidocaine are rare
and are usually the result of raised plasma concentrations due to accidental
intravascular injection, excessive dosage or rapid absorption from highly vascular
areas, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance
on the part of the patient. Systemic toxicity mainly involves the central nervous
system and/or the cardiovascular system (See also section 4.9).

Blood and Lymphatic System Disorders
Lidocaine may also produce methaemoglobinaemia.
Immune system disorders

Hypersensitivity reactions (allergic or anaphylactoid reactions, anaphylactic shock)
– see also Skin & subcutaneous tissue disorders) are rare. They may be
characterised by cutaneous lesions,
Skin testing for allergy to lidocaine is not considered to be reliable.
Localised nerve damage at the site of injection (very rare).
Nervous & Psychiatric disorders
Neurological signs of systemic toxicity include dizziness or light-headedness,
nervousness, tremor, circumoral paraesthesia, tongue numbness, drowsiness,
convulsions, coma.
Nervous system reactions may be excitatory and or depressant. Signs of CNS
stimulation may be brief, or may not occur at all, so that the first signs of toxicity
may be confusion and drowsiness, followed by coma and respiratory failure.

CNS (central nervous system) reactions may be excitatory and/or depressant..
Signs of CNS stimulation may be brief or may not occur at all, so that the first
signs of toxicity may be confusion and drowsiness, followed by coma and
respiratory failure.
Neurological complications of spinal anaesthesia include transient neurological
symptoms such as pain of the lower back, buttock and legs. These symptoms
usually develop within twenty-four hours of anaesthesia and resolve within a few
days. Isolated cases of arachnoiditis or cauda equina syndrome, with persistent
paraesthesia, bowel and urinary dysfunction, or lower limb paralysis have been
reported following spinal anaesthesia with lidocaine and other similar agents. The
majority of cases have been associated with hyperbaric concentrations of
Lidocaine or prolonged spinal infusion.
Psychotic reactions have been reported following infusion for the control of
arrhythmia.

Eye disorders
Blurred vision, diplopia and transient amaurosis may be signs of lidocaine toxicity.
Bilateral amaurosis may also be a consequence of accidental injection of the optic
nerve sheath during ocular procedures. Orbital inflammation and diplopia have
been reported following retro or peribulbar anaesthesia (see section 4.4)

Ear and labyrinth disorders
Tinnitus, hyperacusis
Cardiac and vascular disorders
Cardiovascular reactions are depressant and may manifest as hypotension,
bradycardia, myocardial depression, cardiac arrhythmias and possibly cardiac
arrest or circulatory collapse.
Hypotension may accompany spinal and epidural anesthesia. Isolated cases of
bradycardia and cardiac arrest have also been reported.
Profound hypotension may be associated with B blockade, widespread sympathetic
block from spinal or epidural block, intercostal nerve block administration or
supine hypotension in pregnancy.
The major adverse effects on the CNS and CVS are primarily due to the absorption
of lidocaine into the systemic circulation.

Ventricular fibrillation occurs less frequently than that seen with bupivacaine.
Respiratory, thoracic or mediastinal disorders
Dyspnoea, bronchospasm and respiratory depression
Gastrointestinal
Nausea, vomiting.
Skin and subcutaneous tissue disorders
Rash, urticaria, oedema (including angioedema, face oedema)

Prolonged neural blockade following epidural may be due to delayed spread.
Permanent neural blockade may be more likely associated with hypotension and
cord ischaemia.
Following regional blockade as when lidocaine is injected intrathecally or
extradurally, hypotension, hypoventilation, Horners Syndrome and hypoglycaemia
may be seen. The degree of these effects will depend on the dose and the height of
the block. Urinary retention may occur following sacral or lumbar epidural block.
It should not outlast the duration of the block. Apnoea and coma followed by
aphasia and hemiparesis may occur following stellate ganglion block. The

probable cause is a direct injection of lidocaine into the vertebral or carotid
arteries.
Profound lethargy and death have been reported following the injection of only 10
– 32 mg of lidocaine for dental blocks.
The initial CNS toxic effects are demonstrated by a gradual onset of drowsiness or
inebriation similar to alcoholic intoxication. Balance is disturbed, dizziness or
light-headedness, nervousness, circumoral pins and needles (circumoral
paraesthesia), tongue numbness, tinnitus, hyperacusis, visual disturbances,
restlessness and twitching may occur. Severe intoxication of rapid onset may
immediately lead to convulsions followed by circulatory depression. Major
overdosage may depress all systems simultaneously.

Symptoms of acute systemic toxicity
Central nervous system toxicity presents with symptoms of increasing severity.
Patients may present initially with circumoral paraesthesia, numbness of the
tongue, light-headedness, hyperacusis and tinnitus. Visual disturbance and
muscular tremors or muscle twitching are more serious and precede the onset of
generalised convulsions. These signs must not be mistaken for neurotic behaviour.
Unconsciousness and grand mal convulsions may follow, which may last from a
few seconds to several minutes. Hypoxia and hypercapnia occur rapidly following
convulsions due to increased muscular activity, together with the interference with
normal respiration and loss of the airway. In severe cases, apnoea may occur.
Acidosis increases the toxic effects of local anaesthetics.
Effects on the cardiovascular system may be seen in severe cases. Hypotension,
bradycardia, arrhythmia and cardiac arrest may occur as a result of high systemic
concentrations, with potentially fatal outcome.

Recovery occurs as a consequence of redistribution of the local anaesthetic drug
from the central nervous system and metabolism and may be rapid unless large
amounts of the drug have been injected.
Treatment of acute toxicity
If signs of acute systemic toxicity appear, injection of the anaesthetic should be
stopped immediately.

Treatment will be required if convulsions and CNS depression occurs. The
objectives of treatment are to maintain oxygenation, stop the convulsions and
support the circulation. A patent airway should be established and oxygen should
be administered, together with assisted ventilation (mask and bag) if necessary.
The circulation should be maintained with infusions of plasma or intravenous
fluids. Where further supportive treatment of circulatory depression is required,
use of a vasopressor agent may be considered although this involves a risk of CNS
excitation. Convulsions may be controlled by the intravenous administration of
Diazepam or Thiopentone Sodium, bearing in mind that anti-convulsant drugs may
also depress respiration and the circulation. Prolonged convulsions may jeopardize
the patient's ventilation and oxygenation and early endotracheal intubation should
be considered. If cardiac arrest should occur, standard cardiopulmonary
resuscitation procedures should be instituted. Continual optimal oxygenation and
ventilation and circulatory support as well as treatment of acidosis are of vital
importance.

Dialysis is of negligible value in the treatment of acute overdosage with lidocaine.

ATC Code:N01BB02
Lidocaine is a local anaesthetic of the amide type. It is used to provide local
anaesthesia by nerve blockade at various sites in the body and in the control of
dysrhythmias. It acts by inhibiting the ionic refluxes required for the initiation and
conduction of impulses, thereby stabilising the neuronal membrane. In addition to
blocking conduction in nerve axons in the peripheral nervous system, lidocaine has
important effects on the central nervous system and cardiovascular system. After
absorption, lidocaine may cause stimulation of the CNS followed by depression
and in the cardiovascular system, it acts primarily on the myocardium where it may
produce decreases in electrical excitability, conduction rate and force of
contraction. It has a rapid onset of action (about one minute following intravenous
injection and fifteen minutes following intramuscular injection) and rapidly
spreads through the surrounding tissues. The effect lasts about ten to twenty
minutes and about sixty to ninety minutes following intravenous and intramuscular
injection respectively.

The concentration of Lidocaine in the blood will be determined by its rate of
absorption from the site of injection, the rate of tissue distribution and the rate of
metabolism and excretion.
The systemic absorption of Lidocaine is determined by the site of injection, the
dosage and its pharmacological profile. The maximum blood concentration occurs
following intercostal nerve blockade followed in order of decreasing concentration,
the lumbar epidural space, brachial plexus site and subcutaneous tissue. The total
dose injected regardless of the site is the primary determinant of the absorption rate
and blood levels achieved. There is a linear relationship between the amount of
Lidocaine injected and the resultant peak anaesthetic blood levels.
The lipid solubility and vasodilator activity will also influence its rate of
absorption. This is seen in the epidural space where Lidocaine is absorbed more
rapidly than prilocaine.
Lidocaine is distributed throughout the total body water. Its rate of disappearance

from the blood can be described by a two or three compartment model. There is a
rapid disappearance (alpha) phase which is believed to be related to uptake by
rapidly equilibrating tissues (i.e. tissues with a high vascular perfusion). The
slower phase is related to distribution, to slowly equilibrating tissues (Betaphase)
and to its metabolism and excretion (Gamma phase).
Lidocaine is distributed less rapidly than prilocaine (an amide drug of similar
potency and duration of action) but equally as with mepivacaine. Its distribution is
throughout
all body tissues. In general, the more highly perfused organs will show higher
concentrations of Lidocaine. The highest percentage of this drug will be found in
skeletal muscle. This is because of the mass of muscle rather than an affinity.
Lidocaine undergoes enzymatic degradation primarily in the liver. Some
degradation may take in tissues other than liver. The main pathway involves

oxidative deethylation to monoethylglycinexylidide followed by a subsequent
hydrolysis to xylidine.
The excretion occurs via the kidney with less than 5% in the unchanged form
appearing in the urine. The renal clearance is inversely related to its protein
binding affinity and the pH of the urine. This suggests by the latter that excretion
of Lidocaine occurs by non-ionic diffusion..

No further relevant information other than that which is included in other sections
of the Summary of Product Characteristics.

Sodium Chloride
Methyl Paraben
Water for Injections

Lidocaine solution for injection should not be mixed with other preparations unless
compatibility is known.

Do not store above 25 °C for:
1% Lidocaine size: 5ml and 10ml plastic ampoule.
2% Lidocaine size: 5ml plastic ampoule.
Do not store above 30 °C for:
1% Lidocaine size: 20ml plastic ampoule and 20 ml, 50 ml glass vials.
2% Lidocaine size: 10ml and 20ml plastic ampoule and 50 ml glass vials.

The product is a clear, colorless solution in Polyethylene Plastic Ampoule and
Glass vials (contain Methyl Paraben used as preservative in glass vials).
The solutions are supplied in:
1% Lidocaine:
Polyethylene Plastic Ampoule: 5 ml, 10 ml and 20 ml.
Glass Vials: 20 ml and 50 ml

2% Lidocaine:
Polyethylene Plastic Ampoule: 5 ml, 10 ml and 20 ml.
Glass Vials: 50 ml

For single use only.
Use immediately after opening.
If only part of an ampoule is used, discard the remaining solution.
The injection should not be used if particles are present.