Lidocaine Hydrochloride Injection BP 1.0% w / v

1. Name Of The Medicinal Product

Lidocaine Hydrochloride Injection BP 1.0% w/v.

2. Qualitative And Quantitative Composition

Each 1ml of solution contains 1.0% w/v of Lidocaine Hydrochloride BP (Lidocaine Hydrochloride).

3. Pharmaceutical Form

Clear, colourless, sterile solution for injection, intended for parenteral administration to human beings.

4. Clinical Particulars

4.1 Therapeutic Indications

Lidocaine is a local anaesthetic of the amide group. The injectable form has a wide range of applications for nerve blockade. It can be used by percutaneous infiltration; to block a major nerve plexus such as the brachial; for epidural anaesthesia; for intravenous regional analgesia.

4.2 Posology And Method Of Administration

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 200mg.

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

4.3 Contraindications

Known hypersensitivity to anaesthetics of the amide type.

4.4 Special Warnings And Precautions For Use

Lidocaine should be administered by persons with resuscitative skills and equipment. Extreme care should be observed in patients with hypovolaemia, heart block or other conduction disturbances. It should be used with caution in patients with congestive heart failure, bradycardia or respiratory depression, 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.

Intramuscular Lidocaine may increase creatinine phosphokinase concentrations which can interfere with the diagnosis of acute myocardial infarction. The use of Lidocaine for the treatment of ventricular arrhythmias not associated with a myocardial infarction might be hazardous in patients with hypoxia where there is a depression of the cough reflex. Lidocaine has been shown to be porphyrinogenic in animals and should be avoided in persons suffering from porphyria.

The effect of Lidocaine may be reduced if it is injected into inflamed or infected areas. Care should be observed in patients suffering from epilepsy.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Lidocaine toxicity is enhanced by the co-administration of cimetidine and propranolol. Both drugs decrease hepatic blood flow. Also, cimetidine depresses microsomial activity. Ranitidine produces a small reduction in Lidocaine clearance.

Cardiovascular collapse has been reported following the use of bupivacaine in patients on treatment with verapamil and timolol; Lidocaine is closely related to bupivacaine.

Prenylamine and Lidocaine Infusion may precipitate atrioventricular block and ventricular tachycardia.

Dopamine and 5 hydroxytryptamine reduce the convulsant threshold to Lidocaine.

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 Lidocaine and increase the CNS depressant effect.

While adrenaline when used in conjunction with Lidocaine might decrease vascular absorption, it greatly increases the danger of ventricular tachycardia and fibrillation if accidentally injected intravenously.

Hypoxia and acidosis will enhance the cardiovascular and central nervous system toxicity of Lidocaine in animals. In man, such changes commonly accompany convulsions and can be expected to exacerbate cardiac sequelae.

4.6 Pregnancy And Lactation

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.

Moderate doses of Lidocaine over short periods have been used in mothers receiving antiarrhythmic drugs in late pregnancy. Foetal blood concentrations are about half of the maternal values and by term the foetus is capable of metabolising Lidocaine.

Local anaesthetics are not noted for producing congenital malformations. Foetal bradycardia may occur during extradural analgesia using Lidocaine. This may result from placental drug transfer or it may be secondary to maternal circulatory changes.

Symptoms of overdose will occur in the same order as in the adult. In clinical practice, neonatal effects are generally slight and are largely limited to hypotonia and neonatal depression. Excessive doses can occur following paracervical block probably resulting from direct entry of drug to the placental circulation, or because solution is injected to the head in mistake for the caudal canal or the paracervical region.

Lidocaine is secreted into the breast milk. Although mothers on infusions of Lidocaine could probably continue to breast feed with safety, caution should be exercised. There is a remote possibility of an idiosyncratic or allergic reaction.

4.7 Effects On Ability To Drive And Use Machines

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.

4.8 Undesirable Effects

Localised nerve damage at the site of injection (very rare).

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 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 - 32mg of Lidocaine for dental blocks.

Diplopia and temporary blindness has been reported following Lidocaine for maxillary block, also respiratory arrest following retrobulbar block.

The major adverse effects on the CNS and CVS are primarily due to the absorption of Lidocaine into the systemic circulation. Lidocaine may also produce methaemoglobinaemia.

The initial CNS toxic effects are demonstrated by a gradual onset of drowsiness or inebriation similar to alcoholic intoxication. Balance is disturbed, circumoral pins and needles, numb tongue, roaring in the ears, 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. Psychotic reactions have been reported following infusion for the control of arrhythmia.

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.

Ventricular fibrillation occurs less frequently than that seen with bupivacaine.

Respiratory Depression

Medullary depression associated with systemic effects, following retrobulbar nerve blockade, high spinal or extradural blocks causing motor block, possible subarachnoid spread following on excessive dose by interscalene brachial plexus block. An increase in extradural pressure may cause transient respiratory depression. Respiratory distress as an allergic response can occur.

Allergic reactions (including anaphylaxis) have been reported rarely.

4.9 Overdose

Systemic toxicity affecting principally the CNS and secondarily the CVS may arise because of acute or cumulative overdosage. Acute toxicity can occur due to excessive doses above that recommended minimum by rapid entry of Lidocaine into the circulation from accidental or deliberate intravenous injection, rapid absorption from a vascular site or transplacental passage. Cumulative toxicity may slow elimination or drug interaction.

Symptoms relating to the central nervous and cardiovascular systems are: gradual onset of drowsiness or inebriation, disturbance in balance, later circumoral pins and needles, numb tongue, roaring in the ears, visual disturbances, restlessness and twitching, progressing to convulsions and coma in severe states. If the overdose is of rapid onset, convulsions may occur closely followed by cardiovascular depression. Major overdosage may depress all symptoms simultaneously.

Psychotic reactions have been reported following I.V. infusions of Lidocaine. Bradycardia and hypotension, the latter being due to sympathetic blockade and vasomotor and cardiac centres depression. In the medulla, cardiac depression, allergic reaction.

Heavy pre-anaesthetic medication should be avoided, which will mask early signs of CNS toxicity, while an anticonvulsant may even suppress seizure activity until circulatory collapse supervenes.

Initially, oxygen should be administered. It may be necessary to give an anticonvulsant. Thiopentone has a more rapid onset of action than diazepam. Both drugs especially thiopentone may seriously exacerbate circulatory and respiratory depression.

Persistent convulsion may require the use of suxamethonium to stop muscle activity and allow for intubation, control of the airway and artificial ventilation. Agents to support the cardiovascular system may also be required. The correction of acidosis is very important.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Lidocaine is used to provide anaesthesia by nerve blockade at various sites in the body and in the control of dysrhythmias. 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.

5.2 Pharmacokinetic Properties

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 de-ethylation 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.

5.3 Preclinical Safety Data

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

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sodium Chloride

Sodium Hydroxide 10% w/v

Dilute Hydrochloric Acid

Water for Injections

6.2 Incompatibilities

Lidocaine has been found to be incompatible when mixed with amphotericin, methohexitone and glyceryl trinitrate. It is not advisable to mix Lidocaine with other agents.

6.3 Shelf Life

4 years (48 months).

If only part of an ampoule is used, the remainder should be discarded.

6.4 Special Precautions For Storage

Do not store above 25°C.

Keep in outer carton.

6.5 Nature And Contents Of Container

2ml, 5ml, 10ml & 20ml clear glass ampoules, glass type 1 Ph.Eur. presented in cardboard cartons to contain 10 x 2ml ampoules; 10 x 5ml ampoules; 10 x 10ml ampoules and 10 x 20ml ampoules.

6.6 Special Precautions For Disposal And Other Handling

For S.C., I.M. or I.V. injection.

Use as directed by the physician.

Keep out of reach of children.

If only part used, discard the remaining solution.

7. Marketing Authorisation Holder

Antigen International Ltd.

Roscrea

Co. Tipperary

Ireland

8. Marketing Authorisation Number(S)

PL 02848/0002R

9. Date Of First Authorisation/Renewal Of The Authorisation

25 November 1986 / 24 June 1992

10. Date Of Revision Of The Text

April 2008