This information is intended for use by health professionals

1. Name of the medicinal product

Lidocaine Injection BP with Preservative 2 %

2. Qualitative and quantitative composition

Each 1 ml contains 20.0 mg of lidocaine hydrochloride, corresponding to 16.2 mg lidocaine.

Each 20 ml solution contains 400 mg Lidocaine Hydrochloride

For the full list of excipients, see section 6.1

3. Pharmaceutical form

Solution for injection.

Clear and colourless solution.

4. Clinical particulars
4.1 Therapeutic indications

Lidocaine Injection is used as a local anaesthetic.

4.2 Posology and method of administration

Lidocaine Injection is used as a local anaesthetic when injected subcutaneously.

This solution is not intended for use intravenously. Solutions of lidocaine which contain preservatives should not be used for spinal, epidural, caudal or intravenous regional anaesthesia.

The dosage should be adjusted according to the response of the patient and the site of administration. The lowest concentration and the smallest dose producing the required effect should be given. The maximum single dose for healthy adults should not exceed 200 mg corresponding to 10 mls.

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

4.3 Contraindications

• Known hypersensitivity to lidocaine or other anaesthetics of the amide type

• Known hypersensitivity to hydroxybenzoates

• Complete heart block

• Hypovolaemia

4.4 Special warnings and precautions for use

As with other local anaesthetics, lidocaine should be used with caution in patients with epilepsy, cardiac conduction disturbances, (see also section 4.3 Contraindications) congestive cardiac failure, bradycardia, severe shock, impaired respiratory function or impaired renal function with a creatinine clearance of less than 10mL/minute. Lidocaine is metabolised in the liver and it should be used with caution in patients with impaired hepatic function. Lidocaine should not be used in cases of acute porphyrias.

Patients with myasthenia gravis are particularly susceptible to the effects of local anaesthetics.

Facilities for resuscitation should be available when administering local anaesthetics.

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

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

• 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 motor 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.

Hameln 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.

4.5 Interaction with other medicinal products and other forms of interaction

Effects of Lidocaine on other medicinal products

Lidocaine should be used with caution in patients receiving other local anaesthetics or agents structurally related to amide-type local anaesthetics (e.g. anti-arrhythmics, such as mexiletine), since the systemic toxic effects are additive. Specific interaction studies with lidocaine and class III anti-arrhythmic drugs (e.g. amiodarone) have not been performed, but caution is advised.

There may be an increased risk of enhanced and prolonged neuromuscular blockade in patients treated concurrently with muscle relaxants (e.g. suxamethonium).

Effects of other medicinal products on Lidocaine

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), or 5HT3 antagonists (e.g. tropisetron, dolasetron).

Concomitant use of quinupristin/dalfopristin should be avoided.

Hypokalaemia produced by acetazolamide, loop diuretics and thiazides antagonises the effect of lidocaine.

The clearance of lidocaine may be reduced by beta-adrenoceptor blocking agents (e.g. propranolol) and by cimetidine, requiring a reduction in the dosage of lidocaine. Increase in serum levels of lidocaine may also occur with anti-viral agents (e.g. amprenavir, atazanavir, darunavir, lopinavir).

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

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.

4.6 Fertility, pregnancy and lactation

Pregnancy

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

Lidocaine given by local perineal infiltration prior to delivery crosses rapidly into the foetal circulation. Elevated lidocaine levels may persist in the newborn for at least 48 hours after delivery. Foetal bradycardia or 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.

4.7 Effects on ability to drive and use machines

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.

4.8 Undesirable effects

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 4.9 Overdose).

Solutions of lidocaine which contain preservatives are not suitable for spinal, epidural or caudal anaesthesia. Adverse effects reported following unpreserved lidocaine solutions administered by this route include hypotension and isolated cases of bradycardia and cardiac arrest.

Immune system disorders

Hypersensitivity reactions (allergic or anaphylactoid reactions, anaphylactic shock) – see also Skin & subcutaneous tissue disorders)

Skin testing for allergy to Lidocaine is not considered to be reliable.

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.

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.

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 Special warnings and precautions for use)

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.

Respiratory, thoracic or mediastinal disorders

Dyspnoea, bronchospasm, respiratory depression, respiratory arrest

Gastrointestinal disorders

Nausea, vomiting

Skin & subcutaneous tissue disorders

Rash, urticaria, oedema (including angioedema, face oedema)

Blood and the lymphatic system disorders

Methaemoglobinaemia.

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

4.9 Overdose

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 central nervous system excitation.

If the convulsions do not stop spontaneously in 15-20 seconds, they 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 jeopardise 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.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Local anaesthetic, ATC code: N01BB02.

Lidocaine is a local anaesthetic of the amide group. It is used to provide local anaesthesia at various sites in the body and 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. In the cardiovascular system, it acts primarily on the myocardium where it may produce decreases in electrical excitability, conduction rate and force of contraction.

5.2 Pharmacokinetic properties

Lidocaine is absorbed from injection sites including muscle and its rate of absorption is determined by factors such as the site of administration and the tissue vascularity. Except for intravascular administration, the highest blood levels occur following intercostal nerve block and the lowest after subcutaneous administration. Lidocaine is bound to plasma proteins, including alpha-1-acid-glycoprotein. The drug crosses the blood-brain and placental barriers.

Lidocaine is metabolised in the liver and about 90 % of a given dose undergoes N-dealkylation to form monoethylglycinexylidide and glycinexylidide, both of which may contribute to the therapeutic and toxic effects of lidocaine. Further metabolism occurs and metabolites are excreted in the urine with less than 10 % of unchanged lidocaine. The elimination half-life of lidocaine following an intravenous bolus injection is one to two hours, but this may be prolonged in patients with hepatic dysfunction.

5.3 Preclinical safety data

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

6. Pharmaceutical particulars
6.1 List of excipients

Sodium Chloride Ph. Eur.

Methylhydroxybenzoate Ph. Eur. (1.7 mg/ml)

Propylhydroxybenzoate Ph. Eur. (0.3 mg/ml)

Hydrochloric acid Ph. Eur. (QS)

Sodium Hydroxide Ph. Eur. (QS)

Water for Injections Ph. Eur.

6.2 Incompatibilities

Lidocaine causes precipitation of amphotericin, methohexitone sodium and sulfadiazine sodium in glucose injection. It is recommended that admixtures of lidocaine and glyceryl trinitrate should be avoided.

6.3 Shelf life

24 months.

6.4 Special precautions for storage

Keep container in the outer carton in order to protect from light.

Store between 10°C and 25°C.

6.5 Nature and contents of container

Type II clear glass vial, 20 ml and 50 ml, with chlorbutyl rubber stopper, plastic outer cap and inner aluminium ring. Packed in cardboard cartons to contain 10 vials.

6.6 Special precautions for disposal and other handling

Use as directed by a physician.

7. Marketing authorisation holder

hameln pharma ltd

Nexus, Gloucester Business Park

Gloucester, GL3 4AG

UK

8. Marketing authorisation number(s)

01502/0036

9. Date of first authorisation/renewal of the authorisation

02/09/2005

10. Date of revision of the text

01/04/2020