Summary of medicine characteristics - 1%W/V LIDOCAINE INJECTION BP
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT1 NAME OF THE MEDICINAL PRODUCT
1% w/v Lidocaine Injection BP.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ampoule contains 2ml 5ml 10ml 20ml
Lidocaine Hydrochloride H2O 20mg 50mg 100mg 200mg
3. PHARMACEUTICAL FORM
Solution for injection.
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
Infiltration and nerve block anaesthesia and intravenous regional anaesthesia
4.2. Posology and method of administrationRecommended dosage schedule
Unless directed otherwise, up to 200 mg of Lidocaine hydrochloride, corresponding to approx. 20 ml of 1 % w/v Lidocaine Injection BP, are given to adults.
The maximum daily dose is 200 mg of Lidocaine hydrochloride.
The dosage should be calculated in ml per kg body weight. Unless prescribed otherwise, children are administered up to 4 mg of Lidocaine hydrochloride, corresponding to approx. 0.4 ml of 1 % w/v Lidocaine Injection BP.
The maximum daily dose is 4 mg of Lidocaine hydrochloride per kg B.W.
When Lidocaine is used in obstetrics, it must be remembered that pregnant women need 1/3 less of local anaesthetics.
The dose should be reduced for patients with heart failure, liver diseases, for patients receiving drugs which enhance the effects of Lidocaine (see Interactions), in pregnancy, for newborns and infants, and for patients who are more than 60 years old.
As a matter of principle, the lowest possible dose and concentration of the local anaesthetic should be used.
Method of administration
Intracutaneous, subcutaneous, intramuscular for infiltration anaesthesia, perineural injection and intravenous infusion for nerve block anaesthesia.
In order to exclude inadvertent intravasal injection, the injection must be performed under repeated aspiration attempts.
When injection in the spinal chord region is intended, a small test dose should be given 5 min prior to the full dose in order to exclude subarachnoidal injection.
Every local anaesthetic procedure must be performed under strictly aseptic conditions.
Before undertaking any local anaesthetic procedure, appropriate instruments and drugs for emergency treatment should be made available.
If more than 25 % of the maximum dose are to be given, (i.e. 50 mg of Lidocaine hydrochloride, corresponding to 5 ml of 1 % w/v Lidocaine Injection BP) creation of venous access is recommended.
1 % w/v Lidocaine Injection BP must not be used in cases of
– Severely disturbed cardiac conduction (sino-atrial, atrioventricular or intraventricular blocks of higher degree, eg. 2nd and 3rd degree A-V Block) – bradycardia with heart rate below 50 bpm,
– ADAMS-STOKES syndrome
– WOLF-PARKINSON-WHITE syndrome,
– sudden heart failure (acute cardiac decompensation)
– hypersensitivity to amide-type local anaesthetics,
– suspicion of hereditary tendency to malignant hyperthermia,
– disorders of blood coagulation, anticoagulant therapy,
– infections in the region of injection
– uncooperative patient
4.4. Special warnings and precautions for use
Precautions for use
Especially careful medical monitoring is mandatory if 1 % w/v Lidocaine Injection BP is used in the following conditions:
– Disorders of cardiac impulse generation and conduction (sick sinus syndrome, 1st degree A-V Block, bundle branch block),
– respiratory depression,
– increased tendency to convulsions,
– diseases of liver and kidneys,
– myocardial weakness (cardiac insufficiency),
– severe hypotension (systolic blood pressure below 90 mm Hg)
Before undertaking any local anaesthetic procedure, venous access is recommended. Appropriate instruments and drugs for emergency treatment should be made available.
4.5. Interactions with other medicinal products and other forms of interaction
Beta blockers (e.g. propranolol, metoprolol), cimetidine, and norepinephrine have a synergetic effect on the action of Lidocaine; in acidosis, the plasma concentration of free Lidocaine is increased. These conditions may necessitate dose reduction.
If epinephrine or norepinephrine are given additionally, but separately, frequency or seriousness of side effects on the heart may be markedly increased.
Drugs stimulating the hepatic metabolism of drug substances by microsomal enzyme induction, e.g. phenobarbitone or phenytoin, reduce the efficacy of Lidocaine.
Lidocaine may have a synergetic effect on peripheral muscle relaxants, esp. suxamethonium chloride.
Simultaneously administered diazepam raises the threshold for Lidocaine to produce convulsions. This must be kept in mind when monitoring patients for signs of toxicity of Lidocaine.
4.6. Pregnancy and lactation
Lidocaine crosses the placental barrier. During pregnancy, 1 % w/v Lidocaine Injection BP should only be used if the expected benefits clearly outweigh potential hazards. The doses applied should be as low as possible. 1 % Lidocaine Injection BP should also be used very cautiously in obstetrics, especially in situations of fetal hypoxia and acidosis.
Lidocaine is secreted into breast milk. Therefore, caution should be exercised when administering 1 % w/v Lidocaine injection BP to nursing women: In general, however, nursing does not have to be discontinued.
4.7. Effects on ability to drive and use machines
Because of the effects of Lidocaine on the C.N.S. impaired ability to drive or to operate machinery must be considered.
Therefore, after use of 1 % w/v Lidocaine Injection BP in surgery, operative dentistry or after procedures involving the use on extended body areas, the physician has to decide whether the patient is fit for driving or operating machines
4.8 Undesirable effects
Frequently, especially under too rapid administration, central nervous disorders are observed, such as sleepiness, dizziness, vertigo, confusion, blurred vision, dysarthria, dysphagia, tinnitus, trembling, flushing, chills, tingling and skin paraesthesia, further restlessness, irritability, euphoria, hallucinations and depression. Frequently observed gastrointestinal disorders include anorexia, nausea, and vomiting. These adverse effects are more frequent under rapid onset of systemic effects of lidocaine hydrochloride.
Rarely, neurological complications following central nervous blocks -mainly spinal anaesthesia – may occur such as persistent anaesthesia, paraesthesia, paresis or plegia of the lower extremities and loss of sphincter control (e.g. cauda equina syndrome).
After spinal anaesthesia, transient pain in the lower extremities and lower back pain is commonly observed. The pain may last several (up to 5) days and will resolve spontaneously.
Rarely, especially in cases of overdosage, serious adverse effects such as muscular convulsions, possibly up to spasms of the entire body, impaired conscience up to deep unconsciousness (coma), respiratory depression or even arrest, drop of blood pressure, bradycardia, tachyarrhythmia, and shock are observed.
Foetal bradycardia in connection with the use of lidocaine hydrochloride in obstetrics has been reported.
Allergic reactions such as exanthema, urticaria, oedema, hypotension and anaphylactic shock have been observed sporadically.
In elderly patients the incidence of side effects may be increased.
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.
Minor overdosage mainly affects the C.N.S. symptoms (see „Undesirable Effects“) disappear in most cases after discontinuation of the administration of Lidocaine.
Gross overdosage will cause convulsions, disturbance of conscience and even coma, respiratory depression, shock, myocardial conduction disorders or blocks.
Immediately discontinue administration!
Give respiratory support; ensure sufficient ventilation and patency of the respiratory tract; if required, perform mouth-to-mouth or mouth-to-nose ventilation; give oxygen.
Immediately start cardio-pulmonary resuscitation, if necessary.
For treatment of spasms / convulsions give diazepam or a short-acting barbiturate, institute artificial respiration.
In case of sudden drop of blood pressure ensure appropriate positioning of the patient (head-down position); give vasopressors and volume replacement fluids. Epinephrine and analeptics acting on the C.N.S. are contraindicated.
For bradycardias give atropine i. v. for therapy of A-V blocks orciprenaline may be given; transient pacemaker therapy may be instituted if necessary.
There is no specific antidote.
Lidocaine cannot be eliminated by haemodialysis.
5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic properties
The local anaesthetic effect of lignocaine results from blockage of the sodium channels of neural fibres: Impulse generation and conduction are suppressed and the sensation of pain is discontinued without effects on consciousness. The anaesthetising effect is reversible and confined to the area of application.
The sensitivity of neural fibres to lidocaine depends on their diameter; thin fibres are anaesthetised earlier than thicker ones. The order of loss of nerve function is as follows: pain, temperature, touch and pressure. The order of return of nerve function is inverse, i.e. return of pain sensation is latest.
In inflamed tissues, the efficacy of lidocaine may be reduced due to the lower pH in such regions.
5.2. Pharmacokinetic properties
Onset of the local anaesthetic effect of lignocaine is rapid, i.e. within less than 5 min. Its duration is between 1 and 2 hours. The elimination of lignocaine from the region of application depends on tissue perfusion: Due to the concentration gradient in the area of application lignocaine diffuses into the surrounding tissue, into blood vessels and is eventually washed away by the bloodstream.
Most of an administered lignocaine dose ( 90 – 95 %) is hepatically metabolised by desalkylation to monoethyl glycine xylidide (MEGX) and
further to glycine xylidide (GX). The degree of formation of 2,6-xylidine is not exactly known. Metabolisation of lignocaine strongly depends on liver perfusion. Vasoactive substances, e.g. glucagon or isoprenaline increase the hepatic perfusion and consecutively the elimination of lignocaine.
The elimination of lignocaine from the plasma is biphasic with an initial half life time of approx. 10 min. (distribution phase) and a terminal half life time of 1.5 – 3 hours (elimination phase). The half life time of lignocaine is prolonged in newborns (2.9 – 3.3 hours) in patients with cardiac and particularly with hepatic insufficiency (3 – 19 hours).
The half life times of the metabolites are longer than that of lignocaine (MEGX: 2 hours, GX: 10 hours). In situations of renal insufficiency, further extension of the half life time and accumulation of GX in the plasma must be considered
5 – 10 per cent of lignocaine are excreted unchanged in urine, the remaining proportion in the form of the metabolites.
The predominant metabolite in the urine is 4-hydroxy-2,6-xylidine (65 %). The plasma protein binding is 60 – 80 per cent in adults, 20 – 40 per cent in adolescents and about 25 per cent in newborns.
Lignocaine passes across the placental barrier and in fetal blood its concentration is about 60 per cent of that in maternal blood. Because of the low protein binding in fetal blood the concentration of free lignocaine is about 1.4 times that of the maternal value.
Lignocaine is metabolised by the foetus; the half life time is about 3 hours.
Lignocaine appears in breast milk. Its concentration is about 40 per cent of the concentration in maternal blood.
Preclinical safety data
The toxic effects of lignocaine become manifest in the central nervous system and the cardiovascular system.
The toxic effects of lignocaine depend on the level of the plasma concentration; the higher the plasma concentration and the more rapid its rise, the more frequent and more serious are the toxic reactions.
The basic causes of high plasma concentrations are actual overdose of lignocaine, injection into a vein or artery and too rapid resorption from the injection site.
Depending on the individual sensitivity toxic reactions occur from a concentration of ca. 4 – 6 pg lignocaine/ml venous blood.
6.1. List of excipients
Sodium chloride, sodium hydroxide, water for injections
Lidocaine hydrochloride is incompatible with solutions containing sodium bicarbonate, with injectable preparations of amphotericin B, sulfadiazine sodium, methohexital sodium, cephazolin sodium, phenytoin, and other alkaline solutions. Therefore, 1 % Lidocaine Injection BP must not be mixed with such solutions.
6.3. Shelf life
2 ml: 18 months
5 ml: 24 months
10 ml: 30 months
20 ml: 30 months
6.4. Special precautions for storage
Do not store above 25°C.
6.5. Nature and contents of container
1 % w/v Lidocaine Injection BP is supplied in plastic ampoules of low-density polyethylene (Mini-Plasco) of 2 ml, 5 ml, 10 ml, 20 ml.
6.6. Instructions for use/handling
The product is supplied in single-dose containers.
Disinfect the exterior of the ampoule prior to use.
7. MARKETING AUTHORISATION HOLDER
B. Braun Melsungen AG
D – 34212 Melsungen
8. MARKETING AUTHORISATION NUMBER
9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION
13 June 1996