Lidocaine-«Grindeks»

Therapeutic indications
Infiltration or regional anaesthesia, nerve blocks, epidural (lumbar and caudal) anaesthesia.
Ventriculararrhythmias (extrasystole, tachycardia, fibrillation) particularlyafter myocardial infarction; cardiac glycosides toxicity; cardiacsurgery, cardiac catheterization, coronography.

Posology and methods of administration

Local anaesthesia
Lidocaineis used for infiltration, regional and epidural anaesthesia inconformity with technical requirements and safety actions for each typeof anaesthesia. The dosage varies depending upon individual tolerance,planned procedure, the extent of the site to be anaesthetised andperfusion of tissues, required depth and duration of anaesthesia, etc.
Usually the smallest dose required to produce the desired effect should be used.
Adults. Usual dose of lidocaine should not exceed 200 mg.
Children. Usual dose of lidocaine should not exceed 3 mg/kg.
Forepidural anaesthesia, a test dose should be administered at least 5minutes before total dose to prevent inadvertent intravascular orsubarachnoid injection. It is suggested that aspiration should beperiodically done so as to be sure that blood has not entered thesyringe.
For continuous epidural, caudal or paracervicalanaesthesia, the maximal dose should not be repeated at intervals under90 minutes.
For intravenous regional anaesthesia (Bier’s block), thetourniquet should not be released until at least 20 minutes afteradministration.
Cardiac arrhythmias
The drug is used intravenously.
Adults.The usual dose is 50 – 100 mg administered under ECG monitoring. Thisdose is injected at a rate of 25 – 50 mg (1.25 – 2.5 ml 20 mg/mlsolution for injections) per minute. If necessary a second dose may begiven after 5 minutes. No more than 200 - 300 mg of lidocaine should beadministered during 1 - hour period.
In those patients in whomarrhythmia tends to recur and who are incapable of receiving oralantiarrhythmic therapy, intravenous infusions of lidocaine may beadministered at the rate of 1 – 4 mg/minute (20 - 50 µg/kg/min).Intravenous infusion must be given under ECG monitoring to avoidpotential overdose and toxicity. The infusion should be terminated assoon as the patient’s basic cardiac rhythm appears to be stable or atthe earliest signs of toxicity. It should rarely be necessary tocontinue the infusion beyond 24 hours. As soon as possible, patientsshould be changed to an oral antiarrhythmic agent for maintenancetherapy.
Children. Experience with lidocaine is limited. Itis recommended to use loading dose of 0.8 – 1 mg/kg repeated up to 3 –5 mg/kg, followed by continuous infusion of 10 – 50 µg/kg/min.
Inelderly and debilitated patients, and in patients with hepatic andrenal impairment lidocaine doses should be reduced; monitoring oflidocaine concentration in blood is needed.

Contraindications
Hypersensitivity to lidocaine and to other local anaesthetics of the amide type. Hypokalaemia.
Severeheart conduction disturbances (Adams-Stokes syndrome, severesinoatrial, atrioventricular block), acute heart failure, hypovolaemia,porphyria.

Special Warnings and Special Precautions for Use
Lidocaineshould be administered with caution in patients with epilepsy, hepaticor pulmonary impairment, congestive heart failure, severe renaldisease, marked hypoxia, severe respiratory depression, hypovolaemia orshock and in patients with impaired cardiac conduction or sinusbradycardia. Hypokalaemia, hypoxia and disorders of acid-base balanceshould be corrected before treatment with lidocaine begins.
Inpatients with heart failure, elderly and debilitated patients, in caseof hepatic impairment or after cardiac surgery lidocaine should beadministrated in lower doses.
Special caution is necessary whenintroducing lidocaine in head or neck region. Due to good blood supplyin this region there is a risk of drug injection exactly into bloodvessel and it may cause severe side effects. Therefore, in the case ofnerve blocks it is necessary to do aspiration so as to be sure thatblood has not entered the syringe. Respiration and ECG monitoring isrecommended during intravenous administration, it is advisable to keepreanimation equipment and drugs for urgent treatment of complications.
Inpatients with a bleeding tendency (an abnormality of the blood clottingmechanisms, anticoagulant therapy) administration of lidocaine forinjections into region of truncus sympaticus and its ganglia, anddeeply into muscle or epidural administration should be avoided.
The drug is not recommended for use if the anamnesis shows malignant hyperthermia.

Interaction with other medicinal products and other forms of interaction
Durationof action of lidocaine is increased by the addition of avasoconstrictor (epinephrine or norepinephrine) and absorption from thesite of injection is reduced. Prepared solution should be immediatelyused (see Incompatibilities).
Concomitant use of lidocaine with drugs reducing CNS activity may increase CNS depression.
Simultaneoususe with local anaesthetic bupivacaine may increase free lidocaineconcentrations in plasma. Free fraction of lidocaine may also beincreased by concomitant use of cocaine, as well as of oestrogensleading to a higher lidocaine toxicity.
There are advises avoid concomitant use with reboxetine.
Thecardiac depressant effects of lidocaine are additive with those ofother antiarrhythmics (for example, amiodarone, tocainide, etc.).
Concomitant use with antibacterials (quinupristin/dalfopristin) increases the risk of ventricular arrhythmia.
Whenusing lidocaine concomitantly with narcotics or anaesthetics thesynergism should be observed, the risk of respiratory depression isincreased.
Lidocaine may competitively enhance activity of suxamethonium.
Theclearance of lidocaine may be reduced by cimetidine and beta blockers(propranolol) , therefore, the concurrent use of these drugs increasesthe risk of lidocaine side effects.
The use of microsomal enzymeinducers (for example, barbiturates, benzodiazepines, phenytoine) mayenhance the metabolism of lidocaine in liver and increase dosagerequirements of lidocaine.
Hypokalaemia produced by acetazolamide, “loop diuretics”, and thiazides antagonises the effect of lidocaine.

Pregnancy and lactation
Lidocainecrosses the placenta. Studies in animals have not shown that lidocainecauses unfavourable effects in the foetus. Nevertheless, there are noadequate and well-controlled studies in pregnant women, therefore, thedrug is not recommended for use during this period.
Lidocaine may beused for analgesia during labour. When using lidocaine and the otherlocal anaesthetics it should be taken into account that hypotension maybe particularly problematic, the activity of labour may decrease, thechild may have an increased risk of hypoxia, bradycardia, musculartonus may be weakened during the first postnatal days.
It is known the medicine is excreted in human breast milk; therefore, it should be used with caution during lactation.

Effects on ability to drive and use machines
Notapplicable, because the medicine is used in hospital. Nevertheless, itshould be taken into account that sometimes at the result of systemicaction of lidocaine the mental and/or physical abilities may be delayed.

Undesirable Effects
Undesirableeffects are usually due to overdose that may be caused by the excessivedose of lidocaine or errors in technique (injection exactly into bloodvessel, injection into highly vascular sites, for example in head orneck region) , or may be the result of an individual hypersensitivityto this medicine.
The following reactions are possible in thesecases: nausea, vomiting, cardiovascular disturbances (bradycardia,hypotension, atrioventricular block, shock). CNS disturbances may bemanifested by dizziness, paraesthesia, numbness of the tongue, cold orheat, tinnitus, blurred vision, nystagmus, restlessness, excitement,light-headedness, muscle twitching, tremor, confusion; drowsiness mayoccur, especially in the case too rapid injection. In severe cases, iflidocaine plasma concentration is high there may be convulsions,unconsciousness, respiratory depression and coma.
Epidural anaesthesia may produce Cauda equina syndrome.
Sometimes allergic reactions may be observed (dermatitis, asthma, anaphylactic shock), methaemoglobinaemia.

Pharmacodynamic properties

Pharmacotherapeutic group: Local anaesthetic, antiarrhythmic

ATC-CODE: N01 BB02
C01 BB01
Lidocaineblocks sodium and potassium flow through nerve fibre membranes andstabilizes those, resulting in the failure of a generation andconduction of impulses, thereby producing anaesthetic effect. Comparedto procaine, lidocaine has more rapid, strong and prolonged action.
Lidocaineis used for the treatment and prophylaxis of ventricular arrhythmiabecause when used intravenously it influences upon myocardium andcardiovascular system (especially His-Purkinje system). The drugsuppresses diastolic depolarisation process, shortens the actionpotential and the effective refractory period , suppressesautomaticity, has little effect on myocardial contractility,antrioventricular node conduction, excitability and efferentinnervation.

Pharmacokinetic properties
Followingparenteral administration lidocaine is rapidly distributed to all bodytissues. The rate of absorption depends on route of administration.About 65% is plasma bound. The highest blood concentrations wereobserved following intravenous injection, lower - intercostalinjection, and the lowest – following subcutaneous administration.Nevertheless, repeated dosing may result in detectable drug bloodlevels due to gradual accumulation of the parent compound or itsmetabolites. Following intramuscular injection of lidocaine thetherapeutic blood concentrations were achieved in 5 - 15 min andpersisted for 60 – 90 min. Following intravenous dose the effect wasachieved immediately and persisted for 10 – 20 min.
Plasma lidocaineconcentrations of approximately 1.5 – 5 μg/ml (of lidocaine base) arerequired to suppress ventricular arrhythmias. Following intravenousinjection lidocaine distributes into 2 phases. The early phaserepresents drug into the most highly perfused tissues. During thesecond, slower phase, the drug distributes into adipose and skeletalmuscle tissues. The volume of distribution is decreased in patientswith congestive heart failure. Lidocaine readily crosses theblood-brain and the placental barriers.
The drug is rapidly andfully (80% of a dose) metabolized in the liver by microsomal enzymes toform active metabolites. All factors affecting hepatic functions canchanges lidocaine pharmacokinetic. The plasma half-life is 1.5 – 2hours, and in case of continuous infusion – 3 hours and longer. Thehalf-life of lidocaine (T1/2) in patients with liver disease is twotimes longer or more.
Lidocaine is excreted via kidneys - 10%unchanged, the other – as metabolites. In patients with impaired kidneyfunction accumulation of lidocaine metabolites may occur.

List of excipients
Sodium chloride, sodium hydroxide, 1M solution, water for injection.
The pH of the solution is 5.0 – 7.0.

Incompatibilities
Lidocainehydrochloride has been reported to be incompatible in solution withamphotericin, as well as with sulfadiazine sodium, methohexitonesodium, cephafazolin sodium, or phenytoin sodium.
Acid stable drugssuch as epinephrine or norepinephrine, or isoprenaline may begin todeteriorate within several hours of admixture with lidocainehydrochloride as lidocaine solutions may raise the pH of final solutionabove the maximum pH for their stability. Such extemporaneous mixturesshould be used promptly after preparation.

Shelf-life
4 years.

Special precautions for storage
Protect from light. Do not store above 25o C.
Do not use after the expiry date stated on the label.

Prescription drug.

Nature and contents of container
Glass ampoules of 5 ml, 5 ampoules per liner made of polyvinylchloride film; 2 liners per pack.

MARKETING AUTHORISATION HOLDER AND MANUFACTURER
JSC «Grindeks»; 53, Krustpils St., Riga, LV-1057 Latvia
Phone: 371 7083205
Fax: 371 7083505

MARKETING AUTHORISATION NUMBER:
EST 410503

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION: 04.04.2003.