Project Description

Lidocaine hydrochloride

2% injection solution – Solutio Lidocainihydrochloridi 2% proinjectionibus

international nonproprietary name

Lidocaine.

Ref

BP-0074

Pharmacotherapeutic group

Drugsforheartdiseases. Antiarhythmic drugs of class 1b. Drugsforlocalanesthesia. Amides.

Composition of the preparation

1 ampul contains 40 mg of lidocaine hydrochloride.

Pharmacological action

Pharmacodynamics

Antiarhythmic and local anesthetic action.

Antiarhythmic action is conditioned by inhibition of phase 4 (diastolic depolarization) in Purkinje’s fiber, automatism decrease, inhibition of ectopic excitation focus. It doesn’t effect the rate of depolarization (phase 0) or decreases it insignificantly. It increases membrane permeability to potassium ions, increases the process of repolarization and decreases activity potential. It doesn’t change excitation of sinoatrial node, influences a little on conductivity and myocardial contractility. i.v.injection acts quickly and chortly (10-20 min.).

Mechanism of local anesthesia: stabilization of neuronal membrane, decrease of its permeability to sodium ions, barrier of potential activity and impulse conductivity. Possibleantagonismwithcalciumions. Quick hydrolysis in low basic media of tissues and after short latent period the activity is revealed in 60-90 min. in inflammation (tissue acidosis) anesthetic activity is reduced. Itiseffectiveinalltypesoflocalanesthesia. Itisvasodilator. Itdoesn’tcausetissueirritation.

Pharmacokinetics

Parenteral intake: absorption depends on place and dose. i.v. stream injection: maxplasma concentrationof lidocaine is in 45-90 s., i.m. injection: in 5-15 min. plasma protein binding 50-80%. First the drug reached the tissues well supplied with the blood (heart, lungs, brain, liver, spleen), then to fat and muscle tissue. It easily oases histohematogenous barriers, either hematoencephalic barrier, placenta. It penetrates to breast milk (40% concentration on mother’s plasma). It is liver metabolized (90-95%) with the participation of microsomal enzymes by desalkylation of aminogroup and breakage of amide chain with the formation of active metabolites of monoethylglycinxilidine and glycinxilidine. Half-xcretion after i.v. bolus dosing is 1.5-2 h., after long i.v.infusions to 3 h. onlyin hepatic failure half-excretion may increase twice and more. It is liver and renal excreted (to 10% unmodified). In chronic renal failure possible cumulation of metabolites. Urineacidationenhanceslidocaineexcretion.

Indications 

Ventricular premature beats and tachyarrythmia, either in acute myocardial infarction, post-intervention period, ventricular fibrillation, local anesthesia in surgery, obstetrics, gynaecology, stomatology.

special indication

In patients with heart failure, hypotensia, bradycardia, respiratory depression, liver and renal failure, after heart interventions, administer with care and reduce the dose. Becarefulincaseofhypovolemia, geneticpremalignanthyperthermia. In children, broken health and elderly patients correct the dose as per the age and physical state.

DurigntreatmentcontrolEKG. In case of sinus dysfunction, longer P-Q interval, ORS delation or new arrhythmia reduce the dose or cancel the treatment.

Attention! Under rapid i.v.injection possible abrupt drop of arterial pressure and collapse. In this case administer mesaton, ephedrine and other vasoconstrictors.

Introduction in vascularized tissues: perform aspiration test.

special warning

Not established

Dosage and method of administration

Parenteral dosing of the drug.

Antiarhythmic agent: in adults as stress dose i.v. 1-2 mg/kg for 3-4 min.; average dose 80 mg max.single dose 100 mg). This dose may be repeated every 3-4 min. to total dose 300 mg. then immediately change for infusion at the rate of 0.02-0.055 mg/kg/min., and NMT 2 mg/min. in isotonic or Ringer’s solution. Drop infusion for 24-36 h. If necessary against drop-by-drop infusion repeat i.v.stream dosing 40 mg in 10 min, after the first stress dose.

i.m. dosing 2-4 mg/kg of body weigh in gluteus or deltoid with an interval 4-6 h. in myocardial infarction before patient transportation into hospital lidocaine is introduced i.m. 4 mg/kg as a single preventive dose (200-300 mg max.).

Max.dose in adults i.v. or i.m. is 300-400 mg for 1 h. max.daily dose 2000 mg.

In children stream injection 1 mg/kg at the rate 25-50 mg/min.; in 5 min. repeat (total dose is NMT 3 mg/kg). then continuous i.v.infusion 0.03 mg/kg/min. max.daily dose in children is 4 mg/kg/day.

In elderly patients it is recommended to reduce the dose, particularly under long i.v.infusions. in chronic renal failure no need to correct the dose. In hepatic diseases (cirrhosis, hepatitis) and in patients with lower hepatic bloodstream reduce the dose by 40-50%.

Local anesthesia: dosing pattern is individual and subject to the type of anesthesia and intervention. Max.dose of 2% lidocaine solution is 10 ml, do not repeat this dose within 24 h.

overdosage

Symptoms: pscycomotor excitation, vertigo, fatigue, hypotensia, tremor, tonic clonic convulsions, coma, collapse, atrioventricular block, CNS depression, respiratory standstill.

Treatment: at first signs of intoxication cancel the drug, place the patient in horizontal position and start oxigenotherapy. Administer symptomatic therapy: anticonvulsant agents, vasoconstrictors (noradrenaline, mesatone), in bradycardia administer anticholinergic drugs (atropine). If necessary, artificial lung ventilation, reanimation measures. Dialysis is ineffective.

safety measures

Not established

Side effects

Nervous system and sense organs: depression or excitation of CNS, neurotic reaction, euphoria, “blackfly” flicker before eyes, photophobia, sleepiness, headache, vertigo, ear noise, diplopia, impairment of consciousness, respiratory depression or standstill, muscle tic, tremor, disorientation, convulsions.

Cardiovascular system: sinus bradycardia, cardial conduction impair, cardial cross block, hypotensia, collapse.

Digestive system: nausea, vomit.

Аллергические реакции: eruption, itch, generalized exfoliative dermatitis, anaphylactic shock.

Прочие: fever, cold or anemia of extremities, malignant hyperthermia, immune system depression.

Contraindications

Hypersensitivity, marked hypotenisa, epileptiform fit in case of prior administration of lidocaine, heavy heart failure, Wolff-Parkinson-White syndrome, cardiogenic shock, sick sinus syndrome, cardiac block (atrioventricular, intraventricular, sinoatrial), severe hepatic diseases, myasthenia, pregnancy, lactation period (if administered, cancel breast feeding).

Interactions with other medicinal preparations

Beta-adrenoceptor antagonists increase eventual bradycardia and hypotensia. Norepinephrine and Beta-adrenoceptor antagonists, reducing hepatic blood flow, reduce lidocaine clearance (higher toxicity), isadrin and glycagon increases lidocaine clearance. Cimetidine increases plasma concentration of lidocaine (displace from protein binding and inhibits liver inactivation). Barbiturates causing induction of microsomal enzymes stimulate lidocaine degradation and reduce its activity. Anticonvulsant agents (hydantoine derivatives) accelerate biotransformation in liver (blood concentration is reduced), under i.v.dosing possible increase of cardiac depressive activity of lidocaine. Antiarhythmic agents (amiodaron, verapamil, quinidine, aimalin) potentiate cardiaс depression. Combination with procainamide may cause CNS excitation and hallucinations. Anticoagulants increase the risk of hemorrhage.

Lidocaine enhances inhibitory action of anaesthetics (hexobarbital, thiopental sodium), hypnotic agents and sedative agents on respiratory center, inhibits cardiotonic action of digitoxine, decreases antimyastenical drug effect, enhances myotelaxation caused by muscle relaxants (possible paralysis of respiratory muscles). In concurrent administration of analgesics evident additive effect, still repisratory depression if increased. Administration with MAO inhibitors increases the risk of hypotensia.

MAO inhibitors, vasoconstrictors (epinephrine, methoxamine, phenylephrine) prolong local anesthetic action.

The form of release

2% injection solution in ampuls 2 ml. 10 ampuls in a box.