Ультракаин® D-with

General characteristics. Structure:

Active agents: an artikaina a hydrochloride - 40 mg and Epinephrinum a hydrochloride - 0,006 mg (it is equivalent to the maintenance of the basis of Epinephrinum - 0,005 mg that corresponds to the maintenance of Epinephrinum in solution 1:200 000);
excipients: sodium disulphite (sodium metabisulphite), sodium chloride, water for injections.
Description. Transparent colourless liquid.

Pharmacological properties:

Pharmacodynamics. Ультракаин® D-with - the combined drug which part is артикаин (mestnoanesteziruyushchy means of amide type) and Epinephrinum (vasoconstrictor) which is added to composition of drug for prolongation of duration of anesthesia.
Artikain is the mestnoanesteziruyushchy means used for infiltration and conduction anesthesia in dental practice. The amide structure of an artikain is similar that at other mestnoanesteziruyushchy means, but its molecule contains one additional radio group which in a human body is quickly hydrolyzed by esterases. Very low system toxicity of drug allowing to carry out repeated injections of drug is connected with bystry destruction of an artikain to its inactive metabolite (artikainovy acid).
Mestnoanesteziruyushchy means cause a reversible anesthesia due to the termination or reduction of carrying out touch nervous impulses near the place of an injection. They have membrane stabilizing effect due to decrease in permeability of membranes of nervous cells for sodium ions.
Ультракаин® D-with renders bystry (stage of latency - from 1 to 3 minutes) and strong anesthetic effect and has good fabric tolerance. Duration of anesthesia makes not less than 45 min.
Owing to very low content in Epinephrinum drug influence of the last on cardiovascular system is expressed slightly: almost increase in arterial pressure and increase in heart rate is not noted.

Pharmacokinetics. All mestnoanesteziruyushchy means of amide type are metabolized in liver microsomes. Besides, артикаин in fabrics and blood it is still inactivated by nonspecific plasma esterases by hydrolysis in carboxyl group. As hydrolysis happens very quickly and begins right after introduction, about 90% of an artikain are inactivated this way. The main metabolite of an artikain which is formed as a result - artikainovy acid - has no mestnoanesteziruyushchy activity, and it did not reveal system toxicity.
After submucosal introduction removal of an artikain happens exponential to an elimination half-life, components are about 25 minutes old. Artikain, mainly, is brought through kidneys in the form of artikainovy acid (64,2±14,4%), a glucuronide of artikainovy acid (13,4±5,0%) and not changed artikain (1,45±0,77%).
After drug injections in mucous oral cavities the general clearance of an artikain makes 235±27 l/h.
After submucosal introduction of 2 ml of the drug Ultrakain® D-with time of achievement of the maximum concentration in a blood plasma (Tmax) of an artikain makes 10-15 minutes, and average value of the maximum concentration in a blood plasma (Stakh) the artikaina makes about 400 mkg/l, Tmax of artikainovy acid makes 45 minutes, and average value Stakh of artikainovy acid makes 2000 mkg/l. At children comparable pharmacokinetic data were obtained. Distinctions between plasma concentration of an artikain and artikainovy acid reflect bystry hydrolysis of an artikain in fabrics and blood so entered артикаин comes to a system blood stream, generally in the form of an inactive metabolite.
Concentration of an artikain in blood in the field of tooth alveoluses after submucosal introduction to thousands of times exceeds concentration of an artikain in a system blood-groove. Feedback between time after an injection and concentration of an artikain in the field of tooth sockets is revealed.
Communication of an artikain with proteins of plasma makes 95%.

Indications to use:

Infiltration and conduction anesthesia at dental operations: uncomplicated removals of one or several teeth, processing of cavities and grinding of teeth before prosthetics.

Route of administration and doses:

Drug is intended for use in an oral cavity and can be entered only into fabrics where there is no inflammation.
It is impossible to carry out an injection to the inflamed fabrics.
The drug cannot be administered intravenously.
For anesthesia at an uncomplicated exodontia of an upper jaw in the absence of an inflammation there is usually enough creation of D-S Ultrakain® depot in the field of a transitional fold by its introduction in submucosal from the vestibular party (on 1,7 ml of drug on tooth). In rare instances for achievement of full anesthesia additional introduction from 1 ml to 1,7 ml can be required. In most cases it allows not to carry out a painful palatal injection. During removal several the quantity of injections usually manages to be limited to a number of the located teeth.
Anesthesia at cuts and suture in the field of the sky for the purpose of creation of palatal depot requires about 0,1 ml of drug on each injection.
In case of removal of premolar tooths of a mandible in the absence of an inflammation it is possible to do without mandibular anesthesia as the infiltration anesthesia provided with an injection of 1,7 ml on tooth is usually sufficient. If in such way it was not succeeded to reach desirable effect, it is necessary to execute an additional injection of 1-1,7 ml of anesthetic in submucosal in the field of a transitional fold of a mandible from the vestibular party. If and in this case it was not succeeded to reach full anesthesia, it is necessary to carry out conduction blockade of a mandibular nerve.
When processing cavities and grinding teeth under crowns, except for the lower molars, depending on volume and duration of treatment administration of the drug Ultrakain® D-with to the area of a transitional fold from the vestibular party in a dose of 0,5-1,7 ml on tooth is shown.
At implementation of one medical procedure by the adult it is possible to enter артикаин in a dose to 7 mg on 1 kg of body weight. It is noted that patients well transferred doses to 500 mg (there correspond 12,5 ml of solution for injections).
For patients of children's age (4 years are more senior) the dose of the drug Ultrakain® D-with is selected depending on age and the body weight of the child, but it should not exceed 5 mg of an artikain on 1 kg of body weight.
For patients of advanced age and all patients with a heavy renal and liver failure creation of the increased plasma concentration of an artikain is possible. It is necessary to apply the minimum doses necessary for achievement of sufficient depth of anesthesia to these patients.
The drug cannot be administered intravenously. To avoid accidental hit of drug in blood vessels, before its introduction it is always necessary to carry out aspiration test (see. "Special instructions").
Pressure of an injection has to correspond to sensitivity of fabrics.

Features of use:

The drug cannot be administered intravenously!
It is impossible to carry out an injection to the inflamed area!
In order to avoid an intravascular injection before administration of drug it is necessary to carry out the aspiration test surely.
Injection pressure has to correspond to sensitivity of fabric.
For prevention of entering of infections (including, a viral hepatitis) it is necessary to watch that at a solution intake from ampoules new sterile syringes and needles were always used. Open cartridges cannot be used for other patients again!
It is impossible to use the damaged cartridge for injections.
At patients with diseases of cardiovascular system (chronic heart failure, pathology of coronary vessels, stenocardia, disturbances of a heart rhythm, a myocardial infarction in the anamnesis, an arterial hypertension), cerebrovascular frustration, existence of a stroke in the anamnesis, chronic bronchitis, emphysema, a diabetes mellitus, a hyperthyroidism, and also in the presence of the expressed concern, use of the drug Ultrakain® D which is not containing Epinephrinum is reasonable.
It is possible to eat food only after cancellation of local anesthesia (sensitivity recovery).
Influence on ability to drive the car and to perform the works connected with the increased danger.
Local anesthesia the drug Ultrakain® D-with as showed tests, does not cause any noticeable deviation from usual ability to driving and participation in traffic. However the decision on when the patient after dental intervention is able to return to driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions the doctor has to accept.

Side effects:

From the central nervous system
- The reactions depending on a dose from the central nervous system: the stupor sometimes progressing to a loss of consciousness, the respiratory frustration sometimes progressing to an apnoea, the muscular tremor, muscular twitchings sometimes progressing to generalized spasms.
- Dizziness, paresthesia, hypesthesia.
- The passing visual frustration (an illegibility of visual perception, a blindness, doubling in eyes) arising in time or through short time after an injection of mestnoanesteziruyushchy means.
- Sometimes at disturbance of the correct equipment of an injection at introduction of mestnoanesteziruyushchy means in dental practice perhaps injury of a nerve, in particular, in such cases is possible damage of a facial nerve which can lead to development of paralysis of a facial nerve.
- Often: a headache, mainly, owing to existence in composition of drug of Epinephrinum.
From digestive tract
Nausea, vomiting
From cardiovascular system
- Lowering of arterial pressure, bradycardia, heart failure and shock.
- Owing to contents as a part of drug of Epinephrinum development of tachycardia, disturbances of a cordial rhythm, increase in arterial pressure is very seldom possible.
From immune system
Allergic and allergopodobny reactions can develop. In the place of an injection they can be shown as puffinesses or inflammatory reaction of a mucous membrane. The hyperemia of integuments, conjunctivitis, rhinitis and a Quincke's disease can be the manifestations which are not connected with an injection site. The Quincke's disease can be shown by hypostasis of an upper and/or under lip, cheeks, hypostasis of phonatory bands with feeling of "a lump in a throat" and swallowing difficulty, a small tortoiseshell and difficulty of breath. Any of these manifestations can progress to an acute anaphylaxis.
The general disturbances and undesirable reactions in an injection site
In some cases at accidental intravascular introduction emergence of zones of ischemia in an injection site is possible, up to a necrosis of fabrics.

Interaction with other medicines:

Contraindicated combinations
With cardionon-selective beta adrenoblockers, for example, propranolol.
Risk of development of hypertensive crisis and the expressed bradycardia.
Interactions which should be taken into account
With tricyclic antidepressants or monoamine oxidase inhibitors (MAO)
Action of the vasoconstrictors increasing arterial pressure like adrenomimetik, such, for example, as Epinephrinum, can amplify tricyclic antidepressants or MAO inhibitors. Similar observations were described for concentration of Norepinephrinum 1:25 000 and Epinephrinum 1:80 000 at their use as vasoconstrictors. Concentration of Epinephrinum in the drug Ultrakain® D-with is lower - 1:200 000. However it is necessary to consider possibilities of such strengthening of action.
With the medicines oppressing the central nervous system (CNS).
Mestnoanesteziruyushchy means strengthen effect of medicines, the oppressing TsNS. Narcotic analgetics strengthen action of mestnoanesteziruyushchy means, however increase risk of respiratory depression.
With heparin, acetylsalicylic acid
When carrying out injections of the drug Ultrakain® D-with to the patients receiving heparin or acetylsalicylic acid development of bleedings in the place of an injection is possible.
With muscle relaxants
Strengthening and lengthening of action of muscle relaxants.
With anti-myasthenic medicines
Antagonistic impact on skeletal muscles, especially when using in high doses, demands additional correction of treatment of a myasthenia.
With cholinesterase inhibitors
Delay of metabolism of mestnoanesteziruyushchy medicines. With hypoglycemic means for intake
Epinephrinum can inhibit release of insulin from beta cells of a pancreas and reduce effects of hypoglycemic means for intake.
With some means for an inhalation anesthesia (halothane)
The halothane can increase sensitivity of heart to catecholamines and therefore to increase risk of development of disturbances of a cordial rhythm after D-page drug Ultrakain® injections.
With the disinfecting solutions containing heavy metals
When processing the place of an injection of local anesthetic the disinfecting solutions containing heavy metals the risk of development of local reactions - hypostasis, morbidity increases.

Contraindications:

- Hypersensitivity to an artikain or to other mestnoanesteziruyushchy means of amide type, except for cases when at hypersensitivity to mestnoanesteziruyushchy means of amide type the allergy to an artikain was excluded with the help of the corresponding researches conducted with observance of all necessary rules and requirements.
- Hypersensitivity to Epinephrinum; to sulfites (including, shown in the form of bronchial asthma); hypersensitivity to any other auxiliary ingredients of drug.
The contraindications relating to an artikain
- Heavy dysfunctions of a sinus node or heavy disturbances of conductivity (such as the expressed bradycardia, atrioventricular block 2-3 degrees).
- Acute dekompensirovanny heart failure.
- Sharply expressed arterial hypotension.
- Anemia (including V-12 scarce anemia).
- Methemoglobinemia.
- Hypoxia.
- Children's age up to 4 years (lack of clinical experience). The contraindications relating to Epinephrinum
- Bouveret's disease, tachyarrhythmia, closed-angle glaucoma
- Reception of not cardioselective beta adrenoblockers, for example, propranolol (risk of development of hypertensive crisis and heavy bradycardia).
- Hyperthyroidism.
- Pheochromocytoma.
- Heavy arterial hypertension.
With care: at patients with stenocardia, atherosclerosis, a postinfarction cardiosclerosis, disturbances of cerebral circulation, a stroke in the anamnesis, chronic bronchitis, emphysema of lungs, a diabetes mellitus, insufficiency of cholinesterase (use is possible only in urgent cases, as perhaps prolonged and excessively strong effect of drug), disturbances of coagulability of blood, heavy abnormal liver functions and kidneys, the expressed excitement.
Pregnancy and period of a lactation
Artikain passes through a placental barrier.
In view of insufficiency of clinical data, the decision on purpose of drug can be made by the dentist only if the potential advantage of its use for mother justifies potential risk for a fruit. In need of use of an artikain during pregnancy it is better to use the drugs which are not containing Epinephrinum or with smaller concentration of Epinephrinum (that is, drugs Ultrakain ® D and Ultrakain ® D-c).
In the period of a lactation there is no need to interrupt breastfeeding as in breast milk clinically significant concentration of an artikain are not found.

Overdose:

At the first manifestations of toxic action, such as dizziness, motor excitement or a stupor during administration of drug, it is necessary to stop its introduction and to transfer the patient to horizontal position with the raised lower extremities. It is necessary to provide passability of respiratory tracts and to monitorirovat hemodynamics indicators (number of cordial reductions and arterial pressure). It is recommended always even if symptoms of intoxication seem not heavy, to put an intravenous catheter in order that in case of need, to have an opportunity immediately to carry out intravenous administration of necessary medicines.
At breath disturbances, depending on their weight, oxygen supply is recommended, and at emergence of indications to carrying out an artificial respiration - carrying out an endotracheal intubation and artificial ventilation of the lungs.
Introduction of analeptics of the central action is contraindicated.
Muscular twitchings and generalized spasms can be stopped by intravenous administration of barbiturates of short or ultrashort action. It is recommended to administer these drugs slowly, under constant medical control (risk of hemodynamic frustration and respiratory depression) and with simultaneous supply of oxygen and monitoring of hemodynamic indicators.
Often bradycardia or a sharp lowering of arterial pressure can be eliminated at simple convertion of the patient in horizontal position with the raised lower extremities.
At heavy disturbances of blood circulation and shock, regardless of their reason, administration of drug has to be stopped and the patient has to be transferred to horizontal position with the raised lower extremities. Oxygen supply, intravenous administration of electrolytic solutions, glucocorticosteroids (250-1000 mg of Methylprednisolonum), if necessary, plasma substitutes, albumine have to be carried out.
At development of a circulator collapse and strengthening of bradycardia slow intravenous administration of solution of Epinephrinum (0,0025-0,1 mg) under control of a cordial rhythm and arterial pressure is shown. In need of introduction of the doses exceeding 0,1 mg, Epinephrinum should be entered infusionally, having adjusted rate of administering under control of number of cordial reductions and arterial pressure.
Heavy tachycardias and tachyarrhythmias can be stopped by administration of antiarrhytmic drugs, except for cardionon-selective beta adrenoblockers (see the section "Contraindications").
Increase in arterial pressure at patients with arterial hypertension if necessary has to decrease by means of vazodilatator.

Storage conditions:

Ampoules: at a temperature not above 25 °C in the place protected from light. Cartridges: at a temperature not above 30 °C in the place protected from light. To store drug in the place, unavailable to children. List B. Period of validity.
Ampoules: 36 months. Cartridges: 30 months.
After a period of validity drug cannot be used.

Issue conditions:

According to the recipe

Packaging:

Solution for injections of 40 mg/ml +0,005 mg/ml, in ampoules on 2 ml and in cartridges on 1,7 ml.
Ampoules: on 2 ml in an ampoule of transparent colourless glass (type I). On 10 ampoules place in a cardboard pack together with the application instruction.
Cartridges: on 1,7 ml in a cartridge of transparent, colourless glass (type I). On 10 cartridges place in the block from corrugated fibreboard. On 10 blocks from corrugated fibreboard place in a cardboard pack together with the application instruction.