Artifrin-zdorovya

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ARTIFRIN-ZDOROV'YA

Composition:

Active substances:

1 ml of solution contains articaine hydrochloride 40 mg, adrenaline 0.006 mg;

Excipients: sodium metabisulfite (E 223), glycine, sodium chloride, hydrochloric acid, water for injections.

Pharmaceutical form. Solution for injection.

Main physico-chemical properties: clear, colorless or slightly yellowish-green solution.

Pharmacotherapeutic group. Medicinal products for local anesthesia. Articaine, combinations.

ATC code N01B B58.

Pharmacological properties.

Pharmacodynamics. Articaine is an amide-type local anesthetic used in dentistry for infiltration and conduction anesthesia. The drug has a rapid onset of action (latent period – 1–3 minutes) and produces a strong analgesic effect. The duration of effective anesthesia is approximately 45 minutes.

The mechanism of action of articaine is believed to involve reduced impulse conduction along nerve fibers through blockade of voltage-dependent sodium channels in cell membranes.

Use in children aged 3.5 to 16 years at doses up to 5 mg/kg of articaine provides reliable local analgesia when administered via infiltration anesthesia (for the mandible) and conduction anesthesia (for the maxilla). The duration of anesthesia depends on the amount of anesthetic administered.

Pharmacokinetics. Articaine plasma protein binding is 95%. After injection into the oral mucosa, the elimination half-life is 25.3 ± 3.3 minutes. Approximately 10% of articaine is metabolized in the liver, primarily by esterases present in blood plasma and tissues. Articaine is excreted predominantly by the kidneys in the form of articaine acid.

In children, total exposure after infiltration anesthesia on the vestibular side was similar to that in adults, although minimum blood concentrations were reached more rapidly.

Clinical characteristics.

Indications. Routine procedures such as uncomplicated single or multiple extractions, tooth cavity preparation, tooth preparation for crown placement.

Contraindications. The drug must not be used in patients with hypersensitivity to the active substances—adrenaline and articaine—or to sulfites (metabisulfite (E 223)) or to any of the excipients of the drug.

Due to the presence of articaine in the formulation, the drug must not be used in the following cases:

• hypersensitivity to other amide-type local anesthetics;
• severe disturbances in cardiac impulse generation or conduction disorders (II–III degree AV block, marked bradycardia);
• acute decompensated heart failure (acute congestive heart failure);
• severe arterial hypotension.

Due to the presence of adrenaline in the formulation, the drug must not be used:

• in patients with closed-angle glaucoma;
• in patients with hyperthyroidism;
• in patients with paroxysmal tachycardia or atrial fibrillation with tachycardia;
• in patients who have recently (within the past 3 to 6 months) suffered myocardial infarction;
• in patients who have recently (within the past 3 months) undergone aortocoronary bypass surgery;
• in patients taking non-selective beta-blockers, such as propranolol (risk of hypertensive crisis or severe bradycardia);
• in patients with pheochromocytoma;
• in patients with severe arterial hypertension;
• during concomitant treatment with tricyclic antidepressants or monoamine oxidase inhibitors (MAOIs), as their active substances may potentiate the cardiovascular effects of adrenaline. This phenomenon may persist for up to 14 days after discontinuation of MAOI therapy.

Intravenous administration of the drug is contraindicated.

Due to the presence of adrenaline in the formulation, the drug should not be used for anesthesia of extremities (e.g., fingers), as there is a risk of ischemia.

The drug must not be used in patients with bronchial asthma and hypersensitivity to sulfites. In such patients, administration of the drug may provoke an acute allergic reaction with anaphylactic symptoms, such as bronchospasm.

Interaction with other medicinal products and other forms of interaction. Combinations of different anesthetics have an additive effect and produce a more pronounced impact on the cardiovascular system and the central nervous system (CNS).

The hypertensive effects of sympathomimetic vasoconstrictors (e.g., adrenaline) may be enhanced by tricyclic antidepressants or MAO inhibitors. Therefore, such combinations are contraindicated (see section "Contraindications").

The drug is contraindicated in patients taking non-selective beta-blockers, such as propranolol (see section "Contraindications").

Adrenaline may inhibit insulin release from the pancreas, thereby reducing the effectiveness of oral antidiabetic agents.

Some inhalational anesthetics, such as halothane, may increase myocardial sensitivity to catecholamines, potentially causing arrhythmias after administration of the drug.

It should be noted that in patients receiving antithrombotic therapy (e.g., heparin, acetylsalicylic acid), accidental puncture of a blood vessel during local anesthesia may lead to serious bleeding. Such patients generally have an increased tendency to bleeding.

Special precautions for use.

The drug can be administered to patients with cholinesterase deficiency only if there are absolute indications for its use, since in such cases there is a high probability of prolonged duration of action and sometimes of undesirable potentiation of its effects.

The drug should be used with caution in:

• coagulation disorders;
• severe renal or hepatic impairment;
• concomitant use of halogen-containing inhalational anesthetics (see section "Interaction with other medicinal products and other types of interactions");
• history of epilepsy (see section "Adverse reactions").

The drug should also be used with particular caution in the following conditions:

• cardiovascular diseases (e.g. heart failure, ischemic heart disease, angina pectoris, history of myocardial infarction, cardiac arrhythmia, arterial hypertension);
• atherosclerosis;
• cerebrovascular disorders, history of stroke;
• chronic bronchitis, pulmonary emphysema;
• diabetes mellitus;
• pronounced anxiety.

Injections must not be performed in areas of inflammation (infection) (absorption of the drug is enhanced, which leads to reduced efficacy).

Before administering this drug, the patient must be interviewed, a medical history taken, information collected about concomitant medications, and verbal contact with the patient must be maintained continuously during administration of the drug.

To avoid adverse effects, it is necessary:

• to use the lowest possible dose;
• to perform a two-stage aspiration test before injection (to avoid intravascular administration).

It is recommended that the patient eat only after full sensation has returned.

Sodium metabisulfite may rarely cause hypersensitivity reactions and bronchospasm.

The drug contains less than 1 mmol/dose of sodium, i.e. it is practically sodium-free.

Use in children. Caregivers of young children should be warned about the possibility of soft tissue injury due to biting resulting from prolonged numbness of soft tissues after anesthesia.

Use during pregnancy or breastfeeding.

Pregnancy. There is no experience with the use of articaine in pregnant women, except for its use during labor; therefore, the use of the drug during pregnancy is possible only after careful assessment of the benefit-risk ratio.

Breastfeeding. Due to rapid decline in plasma concentrations and rapid elimination of articaine from the body, it does not appear in breast milk in clinically significant amounts. Adrenaline passes into breast milk, but it also breaks down rapidly. With short-term use of the drug, there is no need to interrupt breastfeeding.

Fertility. When used at therapeutic doses, a negative effect of the drug on human fertility is not expected.

Ability to affect reaction speed when driving vehicles or operating machinery. Only the dentist can decide when, after administration of the drug, the patient can resume driving or operating machinery. Fear associated with anticipation of a dental procedure and the stress accompanying it may impair the ability to function effectively. However, relevant studies have shown that local anesthesia with articaine does not cause any noticeable deterioration in the ability to drive a vehicle.

Method of Administration and Dosage.

In uncomplicated forceps removal of maxillary teeth under conditions of absence of inflammation, it is sufficient to inject 1.7 mL of the preparation into the vestibular fold on the vestibular side for each tooth. Sometimes, an additional vestibular injection of 1–1.7 mL of the preparation may be required to achieve complete anesthesia. In most cases, there is no need to perform a painful palatal injection.

If an incision on the palate or suturing of the palate is required, administration of 0.1 mL of the preparation from the palatal side is sufficient to create an anesthetic depot.

In multiple extractions of adjacent teeth, the number of vestibular depot injections can usually be reduced.

In uncomplicated forceps removal of mandibular premolars in the absence of inflammation, mandibular anesthesia may be omitted, as infiltration anesthesia achieved by injecting 1.7 mL of the preparation per tooth is usually sufficient. If complete analgesia is not achieved, an additional vestibular injection of 1–1.7 mL should first be performed. Only if this also fails to provide complete anesthesia is standard inferior alveolar nerve block indicated.

For caries cavity preparation or tooth preparation for crowns, except for mandibular molars, an injection of the preparation from the vestibular side at a dose of 0.5–1.7 mL per tooth is indicated; the dose depends on the extent and duration of the procedure.

For surgical procedures, the dosage of the preparation should be adjusted according to the severity and duration of the surgery.

During a single treatment course, adults may receive up to 7 mg of articaine per kg of body weight. After prior aspiration test, doses up to 500 mg (equivalent to 12.5 mL of the injection solution) have been well tolerated.

Children. The medicinal product should be administered to children in the minimal amount required to achieve adequate analgesia; the amount administered should be individually adjusted according to the child's age and body weight. The maximum dose, which is 7 mg of articaine per kg of body weight, must not be exceeded.

The use of this preparation in children under 1 year of age has not been studied.

In elderly patients and patients with severe hepatic or renal impairment, increased plasma concentrations of articaine are possible. Special caution should be exercised in such patients, and the minimum dose necessary to achieve adequate depth of anesthesia should be used.

Route and Duration of Administration.

The preparation is intended for submucosal administration into the oral cavity.

To avoid intravascular injection, an aspiration test is always recommended before injection. The aspiration test should be performed in two stages, i.e., by rotating the needle 90° or preferably 180°.

Serious systemic reactions resulting from accidental intravascular injection can mostly be avoided by using the following injection technique: after aspiration, slowly inject 0.1–0.2 mL, then, not earlier than 20–30 seconds later, slowly administer the remainder of the preparation. Injection pressure should correspond to tissue sensitivity.

To prevent infection (e.g., transmission of hepatitis virus), new sterile needles and syringes should always be used for drawing up the solution.

Children. The medicinal product should be administered to children in the minimal amount required to achieve adequate analgesia; the amount administered should be individually adjusted according to the child's age and body weight. The maximum dose, which is 7 mg of articaine per kg of body weight, must not be exceeded.

The use of this preparation in children under 1 year of age has not been studied.

Overdose.

Symptoms of overdose

• Signs of central nervous system (CNS) excitation: restlessness, anxiety, confusion, rapid breathing, tachycardia, elevated blood pressure accompanied by facial flushing, nausea, vomiting, tremor, involuntary muscle contractions, tonic-clonic seizures.
• Signs of CNS depression: dizziness, hearing loss, inability to speak, stupor, loss of consciousness, muscular atonia, vasomotor paralysis (weakness, pallor of the skin), respiratory distress, fatal outcome due to respiratory center paralysis.
• Signs of cardiovascular depression: bradycardia, arrhythmia, ventricular fibrillation, decreased blood pressure, cyanosis, cardiac arrest.

Emergency measures and antidotes. At the first signs of adverse reaction or toxic effects (e.g., dizziness, motor excitation, or stupor), the injection should be stopped and the patient placed in a horizontal position. Airway patency should be ensured, and pulse and blood pressure monitored.

Even if intoxication symptoms do not appear severe, it is recommended to place an intravenous catheter to ensure immediate intravenous access if needed.

In case of respiratory disturbances, depending on the severity, oxygen administration is recommended, and if necessary, artificial ventilation. If required, endotracheal intubation combined with controlled lung ventilation should be performed.

Involuntary muscle contractions or generalized seizures should be controlled by intravenous administration of short-acting anticonvulsants (e.g., succinylcholine chloride, diazepam). Artificial ventilation (oxygen) is also recommended.

Decreased blood pressure, tachycardia, or bradycardia can often be corrected simply by placing the patient in a horizontal position or in a position with legs slightly elevated above the head.

In severe circulatory disturbances and shock, regardless of cause, the following emergency measures should be taken immediately after stopping the injection:

• Place the patient in a horizontal position or with legs slightly elevated above the head, and ensure airway patency (oxygen insufflation);
• Initiate intravenous infusion of balanced electrolyte solution;
• Administer intravenous glucocorticoids (e.g., 250–1000 mg of prednisolone or equivalent dose of its derivative, e.g., methylprednisolone);
• Restore circulating blood volume (additionally, if necessary, use plasma expanders, human albumin).

In case of impending circulatory collapse and progressive bradycardia, immediate intravenous injection of adrenaline (epinephrine) should be performed. For this purpose, 1 mL of 1:1000 adrenaline solution should be diluted to 10 mL (alternatively, a 1:10,000 adrenaline solution can be used), and 0.25–1 mL of this solution (containing 0.025–0.1 mg of adrenaline) should be slowly injected while monitoring pulse rate and blood pressure (caution: cardiac arrhythmia may occur). Do not administer more than 1 mL of this solution (0.1 mg of adrenaline) during a single intravenous injection. If this amount of adrenaline is insufficient, it is recommended to add it to the infusion solution (infusion rate should be adjusted according to pulse rate and blood pressure).

Severe forms of tachycardia and tachyarrhythmia can be managed with antiarrhythmic drugs (but not non-selective beta-blockers such as propranolol) (see section "Contraindications"). In such cases, oxygen administration and circulatory monitoring are essential.

In case of elevated blood pressure in patients with arterial hypertension, peripheral vasodilators should be used if necessary.

Side effects.

Immune system disorders: hypersensitivity reactions (allergic and pseudoallergic) may occur. These may manifest as swelling and/or inflammation at the injection site, and also independently of the injection site as skin redness, itching, conjunctivitis, rhinitis, facial swelling resembling angioneurotic edema, including swelling of the upper and/or lower lip and/or cheeks, swelling of the vocal cords causing a sensation of a lump in the throat and difficulty swallowing, urticaria, and breathing difficulties which may progress to anaphylactic shock.

Nervous system disorders: paresthesia, hypoesthesia, headache (mainly due to the presence of adrenaline), dizziness.

When excessively high doses of the drug are used or in case of accidental intravascular administration, dose-dependent reactions from the central nervous system may occur: restlessness, nervousness, stupor (which may sometimes progress to loss of consciousness), coma, respiratory depression which may sometimes progress to respiratory arrest, muscle tremors, involuntary muscle contractions which may sometimes progress to generalized seizures.

Theoretical risk of nerve injury exists during any dental procedure due to incorrect injection technique or anatomical peculiarities of the injection site. In such cases, injury to the facial nerve and subsequent facial nerve palsy may occur. This may lead to decreased taste sensitivity.

Eye disorders: during injection of local anesthetic (or shortly thereafter) in the head area, temporary visual disturbances may also occur (blurred vision, double vision, mydriasis, blindness).

Cardiovascular system disorders: tachycardia, cardiac arrhythmias, increased blood pressure, arterial hypotension, bradycardia, heart failure, and shock (which may be life-threatening).

Gastrointestinal disorders: nausea, vomiting.

General disorders and administration site reactions: in case of accidental intravascular injection, ischemic areas may appear at the injection site, which may sometimes progress to tissue necrosis (see section "Dosage and administration").

Cases of chills have been reported, mainly related to anxiety associated with dental procedures, as well as sweating, tinnitus, and mydriasis.

Special warnings: in rare cases, particularly in patients with bronchial asthma, the drug may cause hypersensitivity reactions due to the presence of sodium metabisulfite in its composition. These reactions may clinically present as vomiting, diarrhea, stridorous breathing, acute asthma attack, disturbances of consciousness, or shock.

Paediatric population: prolonged soft tissue anesthesia has led to accidental soft tissue injuries in children aged 4 to 18 years, particularly in children aged 3 to 7 years. No adverse effects have been reported in children aged 1 to 4 years treated for dental conditions using up to 4.2 mL of the drug.

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach of children.

Incompatibilities. The drug should not be mixed with other medicinal products.

Packaging. 1.7 mL in ampoules, 10 in a box; 5x2, 10x1 in blisters in a box; 1.7 mL in cartridges, 10x5 in blisters in a box.

Prescription status. Prescription only.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA".

LIMITED LIABILITY COMPANY "FARMEKS GROUP".

Manufacturer's address and location of business activity. Ukraine, 61013, Kharkiv region, Kharkiv city, Shevchenka street, building 22.

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA")

Ukraine, 08301, Kyiv region, Boryspil city, Shevchenka street, building 100.

(LIMITED LIABILITY COMPANY "FARMEKS GROUP")