Artifrin-zdorovya forte

INSTRUCTIONS FOR MEDICAL USE|consumption| OF THE MEDICINAL PRODUCT ARTIPHRIN-ZDOROVYE FORTE (ARTIPHRIN-ZDOROVYE FORTE)

Composition:

Active substances: articaine, epinephrine;

1 ml of solution contains 40 mg of articaine hydrochloride and 0.01 mg of adrenaline;

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

Dosage form. Injection solution.

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

Pharmacotherapeutic group. Agents for local anesthesia. Amides. Articaine, combinations.

ATC code N01B B58.

Pharmacological properties.

Pharmacodynamics.

Articaine is a local anesthetic of the amide type 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 75 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.

Due to the very low content of epinephrine (adrenaline) and its potent activity, the drug can be used in patients with cardiovascular disorders.

Pharmacokinetics.

The plasma protein binding of articaine is 95%. After injection into the oral mucosa, the half-life (T½) 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.

Clinical characteristics.

Indications. Surgical procedures on the mucous membranes and bones requiring more intense ischemia; surgical procedures on dental pulp (amputation and extirpation); removal of periodontal or broken teeth (osteotomy); prolonged surgical procedures; transcutaneous osteosynthesis; removal of cysts; surgical procedures on gingival mucosa; root apex resection.

Contraindications. Hypersensitivity to the components of the drug, sulfites, or to other amide-type local anesthetics; severe disturbances in cardiac impulse generation or conduction disorders (AV block II–III degree, pronounced bradycardia); acute decompensated (congestive) heart failure; severe arterial hypotension/hypertension; anesthesia of extremities (e.g., fingers), due to the risk of ischemia development; closed-angle glaucoma; paroxysmal tachycardia; absolute arrhythmia with tachycardia; history of myocardial infarction (within the past 3 to 6 months); history of aortocoronary bypass surgery (within the past 3 months); hyperthyroidism; pheochromocytoma; concomitant use of non-selective β-blockers, such as propranolol (risk of hypertensive crisis or severe bradycardia); treatment with tricyclic antidepressants or MAO inhibitors (cardiovascular effects of the drug may be potentiated for up to 14 days after discontinuation of MAO inhibitors); bronchial asthma in patients with hypersensitivity to sulfites (may cause acute allergic reaction with anaphylactic symptoms, e.g., bronchospasm). Intravenous administration of the drug is contraindicated.

Interaction with other medicinal products and other forms of interaction. Hypertensive effects of sympathomimetic vasoconstrictors (e.g., adrenaline) may be enhanced by tricyclic antidepressants or MAO inhibitors. Therefore, such combinations are contraindicated. The drug must not be used in patients receiving non-selective β-blockers, such as propranolol (see section "Contraindications").

Combinations of different anesthetics exhibit additive effects and produce a more pronounced impact on the cardiovascular and central nervous systems (CNS).

Adrenaline may block insulin release from the pancreas, thereby reducing the efficacy of oral antidiabetic agents.

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

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

Special precautions for use.

To avoid the occurrence of adverse effects, the lowest possible dose should be selected. Before injection, a two-stage aspiration test should be performed (to prevent intravascular administration of the drug).

The drug should be used with caution in patients with coagulation disorders, severe hepatic or renal impairment, concomitant use of halogen-containing inhalational anesthetics (see section "Interaction with other medicinal products and other forms of interaction"), or a history of epilepsy (see section "Adverse reactions").

Injections should not be administered into inflamed (infected) areas, as this enhances drug absorption, leading to reduced efficacy.

Before administering this drug, the patient should be interviewed, a medical history obtained, information collected regarding concomitant medications, and verbal contact with the patient should be maintained continuously during administration. An intradermal test injection of 5 to 10% of the intended dose should be performed if there is a risk of an allergic reaction.

Eating is recommended only after full sensation has returned.

The drug should be prescribed to patients with cholinesterase deficiency only when absolutely indicated, as in such cases there is a higher probability of prolonged drug action and, under certain conditions, undesirable enhancement of its effects.

For patients with cardiovascular diseases (e.g., heart failure, ischemic heart disease, angina pectoris, history of myocardial infarction, cardiac arrhythmias, arterial hypertension), atherosclerosis, cerebrovascular disorders, history of stroke, chronic bronchitis, pulmonary emphysema, diabetes mellitus, or marked anxiety, it is preferable to use Artifrin-Zdorov'ya (rather than Artifrin-Zdorov'ya Forte), as it contains a lower concentration of adrenaline—0.006 mg/mL (1:200000).

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

Sodium metabisulfite (E 223), an ingredient of this medicinal product, may rarely cause hypersensitivity reactions and bronchospasm.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding. There is no clinical experience with the use of articaine in pregnant women, except during labor. No signs of direct or indirect adverse effects of articaine on pregnancy, embryofetal development, labor, or postnatal development have been observed in animal studies. Adrenaline has toxic effects on reproductive function. Adrenaline and articaine cross the placental barrier, although articaine crosses to a significantly lesser extent compared to other local anesthetics. The concentration of articaine in newborn serum is approximately 30% of the concentration in maternal serum. Accidental intravascular administration of adrenaline to the mother may reduce uterine blood flow. The use of this drug during pregnancy should only be considered after a careful benefit-risk assessment. Artifrin-Zdorov'ya is preferred due to its lower adrenaline content (1:200000) compared to Artifrin-Zdorov'ya Forte.

Due to rapid elimination, articaine is not present in breast milk in clinically significant amounts. Adrenaline passes into breast milk but also undergoes rapid degradation. Since no harmful effects on infants have been observed to date, there is no need to interrupt breastfeeding following short-term use of the drug.

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

Ability to affect reaction speed when driving vehicles or operating machinery. Only the dentist should determine when, after drug administration, the patient may resume driving or operating machinery. Fear related to anticipated dental procedures and associated stress may impair the ability to function effectively. However, relevant studies have shown that local anesthesia with articaine does not lead to any clinically significant impairment in the ability to drive a vehicle.

In sensitive patients, adverse reactions from the central nervous system (CNS) may occur.

Method of Administration and Dosage.

The medicinal product is intended for submucosal administration into the oral cavity. Prior to administration, an aspiration test must always be performed to exclude the possibility of intravascular injection. The aspiration test should be carried out 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 wait at least 20–30 seconds before slowly administering the remainder of the dose. Injection pressure should correspond to tissue sensitivity. Damaged cartridges must not be used for injections. To prevent infection (e.g., transmission of hepatitis virus), new sterile needles and syringes must always be used when drawing up the solution. This medicinal product must not be used if it is cloudy or has changed color.

For uncomplicated forceps removal of maxillary teeth in the absence of inflammation, it is sufficient to administer 1.7 mg of the drug per tooth into the vestibular fold from the vestibular side. In individual cases, an additional vestibular injection of 1–1.7 mL of the drug may be required to achieve complete anesthesia. In most cases, painful palatinal injection is unnecessary.

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

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

For uncomplicated forceps removal of mandibular premolars in the absence of inflammation, mandibular anesthesia may be omitted, as infiltration anesthesia achieved by administering 1.7 mL of the drug 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 surgical procedures, the dose should be adjusted according to the severity and duration of the surgery.

During a single treatment session, adults may receive up to 7 mg of articaine per kg of body weight. Doses up to 500 mg (corresponding to 12.5 mL of injection solution) have been well tolerated by patients when the aspiration test was performed prior to injection.

In elderly patients and patients with severe hepatic or renal dysfunction, increased plasma concentrations of articaine may occur. Extreme caution should be exercised in such patients, and the minimum effective dose required to achieve adequate depth of anesthesia should be used.

Children. The drug should be administered to children in the smallest effective amount necessary to achieve adequate analgesia; the administered dose should be individually adjusted according to the child’s age and body weight. The maximum dose of 7 mg of articaine per kg of body weight must not be exceeded. The use of this drug in children under 1 year of age has not been studied.

Overdose.

Symptoms of overdose.

Signs of 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, loss of consciousness, muscle atonia, vasomotor paralysis (weakness, pallor of the skin), dyspnea, and 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 or toxic reaction (e.g., dizziness, motor agitation, or stupor), the injection should be stopped immediately and the patient placed in a supine position. Airway patency must be ensured, and pulse and blood pressure monitored. Even if intoxication symptoms appear mild, it is recommended to establish an intravenous catheter to ensure immediate intravenous access if needed.

In case of respiratory disturbances, depending on severity, oxygen therapy and, if necessary, artificial ventilation should be administered. Endotracheal intubation combined with controlled lung ventilation may be required.

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.

Hypotension, tachycardia, or bradycardia may be resolved simply by placing the patient in a supine position or in a position with legs elevated slightly above the head. In severe circulatory disturbances, after stopping the injection, additional emergency measures should be taken: ensure airway patency (oxygen insufflation), initiate intravenous infusion of balanced electrolyte solution, and intravenous administration of glucocorticoids (e.g., 250–1000 mg of prednisolone or equivalent dose of its derivative, such as methylprednisolone). Circulating blood volume should be restored (plasma substitutes or human albumin may be additionally used if necessary). In case of impending circulatory collapse and progressive bradycardia, immediate intravenous injection of epinephrine (adrenaline) is indicated. To prepare, dilute 1 mL of 1:1000 adrenaline solution to 10 mL (alternatively, use 1:10,000 adrenaline solution) and slowly administer 0.25–1 mL of this solution (= 0.025–0.1 mg adrenaline) under continuous monitoring of pulse rate and blood pressure (caution: risk of cardiac arrhythmia). Do not administer more than 1 mL of this solution (0.1 mg adrenaline) during a single intravenous injection. If this dose is insufficient, adrenaline should be added to the infusion solution (infusion rate adjusted according to pulse and blood pressure).

Severe forms of tachycardia and tachyarrhythmias can be treated with antiarrhythmic agents (excluding non-selective β-blockers). In such cases, oxygen therapy and hemodynamic monitoring are essential. In hypertensive patients, if blood pressure increases, peripheral vasodilators may be used if necessary.

Adverse reactions. The following categories are used to classify the frequency of adverse effects: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated from available data).

Immune system disorders: frequency not known – hypersensitivity reactions (allergic and pseudoallergic) may occur. These may manifest as swelling and/or inflammation at the injection site, or independently of the injection site as skin redness, itching, conjunctivitis, rhinitis, angioedema-like facial swelling 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, breathing difficulties, which may progress to anaphylactic shock.

Nervous system disorders: common – paresthesia, hypoesthesia, headache (mainly due to epinephrine); uncommon – dizziness; frequency not known – when excessively high doses are used or in case of accidental intravascular injection, dose-dependent CNS reactions may occur: restlessness, nervousness, stupor (which may progress to loss of consciousness), coma, respiratory disturbances (which may progress to respiratory arrest), muscle tremor, involuntary muscle contractions (which may progress to generalized seizures). Theoretical risk of nerve injury exists with any dental procedure due to improper injection technique or anatomical peculiarities of the injection site. In such cases, facial nerve injury and facial nerve palsy may occur, potentially leading to reduced taste sensitivity.

Eye disorders: frequency not known – temporary visual disturbances (blurred vision, diplopia, mydriasis, blindness) may also occur during or shortly after local anesthetic injection in the head region.

Cardiovascular system disorders: uncommon – tachycardia; frequency not known – cardiac arrhythmias, increased blood pressure, arterial hypotension, bradycardia, heart failure, and shock (which may be life-threatening).

Gastrointestinal disorders: common – nausea, vomiting.

General disorders and administration site reactions: frequency not known – in case of unintentional intravascular injection, ischemic areas may appear at the injection site, which may sometimes progress to tissue necrosis (see section "Method of Administration and Dosage"). Cases of chills have been reported, mainly related to anxiety associated with dental procedures, as well as excessive sweating, tinnitus, and mydriasis.

In isolated 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 manifest as vomiting, diarrhea, stridor, acute asthma attack, disturbances of consciousness, or shock.

Pediatric population. Published study data indicate that the safety profile in children aged 4 to 18 years is similar to that in adults. However, accidental soft tissue injuries due to prolonged soft tissue anesthesia are more frequently observed, particularly in children aged 3 to 7 years. Data from a retrospective study involving 211 children aged 1 to 4 years showed that dental treatment was performed using up to 4.2 mL of the drug, with no reports of adverse effects.

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children. Do not freeze.

Incompatibility. The drug must not be mixed with other medicinal products.

Packaging. 1.7 mL in cartridges, 10 per blister, 10×5 blisters in a box.

Prescription status. Prescription only.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA".

Limited Liability Company "FARMEKS GROUP".

Manufacturer's location and address of business activity. Ukraine, 61013, Kharkiv region, city of Kharkiv, Shevchenko Street, 22.

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA")

Ukraine, 08301, Kyiv region, city of Boryspil, Shevchenko Street, 100.

(Limited Liability Company "FARMEKS GROUP")