Articaine with epinephrine forte (Solution) Instructions for Use

ATC Code

N01BB58 (Articaine in combination with other drugs)

Active Substances

Articaine (Rec.INN registered by WHO)

Epinephrine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Local anesthetic with a vasoconstrictor component for use in dentistry

Pharmacotherapeutic Group

Local anesthetic agent + alpha- and beta-adrenomimetic

Pharmacological Action

Articaine with epinephrine forte, used for infiltration and conduction anesthesia in dentistry, is a combined preparation which contains articaine (an amide-type local anesthetic agent) and epinephrine (a vasoconstrictor agent), which is added to the preparation to prolong anesthesia.

Articaine exerts a local anesthetic effect by blocking voltage-gated sodium channels in the neuronal cell membrane, leading to reversible inhibition of impulse conduction along the nerve fiber and reversible loss of sensation.

Articaine with epinephrine forte has a rapid onset (latent period from 1 to 3 minutes) and a potent anesthetic effect, and it has good tissue tolerance. The duration of effective anesthesia, including intrapulpal anesthesia, is at least 75 minutes; the duration of soft tissue anesthesia is from 120 to 240 minutes.

Children

Published studies have shown that in children aged 3.5 to 16 years, the use of the drug at a dose of 7 mg of articaine per 1 kg of body weight provided sufficient local anesthetic effect during mandibular infiltration or maxillary conduction anesthesia. The duration of anesthesia was comparable in all age groups and depended on the volume of the drug administered.

Pharmacokinetics

Absorption, Distribution, Metabolism

The binding of articaine to plasma proteins is approximately 95%.

Articaine is rapidly metabolized, almost immediately after administration, by hydrolysis via non-specific plasma esterases in the blood and tissues (90%). Up to 10% of articaine is metabolized in the liver. The main metabolite of articaine formed in this process, articainic acid, does not possess local anesthetic activity or systemic toxicity, which allows for repeated administration of the drug.

In children, the total exposure during infiltration anesthesia from the vestibular aspect is comparable to that in adults; however, the C_max of articaine in plasma is reached faster.

Elimination

Following submucosal administration into the oral cavity, the T_1/2 of articaine is 25.3±3.3 minutes.

Articaine is excreted by the kidneys, mainly in the form of articainic acid.

Indications

For local anesthesia (infiltration and conduction anesthesia) in dentistry during traumatic interventions and when pronounced hemostasis or improved visualization of the surgical field is required.

• Dental operations on the mucous membrane or bones requiring the creation of more pronounced ischemia conditions;
• Dental pulp operations (amputation or extirpation);
• Removal of a fractured tooth (osteotomy) or a tooth affected by apical periodontitis;
• Prolonged surgical interventions;
• Percutaneous osteosynthesis;
• Excision of cysts;
• Interventions on the gingival mucosa;
• Root apex resection.

ICD codes

Dosage Regimen

Solution

The drug is intended for use in the oral cavity and can only be injected into tissues where there is no inflammation.

Injection into inflamed tissues must not be performed.

The drug must not be administered intravenously.

To avoid accidental entry of the drug into blood vessels, a two-step aspiration test with rotation of the needle by 90°C (194°F) and 180° should always be performed before its administration.

Major systemic reactions that may develop as a result of accidental intravascular administration of the drug can be avoided by adhering to the injection technique: after performing the aspiration test, slowly inject 0.1-0.2 ml of the drug, then, no earlier than 20-30 seconds later, slowly inject the remaining dose of the drug. The injection pressure should correspond to tissue sensitivity.

To prevent infection (including with the hepatitis virus), care must be taken to ensure that new sterile syringes and needles are always used when withdrawing the solution from ampoules.

Opened cartridges must not be reused for other patients (risk of hepatitis infection)!

Damaged cartridges must not be used.

The medicinal product should not be used if the solution has changed its color or become cloudy.

For anesthesia during uncomplicated extraction of maxillary teeth in the absence of inflammation, it is usually sufficient to create a depot of Articaine with epinephrine forte in the area of the transitional fold by injecting it into the submucosa from the vestibular side (1.7 ml of the drug per tooth). In some cases, an additional injection of 1 ml to 1.7 ml may be required to achieve complete anesthesia. In most cases, this avoids the need for a painful palatal injection.

For anesthesia during incisions and suturing in the palate area to create a palatal depot, approximately 0.1 ml of the drug is needed per injection.

When removing several adjacent teeth, the number of injections can usually be limited.

In the case of removal of mandibular premolars in the absence of inflammation, administration of 1.7 ml per tooth is generally sufficient. If the desired effect is not achieved in this way, an additional injection of 1-1.7 ml of the anesthetic should be performed into the submucosa in the area of the mandibular transitional fold from the vestibular side. If complete anesthesia is still not achieved in this case, a conduction block of the mandibular nerve is necessary.

During surgical interventions, depending on their severity and duration, Articaine with epinephrine forte is dosed individually.

For a single therapeutic procedure, adults can be administered articaine at a dose of up to 7 mg per 1 kg of body weight. It has been noted that patients tolerated doses of up to 500 mg (corresponding to 12.5 ml of the injection solution) well.

In elderly patients and all patients with severe renal and hepatic impairment, increased plasma concentrations of articaine may occur. For these patients, the minimum doses necessary to achieve sufficient depth of anesthesia should be used.

For pediatric patients over 4 years of age, the minimum doses necessary to achieve adequate anesthesia should be used. The dose of Articaine with epinephrine forte is selected depending on the child’s age and body weight, but it should not exceed 7 mg of articaine per 1 kg of body weight (0.175 ml/kg). The use of the drug in children under 1 year of age has not been studied.

Adverse Reactions

The frequency of adverse effects is presented in accordance with the classification recommended by WHO: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), including isolated reports; frequency unknown (cannot be estimated from the available data).

Immune system disorders: frequency unknown – allergic or allergy-like reactions. They may be expressed as swelling and/or inflammation at the injection site, but can also occur independently of the injection site and manifest as redness, skin itching, conjunctivitis, rhinitis, angioneurotic edema of the face with swelling of the upper lip and/or lower lip, cheeks, laryngeal edema with a sensation of a “lump in the throat” and difficulty swallowing, urticaria, and difficulty breathing, which can progress to anaphylactic shock.

Nervous system disorders: common – paresthesia, hypesthesia, headache (due to the presence of epinephrine in the preparation); uncommon – dizziness; frequency unknown – dose-dependent reactions from the CNS (including reactions with excessively high doses or after accidental intravascular injection), including feeling of anxiety, nervousness, stupor, confusion up to loss of consciousness, coma, respiratory disturbance up to respiratory arrest, muscle tremor and twitching up to generalized convulsions. If the correct injection technique is violated or due to anatomical features in the injection area, damage to the facial nerve is possible, which can lead to facial nerve paralysis and reduced taste sensation.

Eye disorders: frequency unknown – visual disturbances (blurred vision, mydriasis, blindness, diplopia), usually reversible and occurring during or shortly after the injection of the local anesthetic.

Cardiac and vascular disorders: uncommon – tachycardia; frequency unknown – cardiac arrhythmias, increased blood pressure, arterial hypotension, bradycardia, heart failure, and shock.

Gastrointestinal disorders: common – nausea, vomiting.

General disorders and administration site conditions: frequency unknown – in some cases, with accidental intravascular administration, the appearance of ischemic zones at the injection site, up to tissue necrosis, is possible (see section “Dosage Regimen”).

Children

In published works, the safety profile in children and adolescents aged 4 to 18 years is similar to the safety profile in adults. However, accidental injuries to the soft tissues of the oral cavity are more frequently observed in children (up to 16% of children), especially in the age group from 3 to 7 years (due to the longer duration of soft tissue anesthesia). There are data from a retrospective study of children aged 1 to 4 years, during which dental interventions were performed using preparations containing articaine 40 mg/ml + epinephrine 0.005 mg/ml in doses up to 4.2 ml. According to the results of this study, no adverse effects were reported.

Contraindications

Hypersensitivity to articaine or other amide-type local anesthetics, epinephrine, sulfites (particularly in patients suffering from bronchial asthma with hypersensitivity to sulfites, as acute allergic reactions with symptoms of anaphylactic shock, such as bronchospasm, are possible), or to any other auxiliary component of the drug.

Contraindications due to the presence of articaine in the preparation

• Severe sinus node dysfunction or severe conduction disorders (e.g., marked bradycardia, second- or third-degree AV block);
• Acute decompensated heart failure;
• Severe form of arterial hypotension;
• Children under 4 years of age (lack of sufficient clinical experience).

Contraindications due to the presence of epinephrine in the preparation

• Closed-angle glaucoma;
• Hyperfunction of the thyroid gland;
• Paroxysmal tachycardia, tachyarrhythmia;
• Recent myocardial infarction (within the last 6 months);
• Recent coronary artery bypass grafting (within the last 3 months);
• Concomitant use of non-selective beta-blockers, e.g., propranolol (risk of hypertensive crisis and severe bradycardia);
• Pheochromocytoma;
• Severe form of arterial hypertension.

With caution

• In patients with chronic heart failure, coronary artery disease, angina pectoris, atherosclerosis, history of myocardial infarction, cardiac arrhythmias, arterial hypertension;
• In patients with cerebrovascular disorders, history of stroke;
• In patients with chronic bronchitis, pulmonary emphysema;
• In patients with diabetes mellitus (potential risk of changes in blood glucose concentration);
• In patients with cholinesterase deficiency (use is possible only in case of extreme necessity, as prolongation and marked enhancement of the drug’s effect is possible);
• In patients with blood coagulation disorders;
• In patients with severe hepatic and renal impairment;
• In patients with marked agitation;
• In patients with a history of epilepsy;
• With concomitant use with halogen-containing agents during inhalation anesthesia (see section “Drug Interactions”).

Use in Pregnancy and Lactation

Pregnancy

Articaine and epinephrine cross the placental barrier.

The concentration of articaine in the serum of newborns (after administration of the drug to the mother) is approximately 30% of the articaine concentration in the maternal serum.

Due to insufficient clinical data, the decision to use the drug by a dentist can only be made if the potential benefit to the mother justifies the potential risk to the fetus. If it is necessary to use articaine during pregnancy, it is better to use medicinal products that do not contain epinephrine or contain epinephrine at a concentration of 0.005 mg/ml.

In case of accidental intravascular administration, epinephrine may reduce uterine blood flow.

Breastfeeding period

With short-term use of the drug during breastfeeding, it is generally not necessary to interrupt breastfeeding, as clinically significant concentrations of articaine and epinephrine are not detected in breast milk.

Fertility

Experimental studies of the use of articaine 40 mg/ml + epinephrine 0.01 mg/ml in animals did not show any effect on fertility in males and females. When used in therapeutic doses, the drug has no negative effect on human fertility.

Use in Hepatic Impairment

In all patients with severe hepatic impairment, increased plasma concentrations of articaine may occur. In these patients, the minimum doses necessary to achieve sufficient depth of anesthesia should be used.

Use in Renal Impairment

In all patients with severe renal impairment, increased plasma concentrations of articaine may occur. In these patients, the minimum doses necessary to achieve sufficient depth of anesthesia should be used.

Pediatric Use

In pediatric patients (over 4 years of age), the dose of Articaine with epinephrine forte is selected depending on the child’s age and body weight, but it should not exceed 5 mg of articaine per 1 kg of body weight.

Geriatric Use

In elderly patients, increased plasma concentrations of articaine may occur. In these patients, the minimum doses necessary to achieve sufficient depth of anesthesia should be used.

Special Precautions

Anesthesia should be performed by experienced specialists in an appropriately equipped room with readily available equipment and drugs necessary for monitoring cardiac activity and resuscitation measures. The personnel performing anesthesia must be qualified and trained in anesthesia techniques, and must be familiar with the diagnosis and treatment of systemic toxic reactions, adverse events and reactions, and other complications.

The drug should be used in patients with cholinesterase deficiency only if strictly indicated, as its action may be prolonged and, under certain circumstances, enhanced.

Articaine with epinephrine forte should be used with particular caution in patients with blood coagulation disorders, severe renal or hepatic impairment, with concomitant use of halogenated inhalation narcotic agents (see section “Drug Interactions”), history of epilepsy.

In patients with cardiovascular diseases (chronic heart failure, coronary artery disease, angina pectoris, history of myocardial infarction, cardiac arrhythmias, arterial hypertension), atherosclerosis, cerebrovascular insufficiency, history of stroke, chronic bronchitis, pulmonary emphysema, diabetes mellitus, severe forms of anxiety neurosis, it is advisable to use preparations that do not contain epinephrine or contain epinephrine at a concentration of 0.005 mg/ml.

Injection into an inflamed area must not be performed.

Before using the drug, the patient’s history and current concomitant drug therapy should be ascertained. The physician should maintain verbal contact with the patient and, in case of allergy risk, administer a test dose of 5% or 10% of the intended dose.

To avoid adverse events, the following conditions must be observed:

• Select the minimum doses necessary to achieve sufficient depth of anesthesia;
• Before injection, an aspiration test in two planes must be performed (to avoid accidental intravascular administration).

It is not recommended to eat until the effect of local anesthesia ceases (sensation returns).

It should be taken into account that 1 ml of the drug solution contains less than 1 mmol (23 mg) of sodium.

The drug is intended for use in dentistry. Use for anesthesia of the distal parts of the limbs is unacceptable (risk of ischemia due to the presence of epinephrine in the preparation).

Use in pediatrics

Parents (guardians) of young children should ensure that the children do not injure their soft tissues by biting (chewing) them due to the prolonged reduction in tissue sensitivity caused by the drug.

Effect on ability to drive vehicles and operate machinery

The use of Articaine with epinephrine forte does not cause any noticeable deviation from the usual ability to drive vehicles. However, the decision as to when a patient can return to driving vehicles and engaging in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions after a dental intervention should be made by the physician.

Overdose

Symptoms

From the CNS: CNS excitation – feeling of anxiety, fear, confusion, hyperpnea, tachycardia, increased blood pressure with facial flushing, nausea, vomiting, tremor, twitching, tonic-clonic convulsions; CNS depression – dizziness, hearing impairment, loss of speech ability, stupor, unconsciousness, atony, paralysis of vasomotor nerves (weakness, pallor), shortness of breath, death from paralysis of respiratory muscles.

From the cardiovascular system:bradycardia, arrhythmia, ventricular fibrillation, drop in blood pressure, cyanosis, cardiac arrest.

Treatment

At the first signs of intoxication or side effects of the drug, such as dizziness, motor agitation, or stupor during administration, its administration should be discontinued and the patient should be placed in a horizontal position with elevated lower limbs. Airway patency should be ensured and hemodynamic parameters (heart rate and blood pressure) should be monitored. It is recommended always, even if the symptoms of intoxication seem mild, to secure venous access in order to be able to immediately administer necessary medications intravenously if needed.

For respiratory disturbances, depending on their severity, oxygen administration is recommended, and if indications for artificial respiration arise, endotracheal intubation and mechanical ventilation should be performed.

Muscle twitching and generalized convulsions can be controlled by intravenous administration of fast-acting drugs with muscle relaxant and anticonvulsant effects (e.g., diazepam, suxamethonium chloride). Mechanical ventilation (oxygen administration) is also recommended.

A sharp decrease in blood pressure, bradycardia, or tachycardia can often be eliminated by simply placing the patient in a horizontal position with elevated lower limbs.

In cases of severe circulatory disorders and shock, regardless of their cause, the administration of the drug must be discontinued and the patient should be placed in a horizontal position with elevated lower limbs. Oxygen administration, intravenous administration of electrolyte solutions, corticosteroids (e.g., 250-1000 mg of prednisolone or an equivalent amount of its derivative, such as methylprednisolone), and replacement infusion therapy (if necessary, additionally, plasma substitutes, including human albumin) should be carried out.

If collapse develops and bradycardia intensifies, epinephrine (adrenaline) is administered intravenously immediately. After diluting 1 ml of a 0.1% epinephrine solution (1:1000) to 10 ml, or using a 0.01% epinephrine solution (1:10000), a slow intravenous injection of 0.25-1 ml (0.025-0.1 mg of epinephrine) is performed, while monitoring heart rhythm and blood pressure (caution: cardiac arrhythmias may occur!).

Do not exceed the single dose for intravenous administration of 1 ml (0.1 mg of epinephrine). If subsequent administration of doses exceeding 0.1 mg is necessary, epinephrine should be administered by infusion, adjusting the infusion rate under the control of heart rate and blood pressure.

Severe tachycardia and tachyarrhythmia can be treated with antiarrhythmic drugs, excluding non-selective beta-blockers, such as, for example, propranolol. In such cases, oxygen administration and hemodynamic monitoring are necessary. An increase in blood pressure in patients with arterial hypertension, if necessary, is relieved with peripheral vasodilators.

Drug Interactions

Combinations of different local anesthetics cause additional effects on the cardiovascular system and central nervous system.

Contraindicated Combinations

With non-selective beta-blockers, e.g., propranolol

Risk of developing a hypertensive crisis and pronounced bradycardia.

Interaction to be taken into account

With tricyclic antidepressants or MAO inhibitors

The effect of vasoconstrictors (adrenomimetics) that increase blood pressure, e.g., epinephrine, may be enhanced by tricyclic antidepressants or MAO inhibitors. Similar observations have been described for concentrations of norepinephrine 1:25000 and epinephrine 1:80000 when used as vasoconstrictors. Although the concentration of epinephrine in the drug Articaine with epinephrine forte is significantly lower – 1:200000, nevertheless, the possibility of enhanced hypertensive action of epinephrine should be considered.

With drugs that depress the central nervous system

Local anesthetics enhance the effect of drugs that depress the central nervous system. Narcotic analgesics enhance the effect of local anesthetics but increase the risk of respiratory depression.

With anticoagulants and other drugs that reduce blood clotting

When administering injections of the drug Articaine with epinephrine forte to patients receiving heparin or acetylsalicylic acid, bleeding may develop at the injection site.

With cholinesterase inhibitors

Cholinesterase inhibitors reduce the metabolism of local anesthetic drugs, which may result in prolongation and pronounced enhancement of the action of articaine.

With oral hypoglycemic agents

Epinephrine may inhibit the release of insulin from pancreatic β-cells and reduce the effects of oral hypoglycemic agents.

With some agents for inhalation anesthesia (halothane)

Halothane may increase myocardial sensitivity to catecholamines and increase the risk of cardiac arrhythmias following injections of the drug Articaine with epinephrine forte.

With disinfectant solutions containing heavy metals

When treating the injection site of a local anesthetic with disinfectant solutions containing heavy metals, the risk of developing local reactions – edema, pain – increases.

Storage Conditions

The drug in ampoules should be stored in a place protected from light, at a temperature not exceeding 25°C (77°F); do not allow freezing.

Shelf Life

The shelf life is 3 years. Do not use after the expiration date printed on the packaging.

The drug in cartridges should be stored in a place protected from light, at a temperature not exceeding 30°C (86°F); do not allow freezing. The shelf life is 2.5 years. Do not use after the expiration date printed on the packaging.

The drug should be stored out of the reach of children.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.