Orabloc 1:200,000

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ORABLOC 1:200,000 (ORABLOC 1:200,000)

Composition:

Active substances: 1 ml of injection solution contains 40 mg of articaine hydrochloride and 0.005 mg of adrenaline (epinephrine) in the form of adrenaline tartrate;

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

Pharmaceutical form. Injection solution.

Main physicochemical properties: cartridges containing a clear, colorless solution free from visible particles.

Pharmacotherapeutic group.

Local anesthetics. Articaine, combinations.

ATC code N01B B58.

Pharmacological properties.

Pharmacodynamics.

OraBlock 1:200,000 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 provides 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 cellular membranes.

Clinical studies involving up to 210 patients demonstrated that administration of 4% articaine + 0.005 mg/mL epinephrine (adrenaline) at doses up to 5 mg/kg, and 4% articaine + 0.010 mg/mL epinephrine (adrenaline) at doses up to 7 mg/kg, provided reliable local analgesia in children aged 3.5 to 16 years when administered via infiltration anesthesia (for the mandible) and conduction anesthesia (for the maxilla). The duration of anesthesia was similar across all age groups and depended on the amount of anesthetic administered.

Pharmacokinetics.

The plasma protein binding of articaine 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 articainic acid.

In children, total systemic exposure following infiltration anesthesia from the vestibular side was similar to that in adults; however, minimum blood concentrations were reached more rapidly.

Preclinical safety data.

Results of standard preclinical studies in safety pharmacology, chronic toxicity, reproductive toxicity, and genotoxicity indicate no special hazard for humans when therapeutic doses are used. At doses exceeding therapeutic levels, articaine exerts cardiodepressant effects and may produce vasodilatory activity. Adrenaline (epinephrine) counteracts the effects of sympathomimetics.

In embryotoxicity studies, articaine did not increase the incidence of fetal mortality or cause developmental abnormalities when administered intravenously daily at doses up to 20 mg/kg (rats) and 12.5 mg/kg (rabbits). Adrenaline (epinephrine) demonstrated toxic effects on reproductive function in animals at doses ranging from 0.1 to 5 mg/kg (several times higher than the maximum allowable dose of epinephrine (adrenaline) when using OraBlock), manifested by induction of congenital developmental abnormalities and impairment of uteroplacental blood flow.

In studies of embryofetotoxicity of articaine and adrenaline (epinephrine), no increase in the incidence of developmental abnormalities was observed with daily administration of articaine at doses up to 80 mg/kg (rats) and 40 mg/kg (rabbits).

In studies assessing the effect of the drug on fertility and early embryofetal development in rats, no adverse effects on fertility in males or females were observed following administration of doses causing toxic effects in parental animals.

Clinical characteristics.

Indications.

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

Contraindications.

OraBlock 1:200,000 must not be used in cases of hypersensitivity to the active substances – epinephrine and articaine, as well as to sulfites (metabisulfite (E 223)) or to any of the excipients of the product.

Due to the presence of articaine in OraBlock 1:200,000, it must not be used in cases of:

• hypersensitivity to other amide-type local anesthetics;
• severe disturbances of cardiac impulse generation and 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 epinephrine in OraBlock 1:200,000, the product must not be used:

• in patients with closed-angle glaucoma;
• in patients with hyperthyroidism;
• in patients with paroxysmal tachycardia or absolute arrhythmia 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 MAO inhibitors, as their active substances may potentiate cardiovascular effects of epinephrine (adrenaline). This phenomenon may persist for up to 14 days after discontinuation of MAO inhibitors.

Intravenous administration of the product is contraindicated.

Due to the presence of epinephrine in OraBlock 1:200,000, it should not be used for anesthesia of extremities (e.g., fingers), as there is a risk of ischemia.

OraBlock 1:200,000 should not be used in patients with bronchial asthma and hypersensitivity to sulfites. In such patients, administration of OraBlock 1:200,000 may provoke acute allergic reactions with anaphylactic symptoms such as bronchospasm.

Interaction with other medicinal products and other forms of interaction.

Combinations of different anesthetics exhibit additive effects and have a more pronounced impact on the cardiovascular system and CNS.

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

The medicinal product is contraindicated in patients taking non-selective beta-blockers, e.g., propranolol (see section "Contraindications").

Adrenaline (epinephrine) may inhibit insulin release from the pancreas, thereby reducing the efficacy of oral antidiabetic agents.

Some inhalational anesthetics, such as halothane, may increase myocardial sensitivity to catecholamines, causing ventricular arrhythmia after administration of the product.

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

Special precautions for use

Patients with cholinesterase deficiency may be prescribed Orabloc 1:200,000 only if there are absolute indications for its use, since in such cases there is a high probability of prolonged duration of action of the drug and, occasionally, undesirable enhancement of its effect.

Orabloc 1:200,000 should be used with caution in the following cases:

• Coagulation disorders;
• Severe renal or hepatic impairment;
• Concomitant use of halogen-containing inhalational anesthetics (see section "Interaction with other medicinal products and other forms of interaction");
• History of epilepsy (see section "Adverse reactions").

Orabloc should also be used with particular caution in the following conditions. Additionally, Orabloc 1:200,000 contains a lower amount of epinephrine than Orabloc 1:100,000, making it more suitable for patients with:

• 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;
• Marked anxiety.

Injections must not be administered into areas of inflammation (infection) due to enhanced absorption of Orabloc 1:200,000, which leads to reduced efficacy.

Before administering this medicinal product, the patient must be interviewed, a medical history taken, information collected about concomitant medications, and verbal contact maintained continuously during administration. A test dose injection of 5–10% of the total dose should be performed if there is a risk of allergic reaction.

To avoid adverse reactions, the following measures are necessary:

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

Eating is recommended only after full sensation has returned.

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

Sodium metabisulfite (E 223) may cause hypersensitivity reactions and bronchospasm.

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.

Use during pregnancy or breastfeeding

Pregnancy

There is no experience with the use of articaine in pregnant women, except during labor. Animal studies have not revealed any evidence of direct or indirect adverse effects of articaine on pregnancy, embryofetal development, labor, or postnatal development. Animal studies have demonstrated that adrenaline (epinephrine), at doses exceeding the maximum allowable, has a toxic effect on reproductive function (see section "Preclinical safety data").

Adrenaline (epinephrine) and articaine cross the placental barrier, although articaine crosses to a significantly lesser extent compared to other local anesthetics. The concentration of articaine in neonatal serum is approximately 30% of that in maternal serum. Accidental intravascular administration of adrenaline (epinephrine) to the mother may reduce uterine blood flow. Use of Orabloc 1:200,000 during pregnancy is possible only after careful benefit-risk assessment.

Orabloc 1:200,000 should be preferred, as it contains less epinephrine than Orabloc 1:100,000.

Breastfeeding

Due to rapid decline in plasma concentrations and rapid elimination, clinically significant levels of articaine are not reached in breast milk. Adrenaline (epinephrine) passes into breast milk but is also rapidly metabolized.

There is no need to interrupt breastfeeding after short-term use of the drug.

Fertility

Animal studies with articaine 40 mg/mL + epinephrine 0.01 mg/mL did not reveal any negative effect on fertility (see section "Pharmacological properties"). When used at therapeutic doses, a negative effect on human fertility is not expected.

Ability to influence reaction speed when driving or operating machinery

Only the physician can decide in each individual case whether the patient is capable of driving or operating machinery after administration of the drug. Fear associated with anticipation of a dental procedure and the stress accompanying it may impair the ability to act effectively; however, relevant studies have shown that local anesthesia with articaine does not cause any noticeable impairment in the ability to drive a vehicle.

Method of Administration and Dosage

In uncomplicated forceps removal of maxillary teeth in the absence of inflammation, it is sufficient to administer 1.8 mg of the drug per tooth into the vestibular fold. In individual cases, an additional vestibular injection of 1–1.8 mL of the drug may be required to achieve complete anesthesia. In most cases, painful palatal injection is not necessary.

If an incision or suturing on the palate is required, a 0.1 mL injection of the drug on the palatal side is sufficient to create an anesthetic depot. During 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 1.8 mL of the drug per tooth is usually sufficient. If this fails to provide complete analgesia, an additional vestibular injection of 1–1.8 mL should first be administered. Only if this also fails to achieve complete anesthesia is standard inferior alveolar nerve block indicated.

For caries cavity preparation or tooth preparation for crowns, except for lower molars, an injection of OraBlock 1:200,000 from the vestibular side at a dose of 0.5–1.8 mL per tooth is indicated; the dose depends on the extent and duration of the procedure.

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

Geriatric patients and patients with severe hepatic and renal dysfunction

In geriatric patients and patients with severe hepatic and renal dysfunction, increased plasma concentrations of articaine may occur. Such patients require special caution, and the minimum effective dose necessary to achieve adequate depth of anesthesia should be used.

Method of Administration and Duration of Use

OraBlock 1:200,000 is intended for submucosal administration in the oral cavity.

To avoid intravascular injection, an aspiration test must always be performed before injection. The aspiration test should be conducted in two planes, i.e., by rotating the needle 90° or even 180°. Most systemic reactions resulting from accidental intravascular injection can be avoided by proper injection technique: after aspiration, slowly inject 0.1–0.2 mL, then slowly administer the remainder no sooner than 20–30 seconds later.

Injection pressure should correspond to tissue sensitivity.

A specialized injection device with appropriate disposable needles should be used for administration.

This medicinal product must not be used if the solution is cloudy or has changed color.

Children

OraBlock 1:200,000 should be administered to children in the minimal amount required to achieve adequate analgesia; the administered amount 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 the 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, stupor, loss of consciousness, muscle 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 agitation, 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 insert an intravenous catheter to ensure immediate intravenous access if needed.

In case of respiratory disturbances, depending on severity, oxygen should be administered; artificial ventilation may be necessary. If required, tracheal intubation with controlled mechanical 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.

Hypotension, tachycardia, or bradycardia may be corrected simply by placing the patient in a horizontal position or 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 with slightly elevated lower limbs and ensure airway patency (oxygen insufflation);
• Initiate intravenous infusion of balanced electrolyte solution;
• Administer intravenous glucocorticoids (250–1000 mg of prednisolone or equivalent dose of its derivative, e.g., methylprednisolone);
• Restore circulating blood volume (additionally, if necessary, use plasma substitutes or human albumin).

In case of impending circulatory collapse and increasing bradycardia, immediate intravenous injection of adrenaline (epinephrine) is required. For this purpose, 1 mL of epinephrine (adrenaline) 1:1000 solution should be diluted to 10 mL (alternatively, epinephrine (adrenaline) 1:10,000 solution may 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: arrhythmias may occur). Do not administer more than 1 mL of this solution (0.1 mg of adrenaline (epinephrine)) per single intravenous injection. If this amount of adrenaline is insufficient, it is recommended to add it to the infusion solution (infusion rate adjusted according to pulse rate and blood pressure).

Severe forms of tachycardia and tachyarrhythmias may be managed with antiarrhythmic agents, except non-selective beta-blockers such as propranolol (see section "Contraindications"). In such cases, oxygen administration and hemodynamic monitoring are essential.

In hypertensive patients with elevated blood pressure, peripheral vasodilators may be used if necessary.

Adverse Reactions

The following categories are used to classify the frequency of adverse reactions:

Very common (≥ 1/10).
Common (≥ 1/100, < 1/10).
Uncommon (≥ 1/1,000, < 1/100).
Rare (≥ 1/10,000, < 1/1,000).
Very rare (< 1/10,000).
Frequency not known (cannot be estimated from the 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, facial swelling (angioneurotic edema) with 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

Common: paresthesia, hypoesthesia, headache (due to adrenaline content).
Uncommon: dizziness.

Frequency not known:

• When excessively high doses of the drug are used or in case of accidental intravascular administration, 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 tremors, involuntary muscle contractions (which may 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, facial nerve injury and facial nerve palsy may occur. This may lead to reduced taste sensitivity.

Eye disorders

Frequency not known: during or shortly after injection of a local anesthetic in the head region, temporary visual disturbances may occur (blurred vision, diplopia, mydriasis, blindness).

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 conditions

Frequency not known: in case of accidental intravascular injection, ischemic areas may develop at the injection site, which may sometimes progress to tissue necrosis (see section "Dosage and administration").

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

Special warnings

In isolated cases, particularly in patients with bronchial asthma, the drug may cause hypersensitivity reactions due to the presence of sodium metabisulfite (E 223) in its composition. These reactions may clinically present as vomiting, diarrhea, stridorous breathing, acute asthma attack, disturbances of consciousness, or shock.

Pediatric population

According to published study results, the safety profile in children and adolescents aged 4 to 18 years was similar to that in adults. However, accidental soft tissue injury due to prolonged anesthesia was observed more frequently (up to 16% of children), especially in children aged 3 to 7 years. In a retrospective study involving 211 children aged 1 to 4 years, dental treatment was performed using 4% articaine + 0.005 mg/mL or 0.01 mg/mL adrenaline (epinephrine) at doses up to 4.2 mL. During this period, no adverse effects were reported.

Shelf life.

2 years.

Storage conditions.

Keep out of the reach of children. Store at a temperature not exceeding 25 °C in the original packaging to protect from light.

Incompatibilities.

The medicinal product should not be mixed with other medicinal products.

Packaging.

Type I hydrolytic glass cartridges of 1.8 mL, sealed with an aluminum cap, bromobutyl rubber stopper, and bromobutyl rubber plunger.

Cartridges are labeled according to national requirements.

Cartridges are placed in transparent plastic blisters for easy inspection, with each blister containing 10 cartridges. Five blisters are packed in a lithographed carton, together with the patient leaflet.

Prescription category. Prescription only.

Manufacturer.

Pierrel S.p.A., Italy.

Manufacturer/Marketing Authorization Holder and address of the site of activity.

S.S. Appia – 81043 Capua (CE), Italy.

Marketing Authorization Holder.

Pierrel S.p.A., Italy.

Manufacturer/Marketing Authorization Holder and address of the site of activity.

S. S. Appia 7BIS 46-48 – 81043 Capua (CE), Italy.