UBISTESIN FORTE

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT UBISTESIN FORTE (UBISTESINFORTE)

Composition:

Active substances: 1 ml of solution contains articaine hydrochloride 40 mg, epinephrine hydrochloride 0.012 mg (equivalent to 0.01 mg epinephrine);

Excipients: sodium sulfite anhydrous (E 221), hydrochloric acid 14%, sodium hydroxide solution 9%, sodium chloride, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, non-opalescent, colorless liquid.

Pharmacotherapeutic group. Local anesthetics. Amides. Articaine, combinations.

ATC code N01BB58.

Pharmacological properties.

Pharmacodynamics.

Urbestezin Forte contains articaine, which is an amide-type local anesthetic used in dentistry. It causes reversible blockade of sensitivity in autonomic, sensory, and motor nerve fibers. The mechanism of action of articaine is believed to be blockade of voltage-dependent sodium channels in the nerve fiber membrane.

Characteristic features include rapid onset of anesthesia (onset time of 1 to 3 minutes in the case of infiltration anesthesia, and a slightly longer latent period in conduction anesthesia—approximately up to 9 minutes after injection), reliable and strong analgesic effect, and good local tolerance.

The duration of action of Urbestezin Forte in pulpal anesthesia is at least 75 minutes; for soft tissue anesthesia, it ranges from 120 to 240 minutes.

Adrenaline (epinephrine) causes local vasoconstriction and reduced blood supply, thereby slowing the absorption of articaine. This results in higher concentrations of the local anesthetic at the site of injection, prolonged duration of action, and reduced risk of systemic side effects. In surgical procedures, the tendency for bleeding is decreased.

Pharmacokinetics.

Absorption.

Urbestezin Forte is rapidly and almost completely absorbed.

The maximum plasma concentration of articaine after intraoral injection is reached approximately within 10–15 minutes.

Distribution.

The volume of distribution is 1.67 L/kg, elimination half-life (T1/2) is approximately 20 minutes, and time to reach maximum plasma concentration (Tmax) is 10–15 minutes.

Articaine is protein-bound in plasma by up to 95%.

Biotransformation and elimination.

Articaine is rapidly hydrolyzed by plasma cholinesterases to its primary metabolite—articainic acid—which is subsequently metabolized to glucuronide of articainic acid. In vitro studies have demonstrated that the P450 isoenzyme system of human liver microsomes metabolizes approximately 5% to 10% of available articaine, with nearly quantitative conversion into articainic acid. Articaine and its metabolites are predominantly excreted by the kidneys. Articaine crosses the blood-brain and placental barriers.

Adrenaline (epinephrine) is rapidly metabolized in the liver and other tissues. Metabolites are excreted by the kidneys.

Special patient groups.

Age. Pharmacokinetic studies of Urbestezin Forte in children have not been conducted. The pharmacokinetics of articaine do not significantly change with age.

Renal and hepatic impairment.

Studies on the use of Urbestezin Forte in patients with impaired renal or hepatic function have not been conducted. Hepatic dysfunction does not have a significant effect on articaine metabolism. In patients with impaired renal function, the elimination half-life of the inactive metabolite, articainic acid, may be prolonged.

Clinical characteristics.

Indications.

Local (infiltration and conduction) anesthesia in dentistry.

Ubistesin Forte is indicated for complex procedures requiring deep analgesia.

Contraindications.

• Hypersensitivity to articaine or to other amide-type local anesthetics, epinephrine (adrenaline), sulfites, or to any of the excipients of the drug;
• Paroxysmal tachycardia and other tachyarrhythmias;
• Acute heart failure, unstable angina, recent myocardial infarction (within 3 to 6 months), recent coronary artery bypass surgery (within 3 months), refractory arrhythmia and paroxysmal tachycardia or high-frequency prolonged arrhythmia, untreated or uncontrolled congestive heart failure, cardiac conduction disorders (second- to third-degree atrioventricular block, documented bradycardia), severe (untreated or uncontrolled) arterial hypertension, severe arterial hypotension;
• Severe bronchial asthma and hypersensitivity to sulfites;
• Closed-angle glaucoma;
• Concomitant use of non-selective β-adrenergic blockers;
• Severe hepatic insufficiency (porphyria);
• Hemorrhagic diathesis (increased risk of bleeding), especially when conduction anesthesia is used;
• History of abnormal plasma cholinesterase activity (including drug-induced forms);
• Hyperthyroidism;
• Pheochromocytoma;
• Methemoglobinemia, hypoxia, sulfonamide intolerance (especially in bronchial asthma);
• Severe diabetes mellitus;
• Simultaneous terminal anesthesia;
• Injection into inflamed tissue (reduces efficacy of local anesthesia);
• Concomitant treatment with tricyclic antidepressants or monoamine oxidase inhibitors (MAOIs), and within 14 days after discontinuation of MAOI therapy;
• Children under 4 years of age (body weight below 20 kg).

Ubistesin Forte must not be used in acral parts of the limbs.

Intravenous administration of the drug is contraindicated!

Special precautions.

Before administering this medicinal product, it is mandatory to obtain information about the patient's medical history and current treatment.

Skin tests with local anesthetics should be performed in patients with documented hypersensitivity reactions to these agents. Special attention is required when testing local anesthetics containing adrenaline due to an increased frequency of false-negative reactions. Provocation tests are recommended if skin tests yield negative results. Testing of patients with proven allergic reactions to local anesthetics should be performed only by allergologists experienced in local anesthesia.

The injection should be administered slowly, with aspiration test performed in at least two planes (needle rotation – 180°) to avoid intravascular injection. Maintain verbal contact with the patient.

After anesthesia onset, there is a risk of accidental trauma due to biting of the lip, cheek, or tongue mucosa. The patient should be warned not to chew during the anesthetic effect.

Injections into infected or inflamed tissues should be avoided (reduces efficacy of local anesthesia).

Interaction with other medicinal products and other forms of interaction.

Concomitant use is contraindicated in patients taking MAO inhibitors or tricyclic antidepressants (see section "Contraindications"). The sympathomimetic effect of epinephrine may be enhanced when used concomitantly with MAO inhibitors or tricyclic antidepressants.

Not recommended combinations:

• Guanethidine and related drugs (anti-glaucoma agents): significant increase in blood pressure (hyperreactivity due to reduced sympathetic tone and/or impaired uptake of adrenaline into sympathetic nerve fibers). If this combination cannot be avoided, smaller doses of sympathomimetic agents (adrenaline) should be used cautiously;
• Halogenated inhalational anesthetics (e.g., halothane): serious ventricular arrhythmias (increased cardiac excitability). Administration of the anesthetic should be limited, e.g., less than 0.1 mg of adrenaline within 10 minutes or 0.3 mg within 1 hour in adults. Whenever possible, avoid using Ubistesin Forte during or after general inhalational anesthesia;
• Imipramine-type antidepressants: paroxysmal hypertension with possible arrhythmias (inhibition of adrenaline uptake into sympathetic nerve fibers). Administration of the anesthetic should be limited, e.g., less than 0.1 mg of adrenaline within 10 minutes or 0.3 mg within 1 hour in adults;
• Serotoninergic and noradrenergic antidepressants (selective serotonin and norepinephrine reuptake inhibitors – as seen with mianserin and venlafaxine): possible paroxysmal hypertension with possible arrhythmias (inhibition of adrenaline uptake into sympathetic nerve fibers). Administration of the anesthetic should be limited, e.g., less than 0.1 mg of adrenaline within 10 minutes or 0.3 mg within 1 hour in adults. Vasoconstrictor agents enhance and prolong the local anesthetic effect of articaine.

The drug should not be prescribed during treatment with non-selective β-adrenergic blockers, as this increases the risk of hypertensive crisis and pronounced bradycardia.

Adrenaline may inhibit insulin secretion by the pancreas, thereby reducing the effectiveness of oral antidiabetic agents.

Some inhalational anesthetics (e.g., halothane) may increase myocardial sensitivity to catecholamines, promoting the development of arrhythmias.

Caution is recommended when using articaine with epinephrine concomitantly with other local anesthetics. Toxic effects of local anesthetics are additive.

Phenothiazines may reduce or neutralize the pressor effect of adrenaline. Concomitant use of these drugs should be avoided. In situations where concomitant use is necessary, careful patient monitoring is required.

The concomitant use of antithrombotic agents (heparin, acetylsalicylic acid) increases the risk of bleeding. Accidental puncture of a blood vessel during local anesthesia may lead to serious hemorrhage.

The drug should be used with caution in combination with hypoglycemic agents, antiarrhythmics (procainamide, mexiletine, disopyramide, quinidine, amiodarone), antiepileptic drugs, cardiac glycosides, and thyroid hormones.

No differences in interactions of Ubistesin Forte with other drugs in children/adolescents compared to adults have been observed.

Special precautions for use.

Ulbistezin Forte should be used with special caution in the following cases:

• severe impairment of kidney and liver function;
• angina pectoris (see sections "Contraindications" and "Dosage and administration");
• arteriosclerosis;
• significant coagulation disorders; treatment with anticoagulants (e.g. warfarin) or platelet aggregation inhibitors (e.g. heparin or acetylsalicylic acid). The overall risk of bleeding increases (see section "Interaction with other medicinal products and other forms of interaction");
• diabetes mellitus;
• lung diseases, especially allergic asthma;
• cardiovascular dysfunction due to reduced ability to compensate for prolonged atrioventricular conduction.

Since amide-type local anesthetics are also metabolized in the liver, Ulbistezin Forte should be used cautiously in patients with liver disease. Patients with acute liver disease have an increased risk of developing toxic plasma concentrations of articaine.

The drug should be used cautiously in patients with cardiovascular disorders (e.g. heart failure, ischemic heart disease, history of myocardial infarction, cardiac arrhythmia, arterial hypertension), as they have a reduced ability to compensate for functional changes associated with prolonged atrioventricular conduction caused by these drugs.

The drug should be used cautiously in patients with a history of epilepsy; particularly high doses should be avoided, as well as use in patients with marked anxiety, cerebral circulation disorders, or history of stroke.

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

Athletes may test positive in doping tests.

It should be taken into account that during treatment with anticoagulants (e.g. heparin or aspirin), inadvertent puncture of a blood vessel during local anesthetic injection may lead to severe bleeding and an overall increased risk of bleeding (see section "Interaction with other medicinal products and other forms of interaction").

Injections into inflamed tissues should be avoided. Reduced penetration of articaine into inflamed tissue may result in ineffective anesthesia.

Accidental intravascular injection should be avoided (see section "Dosage and administration", subsection "Method of administration"). Accidental intravascular injection or unintentional overdose may cause seizures, central nervous system (CNS) depression, or cardiorespiratory failure. Resuscitation equipment, oxygen, and emergency medications must be available for immediate use.

Patients should be advised to exercise caution to avoid accidental trauma to the lips, tongue, cheek mucosa, or soft palate while these areas are under anesthesia. Therefore, patients should avoid eating until the anesthetic effect has worn off.

When treating a tooth cavity or preparing a tooth for a crown, it should be considered that due to the presence of adrenaline in the preparation, blood flow in pulp tissue is reduced, thus increasing the risk of failing to detect an accidentally exposed pulp.

The medicinal product contains less than 1 mmol sodium (23 mg) per 1.7 mL, i.e. the product is essentially "sodium-free".

Ulbistezin Forte should be used with special caution in patients taking phenothiazines or cardioselective β-blockers (see section "Interaction with other medicinal products and other forms of interaction").

Precautionary measures

Each time a local anesthetic is used, the following medications/therapeutic measures must be available:

• anticonvulsants (medications for seizure treatment, e.g. benzodiazepines or barbiturates), glucocorticoids, muscle relaxants (agents that reduce tension in voluntarily contracting muscles), atropine, vasoconstrictors (medications for treating low blood pressure), electrolyte solutions, or adrenaline in case of acute allergic or anaphylactic reactions;
• resuscitation equipment (especially oxygen sources) for artificial ventilation if necessary;
• careful and continuous monitoring of cardiovascular and respiratory (adequacy of respiration) parameters and the patient's level of consciousness after each local anesthetic injection.

Restlessness, anxiety, tinnitus, dizziness, blurred vision, tremor, depression, or drowsiness are the first signs of toxic effects on the CNS (see section "Overdose").

Use during pregnancy or breastfeeding.

There are no clinical data on the use of the drug in pregnant women or during breastfeeding. The safety of local anesthetics during pregnancy with regard to effects on fetal development has not been established. Animal studies on the use of articaine do not indicate a direct or indirect adverse effect on pregnancy, embryonic/fetal development, labor, or postnatal development. Animal studies with adrenaline have shown reproductive toxicity. The potential risk for humans is unknown.

Ulbistezin Forte should be used during pregnancy only if the benefit outweighs the potential risk to the fetus.

A small amount of articaine passes into breast milk. However, preclinical safety data suggest that the concentration of articaine in breast milk does not reach clinically significant levels. Therefore, women who are breastfeeding should express and discard the first milk after articaine anesthesia.

In animal studies, Ulbistezin Forte did not show any negative effect on fertility.

Ability to affect reaction speed when driving or operating machinery.

Although patient studies have not shown impairment of normal reactions during driving, in sensitive patients injection of Ulbistezin Forte may lead to temporary impairment of reaction ability, for example when driving a vehicle. Therefore, the physician must decide in each individual case whether the patient is able to drive or operate machinery. After injection, the patient should remain in the dental office for at least 30 minutes.

Administration and Dosage

FOR DENTAL ANALGESIA ONLY.

Resuscitation equipment must be available for immediate use.

Intended for adults and children aged 4 years and older.

Dosage Recommendations

To ensure effective anesthesia, the minimum necessary amount of solution should be used.

Adults

For extraction of upper teeth, 1.7 mL of Ubistesin Forte per tooth is usually sufficient, and painful palatal injections are not required. When extracting adjacent teeth consecutively, the injection dose may be reduced.

If palatal incision or suturing is required, palatal anesthesia should be administered with approximately 0.1 mL per injection.

For uncomplicated extraction of lower premolars under infiltration anesthesia, 1.7 mL of Ubistesin Forte per tooth is usually sufficient. In individual cases, an additional injection of 1 to 1.7 mL into the buccal area may be needed. Rarely, injection into the mandibular foramen may be indicated.

Vestibular injections of 0.5 to 1.7 mL of Ubistesin Forte per tooth allow treatment of lower premolar tooth stumps for restorations and prosthetic constructions in uncomplicated cases.

Conduction anesthesia may be used for treatment of lower premolars.

For surgical procedures, the dosage of Ubistesin Forte should be individually determined based on the duration of the procedure and the patient’s general condition.

Children

The amount of drug administered should be determined according to the child’s age, body weight, and extent of surgery.

Generally, a dose of 0.25–1 mL is sufficient for children weighing 20–30 kg; for children weighing 30–50 kg, the dose is 0.5 to 2 mL; for children weighing ≥50 kg, the adult dose should be used.

Due to the rapid tissue distribution of articaine and its lower bone density in children compared to adults, conduction anesthesia may be used in children and adolescents instead of infiltration anesthesia.

Ubistesin Forte must not be used in children under 4 years of age.

Special Patient Groups

In elderly patients, plasma levels of Ubistesin Forte may be elevated due to reduced metabolic capacity and lower volume of distribution. The risk of accumulation of Ubistesin Forte increases especially after repeated injections (e.g., supplemental injection).

A similar effect may occur in patients with general debilitation, as well as in those with impaired cardiac, hepatic, or renal function. In such cases, dosage reduction is recommended (minimum amount required for adequate analgesia).

Dosage should also be reduced in patients with certain medical conditions (e.g., angina pectoris, arteriosclerosis).

Maximum Recommended Dose

Adults

The maximum dose for healthy adults is 7 mg of articaine/kg body weight (500 mg for a patient weighing 70 kg), corresponding to 12.5 mL of Ubistesin Forte.

The maximum dose is 0.175 mL of solution/kg body weight.

Children aged 4 years and older

The amount of drug administered should be determined based on the child’s age, body weight, and duration of surgery. The equivalent of 7 mg of articaine/kg body weight (0.175 mL of Ubistesin Forte/kg body weight) must not be exceeded.

Also available is the preparation Ubistesin, the use of which is more appropriate for standard procedures and/or therapeutic interventions when control of bleeding in the surgical field is not of significant importance.

Administration method

For injection into the oral mucosa.

FOR DENTAL ANESTHESIA ONLY.

Before administration, visually inspect the medicinal product for the presence of particulate matter, discoloration, and container damage. Do not use the cartridge if any such signs or defects are observed.

The preparation should be administered using special reusable cartridge syringes. Immediately before use, the rubber stopper sealed with a puncturable aluminum cap should be disinfected with alcohol.

Under no circumstances should cartridges be immersed in any solutions.

The injection solution must not be mixed with any other medicinal product in the same syringe.

To avoid intravascular injections, always perform careful aspiration testing in at least two planes (rotating the needle by 180°), although a negative aspiration result does not exclude inadvertent and undetected intravascular injection.

Most systemic reactions resulting from accidental intravascular injection can be avoided by proper injection technique: after aspiration, inject slowly 0.1–0.2 mL, then slowly administer the remainder no sooner than 20–30 seconds later.

The injection rate must not exceed 0.5 mL per 15 seconds, i.e., one cartridge per minute.

Cartridges containing residual solution after completion of the dental procedure must be destroyed. Cartridges with residual solution must not be used for other patients.

Children.

Ubistesin Forte may be used only in children aged 4 years and older, as the efficacy and safety of the drug in younger children have not been established.

Overdose.

Acute emergencies resulting from the use of local anesthetics are primarily associated with high plasma levels during therapeutic use or with accidental and rapid intravascular injection of local anesthetics. Symptoms of overdose may occur immediately, in case of accidental intravascular injection or pathologically altered absorption conditions (e.g., in inflamed tissue or tissue with high vascularization), or after some delay, particularly in cases of overdose due to injection of excessive amounts of anesthetics, manifesting as symptoms of central nervous system and/or cardiovascular system involvement.

No cases of overdose have been reported during post-marketing surveillance.

Symptoms that may be caused by articaine

Cardiovascular system: arterial hypertension, arterial hypotension, agitation, palpitations, angina pectoris, generalized vasoconstriction, conduction disturbances, arrhythmia, bradycardia, cardiovascular collapse, cardiac arrest.

Central nervous system: headache, nervousness, anxiety, motor restlessness, stupor, coma, confusion, dizziness, dysgeusia, tinnitus, taste disturbances, nausea, vomiting, tremor, involuntary muscle contractions, tachypnea, restlessness, drowsiness, loss of consciousness, tonic-clonic seizures, respiratory arrest.

The most dangerous symptoms are: arterial hypotension, cardiac arrest, conduction disturbances, tonic-clonic epileptic seizures, respiratory paralysis, and drowsiness/coma.

Symptoms that may be caused by epinephrine (adrenaline)

Circulatory disorders: increased systolic blood pressure, increased diastolic blood pressure, increased venous pressure, increased pulmonary artery pressure, arterial hypotension.

Cardiac disorders: bradycardia, tachycardia, arrhythmia (e.g., atrial tachycardia, AV block, ventricular tachycardia, ventricular extrasystoles).

These symptoms, as well as pulmonary edema, cardiac arrest, renal failure, and metabolic acidosis, may lead to life-threatening consequences.

Treatment

If early signs of adverse reaction or toxic effects develop during administration of the drug, injection should be stopped immediately and the patient placed in a supine position. Ensure airway patency and monitor pulse and blood pressure. Initiate intravenous infusion of symptomatic agents, even if symptoms do not appear severe, to ensure reliable intravenous access. Administer oxygen depending on the severity of the condition; if necessary, apply artificial respiration (mouth-to-nose) or endotracheal intubation combined with controlled ventilation.

Central-acting analeptics are contraindicated.

Involuntary muscle contractions or generalized muscle seizures require intravenous injection of short- or ultra-short-acting barbiturates. Prevent associated injuries in patients; benzodiazepines (e.g., intravenous diazepam) may be used if necessary.

Barbiturates should be administered slowly, depending on the observed effect, while continuing oxygen administration and monitoring cardiac function, to avoid circulatory disturbances and respiratory depression. Barbiturate administration should be accompanied by infusion of fluids through a previously placed cannula. Counteracting tachycardia and lowering of blood pressure can often be achieved simply by placing the patient in a supine position, particularly with elevated lower limbs.

In case of arterial hypotension, place the patient in a supine position; if necessary, perform intravascular infusion of physiological electrolyte solution and administer vasopressors.

In case of bradycardia, atropine may be administered intravenously.

In cases of severe circulatory disturbances and shock, regardless of cause, the following measures should be taken after stopping the injection: ensure the patient is in a supine position with elevated lower limbs, ensure airway patency, administer oxygen insufflation. Additionally, establish intravenous infusion of balanced electrolyte solution; intravenous administration of glucocorticoids (e.g., 250–1000 mg methylprednisolone), fluid replacement (if necessary, also plasma substitutes and human albumin). In cases of life-threatening circulatory collapse and increasing bradycardia—immediate intravenous injection of epinephrine (adrenaline). For this purpose, dilute 1 mL of 1:1000 adrenaline solution to 10 mL and initially administer slowly 0.25–1 mL of this solution (0.025–0.1 mg adrenaline). Monitor pulse rate and blood pressure. Do not administer more than 1 mL of this solution (0.1 mg adrenaline) at once. If this dose is insufficient, add adrenaline to the infusion solution (infusion rate adjusted according to pulse rate and blood pressure).

Severe forms of tachycardia or tachyarrhythmia may also be managed with antiarrhythmic agents (but not non-selective β-blockers).

Oxygen administration and hemodynamic monitoring are mandatory in these cases. In patients with arterial hypertension and elevated blood pressure, peripheral vasodilators should be used. Elevate the upper part of the patient’s body in the supine position; if necessary, administer sublingual nifedipine.

In case of cardiac arrest, immediate cardiopulmonary resuscitation is required.

Adverse Reactions

The use of Ubistesin Forte is generally considered very safe. When adverse reactions occur, it is difficult to assess the causal relationship (exact differentiation is not possible), as the causes of adverse reactions may be related to the underlying dental disease, dental intervention, or the use of local anesthesia.

The most commonly observed adverse reactions in clinical studies were pain or pain due to the intervention (4%), as well as sensitivity, headache, and swelling (1–1.3%). Nervous system disorders as adverse reactions were observed infrequently or rarely in clinical studies. Post-marketing data confirmed the adverse reaction profile reported in published clinical studies but indicated a lower overall frequency.

Based on post-marketing studies, the overall risk of sensory disturbances (e.g., hypoesthesia, paresthesia, taste disturbances) should be considered low. In case of suspected hypersensitivity reactions, appropriate allergy testing is recommended.

Sodium sulfite (E 221) may rarely cause hypersensitivity reactions and bronchospasm.

According to the frequency of occurrence, the adverse reactions listed below are categorized as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10,000, < 1/1000), very rare (< 1/10,000), and not known (cannot be estimated from available data). All adverse events with a frequency listed as "not known" were observed during post-marketing surveillance.

Immune system disorders: not known – allergic reactions, in severe cases anaphylactic shock, angioneurotic edema of varying severity (including swelling of the upper and/or lower lip and/or neck, laryngeal edema with swallowing difficulty, urticaria, breathing difficulties).

Psychiatric disorders: not known – restlessness, anxiety.

Nervous system disorders: common – headache; uncommon – paresthesia, hypoesthesia, and dysaesthesia, dizziness; rare – taste disturbances, peripheral neuropathies, somnolence, consciousness disturbances; not known – metallic taste in the mouth, tinnitus, yawning, fainting, tremor, nervousness, excitement, insomnia, disorientation, clouding of consciousness, loss of consciousness, loss of taste, nystagmus, logorrhea, hypergeusia, facial hypoesthesia, decreased muscle tone, paralysis of the 6th cranial nerve, facial nerve paralysis, pre-syncope, muscle twitching, tonic-clonic seizures, coma, respiratory paralysis, sensory disturbances.

Respiratory, thoracic and mediastinal disorders: rare – nasal congestion; not known – dysphonia, dyspnea, laryngeal edema, pharyngeal edema, pulmonary edema, bronchospasm, rhinitis, tachypnea, bradypnea which may lead to apnea.

Cardiac disorders: rare – palpitations, tachycardia, bleeding, pallor; not known – decreased blood pressure, increased blood pressure, bradycardia, cardiovascular depression with arterial hypotension which may lead to collapse, cardiac arrhythmia (ventricular extrasystoles and ventricular fibrillation), conduction disorders (atrioventricular block). These manifestations may lead to cardiac arrest.

Eye disorders: rare – blepharospasm; not known – mydriasis, ptosis, miosis, enophthalmos, blurred vision, transient blindness, reduced visual acuity, diplopia, conjunctivitis.

Ear and labyrinth disorders: uncommon – vertigo, ear pain; not known – tinnitus.

Skin and subcutaneous tissue disorders: uncommon – pruritus, hyperhidrosis, rash; not known – skin erythema, urticaria, angioneurotic edema.

Musculoskeletal and connective tissue disorders: rare – back pain, muscle tension, trismus; not known – osteonecrosis.

Gastrointestinal disorders: uncommon – gingivitis, nausea, vomiting; rare – diarrhea, abdominal pain, cheilitis, constipation, dry mouth, dyspepsia, oral ulcers, nausea/vomiting, tooth loss, hypersalivation, increased tooth sensitivity, stomatitis; not known – oral hypoesthesia, oral swelling, oral paresthesia.

General disorders and administration site conditions: common – pain, weakness, swelling; uncommon – facial swelling, injection site swelling, injection site pain, hematoma at injection site; rare – asthenia, chills, increased fatigue, malaise, thirst; not known – pain on pressure, necrosis at injection site, mucosal inflammation, mucosal swelling, increased temperature, nerve injury (up to paralysis development) due to incorrect injection technique.

Very rarely – accidental intravascular injection may lead to ischemic areas at the injection site, which may sometimes progress to tissue necrosis.

Investigations: uncommon – decreased blood pressure, increased heart rate, increased blood pressure; rare – signs of myocardial ischemia (on ECG), vital function disturbances, positive allergy test; not known – inability to measure blood pressure, decreased heart rate.

Injury, poisoning and procedural complications: common – pain from intervention; rare – oral injuries, incorrect injection route, nerve injury; not known – gingival injuries, wound complications, injury to the 5th cranial nerve.

Observations indicate that the risk of adverse reactions associated with dental local anesthesia using Ubistesin Forte is very low.

Description of selected adverse reactions

Two types of adverse reactions have particular clinical significance, although they are not the most frequently reported. The description is primarily based on post-marketing surveillance data.

Nerve function disturbances

Nerve function disturbances in dentistry may arise from various causes. They may be due to the underlying dental condition, dental treatment, or direct adverse reactions related to the use of local anesthetics. Considering the frequency of these two adverse reactions, the risk of such disturbances is low. Discussion of data focuses on serious adverse reactions, as their clinical significance lies in the risk of irreversible damage. Most of these adverse effects are reversible.

Hypersensitivity reactions

Hypersensitivity reactions were only rarely observed in post-marketing studies. Most reactions were not actually serious, but life-threatening reactions cannot be entirely ruled out.

In case of suspected hypersensitivity reactions, appropriate allergy testing is recommended, including testing for individual components of the medicinal product.

Sodium sulfite (E 221) may rarely cause severe hypersensitivity reactions and bronchospasm.

Children

Post-marketing observations have not revealed any differences in the safety profile in children compared to adults.

In children, accidental soft tissue injuries due to prolonged soft tissue anesthesia were more frequently observed.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after medicinal product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

Shelf life

2 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of the reach of children. Do not use after the expiry date.

Incompatibilities

The injection solution must not be mixed with any other medicinal product in the same syringe.

Packaging

1.7 ml solution in cartridges; 50 cartridges in a metal can.

Prescription status

Prescription only.

Manufacturer

Solventum Germany GmbH.

Manufacturer's address and place of business

ESPE Platz, 82229 Seefeld, Germany.