Ubistesin

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

Composition:

Active substances: 1 ml of solution contains articaine hydrochloride 40 mg, epinephrine hydrochloride 0.006 mg (equivalent to 0.005 mg of epinephrine);

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

Pharmaceutical form. Solution for injection.

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

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

ATC code N01B B58.

Pharmacological properties.

Pharmacodynamics.

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

Key characteristics include rapid onset of analgesia (onset time of 1 to 3 minutes with infiltration anesthesia and a slightly longer latent period with conduction anesthesia—approximately up to 9 minutes after injection), reliable and strong analgesic effect, and good local tolerance.

The duration of action of Ulbisthesin in pulpal anesthesia is at least 45 minutes, and in soft tissue analgesia—from 120 to 240 minutes.

Adrenaline (epinephrine) causes local vasoconstriction and reduced blood supply, thereby slowing the absorption of articaine. This results in increased concentration of the local anesthetic at the site of injection, prolonged duration of action, and reduced risk of systemic side effects. During surgical procedures, the tendency to bleeding is diminished.

Pharmacokinetics.

Absorption.

Ulbisthesin is rapidly and almost completely absorbed.

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, 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 tissue and plasma cholinesterases to its primary metabolite—articaine acid—which is further metabolized to glucuronide of articaine 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 to articaine 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 Ulbisthesin 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 Ulbisthesin 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, articaine acid, may be prolonged.

Clinical characteristics.

Indications.

Local (infiltration and conduction) anesthesia in dentistry for minor procedures.

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 sustained high-frequency arrhythmia, untreated or uncontrolled congestive heart failure, cardiac conduction disorders (second- or 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 nonselective β-adrenergic blockers;
• Severe hepatic insufficiency (porphyria);
• Hemorrhagic diatheses (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 patients with bronchial asthma);
• Severe diabetes mellitus;
• Concomitant terminal anesthesia;
• Injection into inflamed tissue (reduces the effectiveness of local anesthesia);
• Concomitant treatment with tricyclic antidepressants or monoamine oxidase inhibitors (MAOIs), and within 14 days after discontinuation of MAOI therapy;
• Age under 4 years (body weight less than 20 kg).

Ubistesin must not be used in the acral parts of the extremities.

Intravenous administration of the drug is contraindicated!

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

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

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

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

Interaction with other medicinal products and other forms of interaction.

Concomitant use is contraindicated in patients receiving MAO inhibitors or tricyclic antidepressants (see section "Contraindications"). The sympathomimetic effect of epinephrine may be potentiated by concomitant use of MAO inhibitors or tricyclic antidepressants.

Not recommended combinations:

• Guanethidine and related agents (anti-glaucoma agents): significant increase in blood pressure (hyperreactivity associated with 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 inhalation 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 during or after general inhalation 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;
• Serotonin-noradrenaline reuptake inhibitors (SNRIs) (e.g., milnacipran, 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. Vasoconstrictors enhance and prolong the local anesthetic effect of articaine.

The drug should not be prescribed during treatment with nonselective β-adrenergic blockers, as this increases the risk of hypertensive crisis and marked 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 nullify the pressor effect of adrenaline. Concomitant use of these drugs should be avoided. When concomitant use is unavoidable, 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 severe hemorrhage.

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

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

Special precautions for use.

Ulbistesin 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, Ulbistesin 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 diseases (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 medicinal products.

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

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

A positive result in doping tests may occur in athletes.

It should be taken into account that during treatment with blood coagulation inhibitors (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 injury to the lips, tongue, cheek mucosa, or soft palate while these areas are under the effect of anesthesia. Therefore, the patient should avoid eating until the anesthetic effect has worn off.

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

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

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

Precautionary measures

At each application of a local anesthetic, the following medications/therapeutic measures must be available:

• anticonvulsants (medications for seizure treatment, e.g., benzodiazepines or barbiturates), glucocorticoids, muscle relaxants (medications reducing 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 breathing) 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 women during breastfeeding. The safety of local anesthetics during pregnancy regarding their 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.

Ulbistesin 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 anesthesia with articaine.

In animal studies, no negative effect of Ulbistesin on fertility was observed.

Ability to affect reaction speed when driving or operating machinery.

Although clinical studies in patients have not shown impairment of normal reactions during driving, in sensitive patients, injection of Ulbistesin may temporarily impair reaction ability, for example, when driving a vehicle. Therefore, the physician must decide in each individual case whether the patient is capable of driving or operating machinery. After injection, the patient should remain in the dentist's office for at least 30 minutes.

Method of 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 minimal necessary amount of solution should be used.

Adults

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

If a 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 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 per tooth allow for preparation of lower premolar tooth stumps for restorative and prosthetic procedures in uncomplicated cases.

Conduction anesthesia may be used for treatment of lower premolars.

Children

The amount of drug administered should be determined based on the child's age, body weight, and extent of the procedure.

Generally, for children with a body weight of 20–30 kg, a sufficient dose is 0.25–1 mL; for children with a body weight of 30–50 kg, the dose is 0.5 to 2 mL; for children with a body weight ≥ 50 kg, the adult dose is 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 must not be used in children under 4 years of age.

Special Patient Groups

In elderly patients, plasma levels of Ubistesin may be increased due to impaired metabolic processes and reduced volume of distribution. The risk of Ubistesin accumulation is particularly elevated 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 (the minimal amount required for adequate analgesia).

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

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), equivalent to 12.5 mL of Ubistesin.

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

Children aged 4 years and older

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

Ubistesin can also be used for short-term procedures and/or when control of bleeding in the surgical field is not important (see section “Pharmacological properties” for more detailed information on the duration of anaesthesia).

Ubistesin Forte is also available, which may be more suitable for longer procedures and when there is a risk of significant bleeding into the surgical field.

Method of administration

For injection into the oral mucosa.

FOR DENTAL ANAESTHESIA ONLY.

Before use, the medicinal product should be visually inspected for the presence of particulate matter, discoloration, or container defects. The cartridge should not be used if any such signs or defects are present.

The drug should be administered using special reusable cartridge syringes. Immediately before use, the rubber stopper, sealed with an aluminium puncturable 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, careful aspiration should always be performed in at least two planes (rotating the needle 180°), although a negative aspiration result does not exclude inadvertent and unnoticed intravascular injection.

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

The rate of administration should not exceed 0.5 mL per 15 seconds, i.e., one cartridge per minute.

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

Children.

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

Overdose.

Acute emergencies associated with the use of local anaesthetics are primarily related to high plasma levels during therapeutic use or to inadvertent and rapid intravascular injection of local anaesthetics. 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 vascularity), or may be delayed, particularly in cases of overdose due to injection of excessive amounts of anaesthetic, and may manifest as symptoms of central nervous system and/or cardiovascular system toxicity.

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

Symptoms possibly caused by articaine

Cardiovascular system: arterial hypertension, arterial hypotension, agitation, palpitations, angina pectoris, generalized vasoconstriction, conduction disorders, 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 disorders, tonic-clonic epileptic seizures, respiratory paralysis, and drowsiness/coma.

Symptoms possibly caused by epinephrine (adrenaline)

Cardiovascular 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 an adverse reaction or toxic effects develop during administration, the injection should be stopped immediately and the patient placed in a horizontal position. Airway patency should be ensured, and pulse and blood pressure monitored. Intravenous infusion of symptomatic agents is recommended, even if symptoms do not appear severe, to ensure reliable intravenous access. In case of respiratory depression, oxygen should be administered depending on the severity of the condition; if necessary, artificial respiration (mouth-to-nose) or endotracheal intubation with controlled ventilation should be performed.

Central-acting analeptics are contraindicated.

Involuntary muscle contractions or generalized muscle seizures require intravenous injection of short- or ultra-short-acting barbiturates. Measures should be taken to 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 horizontal position, especially with elevated lower limbs.

In case of arterial hypotension, the patient should be placed in a horizontal position; if necessary, intravascular infusion of physiological electrolyte solution should be performed and vasopressors administered.

In case of bradycardia, intravenous atropine may be used.

In severe circulatory disturbances and shock, regardless of cause, the following measures should be taken after stopping the injection: ensure the patient is in a horizontal position with elevated lower limbs, maintain airway patency, and administer oxygen. Additionally, intravenous infusion of balanced electrolyte solution should be established; intravenous administration of glucocorticoids (e.g., 250–1000 mg methylprednisolone), fluid replacement (and if necessary, plasma substitutes and human albumin) should be performed. In cases of life-threatening circulatory collapse and increasing bradycardia, immediate intravenous injection of epinephrine (adrenaline) is required. For this purpose, 1 mL of 1:1000 adrenaline solution should be diluted to 10 mL, and initially 0.25–1 mL of this solution (0.025–0.1 mg adrenaline) should be administered slowly.

Pulse rate and blood pressure should be monitored. Do not administer more than 1 mL of this solution (0.1 mg adrenaline) at once. If this dose is insufficient, adrenaline should be added to the infusion solution (infusion rate adjusted according to pulse rate and blood pressure).

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

Oxygen administration and monitoring of circulatory parameters are mandatory in these cases. In patients with arterial hypertension and elevated blood pressure, peripheral vasodilators should be used. The upper part of the body should be elevated in the supine position; if necessary, sublingual nifedipine may be administered.

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

Side effects

The use of Ubistesin 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 condition, dental intervention, or the use of local anesthesia.

The most commonly observed adverse reactions in clinical studies were pain or pain associated with the procedure (4%), as well as sensitivity, headache, and swelling (1–1.3%). Neurological 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.

Adverse reactions listed below are categorized according to frequency of occurrence: 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 based on available data). All adverse events listed as "not known" were observed during post-authorization monitoring.

Immune system disorders: not known – allergic reactions, in severe cases anaphylactic shock, angioedema 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 dysesthesia, dizziness; rare – taste disturbances, peripheral neuropathies, somnolence, consciousness disturbances; not known – metallic taste in mouth, tinnitus, yawning, syncope, 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, presyncope, 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 progress 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, decreased 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 redness, urticaria, angioedema.

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, injection site hematoma; rare – asthenia, chills, fatigue, malaise, thirst; not known – tenderness on palpation, necrosis at injection site, mucosal inflammation, mucosal swelling, fever, nerve injury (up to development of paralysis) due to incorrect injection technique.

Extremely rarely, accidental intravascular injection may lead to the development of 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 – procedural pain; 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 following dental local anesthesia with Ubistesin 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 based primarily 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 disease, 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 excluded.

In case of suspected hypersensitivity reactions, appropriate allergy testing is recommended, which should also include 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 injury due to prolonged soft tissue anesthesia was observed more frequently.

Reporting of adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It enables continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are requested 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 reach of children. Do not use after the expiry date.

Incompatibilities.

The injectable 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 category.

Prescription only.

Manufacturer.

Solventum Germany GmbH.

Manufacturer's address and location of operations.

Espe Platz, 82229 Seefeld, Germany.