Ubistesin forte

Package leaflet: Information for the patient

Ubistesin forte, (40 mg + 0,012 mg)/ml, solution for injection
Articaini hydrochloridum + Epinephrini hydrochloridum
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your dentist, doctor, or pharmacist.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your dentist, doctor, or pharmacist. See section 4.

Table of contents of the leaflet

1. What Ubistesin forte is and what it is used for
2. Important information before using Ubistesin forte
3. How to use Ubistesin forte
4. Possible side effects
5. How to store Ubistesin forte
6. Contents of the pack and other information

1. What Ubistesin forte is and what it is used for

Ubistesin forte is used for local anaesthesia of the oral cavity during dental procedures.
This medicine contains two active substances:

• Articaine, a local anaesthetic agent that prevents the sensation of pain, and
• Epinephrine, a vasoconstrictor agent that constricts blood vessels at the injection site, thereby prolonging the effect of articaine. It also reduces bleeding during the procedure.

Ubistesin forte is administered by a dentist.
Ubistesin forte is intended for children above 4 years of age (approximately 20 kg body weight),
adolescents, and adults.

• Ubistesin forte is particularly suitable for longer-lasting procedures or those associated with potentially more pronounced bleeding.

2. Important information before using Ubistesin Forte

Do not use Ubistesin Forte if the patient suffers from any of the following conditions:

• the patient is allergic to articaine or epinephrine or to any of the other ingredients of this medicine (listed in section 6);
• the patient is allergic to other locally acting anaesthetics;
• the patient has epilepsy which is not adequately controlled with medication.

Warnings and precautions
Before starting treatment with Ubistesin Forte, consult your dentist if the patient has any of the following conditions:

• severe heart rhythm disorders (e.g. second- or third-degree atrioventricular block);
• acute heart failure [severe weakening of the heart, e.g. sudden chest pain at rest or after myocardial infarction (i.e. heart attack)];
• low blood pressure;
• abnormally rapid heartbeat;
• myocardial infarction (heart attack) within the last 3–6 months;
• the patient underwent coronary artery bypass grafting within the last 3 months;
• the patient is taking antihypertensive medicines called beta-blockers, such as propranolol. There is a risk of hypertensive crisis (very high blood pressure) or severe slowing of heart function (see "Ubistesin Forte with other medicines");
• very high blood pressure;
• the patient is concurrently taking certain medicines used to treat depression and Parkinson's disease (tricyclic antidepressants). These medicines enhance the effects of epinephrine;
• epilepsy;
• absence in the patient's blood of a natural chemical substance called cholinesterase (plasma cholinesterase deficiency);
• kidney disease;
• severe liver disease;
• a condition called myasthenia, which causes muscle weakness;
• porphyria, which causes neurological complications or skin problems;
• the patient is using other locally acting anaesthetics, medicines causing temporary loss of sensation (including inhalational anaesthetics such as halothane);
• the patient is taking antiplatelet or anticoagulant medicines to prevent narrowing or hardening of blood vessels in arms and legs;
• the patient is over 70 years of age;
• the patient has had or currently has heart disease;
• uncontrolled diabetes;
• severe hyperthyroidism (thyrotoxicosis);
• a tumour called pheochromocytoma;
• a condition called closed-angle glaucoma, which is an eye disease;
• inflammation or infection at the site of injection;
• reduced oxygen levels in body tissues (hypoxia), high potassium levels (hyperkalemia), and metabolic disturbances due to excessive levels of acidic components in the blood (metabolic acidosis).

Ubistesin Forte with other medicines
Inform your dentist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
It is particularly important to inform the dentist if the patient is taking any of the following medicines:

• other locally acting anaesthetics, medicines causing reversible loss of sensation (including inhalational anaesthetics such as halothane);
• sedatives (such as benzodiazepines, opioids), for example, to reduce anxiety before a dental procedure;
• medicines acting on the heart and lowering blood pressure (such as guanadrel, guanethidine, propranolol, nadolol);
• tricyclic antidepressants used in the treatment of depression (such as amitriptyline, desipramine, imipramine, nortriptyline, maprotiline, and protriptyline);
• COMT inhibitors used in the treatment of Parkinson's disease (such as entacapone or tolcapone);
• MAO inhibitors used in the treatment of depressive or anxiety disorders (such as moclobemide, phenelzine, tranylcypromine, linezolid);
• medicines used to treat irregular heartbeat (e.g. digoxin, quinidine);
• medicines used to treat migraine attacks (such as methysergide or ergotamine);
• sympathomimetic vasoconstrictor medicines (such as cocaine, amphetamine, phenylephrine, pseudoephedrine, oxymetazoline) used to raise blood pressure: if these have been used within the last 24 hours, planned dental treatment should be postponed;
• neuroleptic medicines (e.g. phenothiazines).

Ubistesin Forte and food
Avoid eating, including chewing gum, until normal sensation returns, due to the risk of biting the lips, cheeks, or tongue, especially in children.

Pregnancy, breastfeeding and fertility
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her dentist or doctor before using this medicine.
The dentist or doctor will decide whether the patient may use Ubistesin Forte during pregnancy.
Breastfeeding may be resumed 5 hours after administration of the anaesthetic.
No effect on fertility is expected with doses used during dental procedures.

Driving and operating machinery
If any adverse effects occur, including dizziness, blurred vision, or fatigue, the patient should not drive or operate machinery until normal well-being returns (usually within 30 minutes after the dental procedure).

Ubistesin Forte contains sodium and sodium sulfite

• This medicine contains sodium sulfite (E 221), which in rare cases may cause severe allergic reactions and bronchospasm.
• The medicine contains less than 1 mmol (23 mg) of sodium per cartridge, meaning the medicine is considered "sodium-free". If there is a risk of allergic reaction, the dentist will choose an alternative anaesthetic.

3. How to use Ubistesin Forte

Only doctors or dentists with appropriate training should administer Ubistesin Forte.
The dentist will decide whether to use Ubistesin Forte and determine the appropriate dose based on
the patient's age, body weight, general health status, and the dental procedure being performed.
The lowest effective dose required to achieve adequate anesthesia should be used. This medicine is administered by slow injection into the oral cavity.
Use of a higher than recommended dose of Ubistesin Forte
It is unlikely that a patient would receive too high a dose of this medicine, but if the patient feels unwell, they should inform the dentist immediately. Symptoms of overdose include severe weakness, pale skin, headache, feeling of stimulation or hyperexcitability, sensation of disorientation, loss of balance, involuntary tremor or convulsions, pupil dilation, blurred vision, difficulty focusing clearly on an object, speech disturbances, dizziness, seizures, stupor, loss of consciousness, coma, yawning, abnormally slow or rapid breathing which may lead to temporary respiratory arrest, and lack of effective heart contractions (referred to as circulatory arrest).
If you have any further doubts regarding the use of this medicine, consult your dentist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
While the patient is in the dental chair, the patient will be closely monitored by the dentist for the effects of Ubistesin Forte.
Immediately inform the dentist, doctor or pharmacist if the patient experiences any of the following serious adverse reactions:

• swelling of the face, tongue or throat, difficulty swallowing, hives or breathing difficulties (angioedema)
• rash, itching, throat swelling and breathing difficulties: these may be symptoms of an allergic reaction (hypersensitivity)
• combination of drooping eyelid and pupil constriction ( Horner's syndrome ). These adverse reactions may occur rarely (may affect up to 1 in 1,000 patients).

Other adverse reactions not listed above may also occur in some patients.
Common adverse reactions: may occur in up to 1 in 10 patients:

• gingivitis
• neuropathic pain – caused by nerve damage
• numbness or reduced sense of touch in the mouth and around the mouth
• metallic taste, taste disturbances or loss of taste sensation
• increased, unpleasant or abnormal sense of touch
• increased sensitivity to heat
• headache
• abnormally fast heartbeat
• abnormally slow heartbeat
• low blood pressure
• swelling of the tongue, lips and gums.

Uncommon adverse reactions: may occur in up to 1 in 100 patients:

• burning sensation
• high blood pressure
• inflammation of the tongue and oral cavity
• nausea, vomiting, diarrhoea
• rash, itching
• neck pain or reaction at the injection site.

Rare adverse reactions: may occur in up to 1 in 1,000 patients:

• nervousness (anxiety), restlessness
• facial nerve disorders (facial nerve paralysis)
• drowsiness
• involuntary eye movements
• double vision, temporary blindness, reduced visual acuity
• drooping eyelid and pupil constriction (Horner's syndrome)
• displacement with lowering of the eyeball into the orbit ( enophthalmos )
• dilated pupils
• eye pain
• ringing in the ears (tinnitus), hearing hypersensitivity
• palpitations
• hot flushes
• pallor
• wheezing (bronchospasm), asthma
• breathing difficulties
• peeling and ulceration of the gums
• peeling at the injection site
• hives
• minor muscle twitching, involuntary muscle contractions
• fatigue, weakness
• chills.

Very rare adverse reactions: may occur in up to 1 in 10,000 patients:

• transient or permanent loss of sensation, prolonged numbness or loss of taste

Frequency not known: frequency cannot be estimated from the available data

• unusually elevated mood (euphoria)
• feeling of weakness/fainting
• seizures, including generalized seizures
• disturbances in heart coordination (conduction disorders, atrioventricular block, cardiac arrest)
• increased blood flow to a body part, leading to congestion in blood vessels
• dilation or constriction of blood vessels
• hoarseness
• difficulty swallowing
• cheek swelling and local swelling
• burning mouth syndrome
• redness of the skin (erythema)
• abnormally excessive sweating
• exacerbation of neuromuscular symptoms of Kearns-Sayre syndrome
• sensation of heat or cold
• bruxism (teeth grinding).

Reporting of adverse reactions
If the patient experiences any adverse reactions, including any adverse reactions not listed in this leaflet, the patient should inform the doctor, pharmacist or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49-21-301
Fax: +48 22 49-21-309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions allows the collection of additional information on the safety of the medicine.

5. How to store Ubistesin Forte

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and outer packaging following EXP. The expiry date refers to the last day of the specified month.
Store below 25°C. Protect from light.
Do not use this medicine if the solution appears cloudy or discoloured.
To avoid needlestick injuries, remove the cartridges carefully from the container.
The cartridges are intended for single use only. They should be used immediately after opening.
Any unused portion of the solution must be discarded.
Medicines must not be disposed of via the sewage system or in household waste. Your dentist knows how to properly dispose of medicines no longer in use. This practice helps protect the environment.

6. Contents of the pack and other information

What Ubistesin Forte contains

• The active substances in Ubistesin Forte are articaine hydrochloride and epinephrine hydrochloride.
  • Each 1.7 ml cartridge of injection solution contains 68 mg of articaine hydrochloride and 0.0204 mg of epinephrine hydrochloride.
  • 1 ml of Ubistesin Forte contains 40 mg of articaine hydrochloride and 0.012 mg of epinephrine hydrochloride.
• The other components are sodium sulfite (E 221), sodium chloride, hydrochloric acid 14% (for pH adjustment), sodium hydroxide 9% solution (for pH adjustment), and water for injections.

What Ubistesin Forte looks like and contents of the pack
Ubistesin Forte is a clear, colourless solution.
It is supplied in single-use cartridges made of colourless, neutral glass of Type I, sealed with a bromobutyl rubber stopper and an aluminium cap.
Each metal can contains 50 cartridges of 1.7 ml each.

Marketing Authorisation Holder:
Pierrel S.p.A.
Strada Statale Appia 7bis, 46/48
81043 Capua (CE) – Italy
tel: +39 0823 626 111
fax: +39 0823 626 228

Manufacturer:
Pierrel S.p.A.
Strada Statale Appia 7bis, 46/48
81043 Capua (CE) – Italy
tel: +39 0823 626 111
fax: +39 0823 626 228

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Information intended exclusively for healthcare professionals:

Dosage
For all patient populations, the smallest effective dose required to achieve adequate anaesthesia should be administered. The required dose must be determined individually.
For routine procedures in adults, one cartridge is usually administered, although effective anaesthesia may be achieved with less than one full cartridge. For more extensive procedures, multiple cartridges may be necessary, without exceeding the maximum recommended dose; the decision is made by the dentist.

For most routine dental procedures, the medicinal product Ubistesin is preferred.
For more complex dental procedures, such as those requiring intense haemostasis, the medicinal product Ubistesin Forte is preferred.

Concomitant use of sedative drugs to reduce patient anxiety
In patients who have received sedative drugs, the maximum safe dose of local anaesthetic may be reduced due to the additive central nervous system depressant effects of these drugs (see section 4.5).

• Children and adolescents (aged 12 to 18 years)
  In adults and adolescents, the maximum dose of articaine is 7 mg/kg body weight, and the absolute maximum dose of articaine must not exceed 500 mg. A maximum articaine dose of 500 mg corresponds to the dose for a healthy adult weighing more than 70 kg.

The table below shows the maximum recommended doses of the medicinal product Ubistesin Forte:

• Children (aged 4 to 11 years) The safety of using Ubistesin Forte in children under 4 years of age has not been established. No data are available.

The amount of drug to be injected should be determined based on the child's age, body weight, and the extent of the procedure. The average effective dose of articaine is 2 mg/kg body weight for simple procedures and 4 mg/kg body weight for complex procedures. The smallest dose providing effective dental anesthesia should be used. In children aged 4 years and older (or weighing at least 20 kg), the maximum dose of articaine is 7 mg/kg body weight; however, the absolute maximum dose must not exceed 385 mg of articaine in a healthy child weighing 55 kg.

The following table presents the maximum recommended doses of the medicinal product Ubistesin Forte:

• Special patient groups

Elderly patients and patients with renal impairment
Due to lack of clinical data, particular caution should be exercised to administer the lowest dose required to achieve effective anaesthesia in elderly patients and patients with renal impairment (sections 4.4 and 5.2).
Increased plasma concentrations of the product may occur in these patients, especially after repeated administration. If re-administration of the medicinal product is necessary, the patient should be carefully monitored for signs of relative overdose (see section 4.9).

Patients with hepatic impairment
Particular caution should be exercised to administer the lowest effective dose required to achieve effective anaesthesia in patients with hepatic impairment, particularly after repeated administration, even though 90% of articaine undergoes first-pass inactivation by nonspecific plasma esterases in tissues and blood.

Patients with plasma cholinesterase deficiency
Elevated plasma concentrations of the product may occur in patients with plasma cholinesterase deficiency or in those receiving treatment with acetylcholinesterase inhibitors, since the medicinal product is inactivated by plasma esterases by approximately 90% (see sections 4.4 and 5.2). Therefore, the lowest effective dose required to achieve adequate anaesthesia should be used.

Method of administration
Infiltration and peripheral nerve block injections in the oral cavity.
Local anaesthetics should be administered cautiously in the presence of inflammation and/or infection at the injection site. The injection rate should be very slow (1 ml/min).

Precautions to be taken prior to use or administration of the medicinal product
This medicinal product should be used only by physicians or dental practitioners who are adequately trained and experienced in recognizing and managing systemic toxic reactions, or under the supervision of such physicians. Prior to inducing local anaesthesia with a local anaesthetic agent, appropriate resuscitation equipment and medications must be available to allow immediate management of any emergency involving the respiratory or cardiovascular systems. After each injection of a local anaesthetic agent, the patient's level of consciousness should be monitored.
When using Ubistesin Forte for infiltration or conduction anaesthesia, the injection must always be administered slowly and preceded by aspiration.

Special warnings
Epinephrine may impair blood flow in the gingiva, potentially leading to local tissue necrosis.
Very rare cases of prolonged or irreversible nerve damage and taste disturbances have been reported following mandibular conduction anaesthesia.
There is a risk of self-inflicted injury due to biting (lips, cheeks, mucosa, and tongue), particularly in children. Patients should be advised to avoid chewing gum and eating until normal sensation has returned.

Precautions for use
Risks associated with accidental intravascular injection
Accidental intravascular injection may result in rapid systemic distribution of high concentrations of epinephrine and articaine. This may lead to severe adverse effects such as seizures, followed by central nervous system (CNS) and cardiovascular and respiratory depression, coma, and ultimately respiratory and cardiac arrest.
Therefore, prior to injection, aspiration should be performed to ensure that the needle has not entered a blood vessel. However, the absence of blood in the syringe does not guarantee that intravascular injection has been avoided.

Risks associated with intraneural injection
Accidental injection into a nerve may cause retrograde spread of the drug along the nerve.
To avoid intraneural injection and prevent nerve injury related to nerve block, the needle should always be gently withdrawn if the patient experiences an electric shock-like sensation during insertion or if the injection is particularly painful. In case of nerve injury, neurotoxic effects may be exacerbated due to the potential chemical neurotoxicity of articaine and the presence of epinephrine, which may impair perineural blood flow and prevent local clearance of articaine.

Management of overdose
Prior to inducing local anaesthesia with a local anaesthetic agent, appropriate resuscitation equipment and medications must be available to allow immediate management of any emergency involving the respiratory or cardiovascular systems.
The severity of overdose symptoms should prompt physicians/dentists to initiate protocols ensuring timely airway protection and provision of respiratory support.
After each injection of a local anaesthetic agent, the patient's level of consciousness should be monitored.
In case of acute systemic toxic reaction, administration of the local anaesthetic should be immediately discontinued. If necessary, the patient should be repositioned to a supine position.
CNS symptoms (seizures, CNS depression) should be promptly treated with appropriate airway management, respiratory support, and administration of anticonvulsant medications.
Ensuring optimal oxygenation and supporting respiration and circulation, as well as correcting acidosis, may prevent cardiac arrest.
In case of cardiovascular depression (hypotension, bradycardia), appropriate treatment with intravenous fluids, vasopressors, and/or inotropic agents should be considered. Doses in children should be age- and body weight-appropriate.
In case of cardiac arrest, immediate cardiopulmonary resuscitation should be initiated.

Pharmaceutical incompatibilities
Do not mix this medicinal product with other medicinal products, as compatibility studies have not been conducted.

Special precautions for disposal and preparation of the medicinal product prior to use
To avoid the risk of infection (e.g. transmission of hepatitis), syringes and needles used to withdraw the solution must always be fresh and sterile.
Do not use this medicinal product if the solution is cloudy or discoloured.
Cartridges should be carefully removed from the container to avoid needlestick injuries.
Cartridges are intended for single use only. If only part of the cartridge content has been used, the remainder must be discarded.
The product should be used immediately after opening the cartridge.
Any unused medicinal product or waste material should be disposed of in accordance with local regulations.

Other sources of information
Detailed information about this medicinal product is available on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products (URPL): www.urpl.gov.pl.