Ubistesin

Patient Information Leaflet

Ubistesin, (40 mg + 0.006 mg)/ml, solution for injection
Articaini hydrochloridum + Epinephrini hydrochloridum
Please read all of this leaflet carefully before the medicine is administered, because it contains
important information for the patient.

• Keep this leaflet for future reference.
• 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.

Leaflet Contents

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

1. What Ubistesin is and what it is used for

Ubistesin is used to anaesthetize the oral cavity during dental procedures. This medicine contains two active substances:

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

Ubistesin is administered by a dentist.
Ubistesin is intended for use in children over 4 years of age (approximately 20 kg body weight), adolescents, and adults.
Ubistesin is typically used for simple and short dental procedures.

2. Important information before using Ubistesin

Do not use Ubistesin if the patient has 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 local anaesthetic agents;
• The patient has epilepsy that is not adequately controlled with medication.

Warnings and precautions
Before using Ubistesin, discuss with 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. unexpected chest pain at rest or following a myocardial infarction (i.e. heart attack)];
• Low blood pressure;
• Abnormally fast heartbeat;
• Myocardial infarction 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 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 effect 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 local anaesthetic agents, medicines that cause 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 the hands and feet;
• 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 a phaeochromocytoma;
• A condition called closed-angle glaucoma, which is an eye disease;
• Inflammation or infection at the site of injection;
• Reduced oxygen supply to body tissues (hypoxia), high potassium levels (hyperkalemia), and metabolic disturbances due to excessive levels of acidic components in the blood (metabolic acidosis).

Ubistesin 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 especially important to inform the dentist if the patient is taking any of the following medicines:

• Other local anaesthetic agents, 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 affecting 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 and food
Avoid eating, including chewing gum, until normal sensation returns, due to the risk of biting the lip, cheek, 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 physician before using this medicine.
The dentist or physician will decide whether the patient may use Ubistesin during pregnancy.
Breastfeeding may be resumed 5 hours after administration of the anaesthetic.
No effect on fertility is expected following doses used during dental procedures.

Driving and operating machinery
If adverse effects occur, such as dizziness, blurred vision, or fatigue, the patient should not drive or operate machinery until feeling well again (usually within 30 minutes after the dental procedure).

Ubistesin 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

Only doctors or dentists who have received appropriate training should administer Ubistesin.
The dentist will decide whether to use Ubistesin and will 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 anaesthesia should be used.
This medicine is administered by slow injection into the oral cavity.

Use of a higher than recommended dose of Ubistesin
It is unlikely that a patient would receive an excessive dose of this medicine, but if the patient experiences any discomfort, they should inform the dentist immediately. Symptoms of overdose include severe weakness, pale skin, headache, feelings of restlessness or agitation, disorientation, loss of balance, involuntary tremors or convulsions, dilated pupils, blurred vision, difficulty focusing vision 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 (known as cardiac arrest).

If you have any further questions about 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 office, the dentist will closely monitor the patient for the effects of Ubistesin.
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 (affecting 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 no more than 1 in 10 patients:

• gingivitis
• neuropathic pain – caused by nerve damage
• numbness or reduced sensation to touch in the mouth and around the mouth
• metallic taste, taste disturbances or loss of taste sensation
• increased, unpleasant or abnormal sensation to 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 no more than 1 in 100 patients:

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

Rare adverse reactions: may occur in no more than 1 in 1,000 patients:

• nervousness (anxiety), anxiety
• 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)
• pupil dilation
• eye pain
• ringing in the ears, hearing hypersensitivity
• palpitations
• hot flushes
• pallor
• wheezing (bronchospasm), asthma
• breathing difficulties
• peeling and ulceration of the gums
• peeling at the injection site
• urticaria
• minor muscle twitching, involuntary muscle contractions
• fatigue, weakness
• chills.

Very rare adverse reactions: may occur in no more than 1 in 10,000 patients:

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

Frequency unknown: frequency cannot be estimated from available data

• extremely 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 vascular congestion
• dilation or constriction of blood vessels
• hoarseness
• difficulty swallowing
• cheek swelling and local swelling
• burning mouth syndrome
• skin redness (flush)
• abnormally excessive sweating
• exacerbation of neuromuscular symptoms in Kearns-Sayre syndrome
• sensation of heat or cold
• bruxism.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +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 helps to provide more information on the safety of this medicine.

5. How to store Ubistesin

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 stated month.
Store below 25°C. Protect from light.
Do not use this medicine if the solution appears cloudy or discoloured.
To avoid injuries, cartridges should be carefully removed from the canister.
Cartridges are 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 wastewater or household waste. Your dentist knows how to properly dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Ubistesin contains

• The active substances in this medicine are articaine hydrochloride and epinephrine hydrochloride.
  o Each 1.7 ml cartridge of Ubistesin injection solution contains 68 mg of articaine hydrochloride and 0.0102 mg of epinephrine hydrochloride.
  o 1 ml of Ubistesin contains 40 mg of articaine hydrochloride and 0.006 mg of epinephrine hydrochloride.
• The other ingredients are sodium sulfite (E 221), sodium chloride, hydrochloric acid 14% (for pH adjustment), sodium hydroxide 9% solution (for pH adjustment), water for injections.

What Ubistesin looks like and contents of the pack
Ubistesin 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 aluminium cap.
The metal container 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
In all patient populations, the lowest 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 the full content of one cartridge. For more extensive procedures, multiple cartridges may be necessary, without exceeding the maximum recommended dose; the decision is at the discretion of 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 receiving 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 total articaine dose must not exceed 500 mg. A maximum articaine dose of 500 mg corresponds to the dose for a healthy adult with a body weight exceeding 70 kg.

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

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

The amount of solution to be injected should be determined based on the child's age and body weight, as well as 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, and the absolute maximum dose must not exceed 385 mg of articaine in a healthy child weighing 55 kg.

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

• 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 dose required to achieve effective anaesthesia in patients with hepatic impairment, particularly after repeated administration, even though 90% of articaine is inactivated in the first pass 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 those receiving treatment with acetylcholinesterase inhibitors, since the medicinal product is inactivated by plasma esterases by 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 injection and intraoral peripheral nerve block.
Local anaesthetics should be injected carefully if inflammation and/or infection is present at the injection site. The injection rate should be very slow (1 ml/min).

Precautions prior to use or administration of the medicinal product
This medicinal product should be used only by physicians or dental surgeons who have adequate training and are familiar with the recognition and treatment of systemic toxic reactions, or under the supervision of such physicians. Prior to inducing local anaesthesia with a local anaesthetic agent, ensure that appropriate resuscitation equipment and medications are available to allow immediate management of any emergency involving the respiratory tract and cardiovascular system. After each injection of a local anaesthetic agent, the patient's level of consciousness should be monitored.
When using the medicinal product Ubistesin for infiltration or conduction anaesthesia, the injection should always be performed slowly and with prior aspiration.

Special warnings
Epinephrine alters blood flow in the gingiva, which may lead to local tissue necrosis.
Very rare cases of prolonged or irreversible nerve damage and loss of taste have been reported following mandibular nerve block anaesthesia.
There is a risk of injury due to biting (lips, cheeks, mucous membranes, and tongue), particularly in children. Patients should be informed to avoid chewing gum and eating until normal sensation returns.

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 be associated with severe adverse effects such as seizures, followed by central nervous system and cardiovascular and respiratory depression, coma, and progression to respiratory and circulatory arrest.
Therefore, to ensure that the needle does not enter a blood vessel during injection, aspiration should be performed before administering the locally acting anaesthetic medicinal product. However, the absence of blood in the syringe does not guarantee avoidance of intravascular injection.

Risks associated with intraneural injection
Accidental injection into a nerve may lead to 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. If nerve injury occurs, neurotoxic effects may be intensified due to the potential chemical neurotoxicity of articaine and the presence of epinephrine, which may impair perineural blood flow and prevent local washout of articaine.

Treatment of overdose
Prior to inducing local anaesthesia with a local anaesthetic agent, ensure that resuscitation equipment and medications are available to allow immediate management of any emergency involving the respiratory tract and cardiovascular system.
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's position should be changed to supine.
Central nervous system symptoms (seizures, CNS depression) should be promptly treated with appropriate airway management, respiratory support, and administration of anticonvulsant medications.
Ensuring optimal oxygen delivery, as well as respiratory and circulatory support and treatment of acidosis, may prevent cardiac arrest.
In case of circulatory depression (hypotension, bradycardia), appropriate treatment with intravenous fluids, vasopressors, and/or inotropic agents should be considered. Doses for children should be adjusted according to age and body weight.
In case of cardiac arrest, cardiopulmonary resuscitation should be initiated immediately.

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

Special precautions for disposal and preparation of the medicinal product for use
To avoid the risk of infection (e.g. transmission of hepatitis), syringes and needles used to withdraw the solution must always be new and sterile.
Do not use this medicinal product if the solution is cloudy or discoloured.
To avoid needlestick injuries, cartridges should be carefully removed from the container.
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 medicine is available on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products (URPL): www.urpl.gov.pl.