Label: information for the user

ARTINIBSA 40mg/ml + 10 micrograms/ml injectable solution

articaína hydrochloride, / epinephrine (adrenaline)

Read the entire label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any adverse effects, consult your dentist, doctor, or pharmacist, even if they are not listed in this label. See section4.

ARTINIBSA 40mg/ml + 10 micrograms/mlis used to numb (anesthetize) the oral cavity during dental procedures.

This medication contains two active principles:

• articaine, a local anesthetic that prevents pain.
• adrenaline, a vasoconstrictor that narrows the blood vessels at the injection site and, therefore, prolongs the effect of articaine. It also reduces bleeding during surgery.

Your dentist will administer ARTINIBSA 40mg/ml + 5 micrograms/ml or ARTINIBSA 40mg/ml + 10 micrograms/ml.

ARTINIBSA 40mg/ml + 10 micrograms/ml is indicated for children over 4 years old (approximately 20 kg body weight), adolescents, and adults.

Depending on the type of dental procedure performed, the dentist will choose one of the two medications:

• ARTINIBSA 40mg/ml + 5 micrograms/mlis usually used for simple and short dental procedures.
• ARTINIBSA 40mg/ml + 10 micrograms/mlis more suitable for longer procedures or those with significant bleeding.

No useARTINIBSA 40mg/ml + 10 microgramos/mlif you have any of the following medical conditions:

• allergy to articaine or adrenaline or to any of the other components of this medication (listed in section6).
• allergy to other local anesthetics.
• uncontrolled epilepsy.

Warnings and precautions

Consult your dentist before starting to use ARTINIBSA 40mg/ml + 10 microgramos/ml if you have any of the following medical conditions:

• serious heart rhythm disorders (e.g., AV block of second and third degree).
• acute heart failure (acute cardiac weakness, e.g., unexpected chest pain at rest or after a myocardial infarction [i.e., heart attack]).
• low blood pressure.
• abnormally rapid heartbeats.
• myocardial infarction in the last 3-6months.
• coronary revascularization graft in the last 3months.
• you are taking beta-blockers, such as propranolol. There is a risk of hypertensive crisis (very high blood pressure) or severe bradycardia (slow heart rate) (see section "Use ofARTINIBSA 40mg/ml + 10 microgramos/ml withother medications").
• very high blood pressure.
• you are taking antidepressants and Parkinson's disease medications (tricyclic antidepressants) simultaneously. These medications may intensify the effects of adrenaline.
• epilepsy.
• deficiency of a natural chemical substance called plasma cholinesterase.
• renal problems.
• severe liver problems.
• a disease called Myasthenia Gravis that causes muscle weakness.
• porphyria that causes both neurological complications and skin problems.
• you are using other local anesthetics that cause reversible loss of sensation (including volatile anesthetics, such as halothane).
• you are taking antiplatelet or anticoagulant medications to prevent the narrowing or hardening of blood vessels in arms and legs.
• you are over 70years old.
• you have or have had any heart problems.
• you have uncontrolled diabetes.
• you have a severe case of hyperthyroidism (thyrotoxicosis).
• you have a tumor called pheochromocytoma.
• you have a disease called angle-closure glaucoma that affects the eyes.
• you have inflammation or infection of the area where you will receive the injection.
• you have reduced oxygen levels in your body tissues (hypoxia), high potassium levels in your blood (hyperkalemia), and metabolic disorders due to excessive acid in your blood (metabolic acidosis).

Use ofARTINIBSA 40mg/ml + 10 microgramos/mlwith other medications

Inform your dentist if you are taking, have taken recently, or may need to take any other medication.

It is extremely important to inform your dentist if you are taking any of the following medications:

• other local anesthetics that cause reversible loss of sensation (including volatile anesthetics, such as halothane).
• sedatives (such as benzodiazepines, opioids), for example, to reduce anxiety before the dental procedure.
• heart and blood pressure medications (such as guanadrel, guanetidina, propranolol, nadolol).
• tricyclic antidepressants for treating depression (such as amitriptilina, desipramina, imipramina, nortriptilina, maprotilina, and protriptilina).
• COMT inhibitors for treating Parkinson's disease (such as entacapona or tolcapona).
• MAO inhibitors for treating depressive or anxiety disorders (such as moclobemida, fenelzina, tranilcipromina, linezolid).
• medications for irregular heartbeats (e.g., digitals, quinidina).
• medications for migraines (such as metisergida or ergotamina).
• vasopressors (such as cocaína, anfetaminas, fenilefrina, pseudoefedrina, oximetazolina), used to raise blood pressure: if taken in the 24hours prior to the planned dental treatment, this should be postponed.
• neuroleptics (e.g., phenothiazines).

Use ofARTINIBSA 40mg/ml + 10 microgramos/mlwith food

Avoid eating, even chewing gum, until you have recovered normal sensation. Otherwise, there is a risk of biting your lips, cheeks, or tongue, especially in children.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant,consult your dentist or doctor before using this medication.

Your dentist or doctor will decide if you can takeARTINIBSA 40mg/ml + 10 microgramos/mlduring pregnancy.

Breastfeeding can be resumed 5hours after anesthesia.

No adverse effects on fertility are expected with the doses used in dental procedures.

Driving and operating machinery

If you experience adverse effects, including dizziness, blurred vision, or fatigue, do not drive or operate machinery until you have recovered your faculties (usually within 30minutes after the dental procedure).

ARTINIBSA 40mg/ml + 10 microgramos/mlcontains metabisulfito de sodio and sodium

This medication may cause severe allergic reactions and bronchospasm (sudden feeling of choking) due to the presence of metabisulfito de sodio.

This medication contains less than 23 mg of sodium (1 mmol) per dose; it is essentially "sodium-free".

Use in athletes

This medication contains articaine and epinephrine (adrenaline) that may produce a positive result in doping control tests.

If there is any risk of allergic reaction, your dentist will choose another medication for anesthesia.

Only doctors and dentists are trained to use ARTINIBSA 40mg/ml + 10 micrograms/ml.

Your dentist will choose between ARTINIBSA 40mg/ml + 5 micrograms/ml or ARTINIBSA 40mg/ml + 10 micrograms/ml and determine the appropriate dose taking into account your age, weight, general health status, and dental procedure.

The lowest dose that provides effective anesthesia should be used.

This medication is administered via a slow injection into the oral cavity.

If you use moreARTINIBSA 40mg/ml + 10 micrograms/mlthan you should

It is unlikely that you will be administered too much of this injection, but if you start to feel unwell, tell your dentist. Symptoms of an overdose include acute weakness, pallor, headache, agitation or restlessness, disorientation, loss of balance, tremors or involuntary muscle contractions, dilated pupils, blurred vision, difficulty focusing on objects clearly, speech alterations, dizziness, convulsions, stupor, loss of consciousness, coma, yawning, abnormally slow or rapid breathing that may lead to temporary respiratory arrest, inability of the heart to contract (cardiac failure).

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service at 91 562 04 20 indicating the medication and the amount used.

If you have any other questions about the use of this product, ask your doctor or pharmacist.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

When you are at the dentist's office, the dentist will closely monitor the effects ofARTINIBSA 40mg/ml + 10 micrograms/ml

Inform your dentist, doctor or pharmacistimmediatelyif you experience any of the following serious side effects:

• Swelling of the face, tongue or pharynx, difficulty swallowing, hives or difficulty breathing (angioedema)
• Rash, itching, swelling of the throat and difficulty breathing: these may be symptoms of an allergic reaction (hypersensitivity).
• A combination ofdrooping eyelidandpupil constriction(Horner syndrome).

These side effects are rare (they may affect up to 1 in 1,000 people).

Other patients may also experience other side effects not listed above.

Frequent side effects: may affect up to 1 in 10 people

• Gingival inflammation
• Neuropathic pain: pain due to nerve damage
• Numbness or decreased sensation inside and around the mouth
• Metals taste, taste alterations or loss of gustatory function
• Increased, unpleasant or abnormal tactile sensation
• Increased sensitivity to heat
• Headache
• Abnormally rapid heartbeats
• Abnormally slow heartbeats
• Low blood pressure
• Swelling of the tongue, lips and gums

Less frequent side effects: may affect up to 1 in 100 people

• Burning sensation
• High blood pressure
• Inflammation of the tongue and mouth
• Nausea, vomiting, diarrhea
• Rash, itching
• Pain in the neck or injection site

Rare side effects: may affect up to 1 in 1,000 people

• Nervousness, anxiety
• Facial nerve disorder (facial paralysis)
• Drowsiness
• Involuntary eye movement
• Diplopia, temporary blindness
• Drooping eyelid andpupil constrictionof thepupil(Horner syndrome)
• Enophthalmos (hollowing of the eye within the orbit)
• Tinnitus, increased sensitivity of the ear
• Palpitations
• Flushes
• Bronchospasm, asthma, wheezing
• Dyspnea (difficulty breathing)
• Exfoliation and ulceration of the gums
• Exfoliation of the injection site
• Hives
• Involuntary muscle contraction
• Fatigue, weakness
• Chills

Very rare side effects: may affect up to 1 in 10,000 people

• Persistent loss of sensation, extensive numbness and loss of taste

Frequency not known: cannot be estimated from available data

• Extreme euphoria
• Problems with heart rhythm coordination (conduction disorders, atrioventricular block)
• Increased blood volume in a part of the body leading to congestion of blood vessels
• Widening or narrowing of blood vessels
• Snoring
• Difficulty swallowing
• Swelling of the cheeks and local swelling
• Thermalgia (burning sensation in the mouth)
• Enlarged redness of theskin(erythema)
• Abnormal increase in sweating
• Worsening of neuromuscular symptoms of Kearns-Sayre syndrome
• Sensation of heat or cold
• Trigeminal nerve block

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist,even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label and the box after CAD. The expiration date is the last day of the month indicated.

Do not use this medication if you observe visible signs of deterioration.

Store at a temperature below 30°C, protected from light.

Do not use this medication if you see that the solution is cloudy or has changed color.

The cartridges are for single use. Use immediately after opening the cartridge. Unused solution must be discarded.

Medications should not be thrown away through drains or in the trash. Your dentist will know how to dispose of the medications that you no longer use. In this way, you will help protect the environment.

Composition ofARTINIBSA 40mg/ml + 10 micrograms/ml

The active principles are hydrochloride of articaine and adrenaline tartrate.

• Eachcartucho of 1.8ml of injectable solution ofARTINIBSA 40mg/ml + 10 micrograms/mlcontains 72 mg of hydrochloride of articaína and 18micrograms of adrenaline (as tartrate of adrenaline).
• Each milliliter ofARTINIBSA 40mg/ml + 10 micrograms/mlcontains 40mg of hydrochloride of articaína and 10 micrograms of adrenaline (as tartrate of adrenaline).

The other components are: sodium metabisulphite, sodium chloride, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), citric acid monohydrate, water for injectable preparations.

Aspect of the product and content of the package

ARTINIBSA 40mg/ml + 10 micrograms/ml is an injectable solution, colorless and transparent.

Package containing 1 cartridge with flat plunger of 1.8 ml for auto-aspiration.

Package containing 1 cartridge with plunger with cavity of 1.8 ml for manual aspiration.

Package containing 100 cartridges with flat plunger of 1.8 ml for auto-aspiration,

Package containing 100 cartridges with plunger with cavity of 1.8 ml for manual aspiration.

Holder of the marketing authorization and responsible for the manufacture

Holder of the marketing authorization and responsible for the manufacture:

Laboratorios Inibsa, S.A.

Ctra. Sabadell a Granollers, km 14.5

08185 Lliçà de Vall (Barcelona) Spain

Telephone +34 938 609 500

Fax +34 938 439 695

Last review of this leaflet was inFebruary 2020

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

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This information is intended solely for doctors or healthcare professionals:

Dosage

For all populations, the lowest effective dose should be used. The required dose must be determined on an individual basis.

For a routine procedure, the normal dose for adult patients is 1cartridge, but the content of less than one cartridge may be sufficient for effective anesthesia. According to the dentist's judgment, it may be necessary to use more cartridges for more extensive procedures, without exceeding the recommended maximum dose.

For most routine dental procedures, it is preferable to useARTINIBSA 40mg/ml + 5 micrograms/ml injectable solution

For more complex procedures, such as pronounced hemostasis, it is preferable to useARTINIBSA 40mg/ml + 10 micrograms/ml injectable solution

Concomitant use of sedatives to reduce patient anxiety:

The maximum safe dose of the local anesthetic may be reduced in sedated patients due to an additive effect on central nervous system depression.

Adults and adolescents (between 12 and 18years of age)

In adults and adolescents, the maximum dose of articaína is 7mg/kg, with a maximum absolute dose of articaína of 500mg. The maximum dose of articaína of 500mg corresponds to a healthy adult over 70kg of body weight.

Children (between 4 and 11years of age)

No safety data are available forARTINIBSA 40mg/ml + 10 micrograms/ml injectable solutionin children under 4years of age.

The amount to be injected should be determined by the child's age and weight and the magnitude of the operation. The mean effective dose is 2mg/kg and 4mg/kg for simple and complex procedures, respectively. The lowest effective dose should be used. In children of 4years (or over 20kg(44lbs)of body weight) and over, the maximum dose of articaína is only 7mg/kg, with a maximum absolute dose of 385mg of articaína for a healthy child of 55kg of body weight.

Special populations

Older patients and patients with renal disorders:

Due to the lack of clinical data, special precautions should be taken to administer the lowest effective dose in older patients and patients with renal disorders.

High plasma levels of the drug may occur in these patients, especially after repeated use. In case of requiring re-injection, the patient should be closely monitored to identify any signs of relative overdose.

Patients with liver insufficiency

For patients with liver insufficiency, special precautions should be taken to administer the lowest effective dose, especially after repeated use, although 90% of articaína is first inactivated by non-specific plasma esterases of tissues and blood.

Patients with plasma cholinesterase deficiency

High plasma levels of the drug may occur in patients with plasma cholinesterase deficiency or under treatment with cholinesterase inhibitors, as the product is inactivated in 90% by plasma esterases. Therefore, the lowest effective dose should be used.

Administration form

Infiltration and perineural route in the oral cavity.

If there is inflammation and/or infection at the injection site, local anesthesia should be injected with caution. The injection speed should be very slow (1ml/min).

Precautions to be taken before handling or administering the drug

This drug should only be used by a doctor or a dentist with sufficient training and familiar with the diagnosis and treatment of systemic toxicity, or under their supervision. Before the induction of regional anesthesia with local anesthetics, it should be ensured that a resuscitation team and appropriate medication are available to apply immediate treatment for any emergency respiratory or cardiovascular.

The patient's level of consciousness should be monitored after each injection of local anesthesia.

When usingARTINIBSA 40mg/ml + 10 micrograms/mlfor infiltration or regional anesthetic block, the injection should always be administered slowly and with prior aspiration.

Special warnings

Adrenaline reduces blood flow in the gums, which may cause local tissue necrosis.

There have been reports of rare cases of prolonged or irreversible nerve damage and taste loss after mandibular block analgesia.

Precautions for use

Risk associated with accidental intravascular injection:

An accidental intravascular injection may cause high levels of adrenaline and articaína in the systemic circulation.This may be associated with severe adverse reactions, such as convulsions, followed by central nervous system and cardiovascular depression and coma, which progresses to respiratory and cardiac arrest.

Therefore, to ensure that the needle does not penetrate a blood vessel during injection, aspiration should be performed before injecting the local anesthetic. However, the absence of blood in the syringe does not guarantee that the intravascular injection has not occurred.

Risk associated with intraneural injection:

An accidental intraneural injection may cause the drug to move retrogradely through the nerve.

To avoid intraneural injection and prevent nerve damage when performing nerve blocks, the needle should be withdrawn slightly whenever the patient feels a discharge during injection or if the injection is particularly painful. If nerve damage occurs due to the needle, the neurotoxic effect may be exacerbated by the possible chemical neurotoxicity of articaína and the presence of adrenaline, as it may reduce perineural blood flow and prevent local elimination of articaína.

Treatment of overdose

Before administering regional anesthesia with local anesthetics, it should be ensured that a resuscitation team and appropriate medication are available to apply immediate treatment for any emergency respiratory or cardiovascular.

According to the severity of the symptoms of overdose, the doctor or dentist should implement protocols that anticipate the need to protect airways and provide assisted ventilation

The patient's level of consciousness should be monitored after each injection of local anesthesia.

If signs of acute systemic toxicity appear, the injection of local anesthetic should be stopped immediately. If necessary, the patient should be placed in a supine position.

The symptoms of CNS (convulsions, CNS depression) should be treated immediately with appropriate respiratory support and administration of anticonvulsants.

Optimal oxygenation and ventilation, along with circulatory support and treatment of acidosis, may prevent cardiac arrest.

If cardiovascular depression (hypotension, bradycardia) occurs, appropriate treatment with intravenous fluids, vasopressors or inotropic agents should be considered. Children should be given doses appropriate to their age and weight.

In case of cardiac arrest, immediate cardiopulmonary resuscitation should be performed.

Special precautions for elimination and other manipulations

This drug should not be used if the solution is turbid or has changed color.

To avoid the risk of infection (e.g., transmission of hepatitis), the syringe and needles used to prepare the solution should always be new and sterile.

The cartridges are for single use. If only a part of the cartridge is used, the rest should be discarded.

The elimination of unused medication and all materials that have come into contact with it should be carried out in accordance with local regulations.

AUTOASPIRATION

Auto-aspiration requires a syringe with automatic aspiration. Auto-aspiration is performed by applying a gentle pressure on the piston and immediately releasing it. The elastic spring of the cartridge membrane, which is initially pressed against the axis of the base of the syringe, creates a negative pressure inside the cartridge that ensures aspiration.

MANUAL ASPIRATION

Manual aspiration requires a syringe with a hook or harpoon. Manual aspiration is achieved when the harpoon is fixed to the anesthetic cartridge and the plunger is pulled back.