ArtinibsA 40 mg/ml + 5 micrograms/ml solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

ARTINIBSA 40 mg/ml + 5 micrograms/ml solution for injection

articaine hydrochloride / epinephrine (adrenaline)

Read this entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read 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 effects not listed in this leaflet. See section 4.

Leaflet contents:

1. What ARTINIBSA 40 mg/ml + 5 micrograms/ml is and what it is used for.
2. What you need to know before ARTINIBSA 40 mg/ml + 5 micrograms/ml is administered to you.
3. How to use ARTINIBSA 40 mg/ml + 5 micrograms/ml.
4. Possible side effects.
5. How to store ARTINIBSA 40 mg/ml + 5 micrograms/ml.
6. Contents of the pack and other information.

1. What Artinibsa 40 mg/ml + 5 micrograms/ml is and what it is used for

ARTINIBSA 40 mg/ml + 5 micrograms/ml solution for injection is used to numb (anesthetize) the oral cavity during dental procedures.

This medicine contains two active substances:

• Articaine, a local anesthetic that prevents pain.
• Adrenaline, a vasoconstrictor that narrows the blood vessels at the injection site, thereby prolonging the effect of articaine. It also reduces bleeding during surgery.

Your dentist will administer ARTINIBSA 40 mg/ml + 5 micrograms/ml solution for injection.

ARTINIBSA 40 mg/ml + 5 micrograms/ml solution for injection is indicated in children over 4 years of age (approximately 20 kg body weight), adolescents, and adults.

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

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

2. What you need to know before ARTINIBSA 40 mg/ml + 5 micrograms/ml is administered to you

Do not use ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution if you have any of the following conditions:

• Allergy to articaine or adrenaline (epinephrine), or to any of the other components of this medicine (listed in section 6).
• Allergy to other local anesthetics.
• Epilepsy not adequately controlled with medication.

Warnings and precautions

Consult your dentist before starting to use ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution if you have any of the following conditions:

• Severe cardiac rhythm disorders (e.g., second- or third-degree AV block).
• Acute heart failure (acute cardiac weakness, e.g., unexpected chest pain at rest or following myocardial infarction [i.e., heart attack]).
• Low blood pressure (hypotension).
• Abnormally rapid heartbeats.
• Myocardial infarction within the last 3–6 months.
• Coronary artery bypass graft within the last 3 months.
• You are taking medications for blood pressure called beta-blockers, such as propranolol. There is a risk of hypertensive crisis (very high blood pressure) or severe slowing of the heartbeat (see section "Use of ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution").
• Very high blood pressure.
• You are simultaneously taking medications for depression and Parkinson’s disease (tricyclic antidepressants). These medications may enhance the effects of adrenaline.
• Epilepsy.
• Deficiency of a naturally occurring chemical substance called cholinesterase in the blood (plasma cholinesterase deficiency).
• Kidney problems.
• Severe liver problems.
• A disease called Myasthenia Gravis that causes muscle weakness.
• Porphyria causing both neurological complications and skin problems.
• If you are using other local anesthetics that cause reversible loss of sensation (including volatile anesthetics such as halothane).
• If you are taking medications called antiplatelet agents or anticoagulants to prevent narrowing or hardening of blood vessels in arms and legs.
• If you are over 70 years of age.
• You have or have had any heart problems.
• You have uncontrolled diabetes.
• Severe overactivity of the thyroid gland (thyrotoxicosis).
• A tumor called pheochromocytoma.
• A condition called angle-closure glaucoma affecting the eyes.
• Inflammation or infection at the site where the injection will be administered.
• Reduced oxygen levels in body tissues (hypoxia), high potassium levels in blood (hyperkalemia), and metabolic disorders resulting from excess acid in the blood (metabolic acidosis).

Use of ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution with other medicines

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

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

• Other local anesthetics causing reversible loss of sensation (including volatile anesthetics such as halothane).
• Sedatives (such as benzodiazepines, opioids), for example, to reduce anxiety before the dental procedure.
• Medicines for heart conditions and blood pressure (such as guanadrel, guanethidine, propranolol, nadolol).
• Tricyclic antidepressants used to treat depression (such as amitriptiline, desipramine, imipramine, nortriptyline, maprotiline, and protriptyline).
• COMT inhibitors used to treat Parkinson’s disease (such as entacapone or tolcapone).
• MAO inhibitors used to treat depressive or anxiety disorders (such as moclobemide, phenelzine, tranylcypromine, linezolid).
• Medicines for irregular heartbeats (e.g., digitalis, quinidine).
• Medicines for migraine attacks (such as methysergide or ergotamine).
• Sympathomimetic vasoconstrictors (such as cocaine, amphetamines, phenylephrine, pseudoephedrine, oxymetazoline), used to raise blood pressure: if taken within the previous 24 hours before the planned dental treatment, the procedure should be postponed.
• Neuroleptic drugs (e.g., phenothiazines).

Use of ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution with food

Avoid eating, including chewing gum, until normal sensation has returned. 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 are planning to become pregnant, consult your dentist or doctor before using this medicine.

Your dentist or doctor will decide whether you can use ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution during pregnancy.

Breastfeeding may be resumed 5 hours after anesthesia.

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

Driving and using machines

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

ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution contains sodium metabisulfite and sodium

This medicine may cause severe allergic reactions and bronchospasm (sudden sensation of suffocation) because it contains sodium metabisulfite.

This medicine contains less than 23 mg of sodium (1 mmol) per dose unit: this is essentially “sodium-free”.

Use in athletes

This medicine contains articaine and epinephrine (adrenaline), which may lead to a positive result in doping control tests.

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

3. How to use ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution

Only physicians and dentists are trained to administer ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution.

Your dentist will choose between ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution or ARTINIBSA 40 mg/ml + 10 micrograms/ml injectable solution and will determine the appropriate dose based on your age, weight, general health status, and the dental procedure being performed.

The lowest dose providing effective anesthesia should be used.

This medicine is administered by slow injection into the oral cavity.

If you are given more ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution than you should

It is unlikely that you will be given too much of this injection, but if you start to feel unwell, inform your dentist immediately. Symptoms of overdose include severe weakness, pale skin, headache, agitation or restlessness, disorientation, loss of balance, tremors or involuntary shivering, pupil dilation, blurred vision, difficulty focusing objects clearly, speech disturbances, dizziness, seizures, stupor, loss of consciousness, coma, yawning, abnormally slow or rapid breathing that may lead to temporary respiratory arrest, and inability of the heart to contract (cardiac failure).

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

If you have any further questions about the use of this product, ask your dentist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

While you are at the dentist, your dentist will closely monitor the effects of ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution.

Immediately inform your dentist, doctor, or pharmacist if you experience any of the following serious adverse effects:

• Swelling of the face, tongue, or pharynx, difficulty swallowing, urticarial wheals, or breathing difficulty (angioedema)
• Rash, itching, throat swelling, and breathing difficulty: these may be symptoms of an allergic reaction (hypersensitivity)
• A combination of drooping eyelid and pupil constriction (Horner's syndrome)

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

Other adverse effects not listed above may also occur in other patients.

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

• Gum inflammation
• Neuropathic pain: pain due to nerve injury
• Numbness or reduced sense of touch inside and around the mouth
• Metallic taste, taste disturbances, or loss of taste function
• Increased, unpleasant, or abnormal sense of touch
• Increased sensitivity to heat
• Headache
• Abnormally rapid heartbeat
• Abnormally slow heartbeat
• Low blood pressure
• Swelling of the tongue, lips, and gums

Uncommon adverse effects: may affect up to 1 in 100 people:

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

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

• Nervousness, anxiety
• Facial nerve disorder (facial paralysis)
• Drowsiness
• Involuntary eye movements
• Double vision, temporary blindness
• Drooping eyelid and pupil constriction (Horner's syndrome)
• Sunken eyeball within the orbit (enophthalmos)
• Ringing in the ears, increased ear sensitivity
• Palpitations
• Flushing
• Wheezing (bronchospasm, whistling sounds in the bronchi), asthma
• Difficulty breathing
• Exfoliation and ulceration of the gums
• Exfoliation at the injection site
• Urticarial wheals
• Involuntary muscle contractions
• Fatigue, weakness
• Chills

Very rare adverse 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 sense of well-being (euphoria)
• Heart rhythm coordination problems (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
• Hoarseness
• Difficulty swallowing
• Swelling of the cheeks and local swelling
• Burning mouth syndrome
• Skin redness (erythema)
• Abnormal increase in sweating
• Worsening of neuromuscular symptoms in Kearns-Sayre syndrome
• Sensation of heat or cold
• Jaw locking

Reporting of adverse effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution

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

Do not use this medicine after the expiry date stated on the container, label, and carton after EXP. The expiry date refers to the last day of the month indicated.

Do not use ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution if visible signs of deterioration are observed.

Store in the original packaging to protect from light.

Do not use this medicine if the solution appears cloudy or has changed colour.

Cartridges are for single use only. Use immediately after opening the cartridge. Any unused solution must be discarded.

Medicines should not be disposed of via wastewater or household waste. Your dentist can advise you on how to dispose of medicines no longer in use. This helps protect the environment.

6. Contents of the pack and other information

Composition of ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution

The active substances are articaine hydrochloride and adrenaline tartrate.

• Each 1.8 ml cartridge of ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution contains 72 mg of articaine hydrochloride and 9 micrograms of adrenaline (as adrenaline tartrate).
• Each millilitre of ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution contains 40 mg of articaine hydrochloride and 5 micrograms of adrenaline (as adrenaline tartrate).

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

Appearance of the product and contents of the pack

ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution is a colourless, translucent injectable solution.

Pack containing 1 cartridge with flat plunger of 1.8 ml for self-aspiration.

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

Pack containing 100 cartridges with flat plunger of 1.8 ml for self-aspiration.

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

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder and Manufacturer:

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

The latest revision of this leaflet was in February 2020.

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS): http://www.aemps.gob.es/

---

This information is intended for healthcare professionals only:

Dosage

For all populations, the lowest effective dose required to achieve adequate anaesthesia should be used. The necessary dose must be determined individually.

For routine procedures, the normal dose for adult patients is 1 cartridge, although less than one cartridge may be sufficient for effective anaesthesia. According to the dentist's judgement, additional cartridges may be required for more extensive procedures, without exceeding the recommended maximum dose.

For most routine dental procedures, ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution is preferred.

For more complex procedures, such as those requiring pronounced haemostasis, ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution is preferred.

Concomitant use of sedatives to reduce patient anxiety:

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

Adults and adolescents (aged 12 to 18 years)

In adults and adolescents, the maximum dose of articaine is 7 mg/kg, with an absolute maximum dose of articaine of 500 mg. The maximum articaine dose of 500 mg corresponds to a healthy adult weighing more than 70 kg.

Children (aged 4 to 11 years)

The safety of ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution has not been established in children under 4 years of age. No data are available.

The amount to be injected should be determined based on the child's age, weight, and the extent of the procedure. The effective average dose is 2 mg/kg and 4 mg/kg for simple and complex procedures, respectively. The lowest dose providing effective dental anaesthesia should be used. In children aged 4 years (or from 20 kg (44 lbs) body weight) and older, the maximum dose of articaine is only 7 mg/kg, with an absolute maximum dose of 385 mg of articaine for a healthy child weighing 55 kg.

Special populations

Elderly patients and patients with renal impairment:

Due to the absence of clinical data, special precautions should be taken to administer the lowest dose that provides effective anaesthesia in elderly patients and in patients with renal impairment.

Elevated plasma levels of the drug may occur in these patients, especially after repeated use. If re-injection is required, the patient should be closely monitored for any signs of relative overdose.

Patients with hepatic impairment

Special precautions should be taken to administer the lowest dose that provides effective anaesthesia in patients with hepatic impairment, particularly after repeated use, although 90% of articaine is initially inactivated by non-specific esterases in tissues and blood.

Patients with plasma cholinesterase deficiency

Elevated plasma levels of the drug may occur in patients with cholinesterase deficiency or those receiving treatment with acetylcholinesterase inhibitors, as the product is inactivated by 90% via plasma esterases. Therefore, the lowest dose providing effective anaesthesia should be used.

Method of administration

Infiltration and perineural route in the oral cavity.

If inflammation and/or infection is present at the injection site, local anaesthesia should be administered with caution. The injection rate should be very slow (1 ml/min).

Precautions to be taken before handling or administering the medicine

This medicine should only be used by a physician or dentist with adequate training and familiar with the diagnosis and treatment of systemic toxicity, or under their supervision. Prior to inducing regional anaesthesia with local anaesthetics, appropriate resuscitation equipment and medication must be available to allow immediate treatment of any respiratory or cardiovascular emergency. The patient's level of consciousness should be monitored after each local anaesthetic injection.

When using ARTINIBSA 40 mg/ml + 5 micrograms/ml injectable solution for infiltration or regional anaesthetic block, the injection must always be administered slowly and with prior aspiration.

Special warnings

Adrenaline reduces blood flow in the gums, potentially causing local tissue necrosis.

Very rare cases of prolonged or irreversible nerve injury and taste loss have been reported following mandibular block analgesia.

Precautions for use

Risk associated with accidental intravascular injection:

Accidental intravascular injection may result in high systemic levels of adrenaline and articaine. This may lead to serious adverse reactions such as seizures, followed by central nervous system and cardiopulmonary depression, coma, and progressing to respiratory and circulatory arrest.

Therefore, prior aspiration must be performed before injecting the local anaesthetic to ensure the needle has not entered a blood vessel. However, the absence of blood in the syringe does not guarantee that intravascular injection has not occurred.

Risk associated with accidental intraneural injection:

Accidental intraneural injection may cause the drug to travel retrogradely along the nerve.

To avoid intraneural injection and prevent nerve injury during nerve blocks, the needle should be slightly withdrawn whenever the patient experiences a sensation of electric shock or particularly painful injection. If nerve injury occurs from the needle, the neurotoxic effect may be worsened by the potential chemical neurotoxicity of articaine and the presence of adrenaline, which may reduce perineural blood flow and impair local elimination of articaine.

Management of overdose

Prior to administering regional anaesthesia with local anaesthetics, appropriate resuscitation equipment and medication must be available to allow immediate treatment of any respiratory or cardiovascular emergency.

Depending on the severity of overdose symptoms, the physician or dentist should implement protocols that include airway protection and provision of assisted ventilation.

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

If signs of acute systemic toxicity occur, injection of the local anaesthetic must be stopped immediately. If necessary, place the patient in the supine position.

Symptoms of CNS toxicity (seizures, CNS depression) should be treated immediately with appropriate airway/respiratory support and administration of anticonvulsant drugs.

Optimal oxygenation and ventilation, along with circulatory support and correction 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 receive age- and weight-appropriate doses.

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

Special precautions for disposal and other handling

This medicine should not be used if the solution is cloudy or has changed colour.

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

Cartridges are for single use only. If only part of the cartridge is used, the remainder must be discarded.

Disposal of unused medicine and of all materials that have been in contact with it must be carried out in accordance with local regulations.

SELF-ASPIRATION

For self-aspiration, an automatic aspiration syringe is required. Self-aspiration is performed by applying gentle pressure on the piston and immediately releasing it. The elastic spring of the cartridge membrane, initially pressed against the base shaft of the syringe, creates negative pressure within the cartridge, ensuring aspiration.

MANUAL ASPIRATION

For manual aspiration, a syringe with a hook or harpoon is required. Manual aspiration is achieved when the harpoon engages the anaesthetic cartridge and the plunger is pulled backward.