ARTICAINE / EPINEPHRINE DERMOGEN 40 mg/mL + 5 micrograms/mL Injectable Solution

2. What you need to know before you are given ARTICAINE / EPINEPHRINE DERMOGEN

Do not use ARTICAINE / EPINEPHRINE DERMOGENif you have any of the following conditions:

• allergy to articaine or epinephrine or any of the other components of this medicine (listed in section 6).
• allergy to other local anesthetics.
• uncontrolled epilepsy.

Warnings and precautions

Talk to your dentist before starting to use Articaine / Epinephrine Dermogen if you have any of the following conditions:

• severe heart rhythm disorders (e.g., second and third degree AV block).
• acute heart failure (acute cardiac weakness, e.g., unexpected chest pain at rest or after a heart attack).
• low blood pressure.
• abnormally rapid heartbeats.
• heart attack in the last 3-6 months.
• coronary revascularization graft in the last 3 months.
• you are taking medications for high blood pressure called beta-blockers, such as propranolol. There is a risk of hypertensive crisis (very high blood pressure) or severe slowing of the pulse.
• very high blood pressure.
• you are taking medications for depression and Parkinson's disease (tricyclic antidepressants). These medications can enhance the effects of epinephrine.
• epilepsy.
• lack of a natural chemical called cholinesterase in the blood (plasma cholinesterase deficiency).
• kidney problems.
• severe liver problems.
• a disease called Myasthenia Gravis that causes muscle weakness.
• porphyria that causes both neurological complications and skin problems.
• if you are using other local anesthetics that cause reversible loss of sensitivity (including volatile anesthetics, such as halothane).
• if you are taking medications called antiplatelet or anticoagulant to prevent narrowing or hardening of blood vessels in arms and legs.
• if you are over 70 years old.
• you have or have had heart problems.
• you have uncontrolled diabetes.
• a severe case of overactive thyroid (thyrotoxicosis).
• a tumor called pheochromocytoma.
• a disease called glaucoma that affects the eyes.
• inflammation or infection of the area where you will receive the injection.
• reduced oxygen levels in body tissues (hypoxia), high potassium levels in the blood (hyperkalemia), and metabolic disorders due to too much acid in the blood (metabolic acidosis).

Using ARTICAINE / EPINEPHRINE DERMOGEN with other medicines

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

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

• Other local anesthetics that cause reversible loss of sensitivity (including volatile anesthetics, such as halothane).
• Sedatives (such as benzodiazepines, opioids), for example, to reduce anxiety before the dental procedure.
• Medications for the heart and blood pressure (such as guanadrel, guanethidine, propranolol, nadolol).
• Tricyclic antidepressants for treating depression (such as amitriptyline, desipramine, imipramine, nortriptyline, maprotiline, and protriptyline).
• COMT inhibitors for treating Parkinson's disease (such as entacapone or tolcapone).
• MAO inhibitors for treating depressive or anxiety disorders (such as moclobemide, phenelzine, tranylcypromine, linezolid).

• Medications for irregular heartbeats (such as digitalis, quinidine).
• Medications for migraine attacks (such as methysergide or ergotamine).
• Sympathomimetic vasopressors (such as cocaine, amphetamines, phenylephrine, pseudoephedrine, oxymetazoline), used to raise blood pressure: if taken in the 24 hours prior to the planned dental treatment, it should be postponed.
• Neuroleptic drugs (such as phenothiazines).

Using Articaine / Epinephrine Dermogen with food

Avoid eating, even chewing gum, until you have regained normal sensitivity. Otherwise, there is a risk that you may bite 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 have a baby, ask your dentist, doctor, or pharmacist for advice before taking this medicine.

Your dentist or doctor will decide whether you can take Articaine / Epinephrine Dermogen during pregnancy.

Breastfeeding can be resumed 5 hours after anesthesia.

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

Driving and using machines

If you experience side effects, including dizziness, blurred vision, or fatigue, do not drive or use machines until you have recovered (usually within 30 minutes after the dental procedure).

ARTICAINE / EPINEPHRINE DERMOGEN contains sodium and metabisulfite

• Sodium: this medicine contains less than 23 mg (1 mmol) of sodium per cartridge, so it is considered essentially 'sodium-free'.
• Sodium metabisulfite: in rare cases, it can cause severe allergic reactions and breathing difficulties (bronchospasm).

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

3. How to use ARTICAINE / EPINEPHRINE DERMOGEN

Only doctors and dentists are trained to use Articaine / Epinephrine Dermogen.

Your dentist will choose between Articaine / Epinephrine Dermogen 40 mg/ml + 5 micrograms/ml or Articaine / Epinephrine Dermogen 40 mg/ml + 10 micrograms/ml and determine the appropriate dose based on your age, weight, general health, and dental procedure.

The lowest dose that provides effective anesthesia should be used.

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

If you use more ARTICAINE / EPINEPHRINE DERMOGEN than you should

It is unlikely that you will be given too much of this injection, but if you start to feel unwell, tell your dentist. Symptoms of an overdose include acute weakness, pale skin, headache, agitation or restlessness, disorientation, loss of balance, tremors or involuntary shakings, dilated pupils, blurred vision, speech difficulties, dizziness, convulsions, stupor, loss of consciousness, coma, yawning, abnormally slow or rapid breathing that can lead to temporary respiratory arrest, heart failure.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

When you are in the dentist's office, the dentist will closely monitor the effects of Articaine / Epinephrine Dermogen.

Tell your dentist, doctor, or pharmacist immediately if 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: can be symptoms of an allergic reaction (hypersensitivity).
• A combination of drooping eyelid and constricted pupil (Horner's syndrome).

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

In other patients, other side effects not listed above may also occur.

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

• Gingivitis
• Neuropathic pain: pain due to nerve injury
• Numbness or decreased sensation in and around the mouth
• Metallic taste, taste disturbances, or loss of taste function
• Increased, unpleasant, or abnormal sensation
• Increased sensitivity to heat
• Headache
• Abnormally rapid heartbeats
• Abnormally slow heartbeats
• Low blood pressure
• Swelling of the tongue, lips, and gums

Uncommon 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)
• Somnolence
• Involuntary eye movement
• Double vision, temporary blindness
• Drooping eyelid and constricted pupil (Horner's syndrome)
• Sinking of the eyeball into the orbit (enoftalmia)
• Ringing in the ears, increased ear sensitivity
• Palpitations
• Hot flashes
• Wheezing (bronchospasm, wheezing), asthma
• Breathing difficulties
• 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 sensitivity, extensive numbness, and loss of taste

Frequency not known: cannot be estimated from the available data

• Extreme euphoria
• Heart rhythm coordination problems (conduction disorders, atrioventricular block)
• Increased blood flow to 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
• Redness of the skin (erythema)
• Abnormal increase in sweating
• Worsening of neuromuscular symptoms of Kearns-Sayre syndrome
• Sensation of heat or cold
• Jaw locking

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of ARTICAINE / EPINEPHRINE DERMOGEN

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

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date is the last day of the month shown.

Do not store above 30°C. Store the blister in the outer packaging to protect from light.

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

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

Medicines should not be disposed of via wastewater or household waste. Your dentist will know how to dispose of unused medicines. This will help protect the environment.

6. Container Content and Additional Information

Composition of ARTICAINE / EPINEPHRINE DERMOGEN

• The active ingredients are articaína hydrochloride and adrenaline tartrate.
  • Each 1.8 ml cartridge of Articaína / Epinefrina Dermogen 40 mg/ml + 5 micrograms/ml injectable solution contains 72 mg of articaína hydrochloride and 8 micrograms of adrenaline (as adrenaline tartrate).
  • Each milliliter of Articaína / Epinefrina Dermogen 40 mg/ml + 5 micrograms/ml contains 40 mg of articaína hydrochloride and 5 micrograms of adrenaline (as adrenaline tartrate).

• The other components are sodium chloride, disodium edetate, sodium metabisulfite (E-223), sodium hydroxide, and water for injectable preparations.

Appearance of the Product and Container Content

ARTICAINE / EPINEPHRINE DERMOGEN is a clear and colorless solution.

Container containing a 1.8 ml cartridge and a leaflet.

Container containing 50 cartridges of 1.8 ml (clinical container) in 5 PVC blister packs with 10 cartridges each and a leaflet.

Container containing 100 cartridges of 1.8 ml (clinical container) in 10 PVC blister packs with 10 cartridges each and a leaflet.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Name and address of the marketing authorization holder.

FARMALIDER, S.A.

c\ La Granja, nº1

28108– Alcobendas, Madrid

Spain

Name and address of the manufacturer of the specialty.

PIERREL, S.P.A.

Via Nazzionale Appia (Capua, Caserta)

I-81043 Italy

Date of the Last Revision of this Leaflet:February 2020

Other Sources of Information

Detailed information about this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products.

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This information is intended only for healthcare professionals

Dosage

For all populations, the lowest dose that provides effective anesthesia should be used. The necessary dose must be determined individually.

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

In the case of most routine dental procedures, it is preferable to use Articaína / Epinefrina Dermogen 40 mg/ml + 5 micrograms/ml.

For more complex procedures, such as pronounced hemostasis, it is preferable to use Articaína / Epinefrina Dermogen 40 mg/ml + 10 micrograms/ml.

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 18 years of age)

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

Children (between 4 and 11 years of age)

The safety of Articaína / Epinefrina Dermogen has not been established in children under 4 years of age. No data are available.

The amount to be injected must be determined based on the child's age and weight and the magnitude of the operation. The effective median dose is 2 mg/kg and 4 mg/kg for simple and complex procedures, respectively. The lowest dose that provides effective dental anesthesia should be used. In children from 4 years (or from 20 kg (44 lbs) of body weight) and older, the maximum dose of articaína is only 7 mg/kg, with an absolute maximum dose of 385 mg of articaína for a healthy child weighing 55 kg.

Special Populations

Elderly patients and patients with renal disorders:

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

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

Patient with hepatic insufficiency

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

Patient with plasma cholinesterase deficiency

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

Method of Administration

Infiltration and perineural use 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 (1 ml/min).

Precautions to be taken before handling or administering the medication

This medication 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 inducing regional anesthesia with local anesthetics, it should be ensured that resuscitation equipment and adequate medication are available to provide immediate treatment for any respiratory or cardiovascular emergency. The patient's level of consciousness should be monitored after each injection of local anesthesia.

When using Articaína / Epinefrina Dermogen for infiltration or regional anesthetic block, the injection should always be administered slowly and with prior aspiration.

Special Warnings

Adrenaline reduces blood flow to the gums, which can cause local tissue necrosis.

Very rare cases of prolonged or irreversible nerve damage and taste loss have been reported after mandibular block anesthesia.

Precautions for Use

Risk associated with accidental intravascular injection:

An accidental intravascular injection can cause high levels of adrenaline and articaína in the systemic circulation. This can be associated with serious adverse reactions, such as convulsions, followed by central nervous system depression and cardiorespiratory arrest, which progresses to respiratory and circulatory 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 intravascular injection has not occurred.

Risk associated with intraneural injection:

An accidental intraneural injection can 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 slightly withdrawn whenever the patient feels a sensation of discharge during injection or if the injection is particularly painful. If nerve damage occurs due to the needle, the neurotoxic effect may be worsened by the possible chemical neurotoxicity of articaína and the presence of adrenaline, as it can reduce perineural blood flow and prevent local elimination of articaína.

Overdose Treatment

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

Depending on the severity of the overdose symptoms, the doctor or dentist should implement protocols that anticipate the need to protect the 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 the local anesthetic should be stopped immediately. If necessary, the patient should be placed in a supine position.

Symptoms of the CNS (convulsions, CNS depression) should be treated immediately with adequate respiratory support and administration of anticonvulsant medications.

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

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

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

Special Precautions for Elimination and Other Handling

This medication 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 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 will be carried out in accordance with local regulations.