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

2. What you need to know before you start using Articaine/Epinefrine Normon

Do not use Articaine/Epinefrine Normon

• If you are allergic to articaine or other local anesthetics of the amide type.
• If you are allergic to epinephrine or any of the other components of this medicine (listed in section 6).
• If you have severe cardiac arrhythmias (e.g., AV block of second and third degree).
• If you have a very low pulse.
• If you have congestive heart failure (acute cardiac weakness, e.g., unexpected chest pain at rest or after a myocardial injury [e.g., heart attack]).
• If you have very low blood pressure.
• If you have bronchial asthma and are sensitive to sulfite (asthma attacks triggered by sulfite).
• If you have uncontrolled epilepsy.

Due to the effects of the active ingredient epinephrine, articaine/epinefrine should not be used:

• If you have elevated intraocular pressure (glaucoma).
• If you have hyperthyroidism.
• If you have episodes of increased heart rate (paroxysmal tachycardia).
• If you have a specific type of cardiac arrhythmia (absolute arrhythmia with rapid and irregular heartbeat).
• If you have had a heart attack in the last 3 or 6 months.
• If you have had a coronary bypass in the last 3 months.
• If you are taking certain beta-blockers (e.g., propranolol), there is a risk that you may experience a crisis of high blood pressure or severe slowing of the heart rate.
• If you have pheochromocytoma (an adrenaline-producing tumor that is usually found in the adrenal gland).
• If you have very high blood pressure.
• If you are being treated at the same time with certain antidepressants and antiparkinsonian medications (tricyclic antidepressants or MAO inhibitors), as these active ingredients may increase the cardiovascular effects of epinephrine; this may apply up to 14 days after finishing treatment with MAO inhibitors.

Articaine/epinefrine cannot be administered intravenously (into a vein).

Due to the epinephrine content, Articaine/Epinefrine Normon is not indicated for anesthesia of the distal phalanx of the limbs (e.g., fingers and toes) because there is a risk of local blood flow blockage.

Warnings and precautions

Consult your dentist or pharmacist before starting to use Articaine/Epinefrine Normon:

• If you have a deficiency of a specific enzyme (cholinesterase deficiency), as a prolonged and sometimes increased effect of articaine/epinefrine can be expected.

• If you have inflammation or infection of the injection site. In this case, an increased absorption of articaine/epinefrine can be expected, which reduces the efficacy.
• If you are over 70 years old.
• If you have reduced oxygen levels in the body tissue (hypoxia), elevated potassium levels in the blood (hyperkalemia), and metabolic disorders due to excess acid in the blood (metabolic acidosis).

Articaine/Epinefrine Normon should only be used after a thorough medical examination:

• If you have coagulation disorders.
• If you have kidney function disorders (e.g., nephritis).
• If you have liver function disorders (e.g., liver cirrhosis).
• If you are receiving other local anesthetics simultaneously, i.e., medications that cause reversible loss of sensitivity, including inhalation anesthetics such as halothane (see "Other medicines and Articaine/Epinefrine Normon").
• If you have epilepsy (see section 4).
• If you are taking medications called platelet aggregation inhibitors or coagulation inhibitors to prevent constriction and/or hardening of the blood vessels in the arms and legs.
• If you have low blood pressure.
• If you have a disease called myasthenia gravis that causes muscle weakness.
• If you have a disease called porphyria that causes neurological complications or skin problems.
• In case of reduced oxygen levels in the body tissue (hypoxia), elevated potassium levels in the blood (hyperkalemia), and metabolic disorders due to excess acid in the blood (metabolic acidosis).

Similarly, if you have the following diseases, Articaine/Epinefrine Normon can only be used after a thorough medical examination:

• Cardiovascular disorders, such as:
• • Heart failure (cardiac weakness).
  • Coronary artery disease (constriction of the coronary arteries).
  • Angina pectoris (disruption of blood flow to the heart with pain and pressure in the chest).
  • After a heart attack.
  • Cardiac arrhythmias (irregular heart rate).
  • High blood pressure.
  • Arteriosclerosis (narrowing of the arteries due to deposits, e.g., of blood lipids).
  • Disruption of blood flow to the brain.
  • After a stroke.

• Chronic bronchitis, emphysema (abnormal dilation of the lungs).
• Diabetes mellitus.
• Severe anxiety disorder.

Your dentist will review your medical history:

• And the medication you are taking simultaneously to prevent side effects.
• Will perform a test injection in case of a risk of allergy to the medicine.
• Will select the minimum possible dose.
• And will carefully check before the injection that no blood vessel has been hit.

The use of this medicine may lead to prolonged numbness of the mouth area after dental treatment. In small children, caution should be exercised to ensure they do not bite themselves, as this can lead to soft tissue injuries.

After using articaine/epinefrine, do not eat until the local anesthesia has worn off.

Other medicines and Articaine/Epinefrine Normon

Tell your dentist or pharmacist if you are taking/using, have recently taken/used, or might take/use any other medicines.

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

• Sedatives (e.g., benzodiazepines, opioids), for example, to reduce your anxiety due to the dental appointment.
• Tricyclic antidepressants for treating depression (such as amitriptyline, desipramine, imipramine, nortriptyline, maprotiline, and protriptiline), COMT inhibitors for treating Parkinson's disease (such as entacapone or tolcapone).
• MAO inhibitors for treating depressive or anxiety disorders (e.g., moclobemide, phenelzine, tranylcypromine, linezolid).
• Medicines for treating cardiac arrhythmias (e.g., digitalis, quinidine).
• Medicines for migraine attacks (such as methysergide or ergotamine).
• Medicines for the heart and blood pressure (such as guanadrel, guanethidine, propranolol, nadolol).
• Vasoconstrictors (such as cocaine, amphetamines, phenylephrine, pseudoephedrine, oxymetazoline) to increase blood pressure: If they have been used in the last 24 hours, then the scheduled dental treatment should be postponed.
• Neuroleptics (e.g., phenothiazine).

If you are receiving other local anesthetics simultaneously, their effects on the cardiovascular and nervous systems may increase.

Articaine/Epinefrine Normon contains the active ingredient epinephrine. This active substance constricts blood vessels and increases blood pressure. The hypertensive effect of epinephrine can be intensified by other medicines for treating depression and Parkinson's disease. Tricyclic antidepressants and MAO inhibitors should not be taken at the same time (please see section 2 "What you need to know before you start using Articaine/Epinefrine Normon").

If you are taking certain beta-blockers (e.g., propranolol), then articaine/epinefrine should not be administered (see section "Do not use Articaine/Epinefrine Normon").

Epinephrine can inhibit the release of insulin from the pancreas, thereby reducing the efficacy of oral antidiabetic medicines (medicines for treating diabetes mellitus).

If articaine/epinefrine is used simultaneously with certain inhalation anesthetics (e.g., halothane), this can trigger cardiac arrhythmias.

Please note: in patients treated with coagulation inhibitors ("anticoagulants" such as heparin or acetylsalicylic acid), an accidental puncture of a blood vessel when administering local anesthetics can cause severe bleeding; furthermore, these patients have a high tendency to bleed in general.

Using Articaine/Epinefrine Normon with food

After the intervention, avoid eating and chewing gum until you have regained normal sensitivity; otherwise, there is a risk of biting your lips, cheeks, or tongue. This applies especially to children.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your dentist or doctor for advice before using this medicine.

If you are pregnant, your dentist should only use articaine/epinefrine after a thorough assessment of the risks and benefits.

Regarding the use of articaine, there is no documented experience during pregnancy, except at the time of birth. Experimental studies in animals have shown that epinephrine at doses higher than those used in dental anesthesia has had adverse effects on the creatures. After accidental injection of articaine/epinefrine into a maternal blood vessel, epinephrine can lead to a reduction in blood flow to the uterus.

The active substances of Articaine/Epinefrine Normon are rapidly broken down in the body. Consequently, no harmful amounts of the active substances are transferred to the baby in breast milk. Therefore, during short-term use of articaine/epinefrine, it is not necessary to interrupt breastfeeding. Breastfeeding can be resumed 5 hours after anesthesia.

In the doses used for dental treatment, no negative effects on reproductive ability are expected.

Driving and using machines

After the intervention, your dentist will decide when you are allowed to actively participate in road traffic or operate machines. In the corresponding studies, local anesthesia with articaine did not cause any detectable impairment of normal driving ability.

If you experience side effects such as dizziness, vision problems, or fatigue, then you should not drive vehicles or operate machines until you feel better again (usually within 30 minutes after dental treatment).

Use in athletes

This medicine contains epinephrine, which can produce a positive result in doping tests.

Articaine/Epinefrine Normon contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per cartridge; i.e., it is essentially "sodium-free".

Articaine/Epinefrine Normon contains sodium metabisulfite (E233)

It can rarely cause severe hypersensitivity reactions and bronchospasm.

If there is a risk of an allergic reaction, your dentist will choose another anesthetic.

3. How to use Articaine/Epinephrine Normon

Only doctors and dentists are trained to use Articaine/Epinefrine Normon.

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

The lowest dose that is sufficient for effective anesthesia (numbing) should be used.

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

Your dentist will decide on the dosage and method of administration of Articaine/Epinefrine Normon. They will generally follow these recommendations:

Dose

For the extraction of uncomplicated upper teeth in a non-inflamed stage, an injection of 1.7 ml per tooth is usually sufficient. In some cases, a subsequent injection of 1 to 1.7 ml may be necessary to achieve complete local anesthesia. In most cases, a painful injection into the gums is not required.

If a cut or puncture of the gum is necessary, an injection of approximately 0.1 ml per puncture is sufficient.

For the extraction of a row of adjacent teeth, the full dose of articaine/epinephrine is usually not necessary. The number of injections can usually be reduced.

For extractions with a straight forceps of lower premolars in a non-inflamed stage, as a rule, an injection of 1.7 ml per tooth is sufficient. If complete effectiveness is still not achieved after this, your dentist may perform a subsequent injection of 1 to 1.7 ml. Only if complete anesthesia is still not achieved, your dentist may perform a mandibular nerve block (mandibular anesthesia), which is common in these cases.

For the removal of caries, for the preparation of a filling, and for crown shaping, a quantity of 0.5-1.7 ml of articaine/epinephrine per tooth is sufficient, depending on the scope and duration of the treatment. However, this does not apply to lower molars.

In the course of treatment, adults may be administered up to 7 mg of articaine per kilogram of body weight. Amounts of up to 500 mg (corresponding to 12.5 ml of injectable solution) are usually well tolerated.

Elderly patients and patients with severe hepatic and renal impairment

In elderly patients and in patients with severe hepatic and renal impairment (e.g., nephritis or liver cirrhosis), high levels of articaine may occur in the plasma. If you are among these patients, your dentist should take special care to use the smallest amount of anesthesia sufficient.

Use in children and adolescents

If Articaine/Epinefrine Normon is used in children, the minimum volume necessary for sufficient anesthesia should be used. The dosage of the injection should be determined individually, taking into account the child's age and weight. The maximum dose should not exceed 7 mg of articaine per kilogram of body weight (0.175 ml/kg).

This medication has not been studied in children under 1 year of age.

Method of use

Articaine/Epinefrine Normon is intended for use in the oral cavity.

To prevent infections (e.g., transmission of hepatitis), new and sterile syringes and needles should always be used for each injection.

To avoid intravascular injection, as a rule, an aspiration test should be performed before injection, i.e., by rotating the needle 90° or even better 180°. When using cylindrical ampoules, Uniject® K or Uniject® K vario are especially suitable for this purpose. The injection pressure should be adjusted to the sensitivity of the tissue.

Warnings

Adequate functioning and optimal protection against glass breakage are ensured by the use of suitable injection supports (infiltration anesthesia: Uniject® K or Uniject® K vario; intraligamentary anesthesia: Ultraject®). Damaged cylindrical ampoules cannot be used for injection.

For single use. Unused solution should be discarded.

The solution should be clear and colorless. If it is discolored or turbid, the medication should not be used.

If you use more Articaine/Epinephrine Normon than you should

It is unlikely that you will be administered too much of this injection, but if you start to feel unwell, inform your dentist. Symptoms of overdose include extreme weakness, paleness of the skin, headache, feeling of agitation or restlessness, feeling of disorientation, loss of balance, tremors or involuntary twitching, dilated pupils, blurred vision, difficulty focusing clearly on an object, speech disorders, dizziness, convulsions, stupor, loss of consciousness, coma, yawning, abnormally slow or rapid breathing that could lead to temporary interruption of breathing, cardiac failure to contract effectively (called cardiac arrest).

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

If you have any further questions on the use of this medication, contact your dentist, doctor, or pharmacist.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

While you are in your dentist's office, your dentist will closely monitor the effects of Articaine/Epinephrine Normon.

Tell your dentist, doctor, or pharmacist immediately if you notice one of the following serious side effects:

• Swollen face, tongue, or throat, difficulty swallowing, hives, or difficulty breathing (angioedema).
• Rash, itching, swelling of the neck, and difficulty breathing: These can be symptoms of an allergic reaction (hypersensitivity).
• A combination of drooping eyelid and constricted pupils (Horner's syndrome).

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

However, in some patients, other side effects may occur that have not been mentioned above.

Frequent (may affect up to 1 in 10 people)

• Gingivitis.
• Nausea.
• Vomiting.
• Uncomfortable sensations (paresthesias).
• Neuropathic pain (pain due to nerve damage).
• Metallic taste, taste distortions, or loss of taste.
• Reduced sensitivity in the mouth or facial area (hypesthesia).
• Headache.
• Increased tactile perception, unpleasant or unusual.
• Increased sensitivity to heat.
• Abnormally rapid heartbeat.
• Abnormally slow heartbeat.
• Low blood pressure.
• Swelling of the tongue, lips, and gums.

Uncommon (may affect up to 1 in 100 people)

• Dizziness.
• Burning sensation.
• High blood pressure.
• Inflammation of the tongue and mouth.
• Diarrhea.
• Rash, itching.
• Pain in the neck or pain at the injection site.

Rare (may affect up to 1 in 1,000 people)

• Hypersensitivity reactions (allergic or allergic-like reactions) may occur. They can manifest as swelling and/or inflammation at the injection site. Hypersensitivity reactions that are not limited to the injection site manifest as:
• • Redness.
  • Itching.
  • Red, watery eyes.
  • Runny nose.
  • Facial swelling (angioedema) with swelling of the upper and/or lower lip and/or cheeks.
  • Swelling in the throat area with oppression and difficulty swallowing.
  • Hives.
  • Difficulty breathing, even up to anaphylactic shock.

• Nervousness, anxiety states.
• Disorder of the facial nerves (facial paralysis).
• Drowsiness.
• Involuntary eye movement.
• During or shortly after the injection of local anesthetics in the head area, vision problems (blurred vision, double vision, dilated pupils, blindness) may occur. These are usually transient.
• Drooping eyelid and constricted pupils (Horner's syndrome).
• Sinking of the eyeball into the orbit due to a change in the volume of the orbit (enophthalmos).
• Tinnitus, hypersensitivity of hearing.
• Palpitations.
• Hot flashes.
• Wheezing (bronchospasm), asthma.
• Difficulty breathing.
• Scaling and ulceration of the gums.
• Scaling at the injection site.
• Hives (urticaria).
• Muscle spasms, involuntary muscle contractions.
• Fatigue, weakness.
• Chills.

Very rare (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)

• Redness of the skin (erythema).
• Extreme euphoria.
• Disorders of the heart's conduction system (conduction disorders, AV block).
• Cardiac arrhythmias, heart failure, and shock (sometimes potentially fatal).
• Depending on the dose (especially in too high doses or in the case of an accidental injection into a blood vessel), disorders of the central nervous system, e.g.,
• • Restlessness, nervousness.
  • Lethargy, drowsiness, even up to loss of consciousness, coma.
  • Respiratory disorders up to respiratory arrest.
  • Muscle tremors, muscle spasms up to convulsions.

• Nerve damage (e.g., facial nerve damage) may occur during any dental intervention and therefore cannot be ruled out. It is caused by the course of the nerves through the injection area or by incorrect injection technique. Facial nerve paralysis may occur. A reduction in the sense of taste is also possible.

• An accidental injection into a blood vessel in the injection area can lead to inadequate oxygen supply to the tissue and even tissue necrosis.

• Increased blood flow to a part of the body, leading to obstruction of blood vessels.
• Dilation or constriction of blood vessels.
• Hoarseness.
• Difficulty swallowing.
• Swelling of the cheeks and local swelling.
• Burning sensation in the tongue (burning mouth syndrome).
• Unusual sweating.
• Worsening of neuromuscular symptoms of Kearns-Sayre syndrome.
• Sensation of heat or sensation of cold.
• Trismus.

Sodium metabisulfite (E233) may trigger severe hypersensitivity reactions and bronchial spasms (bronchospasm). Hypersensitivity reactions may be expressed as vomiting, diarrhea, wheezing, acute asthma attacks, altered consciousness, or shock.

Additional side effects in children

In young children, compared to adults, there is a higher risk of bite injuries and therefore soft tissue injuries due to prolonged numbness of the mouth area after dental treatment.

Special warnings

In case a undesirable effect occurs suddenly or worsens rapidly, inform a doctor immediately. This is especially important, as some of these side effects (e.g., drop in blood pressure or difficulty breathing) can be life-threatening.

Reporting of side effects

If you consider that any of the side effects you are suffering from is serious, or if you notice any side effect not mentioned in this leaflet. This includes any side effect not mentioned in this leaflet. You can also report them 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 medication.

5. Storage of Articaine/Epinephrine Normon

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

Do not use this medication after the expiration date stated on the label and carton after EXP. The expiration date is the last day of the month indicated.

Store below 25°C.

Do not freeze.

Keep the cartridges in the outer packaging to protect them from light.

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

The cartridges are for single use. Use immediately after opening the cartridge. Discard the unused solution.

Medicines should not be disposed of via wastewater or household waste. Place the packaging and unused medicines in the SIGRE collection point at the pharmacy. Your dentist will know how to dispose of unused medicines. This will help protect the environment.

6. Package contents and additional information

Composition of Articaine/Epinephrine Normon

• The active substances are articaine hydrochloride and epinephrine. One milliliter of injectable solution contains 40 mg of articaine hydrochloride and 5 micrograms of epinephrine (adrenaline).

Each 1.7 ml cartridge of Articaine/Epinephrine Normon injectable solution contains 68 mg of articaine hydrochloride and 8.5 micrograms of epinephrine (adrenaline).

• The other ingredients are: sodium chloride, sodium metabisulfite (E233), hydrochloric acid, and water for injectable preparations.

Appearance of the product and package contents

Articaine/Epinephrine Normon is a clear, colorless solution, practically free of visible particles.

Type I colorless glass cartridge.

Gray bromobutyl rubber plunger.

Aluminum cap with a gray bromobutyl rubber inner disc.

Cartridge support (PVC/Aluminum blister).

Package containing 1 cartridge of 1.7 ml.

Package containing 50 cartridges of 1.7 ml.

Package containing 100 cartridges of 1.7 ml.

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

LABORATORIOS NORMON, S.A.

Ronda de Valdecarrizo, 6 - 28760 Tres Cantos - Madrid (SPAIN)

This medication is authorized in the Member States of the European Economic Area under the following names

Portugal Normocain

Bulgaria Normocain

France CHLORHYDRATE D’ARTICAINE NORMON 40mg/ml ADRENALINE 1/200 000, solution injectable

Romania Normocain 40 mg/0.005 mg/ml solutie injectabila

Date of last revision of this leaflet:May 2023

Detailed information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).