Label: information for the user

Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution

articaína hydrochloride/epinephrine (adrenaline)

Contents of the package and additional information

Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution is 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 Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution or Ultracain with Epinephrine 40 mg/ml + 10 micrograms/ml injectable solution.

Ultracain is indicated for children over 4 years old (around 20 kg of body weight), adolescents, and adults.

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

• Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution is usually used for simple and brief dental procedures.
• Ultracain with Epinephrine 40 mg/ml + 10 micrograms/ml injectable solution is more suitable for longer procedures or those with significant bleeding.

Do not use Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution if you suffer from any of the following conditions:

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

Warnings and precautions

Consult your dentist before starting to use Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution if you suffer from any of the following conditions:

• severe heart rhythm disorders (e.g., second- and third-degree AV block).
• acute heart failure (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 3-6 months.
• coronary revascularization graft in the last 3 months.
• you are taking blood pressure medications called 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 of Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution with other medications").
• very high blood pressure.
• you are taking antidepressants and Parkinson's disease medications (tricyclic antidepressants) simultaneously. These medications can intensify the effects of adrenaline.
• epilepsy.
• deficiency of a natural chemical substance called plasma cholinesterase in the blood.
• renal 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 antiplatelet or anticoagulant medications to prevent the narrowing or hardening of blood vessels in arms and legs.
• if you are over 70 years 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.
• inflammation or infection of the area where you will receive the injection.
• reduced oxygen levels in the body tissues (hypoxia), high potassium levels in the blood (hyperkalemia), and metabolic disorders resulting from excessive acid in the blood (metabolic acidosis).

Use of Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution with 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 sensitivity (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 amitriptiline, desipramine, imipramine, nortriptiline, maprotiline, and protriptiline).
• 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).
• 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, this should be postponed.
• Neuroleptic medications (e.g., phenothiazines).

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

Avoid eating, even chewing gum, until you have recovered normal sensitivity. 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 plan to become pregnant, consult your dentist or doctor before using this medication.

Your dentist or doctor will decide if you can take Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution during pregnancy.

Breastfeeding can be resumed 5 hours 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 30 minutes after the dental procedure).

Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution contains sodium and sodium metabisulfite.

• This medication contains less than 23 mg of sodium (1 mmol) per cartridge, which is essentially "sodium-free".
• This medication may cause severe allergic reactions and bronchospasm (sudden feeling of suffocation) due to the presence of sodium metabisulfite.

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

Only doctors and dentists are trained to use Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution.

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

The lowest effective dose should be used.

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

If you use more Ultracain with Epinephrine 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, tell your dentist. Symptoms of overdose include acute weakness, pale skin, 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).

If you have any other questions about the use of this medication, ask your dentist.

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 of Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution

Inform your dentist, doctor, or pharmacistimmediatelyif you experience any of the following severe 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 of eyelid drooping and pupil constriction (Horner's syndrome).

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

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

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

• Gingival inflammation
• Neuropathic pain: pain due to nerve damage
• Numbness or decreased sensation within 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 fast heartbeats
• Abnormally slow heartbeats
• Low blood pressure
• Swelling of the tongue, lips, and gums

Infrequent 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 at the 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
• Eye lid drooping and pupil constriction (Horner's syndrome)
• Enophthalmia (sinking of the eyeball into the orbit)
• Tinnitus, increased sensitivity of the ear
• Palpitations
• Flushes
• Sibilant sounds (bronchospasm, wheezing, whistling in bronchi), asthma
• Difficulty breathing
• Exfoliation and ulceration of the gums
• Exfoliation at 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
• Thirsty mouth syndrome
• Redness of the skin (erythema)
• Abnormal increase in sweating
• Worsening of neuromuscular symptoms of Kearns-Sayre syndrome
• Sensation of heat or cold
• Masseter muscle 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 not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: 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.

Store below25°C.

Do not freeze.

Store the cartridges in the outer packaging hermetically sealed to protect it 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 down the 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 of Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution

The active principles are articaine hydrochloride and adrenaline base.

• The other components are: sodium metabisulphite (E-223), sodium chloride, hydrochloric acid 0.1 N and water for injectable preparations.

Appearance of the product and contents of the package

Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution is colorless

It is packaged in single-use glass cartridges, sealed at the base with a movable rubber bung and at the top with a rubber seal held by an aluminum cap.

Package containing one cartridge and a leaflet.

Package containing 100 cartridges (clinical package) in 10 PVC blister packs with 10 cartridges each and a leaflet.

Other presentations:

Ultracain with Epinephrine 40 mg/ml + 10 micrograms/ml injectable solution.

Holder of the marketing authorization and responsible for manufacturing

LABORATORIOS NORMON, S.A.

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

Date of the last review of this leaflet:February 2020.

Other sources of information

The 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.

This information is intended solely for healthcare professionals:

Dosage

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

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

For most routine dental procedures, it is preferable to use Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution.

For more complex procedures, such as pronounced hemostasis, it is preferable to use Ultracain with Epinephrine 40 mg/ml + 10 micrograms/ml injectable solution.

Concomitant use of sedatives to reduce patient anxiety:

The maximum safe dose of 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 articaine is 7 mg/kg, with a maximum absolute dose of articaine of 500 mg. The maximum dose of articaine of 500 mg corresponds to a healthy adult of more than 70 kg of body weight.

Children (between 4 and 11 years of age)

The safety of Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution has not been established in children under 4 years of age. There are no available data.

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

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 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 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 a resuscitation team and appropriate medication are available to apply immediate treatment for any emergency respiratory or cardiovascular situation. The patient's level of consciousness should be monitored after each injection of local anesthesia.

When using Ultracain with Epinephrine 40 mg/ml + 5 micrograms/ml injectable solution for 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 very 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 articaine 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 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 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 articaine and the presence of adrenaline, as it may reduce perineural blood flow and prevent local elimination of articaine.

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 situation.

Depending on the severity of the symptoms of overdose, 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 occur, the injection of local anesthetic should be stopped immediately. If necessary, the patient should be placed in a supine position.

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

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 receive 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 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 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.