4. CLINICAL PARTICULARS

4.1    Therapeutic indications

Local anaesthesia (infiltration and nerve-block anaesthesia) in dentistry. Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) is especially indicated for complicated procedures requiring prolonged anaesthesia.

4.2    Posology and method of administration

The following dosage instructions apply:

The smallest possible volume of solution which will lead to an effective anaesthesia should be used.

For extraction of maxillary teeth, 1.7 ml Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) per tooth suffices in most cases; painful palatal injections can thus be avoided, in the case of serial extractions of neighbouring teeth, a reduction of the injection volume is often possible.

If a cut or suture is required in the palate, a palatal injection of approx 0.1 mi per puncture is indicated.

For smooth extractions of mandibular premolar teeth, infiltration anaesthesia of 1.7 ml Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) per tooth is mostly sufficient; in single cases a buccal re-injection of 1 to 1.7 ml is required. An injection into the mandibular foramen can be indicated in rare cases.

Vestibular injections of 0.5-1.7 ml Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) per tooth enable cavity and crown-stump preparations.

Nerve-block anaesthesia should be used in the treatment of mandibular molar teeth.

In surgical procedures Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) should be dosed individually depending on the extent and duration of the operation and factors relating to the patient.

Generally, in children weighing about 20-30 kg, doses of 0.25-1 mi are sufficient; in children weighing 30-45 kg, 0.5-2 ml.

Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) must not be used with children aged under 4 years (see section 4.3).

Increased plasma levels of Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) can occur in older patients due to diminished metabolic processes and lower distribution volume. The risk of accumulation of Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) is increased in particular after repeated application (e.g. re-injection).

A similar effect can ensue from the reduced general condition of the patient, as well as severely impaired hepatic and renal function (see also section 4.4).

A lower dosage range is thus recommended in all such cases (minimum quantity for sufficient anaesthetic depth).

The dose has to be likewise reduced in patients with certain pre-existing diseases (angina pectoris, arteriosclerosis) (see also section 4.4).

Maximum Recommended Dosage:

Adults:

For healthy adults, the maximum dose is 7 mg/kg body weight articaine (500 mg for a 70 kg patient), equivalent to 12.5 ml Espestesin 4% articaine with 1/100000 adrenaline (epinephrine).

The maximum dose represents 0.175 ml of solution per kg.

Children:

The quantity to be injected should be determined by the age and weight of the child and the magnitude of the operation. Do not exceed the equivalent of 7 mg articaine/kg (0.175 mi Espestesin 4% articaine with 1/100000 adrenaline (epinephrine)/kg) of body weight.

Espestesin 4% articaine with 1/200000 adrenaline (epinephrine) is also available and may be more appropriate for short procedures and/or where control of bleeding in the operative field is not relevant (see section 5.1 for more information on duration of analgesia).

Method of administration

For irijection/oromucosai use

FOR USE IN DENTAL ANAESTHESIA ONLY

To avoid intravascular injection, aspiration control at least in two planes (rotation of the needle by 180°) must always be carefully undertaken, although a negative aspiration result does not safely rule out an unintentional and unnoticed intravascular injection.

The injection rate should not exceed 0.5 ml in 15 seconds, i.e. 1 cartridge per minute.

Major systemic reactions as a result of accidental intravascular injection can be avoided in most cases by an injection technique - after aspiration slow injection of 0.1-0.2 mi and slow application of the rest - not earlier than 20-30 seconds later.

Opened cartridges must not be used in other patients. Residues must be discarded.

4.3    Contraindications

Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) is not allowed to be used in the event of

-    children under 4 years of age

-    hypersensitivity to the active substances, sodium sulphite (E221) or to any of the other excipients

Due to the local anaesthetic ingredient articaine, Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) is not allowed to be used in the event of

-    known allergy or hypersensitivity to local anaesthetics of the amide type

-    severe impairment of the impulse initiation and conduction system of the heart (e.g. grade li and III AV block, pronounced bradycardia)

-    acutely decompensated cardiac insufficiency

-    severe hypotension

-    patients who are known to have a deficiency in plasma cholinesterase activity

-    haemorrhagic diatheses - particularly with nerve-block anaesthesia

-    injection into an inflamed area

Due to the content of epinephrine as a vasoconstrictor admixture, Espestesin 4% articaine with 1/100000adrenaline (epinephrine) is not allowed to be used in the event of

-    Heart diseases such as:

-    unstable angina pectoris

-    recent myocardial infarction

-    recent coronary artery bypass surgery

-    refractory arrhythmias and paroxysmal tachycardia or high-frequency, continuous arrhythmia

-    untreated or uncontrolled severe hypertension

-    untreated or uncontrolled congestive heart failure

-    concomitant treatment with monoamine oxidase (MAO) inhibitors or tricyclic antidepressants (see section 4.5)

Due to the content of sulphite as excipient Espestesin 4% articaine with 1/100000 adrenaline lepinephrine) is not allowed to be used in the event of

-    allergy or hypersensitivity to sulphite

-    severe bronchial asthma

Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) can provoke acute allergic reactions with anaphylactic symptoms (e.g. bronchospasm).

4.4    Special warnings and precautions for use

Espestesin 4% articaine with 1/100000 adrenaline lepinephrine) must he used with particular caution in the event of

-    severe impairment to the renal function

-    angina pectoris (see section 4.2 and 4.3)

-    arteriosclerosis

-    considerably impaired blood coagulation (see section 4.5)

-    thyrotoxicosis

-    narrow-angle glaucoma

-    diabetes mellitus

-    lung diseases - particularly allergic asthma

-    pheochromocytorna

Due to the content of epinephrine as a vasoconstrictor admixture, the following undesirable effects can occur

Cardiovascular disorders

Rare (> 1/10,000 to < 1/1,000}

Heat sensation, sweating, heart racing, migrainelike headache, blood pressure increase, angina pectoris disorders, tachycardias, tachyarrhythmias and cardiovascular arrest and acute oedematous thyroid swelling.

Due to the content of sulphite as excipient the following undesirable effects can occur in very rare cases:

Allergic reactions or hypersensitivity reactions, particularly in bronchial asthmatics, which are manifested as vomiting, diarrhoea, wheezing, acute asthma attack, clouding of consciousness or shock.

Due to the content of both articaine and epinephrine, the following undesirable effects can occur

Nervous system disorders

2 weeks delayed onset of facial nerve paralysis has been described with articairie/epiriephririe, the event still occur 6 months later.

Interferences in the clinical picture can result from the simultaneous occurrence of various complications and side effects.

Within each freguericy grouping, undesirable effects are presented iri order of decreasing seriousness.

4.9 Overdose

Undesirable effects (showing an abnormally high concentration of local anaesthetic iri the blood) may appear either immediately, caused by accideritial intravascular injection or abnormal absorption conditions, e.g. in inflamed or intensive vascularised tissue, or later, caused by true overdose following an injection of excessive guantity of anaesthetic solution, and manifest themselves as central nervous and/or vascular symptoms.

Symptoms caused by the local anaesthetic Ingredient articaine:

Milder central nervous symptoms involve metallic taste, tinnitus, dizziness, nausea, vomiting, restlessness, anxiety, initial increase in respiratory rate. More severe symptoms are drowsiness, confusion, tremor, muscular twitching, tonic-clonic seizures, coma and respiratory paralysis.

Severe cardiovascular episodes are seen iri the form of a drop in blood pressure, cardiac impulse conduction disorders, bradycardia, cardiovascular arrest.

Symptoms caused by epinephrine as a vasoconstrictor:

Cardiovascular symptoms such as heat sensation, sweating, heart racing, migrairielike headache, blood pressure increase, angina pectoris disorders, tachycardias, tachyarrhythmias, cardiovascular arrest arid acute oedematous thyroid swelling.

Interferences in the clinical picture can result from the simultaneous occurrence of various complications arid side effects.

Therapy

If adverse reaction arise the application of the local anaesthetic has to be stopped.

Genera! basic measures:

Diagnostics (respiration, circulation, consciousness), maintenance/ restoration of the vital functions of respiration and circulation, oxygen administration, intravenous access.

Elevation of the upper body, if necessary sublingual nifedipine.

Protect patients from concomitant injuries, if necessary berizodiazepiris (e.g. diazepam iv).

Horizontal position, if necessary intravascular infusion of a whole electrolyte solution, vasopressors (e.g. etilefrine iv).

Atropine iv.

Anaphylactic shock: Contact emergency physician, iri the meantime shock positioning, generous infusion of a whole electrolyte solution, if necessary epinephrine iv, cortisone iv.

Cardiovascular arrest: Immediate cardiopulmonary resuscitation, contact emergency physician.

5. PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: Anaesthetics, local, ATC code N01B B58 Espestesiri 4% articairie with 1/100000 adrenaline (epinephrine) contains articairie which is a local anaesthetic of the amide type for dentistry and leads to a reversible inhibition of the irritability of vegetative, sensory and motor nerve fibres. The blocking of voltage dependent Na⁺ channels ori the membrane of the nerve fibre is supposed to be the mechanism of effect of articairie.

The rapid onset of anaesthesia - latency period of 1-3 minutes - the reliable effect with strong analgesic effect and good local tolerability are characteristic. The duration of effect of Espestesiri 4% articairie with 1/100000 adrenaline (epinephrine) iri pulpal anaesthesia lasts at least 75 minutes, arid in soft-tissue anaesthesia 120 to 240 minutes.

Epinephrine leads locally to vasoconstriction, whereby the absorption of articairie is delayed. The result is a higher concentration of the local anaesthetic at the site of effect over a longer period, as well as the reduction iri the occurrence of systemic adverse side effects.

5.2    Pharmacokinetic properties

Espestesiri 4% articairie with 1/100000 adrenaline (epinephrine) is rapidly and almost completely absorbed.

The maximum plasma level of articairie from iritraoral injection is achieved approximately after 10-15 minutes (T_max).The distribution volume is 1.67 l/kg and the elimination half-life is approximately 20 minutes.

Articaine is bound up to 95% in the serum to plasma proteins.

Articaine is rapidly hydrolysed by plasma cholinesterases to its primary metabolite articairiic acid which is further metabolised to articairiic acid glucuronide. Articairie arid its metabolites are mainly eliminated iri urine. Epinephrine is rapidly catabolized iri the liver and other tissues. The metabolites are excreted renally.

5.3    Preclinical safety data

Symptoms of articairie toxicity were independent of the route of administration (IV, IM, SC arid PO) arid of the animal species and included trembling, vertigo, and tonic and clonic convulsions. The duration and intensity of these symptoms were dose-dependent; at high doses (single dose of approx 50-100 mg/kg) the convulsions resulted in death and at low doses all symptoms dissipated iri 5 to 10 minutes. Lethal doses of articairie resulted iri pulmonary oedema iri mice (IV arid SC) and iri rats (IV, IM, SC and PO).

In rats, rabbits and cats, articaine showed no effect on embryo or fetal development in utero and no skeletal or organ abnormalities. Cups of lactatirig rats receiving articaine iri high doses (80 mg/kg/day) causing maternal toxicity showed delayed eye opening and increased likelihood of failure iri the passive avoidance test.

Epinephrine was potentially teratogenic iri rats albeit at doses 25 times the human therapeutic dose.

Following IVadministration, the presence of 1:100000 epinephrine increased the toxicity of articaine in the rat, mouse, but riot in the rabbit.

6. PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Anhydrous sodium sulphite (E221)

Sodium chloride

Hydrochloric acid 14% (for pH adjustment)

Sodium hydroxide solution 9% (for pH adjustment) Water for injections

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

2 years

6.4    Special precautions for storage

Do not store above 25°C. Store in the original package in order to protect from light.

6.5    Nature and contents of container

Cartridge made of colourless neutral glass I.

Stopper and rubber disc are made of brornobutyl rubber.

Aluminium cap made of aluminium-iron-silicon-alloy.

Tin with 50 cartridges of 1.7 ml each.

6.6    Special precautions for disposal

The product should be inspected visually for particulate matter, discoloration or damage of container prior to administration. The product should not be used if such defects are observed.

The product is for single use only. Any unused product should be discarded immediately after first use.

7.    MARKETING AUTHORISATION HOLDER

3M Deutschland GmbH Carl-Schurz-StraSe 1 41453 Neuss Germany

8.    MARKETING AUTHORISATION NUMBER(S)

PL 40356/0002

9.    DATE OF FIRST AUTHORISATION/RENEWAL OFTHE AUTHORISATION

Date of first authorisation: 17/06/2003 Date of last renewal: 17/07/2006

10.    DATE OF REVISION OFTHE TEXT

August 2012

Pregnancy

if you are pregnant, think you may be pregnant or you are planning on becoming pregnant tell your dentist as Espestesiri 4% articairie with 1/100000 adrenaline (epinephrine) should only be used during pregnancy on the advice of your dentist.

Breast-feeding

Ask your dentist for advice before taking any medicine.

Following anaesthesia with Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) nursing mothers should milk and discard this first milk before resuming breast-feeding.

Driving and using machines

Although Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) should not impair your ability to drive, the dentist should assess you, for your individual safety, after treatment and you should not leave the dental office until at least 30 minutes after the injection.

Important information about some of the ingredients of Espestesin 4% articaine with 1/100000 adrenaline (epinephrine).

Anhydrous sodium sulphite (one of the ingredients of Espestesin 4% articaine with 1/100000 adrenaline (epinephrine)) can cause allergic-type reactions including anaphylactic symptoms and brorichospasm in susceptible people, especially those with a history of asthma or allergy.

The medicinal product contains less than 1 mmol sodium (23 mg) per 1 ml, i.e. essential "sodium-free".

There is a possibility that Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) may show up as positive in routine blood screening tests on athletes.

3.    HOWTO USE ESPESTESIN 4% ARTICAINE WITH 1/100000 ADRENALINE (EPINEPHRINE):

Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) will be administered to you as an injection into your oral cavity by the dentist.

The dentist will choose the dose of Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) that is appropriate for you. Generally treatment with Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) is a single treatment.

if you have any further questions on the use of this product, ask your doctor or pharmacist.

4.    POSSIBLE SIDE EFFECTS

Like all medicines, Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) can cause side effects, although not everybody gets them.

Frequencies of side effects are defined as:

very common (more than 1 out of 10 persons)

common (more than 1 out of 100 persons and less than 1 out of 10 persons)

uncommon (more than 1 out of 1,000 persons and less than 1 out of

100 persons)

rare (more than 1 out of 10,000 persons and less than 1 out of 1,000 persons) very rare (less than 1 out of 10,000 persons, including isolated reports)

Cardiovascular disorders

Rare

Decrease in heart rate, an abnormal heart rate (irregular heart rate, slow heart rate, racing of the heart or fast heart rate), low blood pressure, a tali or rise in blood pressure, cardiac arrest, sensation of heat, sweating, migraine-like headache, tightness of the chest, and swelling of the thyroid.

Nervous system disorders

Rare

Other rare effects that you may experience are metallic taste, ringing in the ears, dizziness, nausea, vomiting, restlessness, anxiety, yawning, shaking, nervousness, tremble of the eyes, compulsive talking, headache, and an increase in your breathing rate. You may also experience a loss of sensation and a burning, tingling feeling of the lip, tongue, or both, if you experience any of the following symptoms inform your dentist/doctor immediately in order to avoid possible worsening of the symptoms: Drowsiness, confusion, tremor, muscle twitching, convulsion, coma and severe breathing difficulties which may result in your breathing stopping.

Allergic reactions

Very rare

Very rare cases of allergic reactions have been reported following administration of Espestesin 4% articaine with 1/100000 adrenaline (epinephrine). You should inform your dentist or doctor immediately if you experience any of the following side effects:

Rash, itching, itchy swelling, and redness of the skin as well as nausea, vomiting, diarrhoea, wheezing, acute asthma attack, effects on consciousness, shock or anaphylaxis.

If you have the condition effecting the blood known as a subcliriical methaemoglobiriaemia you should inform the dentist as the administration of Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) may cause a condition called methaemoglobinaemia.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your dentist or doctor.

5.    HOWTO STORE ESPESTESIN 4% ARTICAINE WITH 1/100000 ADRENALINE (EPINEPHRINE)

Keep out of the reach and sight of children.

Do not use Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) after the expiry date witch is stated on the bottom of the tin and the cartridge after EXP. The expiry date refers to the last day of the month.

Do not store above 25 °C.

Store in the original package in order to protect from light.

The product should be inspected visually for particulate matter, discoloration or damage of container prior to administration. Do not use Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) if such defects are observed.

The product is for single use only. Any unused product should be discarded immediately after first use.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6.    FURTHER INFORMATION

What Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) contains

-    The active substances are Articaine hydrochloride and Epinephrine (adrenaline) (as epinephrine (adrenaline) hydrochloride).

-    1 mi solution contains 40 mg Articaine hydrochloride and 10 micrograms Epinephrine (adrenaline) (as epinephrine (adrenaline) hydrochloride).

-    1 cartridge with 1.7 ml solution for injection contains 68 mg Articaine hydrochloride and 17 micrograms Epinephrine (adrenaline) (as Epinephrine (adrenaline) hydrochloride).

-    The other ingredients are anhydrous sodium sulphite (E221), sodium chloride, and water for injections as well as hydrochloric acid 14% and sodium hydroxide 9% for adjusting the pH-value.

What Espestesin 4% articaine with 1/100000 adrenaline (epinephrine) looks like and contents of the pack

Solution for injection

The solution is a clear, not opalescent, colourless liquid Tin with 50 cartridges of 1.7 ml each

Marketing Authorization Holder

3M Deutschland GmbH Carl-Schurz-StraSe 1 41453 Neuss Germany

Manufacturer:

3M Deutschland GmbH, Cari-Schurz-StraKe 1,41453 Neuss, Germany

This medicinal product is authorised in the Member States of the EEA underthe following names:

Germany:    Espestesin 1/100000 solution for injection

United Kingdom:    Espestesin 4% articaine with 1/100000 adrenaline

(epinephrine), solution for injection

This leaflet was last approved in August 2012