SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Scandonest 2% Special

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Mepivacaine hydrochloride 2%

Adrenaline base 1/100,000.

3    PHARMACEUTICAL FORM

Solution for injection

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Local anaesthesia in the dental practice

4.2    Posology and method of administration

Route of administration:

Infiltration or nerve block injection.

Posology:

Adults:

1 cartridge for routine work.

Do not exceed 3 cartridges.

Pediatric population:

Children from 4 years of age (ca. 20 kg body weight) and older (see 4.3) Recommended therapeutic dose:

The quantity to be injected should be determined by the age and weight of the child and the magnitude of the operation. The average dosage is 0.75 mg/kg = 0.0375 ml of mepivacaine solution per kg body weight.

Maximum recommended dosage:

Do not exceed the equivalent of 3 mg mepivacaine/kg (0.15 ml mepivacaine/kg) of body weight.

4.3 Contraindications

SCANDONEST 2% SPECIAL is not to be used:

■    In children below 4 years of age (ca. 20kg body weight)

■    In patients presenting specific allergies to amide-type anaesthetics, or to any components of the injectable formulation.

SCANDONEST 2% SPECIAL, due to the presence of a vasoconstrictor (adrenaline) in the formula, is also contraindicated for patients:

■    suffering from arterial hypertension,

■    suffering from cardiovascular disease,

■    if they are under MAOI treatment,

■    under tricyclic antidepressant treatment,

■    presenting any coronary disease,

■    suffering from any valvular affection (usually following infectious rheumatism), which constitutes a special risk.

4.4 Special warnings and precautions for use

Warnings

Dental practitioners who employ local anaesthetic agents should be well versed in diagnosis and management of emergencies which may arise from their use. Resuscitative equipment, oxygen and other resuscitative drugs should be available for immediate use.

Do not inject into a blood vessel inject slowly:

• to minimise the likelihood of intravascular injection, aspiration should be performed before the local anaesthetic solution is injected. If blood is aspirated, the needle must be repositioned until no return of blood can be elicited by aspiration. Note, however, that the absence of blood in the syringe does not assure that intravascular injection will be avoided and a double aspiration is always recommended.

Local anaesthetic procedures should be used with caution when there is inflammation and/or sepsis in the region of the proposed injection.

Scandonest 2% Special containing a vasoconstrictor should not be injected repeatedly at the same site because reduced blood flow and increased oxygen consumption in the affected tissues may cause tissue anoxia, delay healing, oedema or necrosis at the injection site.

Use of the cartridges:

Use on one patient during one session of treatment only. If only part is used, the remainder must be discarded.

Precautions

General:

The safety and effectiveness of mepivacaine depend on proper dosage, correct technique, adequate precautions and readiness for emergencies. Resuscitative equipment, oxygen and other resuscitative drugs should be available for immediate use.

The lowest dosage that results in effective anaesthesia should be used to avoid high plasma levels and serious adverse effects. Repeated doses of mepivacaine may cause significant increases in blood levels with each repeat dose due to slow accumulation of the drug or its metabolites. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients, acutely ill patients, and children should be given reduced doses commensurate with their age and physical condition. (See Posology and Method of Administration):

•    Patients with peripheral vascular disease may exhibit exaggerated vasoconstrictor response.

•    Cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient’s state of consciousness should be monitored after each local anaesthetic injection.

•    Restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression or drowsiness should alert the practitioner to the possibility of central nervous system toxicity.

•    Signs and symptoms of depressed cardiovascular function may commonly result from a vasovagal reaction, particularly if the patient is in an upright position.

Mepivacaine should be used with caution in:

•    Patients with hepatic disease, since amide-type local anaesthetics are metabolised by the liver. Patients with severe hepatic disease, because of their inability to metabolise local anaesthetics normally, are at greater risk of developing toxic plasma concentration,

•    Patients with renal disease, since local anaesthetics are excreted by the kidneys, and the patient due to his condition is also at a greater risk of developing toxic plasma concentrations.

The use of mepivacaine should be carefully considered if:

•    there is inflammation and/or sepsis in the region of injection, since this may alter the pH at the site of injection, resulting in decrease or loss of anaesthetic effect,

•    there is a history of severe disturbances of cardiac rhythm or heart block, since the cardiac depressant effects of the anaesthetic are detrimental to the patient.

•    Scandonest 2% Special should be administered with caution to subjects with epilepsy and impaired respiratory function.

4.5 Interaction with other medicinal products and other forms of interaction

Interaction with other medicaments

•    As in the case of all other anaesthetic solutions containing adrenaline, the administration of SCANDONEST 2 % SPECIAL in patients receiving phenothiazines may produce severe prolonged hypotension or hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential.

•    Concurrent administration of vasopressor drugs and ergot-type oxytoxic drugs may cause severe, persistent hypertension or cerebrovascular accidents.

•    If sedatives are employed to reduce patient apprehension, reduced doses of anaesthetic solution should be used since local anaesthetic agents, like sedatives, are central nervous system depressants which in combination may have an additive effect.

•    Concurrent use of beta-adrenergic blocking agents with an anaesthetic solution containing a vasoconstrictor, may result in dose-dependent hypertension and bradycardia.

•    Serious cardiac arrhythmias may occur if preparations containing a vasoconstrictor are employed in patients during or following the administration of chloroform, halothane, cyclopropane, trichloroethylene or other related agents.

•    Monoamine oxydase inhibitors (MAOI) and tricyclic antidepressants may increase the cardiovascular effects of adrenaline (produce severe prolonged hypertension).

4.6    Pregnancy and lactation

Pregnancy

On the basis of long usage, anaesthetics of the mepivacaine type are considered to be reasonably safe for use on pregnant women.

Retrospective studies of pregnant women receiving local anaesthetics for emergency surgery early in pregnancy have not shown that local anaesthetics cause birth defects.

However, no controlled studies have been carried out in pregnant women. Moreover, no animal reproduction studies have been performed with mepivacaine. Therefore, caution should be taken before administering this anaesthetic during early pregnancy.

Nursing mothers

It is not known whether local anaesthetics are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when mepivacaine is administered to a nursing woman.

4.7    Effects on ability to drive and use machines

None stated

4.8    Undesirable effects

Adverse experiences following the administration of mepivacaine are similar in nature to those observed with other amide local anaesthetic agents. These adverse experiences are, in general, dose-related and may result from high plasma levels caused by excessive dosage, rapid absorption or unintended intra-vascular injection, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient. Serious adverse experiences are generally systemic in nature. The following types are those most commonly reported:

Central Nervous System

CNS manifestations are excitatory and/or depressant and may be characterised by lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest The excitatory manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory arrest

Drowsiness following the administration of mepivacaine is usually an early sign of a high blood level of the drug and may occur as a consequence of rapid absorption.

Cardiovascular system

Cardiovascular manifestations are usually depressant and are characterised by bradycardia, hypotension and cardiovascular collapse, which may lead to cardiac arrest.

Signs and symptoms of depressed cardiovascular function may commonly result from a vasovagal reaction, particularly if the patient is in an upright position. Less commonly, they may result from a direct effect of the drug. Failure to recognise the premonitory signs such as sweating, a feeling of faintness, changes in pulse or sensorium may result in progressive cerebral hypoxia and seizure or serious cardiovascular catastrophe. Management consists of placing the patient in the recumbent position and ventilation with oxygen. Supportive treatment of circulatory depression may require the administration of intravenous fluids, and when appropriate, a vasopressor as directed by the clinical situation.

Allergic reactions

Allergic reactions are characterised by cutaneous lesions, urticaria, oedema or anaphylactoid reactions. Allergic reactions as a result of sensitivity to mepivacaine are extremely rare and, if they occur, should be managed by conventional means. The detection of sensitivity by skin testing is of doubtful value.

Due to adrenaline

The clinical manifestations relate to CNS stimulation and include increasing fear and anxiety, tension, restlessness, throbbing headache, tremor, weakness, dizziness, pallor, respiratory difficult, and palpitation.

With increasing levels of adrenaline in the blood, cardiac dysrhythmias become more common; ventricular fibrillation is a rare but possible consequence. Dramatic increases in both systolic and diastolic pressures may be noted, which have led to cerebral haemorrhage. Anginal episodes may be precipitated in patients with coronary insufficiency. Because of the rapid inactivation of adrenaline, the stimulatory phase of the overdose reaction is usually very brief.

Allergic-type reactions may occur an patients with bronchial asthma due to hypersensitivity to the sulphites component and may be manifested by dermatological reactions, oedema, urticaria and other allergy symptoms (anaphylactic reactions and bronchospasm).

4.9 Overdose

Acute emergencies from local anaesthetics are generally related to high plasma levels encountered during therapeutic use of excessive dosage of local anaesthetics, or to unintended intravascular injection of local anaesthetic solution. (See adverse effects, special warnings and precautions for use).

Management of local anaesthetic emergencies:

The first consideration is prevention, best accomplished by careful and constant monitoring of cardiovascular and respiratory vital signs and the patient’s state of consciousness after each local anaesthetic injection. At the first sign of change, oxygen should be administered.

The first step in the management of convulsions consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation with oxygen and a delivery system capable of permitting immediate positive airway pressure by mask.

Immediately after institution of these ventilatory measures, the adequacy of the circulation should be evaluated, keeping in mind that drugs used to treat convulsions sometimes depress the circulation when administered intravenously. Should convulsions persist despite adequate respiratory support, and if the status of the circulation permits, small increments of an ultra-short acting barbiturate (such as thiopental or thiamylal) or a benzodiazepine (such as diazepam) may be administered intravenously. The clinician should be familiar, prior to use of local anaesthetics, with these anticonvulsant drugs. Supportive treatment of circulation depression may require administration of intravenous fluids and, when appropriate, a vasopressor as directed by the clinical situation (e.g., ephedrine).

If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia, acidosis, bradycardia, arrhythmias and cardiac arrest. If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted.

Endotracheal intubation, employing drugs and techniques familiar to the clinician, may be indicated, after initial administration of oxygen by mask, if difficulty is encountered in the maintenance of a patent airway or if prolonged ventilatory support (assisted or controlled) is indicated.

Dialysis is of negligible value in the treatment of acute overdosage with mepivacaine.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Local anaesthetic - ATC code: N01BB53

Mepivacaine stabilises the neuronal membrane and prevents the initiation and transmission of nerve impulses, thereby effecting local anaesthesia.

Mepivacaine has a slight intrinsic vasoconstrictive action permitting its use alone for an anaesthesia of a relatively short duration.

In the Scandonest 2% Special solution, adrenaline is included with the anaesthetic in order to achieve a deeper and more prolonged anaesthesia:

•    By localising the solution at the site of the injection, this vasoconstrictor intensifies and prolongs the anaesthetic effect and decreases the rate at which the anaesthetic drug enters the systemic circulation.

•    The presence of a vasoconstrictor also decreases surgical haemorrhage in the immediate area of injection.

Onset and duration of anaesthesia:

The onset of action is rapid, 30 to 120 seconds in the upper jaw: 1 to 4 minutes in the lower jaw. SCANDONEST 2% SPECIAL will ordinarily provide an operating anaesthesia of 1 to 2 hours in the upper jaw and 2 to 4 hours in the lower jaw.

5.2    Pharmacokinetic properties

Information derived from diverse formulations, concentrations and usages reveals that systemic absorption of mepivacaine is complete following parenteral administration, its rate of absorption depending upon various factors, such as the site of injection and the presence or absence of a vasoconstrictor agent.

Mepivacaine, because of its amide structure, is not detoxified by the circulating plasma esterases. Mepivacaine is rapidly metabolised. The liver is the principal site of metabolism, with over 50 per cent of the administered dose being excreted into the bile as metabolites. Most of the metabolised mepivacaine is probably absorbed in the intestine and then excreted into the urine, since only a small percentage is found in the faeces. The principal route of excretion is via the kidneys. Most of the anaesthetic and its metabolites are eliminated within 30 hours.

A percentage of up to 16 per cent of the dose administered is excreted unchanged in the urine.

It has been shown that hydroxylation and N-demethylation, which are detoxification reactions, play important roles in the metabolism of the anaesthetic. These metabolites of mepivacaine have been identified from adult humans: two phenols, which are excreted almost exclusively as their glucuronide conjugates, and the N demethylated compound (2’, 6’-pipecoloxylidide).

5.3    Preclinical safety data

Not applicable

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Sodium chloride, potassium metabisulphite, sodium edetate, hydrochloric acid, sodium hydroxide, water for injection.

6.2    Incompatibilities

None stated

6.3    Shelf life

2 years

6.4    Special precautions for storage

The product should be stored in a dry place below 25°C (77°F).

To protect from light and to aid stability, each time cartridges are taken, remember to replace the blister into the carton and to close this latter.

6.5    Nature and contents of container

-    Glass cartridges with rubber closures.

-    50 dental cartridges of 1.8 ml or 2.2 ml in blister packs grouped in a cardboard box.

6.6    Special precautions for disposal

See Special Warnings and precautions for Use

7    MARKETING AUTHORISATION HOLDER

Septodont UK Ltd.

Units R & S Orchard Business Centre,

St Barnabas Close,

Allington, Maidstone Kent ME16 0JZ England

8    MARKETING AUTHORISATION NUMBER

PL 08313/0026

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10/12/1987 / 28/11/2003

16/05/2013