Document: Scandonest solution for injection ENG SmPC change

• Scandonest solution for injection SmPC
• Scandonest solution for injection ENG SmPC

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Summary of Product Characteristics

Scandonest30 mg/ml, solution for injection

1 ml solution for injection contains 30 mg mepivacaine hydrochloride.

Excipients with known effect: 6 mg/ml of sodium chloride, sodium hydroxide (for pH-adjustment).

For the full list of excipients, see section 6.1.

Solution for injection.

Clear and colourless solution.

Local anaesthesia (infiltration and nerve-block anaesthesia) in dentistry during minor procedures.

Posology

The smallest volume of solution which will lead to an effective anaesthesia should be used. The dosage should be tailored to the age, weight and general condition of the individual patient.

The recommended doses as well as the maximum doses not to be exceeded for adults and children are gathered in the following table:

		ADULTS	CHILDREN
			20 kg child	40 kg child
Recommended therapeutic dose	in cartridge of 1.8 ml	1 cartridge	~¼ cartridge	~½ cartridge
	in mg of mepivacaine hydrochloride	54 mg	15 mg	30 mg
Maximum recommended dosage	in cartridge of 1.8 ml	5.5 cartridges	~1cartridge	~2cartridges
	in mg of mepivacaine hydrochloride	300 mg	60 mg	120 mg

The dose should be minimised for patients with liver and kidney disease. See section 5.2.

Paediatric population

Children from 4 years of age (ca.20kg body weight) and older (see section 4.3.)

Recommended therapeutic dose:

The quantity to be injected should be administrated by the age and weight of the child and the magnitude of the operation. The average dosage is 0,75mg/kg=0.025ml of mepivacaine solution per kg body weight.

Maximum recommended dosage:

Do not exceed the equivalent of 3 mg mepivacaine/kg (0,1ml mepivacaine/kg) of body weight.

Method of administration

Local injection (block or infiltration).

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 1 ml 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 ml and slow application of the rest – not earlier than 30 seconds to 1 minute after.

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

- Hypersensitivity to local anaesthetics of the amide type.

- Patients with severe disorders of atrioventicular conduction not compensated by pace maker

- Epilepsy not controlled by any treatment

- Intermittent acute porphyria.

- Children below 4 years of age (ca.20kg body weight).

Warnings

The patient should be made aware of the fact that the anaesthesia can increase the risk of damage to lips, tongue, and to the mucous membrane or soft palate. Intake of food should be avoided until the anaesthesia has worn off.

Injection of local anaesthetics must be avoided in infected areas.

Athletes should be warned that this medicinal product contains an active substance likely to induce a positive reaction to tests undertaken in anti doping controls.

This product contains less than 1 mmol sodium (23 mg) per cartridge, i.e. it is considered as essentially “sodium free‟.

Precautions for use

Dental local anaesthetics contain high concentrations of active substance. This means that rapid injection under high pressure can lead to complications even after administration of small volumes (see section 4.9). The risk is especially high in the event of inadvertent intravascular injection, since the injected drug may transfer in a retrograde manner. Intra-arterial injection in the head and neck region results in higher concentrations of the drug reaching the brain than in the case of intravenous injection. Careful aspiration prior to injection is recommended to reduce the risk of intravascular injection.

In the case of intraneural injection, there is a risk that, owing to the high pressure, the drug may transfer in a retrograde manner along the nerve. In order to avoid intraneural injection, and to prevent nerve damage in connection with nerve blocks, the needle should always be withdrawn slightly if paraesthesia occurs during injection.

Care should be taken in patients with second- or third-degree AV heart block, since local anaesthetics can depress myocardial conduction. Special vigilance is also required in the elderly and in patients with severe or untreated hypertension, severe heart disease, severe anaemia, severe liver disease, severely impaired renal function, circulatory insufficiency or whose general condition is impaired.

Mepivacaine use requires:

• Consultation to assess medical history and ongoing concomitant medications

• To perform a test injection of 5 to 10% of the dose in case of allergic risk

• To perform the injection slowly with careful repetitive aspiration to avoid inadvertent intravascular injection

• To talk to the patient

• To have at disposal the appropriate resuscitating equipment (in particular a source of oxygen) as well as anti-convulsant medicines (benzodiazepines or barbiturates) myorelaxants, atropine and vasopressors or adrenaline for a severe allergic or anaphylactic reaction

Monitoring should be increased in patients with blood coagulation disorders or under anticoagulants (monitoring of the INR).

Care must be exercised when co-administering mepivacaine with drugs that are similar in structure to local anaesthetics (i.e. class IB antiarrhythmic drugs), since the toxic effects are additive.

Long or permanent treatment with antiarrhythmic drugs, psychopharmaceuticals, or anticonvulsant drugs, and alcohol consumption, could reduce sensitivity to anaesthetics. Increase the anaesthetic dose should be enough or just wait longer for the effect, before the intervention.

Special dosage attention should be taken, with a simultaneous use of CNS depressors, which could cause additive effects.

Local anaesthetics might release heavy metal ions from some type of disinfectant solutions. Before the anaesthetic administration, special measures should be taken when these types of disinfectants are used. These released ions could cause local irritation, swelling and oedema.

Heparin, nonsteroidal anti-inflammatory drugs or plasma substitutes (dextrane) administration could increase bleeding tendency after local anaesthetic injection.

Pregnancy

Data on a limited number of exposed pregnancies indicate no adverse effects of mepivacaine on pregnancy or on the health of the foetus/ new-born child. To date, no other relevant epidemiological data are available. The potential risk for humans is unknown.

Breastfeeding

Mepivacaine is excreted in breast milk. However, at therapeutic doses of Scandonest no effects on the suckling child are anticipated. Scandonest can be used during breast- feeding.

Scandonest has minor influence on the ability to drive and use machines.

Adverse effects, strictly attributed to the local anaesthetic, occur in less than 1/1000 patients treated with local anaesthetics. However, physiological effects from nerve block are common, but these vary markedly depending on what type of block is administered. The effects of relative overdose (e.g. in connection with inadvertent intravascular injection) or absolute overdose can be serious and must be taken into consideration (see also section 4.9).

Rare (<1/1000)

Nervous system disorders.: Unconsciousness and seizures (in the event of absolute or relative overdose) Neurological effects (e.g. sensation of numbness, residual paraesthesia and other sensory disturbances) have been observed. It has not been established for certain to what extent these symptoms are dependent on technical factors (e.g. intraneural injection) or on the anaesthetic. Cardiac disorders: Myocardial depression and cardiac arrest (in patients with absolute or relative overdose). Immune system disorders: Allergic reactions (rash; erythema; pruritus; oedema of tongue, mouth, lips, or throat; urticaria, angiooedema) and, in the most serious cases, anaphylactic shock. Methaemoglobinemia.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in

[To be completed nationally]

Toxicity:

Undesirable toxic effects may appear with 5-6 mg/l or higher plasma levels, and convulsions could appear with 10 mg/l or higher. These excessive plasma levels could be caused by accidental intravascular injection or due to abnormal patient’s condition.

Limited experience of overdose. Intravenous administration of 300 mg to an 8-year old (approx. 25 kg) gave rise to seizures.

Symptoms:

Relative overdose occurs if a local anaesthetic is inadvertently injected intravascularly (for example if a small artery in the upper half of the body is accidentally punctured and the compound reaches the brain via injection in a retrograde direction). CNS symptoms will occur in such a case, possibly accompanied by seizures, even after a dose that would otherwise not be regarded as toxic. Absolute overdose is characterised principally by the occurrence of central-nervous-system and cardiovascular adverse effects.

CNS toxicity occurs gradually, with symptoms and reactions of progressively increasing severity. Initially, symptoms include agitation, a feeling of intoxication, a sensation of numbness in the lips and tongue, paraesthesias around the mouth, dizziness, vision and hearing disturbances, and buzzing in the ears. If these effects are observed while the injection is in progress, they are a warning signal and the injection should be stopped immediately. Articulatory difficulties, muscle stiffness and twitching are more serious symptoms and precede generalised seizures. These symptoms must not be misinterpreted as neurotic behaviour. Unconsciousness and grand mal seizures may follow and persist for a few seconds up to several minutes. Oxygen deficit and hypercapnia occur rapidly during the seizures owing to increased muscle activity and insufficient ventilation. Respiratory arrest may even occur in severe cases. Acidosis exacerbates the toxic effects of local anaesthetics.

Recovery is dependent on metabolism of the local anaesthetic and distribution away from the central nervous system. This occurs rapidly providing very large amounts of the drug are not injected.

In general, cardiovascular effects imply a more serious situation. A fall in blood pressure, bradycardia, arrhythmia and cardiac arrest can occur as a result of high systemic concentrations of local anaesthetics. These effects are usually preceded by signs of CNS toxicity unless the patient has received general anaesthesia or is heavily sedated with such compounds as benzodiazepines or barbiturates. It should be noted, however, that central blocks themselves often give rise to a sympathetic block, resulting in a fall in blood pressure and, possibly, bradycardia.

Treatment:

If signs of acute systemic toxicity appear, administration of local anaesthetics should be stopped immediately. Treatment must aim to quickly stop the seizures and also to maintain good oxygenation and circulation. Oxygen is always given, together with controlled ventilation (if required). Diazepam is given in the event of seizures. Patients with asystole are given cardiac massage. It is also important that acidosis should be treated, if present.

Pharmacotherapeutic group: Nervous System / Local Anaesthetics / Anaesthetics, local / Amides Local

ATC code: N01BB03

Scandonest contains mepivacaine, which is an amide local anaesthetic. Mepivacaine reversibly blocks nerve impulses owing to its effects on ionic transport across the cell membrane. Mepivacaine has a rapid onset, high frequency of anesthesia and low toxicity. When peripheral nerve block is performed, mepivacaine’s effect occurswithin 2-4 minutes. The duration of effect is determined by the degree of vascularity and diffusion to the blood vessels.

Scandonest produces rapid anaesthesia which lasts 20-30 minutes when administered by infiltrationand 1-2 hours in the case of conduction anaesthesia. Owing to the lack of vasoconstriction, it is possible to keep the pH of the solution close to neutral.

The absorption of local anaesthetics is dependent on physico-chemical properties (e.g. lipid solubility), pharmacological properties (e.g. the vasodilating effect) and also on the vascularity of the injection site.

The bioavailability is 100% at the action site.

The maximum plasma level of mepivacaine is achieved approximately after 30- 60 minutes.

The plasma protein binding of mepivacaine is 60-78% (principally with alpha-glycoprotein acid).

Mepivacaine distribution covers all body tissues. Liver, lungs, heart and brain achieves maximum mepivacaine levels. Mepivacaine cross placental barrier by simple diffusion. Relation maternal: fetal plasma levels is 0.4-0.8.

The plasma half-life is 2-3 hours for adults and 9 hours for newborns. Clearance of amides is dependent on hepatic blood flow. The plasma half-life is prolonged if the patient is suffering from liver disease and/or uraemia.

Metabolism principally occurs through oxidation in the liver. The metabolites are principally eliminated via the bile and 99% are glucuronidated. The metabolites are then reabsorbed and eliminated via the urine. The pH of the urine influences the elimination of the metabolites.

In adults, only 3–5% of the mepivacaine is eliminated in an unchanged form and in newborns, approx. 40%.

Studies performed in animals showed that mepivacaine was well tolerated.

Mutagenicity studies showed that mepivacaine is devoid of mutagenic effect in a reverse mutation assay in bacteria (Ames test) and in the micronucleus test in mouse.

As for any other amide type local anaesthetic, the active substance, in high doses, may induce toxic reactions on the central nervous and the cardiovascular systems (see section 4.8. Undesirable effects).

Sodium chloride,

Sodium hydroxide(for pH-adjustment),

Water for injections.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

3 years.

Do not store above 25°C.

Glass cartridges of 1.8 ml, sealed with rubber stoppers.

Pack size: 50 x 1.8 ml

The cartridges are intended for single use.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

[To be completed nationally]

[To be completed nationally]

1999-11-19/ 2009-11-19

2015-02-18