Summary of Product Characteristics (SmPC) - Anestadent 4% w/v and 1:100 000 solution for injection
1 NAME OF THE MEDICINAL PRODUCT
Anestadent 4% w/v and 1:100,000 solution for injection
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Articaine hydrochloride……………………...40.00 mg/mL
Adrenaline tartrate
Quantity corresponding to adrenaline………..0.01 mg/mL
Excipient(s) with known effect:
Sodium metabisulphite (E223)……………….0.5 mg/mL
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Solution for injection for dental use.
Sterile, clear and colourless solution for injection with a pH between 2.7 – 4.5 and osmolality of aproximately 267 mOsm/kg.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Local or local-regional anesthesia in dentistry and dental surgical procedures in patients at least 4 years old.
4.2 Posology and method of administration
Posology
The smallest possible volume of solution which will lead to an effective anaesthesia should be used.
Adults
The quantity to be injected will be adjusted as a function of the extent of the intervention.
As a general rule, one to three cartridges per session.
The dose should not exceed 7 mg of articaine hydrochloride per kilogram of body weight. Paediatric population
Articaine hydrochloride/Epinephrine NewLine Pharma should not be used in children aged below 4 years because of safety and efficacy concerns.
The quantity to be injected depends on the age and the weight of the child as well as the type of intervention to be performed.
The maximum dose is 5 mg of articaine hydrochloride (0.125 mL of anaesthetic solution) per kilogram of body weight.
The average dose in mg of articaine hydrochloride that can be administered in children can be calculated as follows:
Weight of the child (in kilograms) x 1.33
Elderly
Reduce to one-half the dose used for adults.
Method of administration
Local or regional intraoral submucosal injection.
The injection rate must not exceed 1 mL of solution per minute
4.3 Contraindications
This medicinal product is contraindicated in the following situations:
- Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1
- Known allergy or hypersensitivity to other local anaesthetics of the amide type
4.4 Special warnings and precautions for use
Special warnings
This product contains 0.01 mg/mL of adrenaline (epinephrine).
Be aware of a risk of local necrosis in hypertensive or diabetic subjects.
Risk of self-biting under anesthesia: various bite wounds (lips, cheeks, mucosa, and tongue); warn the patient to avoid chewing gum or food for as long as the insensitivity persists.
Precautions for use
This medicinal product should be used with caution in cases of:
- severe alterations of renal and hepatic functions;
- angina pectoris;
- arteriosclerosis (vessel calcification);
- blood coagulation disturbances (e.g. in patients receiving anticoagulants);
- patients with cholinesterase deficiency, as a prolonged and possibly pronounced drug effect can be expected;
- epilepsy.
Due to the presence of adrenaline, precautions and monitoring should be increased in the case of:
- rhythm disorders, except bradycardia;
- severe cardiovascular diseases such as unstable angina, recent myocardial infarction, recent coronary artery bypass surgery, coronary heart disease, congestive heart failure;
- severe arterial hypertension;
- uncontrolled or poorly controlled hypertension;
- hyperthyroidism;
- diabetes mellitus.
In the case of serious liver failure, it may be necessary to reduce the doses of articaine due to the principally hepatic metabolism of local anesthetics with amide function.
This medicinal product contains less than 1 mmol sodium (23 mg) per cartridge, i.e. essentially ‘sodium- free’.
Due to the presence of sodium metabisulphite, it may rarely cause severe hypersensitivity reactions and bronchospasm.
Overdose of the medicinal product should be avoided and two maximal doses of the drug should be administered with a minimum interval of 24 hours.
Although nerve injuries may be rare (see section 4.8), usual precautions for nerve-block anaesthesia should be observed.
Food intake should only commence after the anaesthetic effect has worn off.
4.5 Interaction with other medicinal products and other forms of interaction
Combinations requiring precautions for use
Due to the presence of adrenaline:
Halogenated volatile anesthetics:
Serious ventricular rhythm disorders (increase of cardiac reactivity).
Tricyclic antidepressants (imipramine):
Paroxysmal hypertension with the possibility of rhythm disorders (inhibition of adrenaline uptake into sympathetic fibers).
SNRI’s antidepressants (minalcipran, venlafaxine):
Paroxysmal hypertension with possibility of rhythm disorders (inhibition of adrenaline uptake into sympathetic fibers).
Nonselective MAOIs (iproniazide):
Increase in the hypertensive effect of adrenaline, most often moderate.
For use only with strict medical supervision
Selective MAOIs (moclobemide, toloxatone) by extrapolation from non-selective MAOIs:
Risk of increased hypertensive effect.
For use only with strict medical supervision.
Non-selective betablockers:
The hypertensive effects of adrenaline can be markedly increased in patients taking non-selective beta blockers. There is also an increased risk of bradycardia.
Guanethidine and related medicinal products (antiglaucoma agents):
Significant increase in blood pressure (hyper-reactivity linked to sympathetic tone reduction and/or inhibition of adrenaline uptake into sympathetic fibers).
If the combination cannot be avoided, use smaller doses of sympathomimetics (adrenaline) with precaution.
4.6 Fertility, Pregnancy and lactation
Pregnancy
There are a limited amount of data from the use of articaine in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).
There are a limited amount of data from the use of adrenalin in pregnant women. Animal studies have shown reproductive toxicity at supratherapeutic doses (see section 5.3).
Articaine hydrochloride/Epinephrine NewLine Pharma may not be used during pregnancy, unless strictly necessary.
Breastfeeding
It is unknown if articaine and adrenaline are excreted in breastmilk. However, at therapeutic doses of Articaine hydrochloride/Epinephrine NewLine Pharma exposure to the infant receiving breastfeeding is expected to be very low. Articaine hydrochloride/Epinephrine NewLine Pharma can be used during breastfeeding.
Fertility
There are no available data on the effect of articaine or adrenaline on human fertility
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed.
The dentist will evaluate after surgery, the patient ability to drive and use machines.
4.8 Undesirable effects
Undesirable effects may result from overdose, due in particular to accidental intravascular injection or in cases of abnormal absorption, such as in inflamed or highly vascularised tissues.
The following frequencies are used for the description of the occurrence of adverse reactions: very common (< 1/10), common (< 1/100 to < 1/10), uncommon (< 1/1,000 to < 1/100), rare (< 1/10,000 to < 1/1,000), very rare (< 1/10,000) not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Undesirable effects due to articaine:
Metabolism and nutrition disorders: Rare
Metabolism increase
Nervous system disorders: Rare
Metallic flavour, tinnitus, disorientation, tremors, excitatory reactions, vertigo, midryasis, paraesthesia (of lips, tongue), mandibular spasm and convulsions.
Eye disorders: Rare
During and immediately after anaesthesia rare transient eye disorders may occur (diplopia)
Cardiac disorders: Rare
Bradycardia with myocardial depression, arrhythmia
Vascular disorders: Rare
Hypotension, hypertension
Respiratory, thoracic and mediastinal disorders: Rare
Tachypnea, broncodilatation
Gastrointestinal disorders: Rare
Nausea, vomiting
Skin and subcutaneous tissue disorders: Very rare
Cutaneous rashes, pruritus, urticaria
General disorders and administration site conditions:
Very rare: Allergic reactions (bronchospasm, oedema of the larynx up to cardiorespiratory collapse from anaphylactic shock)
Rare: increase in body temperature
Undesirable effects due to adrenaline:
Cardiac disorders: Rare
Arrhythmia
Vascular disorders: Rare
Hypertension (severe in patients suffering from hypertension and hyperthyroidism)
Gastrointestinal disorders: Rare
Vomiting
General disorders and administration site conditions: Rare
Heat sensation, sweating, headache, anxiety, retrosternal and pharyngeal pain.
Patients with cardiovascular diseases may exhibit exaggerated vasoconstrictor response. Ischemic injury or necrosis may result.
The product contains sodium metabisulphite: this substance may cause allergic-type reactions and severe asthmatic episodes in certain susceptible people and in particular in asthmatic patients.
Due to the content of both articaine and adrenaline, the following undesirable effects can occur:
Nervous System disorders:
Very rare (< 1/10,000):
Persistent hypoesthesia and gustatory loss after mandibular or inferior alveolar nerve blocks 2 weeks delayed onset of facial nerve paralysis has been described with articaine/adrenaline, the event still occur 6 months later.
In some cases, an incorrect injection may cause severe ischemia and necrosis. Lesions to nerves, hyposensitivity and alterations of taste, may occur after an incorrect injection or in case of patient with particular conditions.
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 Yellow Card Scheme (Website: www.mhra.gov.uk/yellowcard or search for the MHRA Yellow Card in the Google Play or Apple App Store).
4.9 Overdose
Toxic reactions
CNS excitation: confusion, fear, and tachypnea, increase in blood pressure and face blushing, nausea, vomiting, tremors, spasms, mandibular spasms and convulsions.
CNS depression: vertigo, inability to speak, hearing difficulties, and loss of consciousness, muscular contractions, vascular-motor complications, tonic-clonic seizures, coma, respiratory difficulties, respiratory block and death.
Cardiovascular depression: bradycardia, arrhythmia, fibrillation, hypotension, cardiac arrest, and cyanosis.
Emergency procedures and therapy
At the first sign of adverse reactions administration must be interrupted, the patient placed in horizontal position and the clear passage of the airways ascertained; respiration, pulse and blood pressure should be monitored. Oxygen must be administered or artificial ventilation applied in cases of serious dyspnoea. Heart rate and arterial pressure should be monitored. An intravenous injection of an isotonic solution is also recommended in cases of not severe symptom appearance. Any seizures may be controlled using anti-convulsant medicines (diazepam) endovenously administered followed by oxygen administration. In cases of circulatory problems and shock, glucocorticoids, as plasmatic mass expander, and human albumin should be intravenously administered. In case of collapse and increasing bradycardias, adrenaline should be immediately administered and heart rateand blood pressure monitored.
Severe tachycardia and arrhythmia require treatment with anti arrhythmic and cardioselective drugs.
Hypertension in hypertonic patients should be treated with peripheral anti-hypertensive drugs.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Local anaesthtics; ATC code: N01BB58
Mechanism of action
Articaine hydrochloride is a local anaesthetic with amide function that interrupts the propagation of nerve pulses along the nerve fiber at the injection site.
The adrenaline (diluted to 1/100,000) that is added to the articaine solution slows the passage of articaine into the general circulation and thus assures the extended maintenance of an active tissue concentration, permitting obtaining an operating field that is relatively devoid of blood.
Anaesthesia is initiated in 2 to 3 minutes. The duration of anaesthesia permitting a surgical intervention is approximately 60 minutes.
5.2 Pharmacokinetic properties
Injected into the oral mucosa, articaine reaches its peak blood concentration approximately 30 minutes after injection.
Articaine is metabolised in approximately 5% to 10% by hepatic cytochrome P-450 isoenzyme systems; 2% is eliminated in unchanged form in the urine. Up to 90% of articaine is rapidly hydrolysed by esterase to its primary inactive metabolite articainic acid which is further metabolised in to articainic acid glucuronide. The elimination half-life of articaine hydrochloride is approximately 110 minutes.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction and development.
Adrenaline is known to induce teratogenicity in rats and human. There is evidence of congenital malformations and a disrupted uteroplacental blood circulation. These effects are considered not relevant at the exposure with the current indication.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium chloride
Sodium metabisulphite
Hydrochloric acid
Sodium hydroxide
Water for injection
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
6.3 Shelf life
18 months
6.4 Special precautions for storage
Store at a temperature below 30ºC.
Do not freeze.
6.5 Nature and contents of container
Cartridge (type I glass) sealed at the base by a grey bromobutyl stopper and at the other end by a bromobutyl disk covered by an aluminum cap.
Box of 50 cartridges of 1.8 mL with self-aspirating stopper
Box of 50 cartridges of 1.8 mL with standard stopper
Box of 50 cartridges of 2.2 mL with self-aspirating stopper
Box of 50 cartridges of 2.2 mL with standard stopper
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
As with any cartridge, the membrane will be disinfected just before use. It will be carefully swabbed:
- either with 70% ethyl alcohol
- or with 90% pure isopropyl alcohol for pharmaceutical use.
The cartridges must never be immersed in any solution whatsoever.
Do not mix the solution for injection in the same syringe with other products.
All opened anaesthetic solution cartridges must not be reused.
7 MARKETING AUTHORISATION HOLDER
DENTSPLY Limited
Building 3, The Heights
Weybridge, Surrey, KT13 0NY
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 04690/0034
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
02/10/2018
10 DATE OF REVISION OF THE TEXT
21/06/2019