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Septocaine Solution For Injection ENG SMPC
Septocaine Solution For Injection ENG SMPC
One cartridge of 1.7 ml of solution for injection contains 68 mg of Articaine hydrochloride and
8.5 micrograms of Adrenaline.
Excipients with known effect: sodium metabisulfite (E223), sodium chloride, disodium edetate,
sodium hydroxide.
3 PHARMACEUTICAL FORM
4 CLINICAL PARTICULARS
Posology
For all populations, the lowest dose leading to efficient anaesthesia should be used. The necessary
dosage must be determined on an individual basis.
Method of Administration
For instructions on the handling of the medicinal product before administration, see section 6.6.
4.3 Contraindications
Hypersensitivity to articaine (or any local anaesthetic agent of the amide type), to adrenaline or
to any of the excipients listed in section 6.1.
Patients with epilepsy not controlled by treatment.
Special warnings
This medicinal product must be used with special caution in patients with the following disorders and
postponement of dental surgery should be considered if the condition is severe and/or unstable.
This medicinal product must be used with caution in patients with the following disorders:
Patients with epileptic disease:
Because of their convulsive actions, all local anaesthetics should be used very cautiously.
Elderly patients:
In patients over 70 years old, the lowest dose leading to efficient anaesthesia should be used.
Use of Septocaine 40 mg/ml + 5 micrograms/ml, solution for injection over Septocaine forte 40 mg/
ml + 10 micrograms/ml, solution for injection should be considered on account of its lower adrenaline
content of 5 micrograms /ml in:
Patients with cardiovascular diseases (e.g. heart failure, coronary heart disease, history of
myocardial infarction, cardiac arrhythmia, hypertension)
Very rare cases of prolonged or irreversible nerve injury and gustatory loss have been reported after
mandibular block analgesia.
The local anaesthetic effects may be reduced when this medicinal product is injected into an inflamed
or infected area.
Risk of biting trauma (lips, cheeks, mucosa, and tongue) exists, especially in children; the patient
should be told to avoid chewing gum or eating until normal sensation is restored.
This medicinal product contains sodium metabisulfite, a sulfite that may rarely cause hypersensitivity
reactions and bronchospasm.
This medicinal product contains less than 1 mmol sodium (23 mg) per cartridge, i.e. it is considered as
essentially “sodium free‟.
Accidental intravascular injection may cause sudden 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 and cardiorespiratory depression and coma, progressing to respiratory and
circulatory arrest.
Thus, to ensure that the needle does not penetrate a blood vessel during injection, aspiration should be
performed before the local anaesthetic medicinal product is injected. However, the absence of blood in
the syringe does not guarantee that intravascular injection has been avoided.
Accidental intraneural injection may lead the drug to move in retrograde manner along the nerve.
In order to avoid intraneural injection and to prevent nerve injuries in connection with nerve
blockades, the needle should always be slightly withdrawn if electric shock sensation is felt by the
patient during injection or if the injection is particularly painful. If needle nerve injuries occur, the
neurotoxic effect could be aggravated by articaine potential chemical neurotoxicity and the presence
of adrenaline as it may impair the perineural blood supply and prevent articaine local wash-out.
Concomitant use of other medicinal products may require thorough monitoring (see section 4.5).
4.5 Interaction with other medicinal products and other forms of interaction
Pregnancy
There is no experience of the use of articaine in pregnant women, except during childbirth. Animal
studies do not indicate that articaine has direct or indirect harmful effects on pregnancy,
embryonal/foetal development, birth or postnatal development.
Animal studies have shown that adrenaline is toxic to reproduction at doses higher than maximal
recommended dose (see section 5.3).
Adrenaline and articaine cross the placental barrier, although articaine does so to a lesser extent than
other local anaesthetics. Serum concentrations of articaine measured in newborn infants were approx.
30% of maternal levels. In the event of inadvertent intravascular administration in the mother,
adrenaline can reduce uterine perfusion. During pregnancy, Septocaine should only be used after a
careful analysis of the benefit-to-risk ratio has been made.
On account of its lower adrenaline content, use of Septocaine 40 mg/ml + 5 micrograms/ml, solution
for injection over Septocaine forte 40 mg/ml + 10 micrograms/ml, solution for injection should be
preferred.
Breastfeeding
As a result of the rapid drop in serum levels and rapid elimination, clinically relevant quantities of
articaine are not found in breast milk. Adrenaline passes into breast milk but also has a short half-life.
It is not usually necessary to suspend breast-feeding for short-term use.
Fertility
Animal studies with articaine 40 mg/ml + adrenaline 0.01 mg/ml have not shown effects on fertility
(see section 5.3). At therapeutic doses, adverse effects on human fertility are not expected.
The combination articaine hydrochloride with adrenaline tartrate solution for injection may have
minor influence on the ability to drive and use machines. Dizziness (including vertigo, vision disorder
and fatigue) may occur following administration of the combination articaine hydrochloride with
adrenaline tartrate (see section 4.8). Patients experiencing these symptoms should not drive or use
machinery until any such symptoms have completely resolved.
Adverse reactions following administration of articaine / adrenaline are similar to those observed with
other local amide anaesthetics / vasoconstrictors. These adverse reactions are, in general, dose-related.
They may also result from hypersensitivity, idiosyncrasy, or diminished tolerance by patient. Nervous
system disorders, local injection site reaction, hypersensitivity, cardiac disorders and vascular
disorders are the most frequently occurring adverse reactions.
Serious adverse reactions are generally systemic.
The reported adverse reactions come from spontaneous reporting, clinical studies and literature.
The frequencies classification follows the convention: 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), and very rare (<1/10,000)
Not known (cannot be estimated from the available data)”.
d) Paediatric population
The safety profile was similar in children and adolescents from 4 to 18 years old compared to adults.
However, accidental soft tissue injury was observed more frequently, especially in 3 to 7 year old
children, due to the prolonged soft tissue anaesthesia.
4.9 Overdose
Types of overdose
Symptomatology
Due to an overdose (absolute or relative), since excitement may be transient or absent, the first
manifestations may be drowsiness merging into unconsciousness and respiratory arrest.
Due to articaine:
The symptoms are dose-dependent and have progressive severity in the realm of neurological
manifestations (presyncope, syncope, headache, restlessness, agitation, confusional state,
disorientation, dizziness (lightheadedness), tremor, stupor, deep CNS depression, loss of
consciousness, coma, convulsion (including tonic-clonic seizure), speech disorder (e.g., dysarthria,
logorrhea), vertigo, balance disorder (disequilibrium)), eyes manifestations (mydriasis, vision blurred,
accommodation disorder) followed by vascular (pallor (local, regional, general)), respiratory (apnoea
(respiratory arrest), bradypnoea, tachypnoea, yawning, respiratory depression), and finally cardiac
(cardiac arrest, myocardial depression) toxicity.
Due to adrenaline:
The symptoms are dose-dependent and have progressive severity in the realm of neurological
manifestations (restlessness, agitation, presyncope, syncope) followed by vascular (pallor (local,
regional, general)), respiratory (apnoea (respiratory arrest), bradypnoea, tachypnoea, respiratory
depression), and finally cardiac (cardiac arrest, myocardial depression) toxicity.
Treatment of overdose
The availability of resuscitation equipment should be ensured before the onset of dental anaesthesia
with local anaesthetics.
If signs of acute toxicity are suspected, the injection of Septocaine must immediately be stopped.
Oxygen should rapidly be administered, if necessary by assisted ventilation.
Change patient position to supine position if necessary.
If seizures do not stop spontaneously within 15 – 20 seconds an anticonvulsant drug must be
administered. Muscle relaxing agents may be necessary but requires tracheal intubation.
Hypotension and/or bradycardia may be treated with ephedrine.
In case of cardiac arrest, immediate initiation of cardiopulmonary resuscitation should be performed
with the combination of epinephrine and atropine.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Mechanism of action: Articaine, a local amide anaesthetic, reversibly blocks nerve conduction through
a well-known mechanism commonly observed with other local amide anaesthetics. This consists in
decreasing or preventing the large transient increase in the permeability of excitable membranes to
sodium (Na+) that is normally produced by slight depolarisation of the membrane.
Onset of action: Septocaine has an onset of 1.5-1.8 min for infiltration and 1.4-3.6 min for nerve
block.
Analgesia duration: Pulpal analgesia lasts from 45 to 75 min, and soft-tissue analgesia lasts from 120
to 360 min depending on administered dose.
Articaine
Absorption: In three published clinical studies describing the pharmacokinetic profile of the
combination articaine hydrochloride 40 mg/ml with adrenaline 0.010 or 0.005 mg/ml, T max values were
between 10 and 12 minutes, with Cmax values ranging from 400 to 2100 ng/ml.
In clinical trials performed in children, C max was 1382 ng/ml and Tmax 7.78 min following infiltration of
a dose of 2 mg/kg body weight.
Distribution: High protein binding of articaine was observed with human serum albumin (68.5-
80.8%), and /-globulins (62.5-73.4%). Binding to -globulin (8.6-23.7%) was much lower.
Adrenaline is a vasoconstrictor added to articaine to slow down absorption into the systemic
circulation and thus prolong maintenance of active articaine tissue concentration.The volume of
distribution in plasma was about 4 l/kg.
Metabolism: Articaine is subject to hydrolysis of its carboxyl group by unspecific esterases in the
tissue and in blood. Since this hydrolysis is very fast, about 90% of articaine is inactivated by this
way. Articaine is additionally metabolised in the liver microsomes. Articainic acid is the major
product of cytochrome P450-induced metabolism of articaine, further metabolised to form articainic
acid glucuronide.
Excretion: Following dental injection, the plasmatic half-life of articaine was shown c.a. 20 min. In a
clinical trial, plasma concentrations of articaine and articainic acid were shown to decrease rapidly
following submucosal injection. Very little articaine was detected in plasma from 12 to 24 hours
following injection. More than 50% of the dose was eliminated in the urine, 95% as articainic acid,
within 8 hours of administration. Within 24 hours, approximately 57% (68 mg) and 53% (204 mg) of
the dose was eliminated in the urine. Renal elimination of unchanged articaine accounted for only
about 2% of total elimination.
5.3 Preclinical safety data
Preclinical data reveal no special hazard for humans at therapeutic doses, based on conventional
studies of safety pharmacology, chronic toxicity, reproductive toxicity and genotoxicity. At
supratherapeutic doses, articaine has cardiodepressant properties and can exert vasodilatory effects.
Adrenaline exhibits sympathomimetic effects.
In embryotoxicity studies with articaine, no increase in the foetal mortality rate or malformations were
observed at daily i.v. doses of up to 20 mg/kg (rat) and 12.5 mg/kg (rabbit). Adrenaline showed
reproductive toxicity in animals at doses ranging from 0.1 to 5 mg/kg (several folds the maximal dose
of adrenaline when using Septocaine) with evidence of congenital malformations and impaired
uteroplacental perfusion.
In a fertility and early embryonic development study in rats no adverse effects on male or female
fertility were noted at doses causing parental toxicity.
6 PHARMACEUTICAL PARTICULARS
Sodium chloride,
Disodium edetate,
Sodium metabisulfite (E223),
Sodium hydroxide (for pH-adjustment),
Water for injections.
6.2 Incompatibilities
Not applicable.
6.3 Shelf-life
2 years.
Cylindrical class I glass cartridge sealed at its base by a mobile rubber plunger and at the top by a
rubber seal kept in place by a metal cap.
This medicinal product should not be used if the solution is cloudy or discoloured.
To avoid risk of infection (e.g. hepatitis transmission), syringe and needles used to draw up the
solution must always be fresh and sterile.
The cartridges are for single use. If only a portion of a cartridge is used, the remainder must be
discarded.
Any unused product or waste material should be disposed of in accordance with local requirements.
2017-04-12