SUMMARY OF THE PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Septocaine 40 mg/ml + 5 micrograms/ml, solution for injection

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml contains articaine hydrochloride 40 mg and adrenaline 5 micrograms as adrenaline tartrate.

Septocaine contains 84.74 mg sodium per 100 ml of solution i.e. 1.44 mg/1.7 ml.

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.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Solution for injection.

Clear colourless solution.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Local and loco-regional anaesthesia in dental procedures.

Septocaine is indicated in adults, adolescents and children above 4 years of age (or from 20 kg (44
lbs) of body weight).

4.2 Posology and method of administration

For professional use by dentists and stomatologists only.

Posology

For all populations, the lowest dose leading to efficient anaesthesia should be used. The necessary
dosage must be determined on an individual basis.

● Adults and adolescents (12 to 18 years of age)

In adults and adolescents, the maximum dose is 7 mg/kg with an absolute maximum dose of 500 mg
for an healthy adult of 70 kg body weight.

● Children (4 to 11 years of age)

Due to lack of clinical data, this medicinal product should not be used in children under 4 years of age.
In children aged 4 years (or from 20 kg (44 lbs) of body weight) and above, the maximum dose is 5
mg/kg only with an absolute maximum dose of 275 mg articaine for a healthy child of 55 kg body
weight.
● Special populations
Due to the lack of clinical data, particular precaution should be used in order to administer the lowest
dose leading to efficient anaesthesia in elderly patients over 70 years old and in patients with renal or
hepatic impairment.

Method of Administration

Infiltration and perineural use in oral cavity.

Precautions to be taken before handling or administering the medicinal product

Before injection, aspiration is always recommended to avoid intravascular injection.

The rate of injection should not exceed 1 ml of solution per minute.

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.

4.4 Special warnings and precautions for use

Before using this medicinal product, it is important:

- To make inquiries into the patient’s current therapies and history;
- To maintain verbal contact with the patient;
- To have resuscitative equipment at hand (see section 4.9)

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.

Patients with cardiovascular disorders:

 Cardiac impulse formation and conduction disturbances (e.g. 2nd or 3rd degree AV block, marked
bradycardia)
 Acute decompensated heart failure (acute congestive heart failure)
 Hypotension
 Patients with paroxysmal tachycardia or absolute arrhythmias with rapid heart rate
 Patients with recent (3 to 6 months) myocardial infarction
 Patients with recent (3 months) coronary artery bypass surgery
 Patients taking non-cardioselective beta-blockers (e.g. propranolol) (risk of hypertensive crisis or
severe bradycardia), (see section 4.5)
 Patients with uncontrolled hypertension
 Concomitant treatment with tricyclic antidepressants, as these active substances can intensify the
cardiovascular effects of adrenaline. (see section 4.5)
The lowest dose leading to efficient anaesthesia should be used.

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.

Patients with plasma cholinesterase deficiency

A plasma cholinesterase deficiency can be suspected when clinical signs of overdose occurs with usual
dosage of anesthesia and when a vascular injection has been excluded. In this case, caution shall be
used for the next injection and reduced dose shall be applied.

Patients with hepatic disease:

The lowest dose leading to efficient anaesthesia should be used.

Patients with renal disease:

The lowest dose leading to efficient anaesthesia should be used.

Patients with concomitant treatment with halogenated inhalation anaesthetics

The lowest dose leading to efficient anaesthesia should be used (see section 4.5).

Patients with myasthenia gravis:

The lowest dose leading to efficient anaesthesia should be used.

Patients receiving treatment with antiplatelets / anticoagulants:

The increased risk of severe bleeding after accidental vessel puncture and during oro-maxillo-facial
surgery should be considered. INR monitoring should be increased in patients taking anticoagulants.

Patients with porphyria:

This product should be used 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)

 Patients with cerebral circulation disturbances, history of strokes

 Patients with uncontrolled diabetes:

This medicinal product should be used cautiously due to hyperglycemic effect of adrenaline.

 Patients with thyreotoxicosis:

This medicinal product should be used cautiously due to the presence of adrenaline.

 Patients with pheochromocytoma:

This medicinal product should be used cautiously due to the presence of adrenaline.

 Patients with susceptibility of acute angle-closure glaucoma:

This medicinal product should be used cautiously due to the presence of adrenaline.
This medicinal product must be used safely and effectively under appropriate conditions:
Adrenaline impairs the flow of blood in the gums, potentially causing local tissue necrosis.

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‟.

Precautions for use

Risk associated with accidental intravascular injection:

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.

Risk associated with intraneural injection:

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

Due to the presence of articaine

Interactions requiring precautions for use:

Other local anaesthetics

Toxicity of local anaesthetics is additive.
The total dose of all local anaesthetics administered should not exceed the maximum recommended
dose of the drugs used.
Sedatives (central nervous system depressants e.g. benzodiazepine, opioids):
In children receiving benzodiazepines or opioids, reduced doses of this medicinal product should be
used due to additive effects.

Due to the presence of adrenaline

Interactions requiring precautions for use:

Halogenated volatile anaesthetics (e.g., halothane):

Reduced doses of this medicinal product should be used due to sensitization of the heart to the
arrhythmogenic effects of catecholamines: risk of severe ventricular arrhythmia.
Discussion with the anaesthetist before local anaesthetic administration during general anaesthesia is
recommended.

Postganglionic adrenergic blocking agents (e.g., guanadrel, guanethidine, and rauwolfia

alkaloids):
Reduced doses of this medicinal product should be used under strict medical supervision followed by
careful aspiration due to possible increase response to adrenergic vasoconstrictors: risk of
hypertension and other cardiovascular effects.

Non-selective beta-adrenergic blockers (e.g., propranolol, nadolol):

Reduced doses of this medicinal product should be used due to possible increase in blood pressure and
an increased risk of bradycardia.

(TCAs) Tricyclic antidepressants (e.g., amitriptyline, desipramine, imipramine, nortriptyline,

maprotiline and protriptyline):
Dose and rate of administration of this medicinal product should be reduced due to an increased risk of
severe hypertension.

COMT inhibitors (Catechol-O-methyl transferase inhibitors) (e.g., entacapone, tolcapone):

Arrhythmias, increased heart rate and blood pressure variations may occur.
A reduced amount of adrenaline in dental anaesthesia should be given to patients on COMT
inhibitors.Drugs causing arrhythmias (e.g., antiarrhythmics like digitalis, quinidine):
Dose of administration of this medicinal product should be reduced due to the increased risk of
arrhythmia when both adrenaline and digital glucosides are administered concomitantly to patients.
Careful aspiration prior to administration is recommended.

Ergot-type oxytocic drugs (e.g., methysergide, ergotamine, ergonovine):

Use this medicinal product under strict medical supervision due to additive or synergistic increases in
blood pressure and/or ischemic response.

Sympathomimetic vasopressors (e.g., mainly cocaine but also amphetamines, phenylephrine,

pseudoephedrine, oxymetazoline):
There is a risk of adrenergic toxicity.
If any sympathomimetic vasopressor has been used within 24 hours, the planned dental treatment
should be postponed.

Phenothiazines (and other neuroleptics):

Use with caution in patients taking phenothiazines considering the risk of hypotension due to possible
inhibition of adrenaline effect.

4.6 Fertility, pregnancy and lactation

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.

4.7 Effects on ability to drive and use machines

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.

4.8 Undesirable effects

a) Summary of the safety profile

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.

b) Tabulated list of adverse reactions

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)”.

MedDRA Sytem Frequency Adverse Reactions

Organ Class
Infections and Common Gingivitis
infestations
Immune system Rare Allergic1, anaphylactic /
disorders anaphylactoid reactions
Urticaria
Psychiatric disorders Rare Nervousness / anxiety
Not known Euphoric mood
Nervous system Common Neuropathy:
disorders Neuralgia (neuropathic pain)
Hypoesthesia / numbness (oral
and perioral)
Hyperesthesia
Dysesthesia (oral and perioral),
including
Dysgeusia (e.g., taste metallic,
taste disturbance)
Ageusia
Allodynia
Thermohyperesthesia
Headache
Uncommon Burning sensation
Rare Facial nerve disorder2 (palsy,
paralysis and paresis)
Horner’s syndrome (eyelid ptosis,
enophthalmos, miosis).
Somnolence (Drowsiness)
Nystagmus
Very rare Paresthesia3 (persistent
hypoesthesia and gustatory loss)
after mandibular or inferior alveolar
nerve blocks
Eye disorders Rare Diplopia (paralysis of oculomotor
muscles)
Visual impairment (temporary
blindness)
Ptosis
Miosis
Enophthalmos
Ear and labyrinth Rare Hyperacusis
disorders Tinnitus
Cardiac disorders Common Bradycardia (also named
bradyarrhythmia)
Tachycardia
Rare Palpitations
Not known Conduction disorders
(atrioventricular block)
Vascular disorders Common Hypotension (with possible
circulatory collapse)
 Uncommon Hypertension
Rare Hot flush
Not known Vasodilatation
Vasoconstriction
Respiratory, thoracic Rare Bronchospasm / asthma
and mediastinal yspnoea2
disorders Not known Dysphonia (Hoarseness)1
Gastrointestinal Common Gingivitis
disorders Swelling of tongue, lip, gums
Uncommon Stomatitis, glossitis
Nausea, vomiting, diarrhoea
Rare Gingival / oral mucosal exfoliation
(sloughing) / ulceration
Not known Dysphagia
Swelling of cheeks
Skin and Uncommon Rash (eruption)
subcutaneous tissue Pruritus
disorders Rare Angioedema (face / tongue / lip /
throat / larynx / periorbital oedema)
Not known Erythema
Hyperhidrosis
Musculoskeletal and Uncommon Neck pain
connective tissue Rare Muscle twitching
disorders C
Not known Aggravation of the neuromuscular
manifestations in Kearns-Sayre
syndrome
General disorders Uncommon Injection site pain
and administration Rare Injection site exfoliation / necrosis
site conditions Fatigue, asthenia (weakness)/ Chills
Not known Local swelling
Feeling hot,
Feeling cold

c) Description of selected adverse reactions

1
Allergic reactions should not be mistaken with syncopal episodes (cardiac palpitations due to
adrenaline).
2
A 2 week delay in the onset of facial paralysis has been described following administration of
articaine combined with adrenaline, and the condition was unchanged 6 months later.
3
These neural pathologies may occur with various symptoms of abnormal sensations. Paresthesia can
be defined as spontaneous abnormal usually nonpainful sensation (e.g., burning, pricking, tingling or
itching) well beyond the expected duration of anesthesia. Most cases of paresthesia reported
following dental treatment are transient and resolve within days, weeks or months.
Persistent paresthesia, mostly following nerve blocks in the mandible, is characterized by slow,
incomplete, or lack of recovery.

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.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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:.
[To be completed nationally]

4.9 Overdose

Types of overdose

Local anaesthetic overdose in the largest sense is often used to describe:

 absolute overdose,
 relative overdose such as:
- inadvertent injection into a blood vessel, or
- abnormal rapid absorption into the systemic circulation, or
- delayed metabolism and elimination of drug.

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

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

Articaine, combinations
ATCcode: N01BB58

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.

Adrenaline, as vasoconstrictor, acts directly on both α- and β-adrenergic receptors; β-adrenergic

effects predominate. Adrenaline prolongs the effect duration of the articaine, and reduces the risk of
excessive uptake of articaine into the systemic circulation.

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.

Paediatric population: No difference was obtained in pharmacodynamic properties.

5.2 Pharmacokinetic properties

 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 embryofoetotoxicity studies with articaine and adrenaline, no increase in malformations were

observed at daily s.c. doses of articaine up to 80 mg/kg (rat) and 40 mg/kg (rabbit).

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

6.1 List of excipients

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.

6.4 Special precautions for storage

Store below 25°C.

Do not refrigerate or freeze.
Keep the cartridge in the outer carton in order to protect from light and moisture.

6.5 Nature and content of container

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.

Box containing glass cartridges 50 x 1.7 ml.

Box containing glass cartridges, self-aspirating 50 x 1.7 ml.
Pack of 4 boxes containing glass cartridges 50 x 1.7 ml.
Pack of 8 boxes containing glass cartridges 50 x 1.7 ml.
Not all pack sizes may be marketed.

6.6 Special precautions for disposal

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.

7 MARKETING AUTHORISATION HOLDER

[To be completed nationally]

8 MARKETING AUTHORISATION NUMBER

[To be completed nationally]

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

[To be completed nationally]

10 DATE OF REVISION OF THE TEXT

2017-04-12