Package Leaflet

SARTICAIN with adrenaline 1:100,000

40 mg/ml + 10 mcg/ml solution for injection
SARTICAIN with adrenaline 1:200,000
40 mg/ml + 5 mcg/ml solution for injection

PHARMACOTHERAPEUTIC CATEGORY
Local anesthetics, amides (articaine in combination).

THERAPEUTIC INDICATIONS
Local anesthetic for infiltration, block, or intraligamentary techniques in cases of:
SARTICAIN with Adrenaline 1:100,000: Deeper surgical procedures such as those involving mucosa, bone, and dental pulp (pulpotomy and extraction), requiring more intense tissue ischemia; tooth extraction in cases of apical periodontitis or fractured teeth (osteotomy); long-duration surgical procedures (e.g., Caldwell-Luc surgery, percutaneous osteosynthesis, cystectomy, mucogingival surgery, complex cavity preparation and core build-up for crown placement).
SARTICAIN with Adrenaline 1:200,000: Routine procedures such as single or multiple tooth extractions, cavity preparation, and core removal for crown placement, particularly in debilitated patients.

CONTRAINDICATIONS
Hypersensitivity to the active substances or to any of the excipients, or to other amide-type local anesthetics, or to adrenaline.
As with all local anesthetics containing adrenaline, intravascular administration is strictly contraindicated. It is therefore absolutely necessary to ensure that the needle used for injection is not within a blood vessel.
Contraindicated in patients treated with monoamine oxidase inhibitors (MAOIs), or who have been treated with such medications within the previous two weeks;
in patients taking tricyclic antidepressants;
in patients with myasthenia gravis or plasma cholinesterase deficiency;
in patients taking beta-blockers;
in children under four years of age;
in various cardiovascular disorders: recent myocardial infarction, rhythm or conduction disturbances, uncompensated acute heart failure, hypertension;
in essential migraine;
in confirmed or suspected pregnancy; during lactation.
The product must not be administered to asthmatic patients who are hypersensitive to sulfites.
Due to the presence of adrenaline, the use of this product is contraindicated in:
diabetic patients, patients suffering from narrow-angle glaucoma, those with paroxysmal tachycardia and absolute arrhythmia at high frequency, cardiac disease, severe arteriopathy, hypertension, any type of ischemic manifestations, nephropathy, hyperthyroidism, diabetes, thyrotoxicosis, pheochromocytoma, and cerebrovascular insufficiency.
Due to its metabolism and elimination mechanisms, administration of the product must be carried out with particular caution in cases of renal or hepatic insufficiency, angina pectoris, arteriosclerosis, epilepsy, respiratory insufficiency, and coagulation disorders.
The product must never be used for anesthesia in areas supplied by terminal circulation.

PRECAUTIONS FOR USE
Before use, the physician must assess the patient's general health and circulatory status, and must inquire about ongoing therapies and any history of allergic reactions.
Any overdose of anesthetic must be avoided, and two maximum doses must never be administered without an interval of at least 24 hours.
In any case, the lowest effective doses and concentrations should be used to achieve the desired effect.
The anesthetic solution must be injected cautiously in small amounts, after approximately 10 seconds of aspiration to exclude intravascular placement.
Especially when infiltrating highly vascularized areas, it is advisable to wait approximately two minutes before proceeding with the actual locoregional block. The patient must be closely monitored, and administration must be immediately suspended at the first sign of alarm (e.g., sensory disturbances: burning, tingling, electric shock sensation).
Emergency equipment, appropriate medications, and trained personnel must be immediately available, as rare but serious, sometimes fatal, reactions have been reported following the use of local anesthetics, even in the absence of individual hypersensitivity.
Local anesthesia should be avoided in infected areas and inflamed tissues.
Like other amide-type anesthetics metabolized by the hepatic microsomal system (cytochrome P-450), Sarticain must be used with caution in patients with liver disease; patients with severe hepatic impairment are at higher risk of toxic plasma concentrations.
Sarticain must be administered with particular care in patients with a history of epilepsy.

INTERACTIONS
No effects different from the desired ones have been observed with routine use of opioids for premedication or supplementary analgesia, other analgesics, atropine, psychotropic drugs, peripheral analeptics, or, in case of supplemental general anesthesia, barbiturates, inhalational anesthetics, ketamine, and neuroleptoanalgesics.
Cimetidine and beta-blockers slow down the hepatic catabolism of local anesthetics; digitalis increases the risk of bradycardia and atrioventricular conduction disturbances. When non-selective beta-blockers are administered concomitantly, an increase in blood pressure may occur due to the adrenaline content in Sarticain (see Special Warnings).
Digitalis increases the risk of bradycardia and atrioventricular conduction disturbances. Guanethidine potentiates and prolongs the action of adrenaline; L-dopa, being a precursor of adrenaline, may cause hypertensive crises.
The pressor effect of sympathomimetic vasoconstrictors such as adrenaline may be enhanced by tricyclic antidepressants or MAOIs (see Contraindications). In patients undergoing treatment with these drugs, the product must be used with absolute caution. Such interactions have been reported with noradrenaline at a concentration of 1:25,000 and adrenaline at 1:80,000; the concentrations contained in the two formulations of this product (1:100,000 and 1:200,000) are lower, but the possibility of such interference must still be considered.

SPECIAL WARNINGS
Intravascular injection must be absolutely avoided. It is therefore necessary to ensure that the needle used for injection is not within a blood vessel; accidental intravascular injection may be associated with seizures followed by central nervous system depression and/or cardiorespiratory depression and coma.
To prevent biting of the lips, tongue, and mucosa, patients must be advised not to chew until sensation has returned.
Opened cartridges must not be reused (risk of hepatitis).
Warning: The product contains anhydrous sodium sulfite as a preservative: this substance may cause allergic-type reactions and severe asthma attacks in sensitive individuals, particularly in asthmatics.
The 20 ml vials contain parahydroxybenzoate, which may cause allergic reactions, usually delayed-type, such as contact dermatitis; more rarely, immediate-type reactions such as urticaria and bronchospasm may occur.
Sarticain contains adrenaline, which may cause local tissue necrosis and systemic toxicity; therefore, standard precautions for adrenaline administration must be observed.
Caution for individuals engaged in sports: the product contains substances prohibited in doping.
Administration differing from the recommended dosage regimen or route is prohibited.

Pregnancy and lactation
Sarticain must not be administered during pregnancy or lactation, as there are insufficient data on the administration of the medicinal product to pregnant women, and no clinical data are available on whether the active substances pass into breast milk.

Effects on ability to drive and use machines
Only the physician can determine whether, after the procedure, the patient is in a safe condition to drive vehicles or operate machinery.

DOSAGE, ADMINISTRATION METHOD AND DURATION
For uncomplicated extractions of non-inflamed teeth in the upper jaw, injection of 1.7 ml (one cartridge) of product into the vestibular fornix per tooth is usually sufficient.
Exceptionally, and particularly to avoid pain from palatal injection, a subsequent injection of 1–1.7 ml may be necessary. In cases requiring incision or suturing of the palate, approximately 0.1 ml injected at a time into the palate is sufficient.
In cases of multiple extractions of adjacent teeth, the number of vestibular injections can often be reduced.
For uncomplicated extractions of lower jaw premolars, block anesthesia may be omitted, as plexus anesthesia with one cartridge (1.7 ml) of product per tooth is sufficient. If complete anesthesia is not achieved, a further injection of 1–1.7 ml at the vestibular site is recommended. Only if anesthesia remains incomplete should the standard injection into the mandibular foramen be performed.
For cavity preparation and core removal for crown placement, depending on the extent and duration of treatment, 0.5 to 1.7 ml of SARTICAIN with Adrenaline 1:200,000 per tooth at the vestibular site is indicated (except for mandibular molars). For surgical procedures, SARTICAIN with Adrenaline 1:100,000 is indicated at doses proportional to the severity and duration of the procedure.

OVERDOSE
Symptoms of intoxication
Central nervous system (CNS) excitation: confusion, fear, tachypnea, tachycardia, increased blood pressure with facial flushing, nausea, vomiting, tremor, trismus, and convulsions.
CNS depression: dizziness, loss of speech, hearing difficulty, loss of consciousness, muscle contractions, vasomotor complications, respiratory difficulty, death due to respiratory arrest.
Cardiocirculatory depression: bradycardia, arrhythmia, fibrillation, hypotension, cardiac arrest, cyanosis.

Emergency measures and treatment
At the first sign of alarm, administration must be stopped immediately. The patient should be placed in a horizontal position, and airway patency ensured, with oxygen administered in case of severe dyspnea or artificial ventilation (Ambu bag) if necessary. The use of analeptics should be avoided, as they may worsen the condition by increasing oxygen consumption. Seizures may be controlled with intravenous diazepam at a dose of 10–20 mg; barbiturates are not recommended as they may exacerbate bulbar depression. Circulation may be supported by intravenous administration of appropriate doses of corticosteroids; diluted solutions of vasoconstrictive stimulants (methylergonovine, metaraminol, and others) or atropine sulfate may be added. Sodium bicarbonate may be used intravenously at targeted concentrations as an antiacid.

UNDESIRABLE EFFECTS
Toxic and allergic reactions may occur to both the anesthetic and the vasoconstrictor.
Toxic reactions: Undesirable effects due to high plasma levels affecting both the central nervous system and cardiovascular system have been described. Effects on the central nervous system include excitation, tremors, disorientation, dizziness, mydriasis, increased metabolism and body temperature, and, at very high doses, trismus and convulsions. If the medulla oblongata is involved, cardiovascular, respiratory, and emetic centers may be affected, resulting in sweating, arrhythmias, hypertension, tachypnea, bronchodilation, nausea, and vomiting. Peripheral cardiovascular effects include bradycardia and vasodilation.
Allergic reactions mostly occur in hypersensitive individuals, but many cases have been reported in patients without a history of individual hypersensitivity. Local manifestations include various types of skin eruptions, urticaria, and pruritus; general manifestations include bronchospasm, laryngeal edema, and cardiorespiratory collapse due to anaphylactic shock.
Allergic reactions: Local manifestations such as various types of skin eruptions, urticaria, pruritus; general manifestations such as bronchospasm, laryngeal edema, up to cardiorespiratory collapse due to anaphylactic shock.
The vasoconstrictor may cause various effects, especially in patients with cardiocirculatory disorders: anxiety, sweating, respiratory distress, cardiac arrhythmias, hypertension (particularly severe in already hypertensive and hyperthyroid patients), acute headache, photophobia, retrosternal and pharyngeal pain, vomiting; if such symptoms occur, administration must be immediately discontinued.
The frequency categories of adverse reactions are defined as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); not known (frequency cannot be estimated from available data).

Immune system disorders: Rare: allergic reactions, in the most severe cases, anaphylactic shock.
Psychiatric disorders: Rare: anxiety, nervousness.
Nervous system disorders: Common: headache.
Uncommon: paresthesia (loss of sensation and burning sensation) of the tongue, lip, or both, hypoesthesia.
Rare: metallic taste, tinnitus, dizziness, restlessness, tremors, tachypnea, somnolence, disorientation, trismus, facial nerve paralysis, convulsions, tonic-clonic seizures, coma, and respiratory paralysis.
Eye disorders: Rare: diplopia, mydriasis, ptosis, miosis and enophthalmos, photophobia.
Cardiac disorders: Common: bradycardia, tachycardia.
Uncommon: hypertension.
Rare: cardiocirculatory depression and cardiac arrest.
Gastrointestinal disorders: Uncommon: nausea and vomiting.
Skin and subcutaneous tissue disorders: Common: facial edema.
Uncommon: pruritus, urticaria.
Rare: angioedema, necrosis.
Respiratory, thoracic and mediastinal disorders: Not known: tachypnea, bronchodilation, bronchospasm, retrosternal and pharyngeal pain.
Systemic disorders: Not known: increased metabolism and body temperature with sweating. Pain and ulcers at the injection site.
Cases of ocular muscle paralysis have been reported after posterior superior alveolar injection (during anesthesia); symptoms include diplopia, mydriasis, ptosis, and difficulty with ocular abduction. These symptoms may appear immediately after injection and persist from a few minutes to several hours.

EXPIRY DATE AND STORAGE
Expiry date: see the date printed on the packaging.
The expiry date refers to the product stored unopened and correctly stored.
Warning: Do not use the medicinal product after the expiry date stated on the packaging.
Store in the original packaging to protect from light. Store at a temperature not exceeding 25°C. Do not freeze.
Medicinal products must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.
KEEP THIS MEDICINAL PRODUCT OUT OF THE SIGHT AND REACH OF CHILDREN.

COMPOSITION
SARTICAIN with adrenaline 1:100,000 40 mg/ml + 10 mcg/ml solution for injection
1 ml of solution contains:
Active substances
Articaine hydrochloride 40.00 mg
Adrenaline bitartrate 0.01 mg (18.2 micrograms)
(equivalent to Adrenaline base 10 micrograms)
Excipients: Sodium chloride, anhydrous sodium sulfite, methylparahydroxybenzoate (vials only), Water for injections.

SARTICAIN with adrenaline 1:200,000 40 mg/ml + 5 mcg/ml solution for injection
1 ml of solution contains:
Articaine hydrochloride 40.00 mg
Adrenaline bitartrate 0.005 mg (9.1 micrograms)
(equivalent to Adrenaline base 5 micrograms)
Excipients: Sodium chloride, anhydrous sodium sulfite, methylparahydroxybenzoate (vials only), Water for injections.

PHARMACEUTICAL FORM AND CONTENT
Solution for injection.
SARTICAIN with adrenaline 1:100,000 40 mg/ml + 10 mcg/ml solution for injection
Pack: 50 cartridges of 1.7 ml.
Pack: 60 cartridges of 1.7 ml.
Pack: 10 vials of 20 ml.
SARTICAIN with adrenaline 1:200,000 40 mg/ml + 5 mcg/ml solution for injection
Pack: 50 cartridges of 1.7 ml.
Pack: 60 cartridges of 1.7 ml.
Pack: 10 vials of 20 ml.

MARKETING AUTHORIZATION HOLDER AND MANUFACTURER
Industria Farmaceutica Galenica Senese srl - Via Cassia Nord, 351 - 53014 Monteroni d’Arbia (SI)

REVISION OF THE PACKAGE LEAFLET BY THE ITALIAN MEDICINES AGENCY
16 May 2012