Ultracain^® D-S forte (Solution) Instructions for Use

Marketing Authorization Holder

Novokol Pharmaceutical of Canada Inc. (Canada)

Contact Information

SANOFI

ATC Code

N01BB58 (Articaine in combination with other drugs)

Active Substances

Articaine (Rec.INN registered by WHO)

Epinephrine (Rec.INN registered by WHO)

Dosage Forms

	Ultracain® D-S forte	Solution for injection 40 mg+10 mcg/1 ml: amp. 2 ml 10 pcs.
		Solution for injection 40 mg+10 mcg/1 ml: cartridges 1.7 ml 100 pcs.

Dosage Form, Packaging, and Composition

Solution for injection transparent, colorless.

Excipients: sodium disulfite (sodium metabisulfite), sodium chloride, water for injections.

2 ml – ampoules of colorless glass (10) – cardboard packs.
1.7 ml – cartridges of colorless glass (10) – corrugated cardboard blocks (10) – cardboard packs.

Clinical-Pharmacological Group

Local anesthetic with a vasoconstrictor component for use in dentistry

Pharmacotherapeutic Group

Anesthetics; local anesthetics; amides

Pharmacological Action

A combined local anesthetic preparation containing articaine (an amide-type local anesthetic) and epinephrine (a vasoconstrictor), which is added to the preparation to prolong the duration of anesthesia.

The amide structure of articaine is similar to that of other local anesthetics, but its molecule contains one additional ester group, which is rapidly hydrolyzed by esterases in the human body. The rapid breakdown of articaine to its inactive metabolite (articainic acid) is associated with the very low systemic toxicity of the drug, allowing for repeated injections.

Local anesthetics cause reversible loss of sensation due to the cessation or reduction of sensory nerve impulse conduction directly at and around the injection site. They have a membrane-stabilizing effect by reducing the permeability of nerve cell membranes to sodium ions.

The drug has a rapid (latent period – from 1 to 3 minutes) and potent anesthetic effect and has good tissue tolerance. The duration of anesthesia is at least 75 minutes.

Pharmacokinetics

Absorption

After submucosal administration of 2 ml of the drug, the T_max of articaine in blood plasma is 10-15 minutes, and the mean C_max of articaine in blood plasma is approximately 400 mcg/l, the T_max of articainic acid is 45 minutes, and the mean C_max of articainic acid is 2000 mcg/l. Comparable pharmacokinetic data were obtained in children. The differences between the plasma concentrations of articaine and articainic acid reflect the rapid hydrolysis of articaine in tissues and blood, so that the administered articaine enters the systemic circulation mainly as an inactive metabolite.

Distribution

After submucosal administration, the concentrations of articaine in the blood in the area of the dental alveoli are thousands of times higher than the concentrations of articaine in the systemic circulation. An inverse relationship was found between the time after injection and the concentration of articaine in the tooth alveolus.

The binding of articaine to plasma proteins is 95%.

Metabolism

All amide-type local anesthetics are metabolized in liver microsomes. In addition, articaine is inactivated in tissues and blood by non-specific plasma esterases through hydrolysis at the carboxyl group. Since hydrolysis occurs very quickly and begins immediately after administration, about 90% of articaine is inactivated in this way. The resulting main metabolite of articaine, articainic acid, has no local anesthetic activity and has not been found to have systemic toxicity.

Excretion

After submucosal administration, articaine is eliminated exponentially with a T_1/2 of approximately 25 minutes. Articaine is excreted mainly by the kidneys in the form of articainic acid (64.2±14.4%), articainic acid glucuronide (13.4±5%), and unchanged articaine (1.45±0.77%).

After injections of the drug into the oral mucosa, the total clearance of articaine is 235±27 l/h.

Indications

Infiltration and conduction anesthesia for dental procedures on the mucous membrane or bones, when conditions of more pronounced ischemia are required

• Dental pulp procedures (amputation or extirpation);
• Removal of a broken tooth (osteotomy);
• Removal of a tooth affected by apical periodontitis;
• Prolonged surgical interventions (e.g., Caldwell-Luc operation);
• Percutaneous osteosynthesis;
• Excision of cysts;
• Interventions on the gingival mucosa;
• Root apex resection;
• Cavity preparation and grinding for prosthetics of highly sensitive teeth.

ICD codes

Dosage Regimen

The drug is intended for use in the oral cavity and can only be injected into tissues where there is no inflammation. Injection into inflamed tissues must not be performed.

The drug must not be administered intravenously.

For anesthesia during uncomplicated extraction of upper jaw teeth in the absence of inflammation, it is usually sufficient to create a depot of the drug Ultracain^® D-S (Ultracain^® D-S forte) in the area of the transitional fold by injecting it into the submucosa from the vestibular side – 1.7 ml of the drug per tooth. In rare cases, to achieve complete anesthesia, an additional injection of 1 ml to 1.7 ml may be required. In most cases, this avoids the painful palatal injection. When removing several adjacent teeth, the number of injections can usually be limited.

For anesthesia during incisions and suturing in the palate area to create a palatal depot, about 0.1 ml of the drug is needed for each injection.

In the case of removal of lower jaw premolars in the absence of inflammation, mandibular anesthesia can be avoided, as infiltration anesthesia provided by an injection of 1.7 ml of the drug per tooth is usually sufficient. If the desired effect is not achieved in this way, an additional injection of 1-1.7 ml of the drug should be performed into the submucosa in the area of the lower jaw transitional fold from the vestibular side. If complete anesthesia is still not achieved, a conduction block of the mandibular nerve must be performed.

For surgical interventions, the dose of Ultracain^® D-S forte is set individually depending on the severity and duration of the intervention.

When performing one therapeutic procedure, adults can be administered articaine in a dose of up to 7 mg per 1 kg of body weight. It has been noted that patients tolerated doses up to 500 mg (corresponding to 12.5 ml of solution for injection) well.

In children over 4 years of age, the dose of the drug is selected depending on the age and body weight of the child; the dose should not exceed 5 mg of articaine per 1 kg of body weight.

In elderly patients and patients with severe renal and hepatic impairment, increased plasma concentrations of articaine may occur. In these patients, the drug should be used in the minimum dose necessary to achieve sufficient depth of anesthesia.

To avoid accidental intravascular administration of the drug, an aspiration test should always be performed before its injection.

Injection pressure should correspond to tissue sensitivity.

Adverse Reactions

From the central nervous system dose-dependent reactions – stupor, sometimes progressing to loss of consciousness, respiratory disorders, sometimes progressing to respiratory arrest, muscle tremor, muscle twitching sometimes progressing to generalized convulsions; possible – dizziness, paresthesia, hypesthesia, transient visual disturbances (blurred vision, blindness, double vision), occurring during or shortly after injection of the local anesthetic.

Sometimes, if the injection technique is incorrect when administering a local anesthetic in dental practice, nerve damage is possible, in particular, in such cases, damage to the facial nerve is possible, which can lead to the development of facial nerve paralysis.

Frequently – headache, mainly due to the presence of epinephrine in the drug.

From the digestive system: nausea, vomiting.

From the cardiovascular system: decreased blood pressure, bradycardia, heart failure, shock. Very rarely, due to the content of epinephrine in the drug, tachycardia, cardiac arrhythmias, and increased blood pressure may develop.

Allergic reactions: possible – skin hyperemia, conjunctivitis, rhinitis, and angioedema. Angioedema may manifest as swelling of the upper and/or lower lips, cheeks, swelling of the vocal cords with a sensation of a “lump in the throat” and difficulty swallowing, urticaria, difficulty breathing. Any of these manifestations can progress to anaphylactic shock.

Local reactions swelling or inflammation of the mucous membrane at the injection site. In some cases, with accidental intravascular injection, the appearance of ischemic zones at the injection site, up to tissue necrosis, is possible.

Contraindications

• Hypersensitivity to articaine or other amide-type local anesthetics, except in cases where, in case of hypersensitivity to these agents, allergy to articaine was excluded by appropriate studies conducted in compliance with all necessary rules and requirements;
• Hypersensitivity to epinephrine;
• Hypersensitivity to the excipients of the drug, including sulfites (including manifested as bronchial asthma).

Contraindications related to articaine

• Severe sinus node dysfunction or severe conduction disorders (such as severe bradycardia, AV block II and III degree);
• Acute decompensated heart failure;
• Severely pronounced arterial hypotension;
• Anemia (including B₁₂-deficiency anemia);
• Methemoglobinemia;
• Hypoxia;
• Children under 4 years of age (lack of clinical experience);

Contraindications related to epinephrine

• Paroxysmal tachycardia, tachyarrhythmia;
• Closed-angle glaucoma;
• Concomitant use of non-cardioselective beta-blockers, for example, propranolol (risk of hypertensive crisis and severe bradycardia);
• Hyperthyroidism;
• Pheochromocytoma;
• Severe arterial hypertension.

With caution the drug should be used in patients with angina pectoris, atherosclerosis, post-infarction cardiosclerosis, cerebrovascular disorders, history of stroke, chronic bronchitis, pulmonary emphysema, diabetes mellitus, cholinesterase deficiency (use is possible only in case of extreme necessity, as prolonged and excessively strong action of the drug is possible), blood coagulation disorders, severe hepatic and renal impairment, pronounced agitation

Use in Pregnancy and Lactation

Articaine crosses the placental barrier.

Due to insufficient clinical data, the decision to prescribe the drug by a dentist can only be made if the potential benefit of its use justifies the potential risk to the fetus. If it is necessary to use articaine during pregnancy, it is preferable to use preparations that do not contain epinephrine (Ultracain^® D) or with a lower concentration of epinephrine (Ultracain^® D-S).

During lactation, there is no need to interrupt breastfeeding, as clinically significant concentrations of articaine are not detected in breast milk.

Use in Hepatic Impairment

With caution the drug should be used in patients with severe hepatic impairment.

Use in Renal Impairment

With caution the drug should be used in patients with severe renal impairment.

Pediatric Use

Contraindicated for use in children under 4 years of age (lack of clinical experience).

Geriatric Use

In elderly patients, increased plasma concentrations of articaine may occur. In these patients, the drug should be used in the minimum dose necessary to achieve sufficient depth of anesthesia.

Special Precautions

The drug must not be administered intravenously. Injection into an inflamed area must not be performed. To avoid intravascular injection, an aspiration test must always be performed.

Injection pressure should correspond to tissue sensitivity.

To prevent the introduction of infections (including viral hepatitis), care must be taken to ensure that new sterile syringes and needles are always used when drawing the solution from ampoules. Opened cartridges must not be reused for other patients.

A damaged cartridge must not be used for injection.

In patients with cardiovascular diseases (chronic heart failure, coronary artery disease, angina pectoris, cardiac arrhythmias, history of myocardial infarction, arterial hypertension), cerebrovascular disorders, history of stroke, chronic bronchitis, emphysema, diabetes mellitus, hyperthyroidism, as well as in the presence of severe anxiety, it is advisable to use the drug Ultracain^® D-S, which contains a lower amount of epinephrine, or the drug Ultracain^® D, which does not contain epinephrine.

Food can be taken only after the local anesthesia has worn off (sensitivity has returned).

Effect on ability to drive vehicles and operate machinery

Local anesthesia with Ultracain^® D-S forte, as tests have shown, does not cause any noticeable deviation from the usual ability to drive a car and participate in traffic. However, the decision on when a patient can return to driving vehicles and engaging in potentially hazardous activities requiring increased concentration and speed of psychomotor reactions after a dental intervention should be made by the doctor.

Overdose

Symptoms the first manifestations of toxic action are dizziness, motor agitation or stupor; bradycardia, sharp decrease in blood pressure, respiratory disturbances, muscle twitching, generalized convulsions, severe circulatory disorders, shock are possible.

Treatment at the first manifestations of symptoms of toxic action during the administration of the drug, its administration should be stopped and the patient should be placed in a horizontal position with raised lower limbs. Airway patency should be ensured and hemodynamic parameters (heart rate and blood pressure) should be monitored. It is recommended to always, even if the symptoms of intoxication seem mild, place an intravenous catheter in order to have the opportunity, if necessary, to immediately administer the necessary medications intravenously.

In case of respiratory disturbances, depending on their severity, oxygen supply is recommended, and if indications for artificial respiration arise, endotracheal intubation and mechanical ventilation should be performed.

Administration of centrally acting analeptics is contraindicated.

Muscle twitching and generalized convulsions can be controlled by intravenous administration of short or ultra-short-acting barbiturates. It is recommended to administer these drugs slowly, under constant medical supervision (risk of hemodynamic disturbances and respiratory depression) and with simultaneous oxygen supply and monitoring of hemodynamic parameters.

Often bradycardia or a sharp decrease in blood pressure can be eliminated by simply placing the patient in a horizontal position with raised lower limbs.

In case of severe circulatory disorders and shock, regardless of their cause, the administration of the drug should be stopped and the patient should be placed in a horizontal position with raised lower limbs. It is necessary to ensure oxygen supply, intravenous administration of electrolyte solutions, corticosteroids (250-1000 mg methylprednisolone), if necessary, plasma substitutes, including albumin.

In case of collapse development and increasing bradycardia, slow intravenous administration of epinephrine solution (0.0025-0.1 mg) under control of heart rate and blood pressure is indicated. If administration in doses exceeding 0.1 mg is necessary, epinephrine should be administered by infusion, adjusting the rate of administration under control of heart rate and blood pressure.

Severe tachycardia and tachyarrhythmias can be controlled by the administration of antiarrhythmic drugs, except for non-cardioselective beta-blockers.

Increased blood pressure in patients with arterial hypertension should, if necessary, be reduced with vasodilators.

Drug Interactions

Contraindicated combinations

Combination with non-cardioselective beta-blockers, for example, propranolol, is contraindicated, as there is a risk of developing a hypertensive crisis and severe bradycardia.

Interactions to be taken into account

It is possible to enhance the effect of vasoconstrictors that increase blood pressure, such as epinephrine, with the simultaneous use of tricyclic antidepressants or MAO inhibitors. Similar observations have been described for norepinephrine concentrations of 1:25,000 and epinephrine concentrations of 1:80,000 when used as vasoconstrictors. The concentration of epinephrine in Ultracain^® D-S forte is lower – 1:100,000. However, the possibility of such an enhancement of action must be taken into account.

Local anesthetics enhance the effect of drugs that depress the central nervous system. Opioid analgesics enhance the effect of local anesthetics but increase the risk of respiratory depression.

When performing injections of Ultracain^® D-S forte in patients receiving heparin or acetylsalicylic acid, bleeding may develop at the injection site.

Ultracain^®D-S Forte increases the intensity and duration of action of muscle relaxants.

Ultracain^®D-S Forte exhibits antagonism towards the effect on skeletal muscle with drugs for the treatment of myasthenia, therefore, when using it, especially in high doses, additional correction of myasthenia treatment is required.

Ultracain^®D-S Forte causes a slowdown in the metabolism of local anesthetic drugs.

With simultaneous use with cholinesterase inhibitors, the metabolism of local anesthetic drugs slows down.

Epinephrine is capable of inhibiting insulin release from pancreatic beta cells and reducing the effects of oral hypoglycemic agents.

Halothane may increase the sensitivity of the heart to catecholamines and therefore increase the risk of cardiac arrhythmias after injections of Ultracain^®D-S Forte.

When treating the injection site of a local anesthetic with disinfectant solutions containing heavy metals, the risk of local reactions – swelling, pain – increases.

Storage Conditions

List B.

Ampoules should be stored in a place protected from light at a temperature not exceeding 25°C (77°F); shelf life is 36 months.

Cartridges should be stored in a place protected from light at a temperature not exceeding 30°C (86°F); shelf life is 30 months.

The drug should be stored out of the reach of children.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.