ORABLOC

Articaine is a dental local anesthetic.

Articaine is widely used around the world and is the most popular local anesthetic in many European countries.

Not Available

HCl is an amide local anesthetic.

Local anesthetics block the generation and conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse and by reducing the rate of rise of the action potential.

In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of the affected nerve fibers.

Epinephrine is a vasoconstrictor added to articaine HCl to slow absorption into the general circulation and thus prolong maintenance of an active tissue concentration. 12.2 Pharmacodynamics Clinically, the order of loss of nerve function is as follows: pain; temperature; touch; proprioception; and skeletal muscle tone.

The onset of anesthesia has been shown to be within to 9 minutes of injection of Articaine HCl and Epinephrine.

Complete anesthesia lasts approximately 1 hour for infiltrations and up to approximately 2 hours for nerve block.

Administration of Articaine HCl and

Epinephrine results in a 3.

• to 5-fold increase in plasma epinephrine concentrations compared to baseline; however, in healthy adults it does not appear to be associated with marked increases in blood pressure or heart rate, except in the case of accidental intravascular injection. 12.3 Pharmacokinetics Absorption Following dental injection by the submucosal route of an articaine solution containing epinephrine 1:200,000, articaine reaches peak blood concentration about 25 minutes after a single dose injection and 48 minutes after three doses.

Peak plasma levels of articaine achieved after 68 mg and 204 mg doses are 385 ng/mL and 900 ng/mL, respectively.

Following intraoral administration of a near maximum dose of 476 mg, articaine reaches peak blood concentrations of 2037 ng/mL and 2145 ng/mL for articaine solution containing epinephrine 1:100,000 and 1:200,000, respectively, approximately 22 minutes post-dose.

Approximately 60% to 80% of articaine HCl is bound to human serum albumin and γ -globulins at 37°C in vitro.

Articaine HCl is metabolized by plasma carboxyesterase to its primary metabolite, articainic acid, which is inactive.

In vitro studies show that the human liver microsome P450 isoenzyme system metabolizes approximately 5% to 10% of available articaine with nearly quantitative conversion to articainic acid.

At the dose of 476 mg of articaine, the elimination half-life was 43.8 minutes and 44.4 minutes for articaine solution containing epinephrine 1:100,000 and 1:200,000, respectively.

Articaine is excreted primarily through urine with 53% to 57% of the administered dose eliminated in the first 24 hours following submucosal administration.

Articainic acid is the primary metabolite in urine.

A minor metabolite, articainic acid glucuronide, is also excreted in urine.

Articaine constitutes only 2% of the total dose excreted in urine.

Improve decision support & research outcomes With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.

View sample adverse effects data in our new Data Library! See the data Improve decision support & research outcomes with our structured adverse effects data.

Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics or to unintended subarachnoid injection of local anesthetic solution.

The first consideration is prevention, best accomplished by careful and constant monitoring of cardiovascular and respiratory vital signs and the patient’s state of consciousness after each local anesthetic injection.

At the first sign of change, oxygen should be administered.

The first step in the management of convulsions, as well as hypo-ventilation, consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation as needed.

The adequacy of the circulation should be assessed.

Should convulsions persist despite adequate respiratory support, treatment with appropriate anticonvulsant therapy is indicated.

The practitioner should be familiar with the use of anticonvulsant drugs, prior to the use of local anesthetics.

Supportive treatment of circulatory depression may require administration of intravenous fluids and, when appropriate, a vasopressor.

If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia, acidosis, bradycardia, arrhythmias, and/or cardiac arrest.

If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted.

For additional information about overdose treatment, call a poison control center.

Articaine HCl and

Epinephrine is contraindicated in patients who are hypersensitive to products containing sulfites.

Products containing sulfites may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.

Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

Known hypersensitivity to sulfite.

For dental procedures by intraoral submucosal infiltration or nerve block: For infiltration: 0.5 mL-2.5 mL (20 mg-100 mg articaine HCl) For nerve block: 0.5 mL-3.4 mL (20 mg-136 mg articaine HCl) For oral surgery: 1 ml-5.1 mL (40 mg-204 mg articaine HCl) For most routine dental procedures, Articaine HCl and Epinephrine containing epinephrine 1:200,000 is preferred.

However, when more pronounced homeostasis or improved visualization of the surgical field are required, Articaine HCl and Epinephrine containing epinephrine 1:100,000 may be used.

Maximum recommended dosages

Healthy adults: 7 mg/kg of articaine HCl and 0.0017mg/kg of epinephrine (equivalent to 0.175 mL/kg for either product presentation, articaine HCl and epinephrine 1:100,000 or 1:200,000) Pediatric patients 4-16 years: 7 mg/kg of articaine HCl and 0.0017mg/kg of epinephrine (equivalent to 0.175 mL/kg for either product presentation, articaine HCl and epinephrine 1:100,000 or 1:200,000) 2.1 General Dosing Information Table 1 summarizes the recommended dosages of Articaine HCl and Epinephrine administered by intraoral submucosal infiltration or nerve block for various types of anesthetic dental procedures in healthy adults and pediatric patients.

Table 1: Recommended Dosages for Both Strengths Procedure Articaine HCl and Epinephrine Injection Volume (mL) Total dose of articaine HCl (mg) Infiltration 0.5 mL to 2.5 mL 20 mg to 100 mg Nerve block 0.5 mL to 3.4 mL 20 mg to 136 mg Oral surgery 1 mL to 5.1 mL 40 mg to 204 mg The recommended dosages of Articaine HCl and Epinephrine in healthy adults serve only as a guide to the amount of anesthetic required for most routine dental procedures.

The dosage to be used in adults depend on several factors such as type and extent of surgical procedure, depth of anesthesia, degree of muscular relaxation, and condition of the patient.

In all cases, administer the lowest dosage that will produce the desired result.

The dosages of Articaine HCl and

Epinephrine to be used in pediatric patients aged to 16 years old are determined by the age and weight of the patient and the type of dental procedure.

For most routine dental procedures, Articaine HCl and Epinephrine containing epinephrine 1:200,000 is preferred.

However, when more pronounced hemostasis or improved visualization of the surgical field are required, Articaine HCl and Epinephrine containing epinephrine 1:100,000 may be used.

The onset of anesthesia and the duration of anesthesia are proportional to the dosage of the local anesthetic used.

Exercise caution when employing large volumes because the incidence of adverse reactions may be dose-related. 2.2 Maximum Recommended Dosages Healthy Adults: The maximum dosage of Articaine HCl and Epinephrine is 7 mg/kg of articaine and 0.0017mg/kg of epinephrine (equivalent to 0.175 mL/kg for either product presentation, articaine HCl and 1:100,000 or 1:200,000 epinephrine).

Ages to 16 Years: The maximum dosage of Articaine HCl and Epinephrine is 7 mg/kg of articaine and 0.0017mg/kg of epinephrine (equivalent to 0.175 mL/kg for either product presentation, articaine HCl and 1:100,000 or 1:200,000 epinephrine) . 2.3 Dosing in Special Populations Lower dosages or dosage reduction may be required in debilitated patients, acutely ill patients, elderly patients, and pediatric patients commensurate with their age and physical condition.

No studies have been performed in patients with renal or liver impairment.

Exercise caution when using Articaine HCl and Epinephrine in patients with severe liver disease. 2.4 Important Administration Instructions Visually inspect Articaine HCl and Epinephrine for particulate matter and discoloration prior to administration.

Articaine HCl and

Epinephrine (articaine HCl and epinephrine) Injection is available in glass cartridges.

Prior to using the glass cartridges, disinfect by wiping the cap thoroughly with USP isopropyl alcohol (70%).

Avoid use of isopropyl alcohol, as well as solutions of ethyl alcohol that are not of USP grade because they may contain denaturants that are injurious to rubber.

Immersion is not recommended.

Articaine HCl and

Epinephrine (articaine hydrochloride and epinephrine) injection is a clear, colorless solution available in 1.8 mL single-dose glass cartridges, packaged in boxes of and 100 cartridges in the following two strengths (less than a full cartridge or more than one cartridge may be used for an individual patient): Articaine HCl 4% (40 mg/mL) and epinephrine 1:200,000 (as epinephrine bitartrate 0.09 mg/mL): NDC 67239-0210-1 (50 cartridges/box) Articaine HCl 4% (40 mg/mL) and epinephrine 1:100,000 (as epinephrine bitartrate 0.018 mg/mL): NDC 67239-0209-1 (50 cartridges/box), Both products are formulated with a 10% overage of epinephrine.

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) .

Protect from light.

Do not freeze.

There are no adequate and well-controlled studies in pregnant women with articaine with epinephrine.

Articaine hydrochloride and epinephrine (1:100,000) has been shown to increase fetal deaths and skeletal variations in rabbits when given in doses approximately 4 times the maximum recommended human dose (MRHD).

Articaine HCl and

Epinephrine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In embryo-fetal toxicity studies in rabbits, 80 mg/kg, subcutaneously (approximately 4 times the MRHD based on body surface area) caused fetal death and increased fetal skeletal variations, but these effects may be attributable to severe maternal toxicity, including seizures, observed at this dose.

In contrast, no embryo-fetal toxicities were observed when articaine and epinephrine (1:100,000) was administered subcutaneously throughout organogenesis at doses up to 40 mg/kg in rabbits and 80 mg/kg in rats (approximately 2 times the MRHD based on body surface area).

In pre.

• and postnatal developmental studies subcutaneous administration of articaine hydrochloride to pregnant rats throughout gestation and lactation, at a dose of 80 mg/kg (approximately 2 times the MRHD based on body surface area) increased the number of stillbirths and adversely affected passive avoidance, a measure of learning, in pups.

This dose also produced severe maternal toxicity in some animals.

A dose of 40 mg/kg (approximately equal to the MRHD on a mg/m2 basis) did not produce these effects.

A similar study using articaine and epinephrine (1:100,000) rather than articaine hydrochloride alone produced maternal toxicity, but no effects on offspring.

It is not known whether Articaine HCl and Epinephrine is excreted in human milk.

Because many drugs are excreted in human milk, caution should be exercised when Articaine HCl and Epinephrine is administered to a nursing woman.

When using Articaine HCl and

Epinephrine, nursing mothers may choose to pump and discard breast milk for approximately 4 hours (based on plasma half-life) following an injection of Articaine HCl and Epinephrine (to minimize infant ingestion) and then resume breastfeeding.

Safety and effectiveness of Articaine HCl and Epinephrine in pediatric patients below the age of 4 years have not been established.

Safety of doses greater than 7 mg/kg (0.175 mL/kg) in pediatric patients has not been established.

The safety and effectiveness of Articaine HCl and Epinephrine for local, infiltrative, or conductive anesthesia in both simple and complex dental procedures have been established in pediatric patients ages to 16 years old.

Safety and effectiveness was established in clinical trials with 61 pediatric patients between the ages of and 16 years administered another product containing articaine hydrochloride 4% and epinephrine 1:100,000 injections.

Fifty-one of these patients received doses from 0.76 mg/kg to 5.65 mg/kg (0.9 mL to 5.1 mL) of articaine HCl for simple dental procedures and 10 patients received doses between 0.37 mg/kg and 7.48 mg/kg (0.7 mL to 3.9 mL) of articaine HCl for complex dental procedures.

Approximately 13% of these pediatric patients required additional injections of anesthetic for complete anesthesia.

Safety of doses greater than 7 mg/kg (0.175 mL/kg) of articaine HCl in pediatric patients has not been established.

Dosages in pediatric patients should be reduced, commensurate with age, body weight, and physical condition.

In clinical trials, 54 patients between the ages of and 75 years, and 11 patients 75 years and over received another product containing articaine and epinephrine 1:100,000.

Among all patients between and 75 years, doses from 0.43 mg/kg to 4.76 mg/kg (0.9 mL to 11.9 mL) of articaine HCl were administered safely to 35 patients for simple procedures and doses from 1.05 mg/kg to 4.27 mg/kg (1.3 mL to 6.8 mL) of articaine HCl were administered safely to 19 patients for complex procedures.

Among the 11 patients ≥ 75 years old, doses from 0.78 mg/kg to 4.76 mg/kg (1.3 mL to 11.9 mL) of articaine HCl were administered safely to 7 patients for simple procedures and doses of 1.12 mg/kg to 2.17 mg/kg (1.3 mL to 5.1 mL) of articaine HCl were safely administered to 4 patients for complex procedures.

Approximately 6% of patients between the ages of and 75 years and none of the 11 patients 75 years of age or older required additional injections of anesthetic for complete anesthesia compared with 11% of patients between and 65 years old who required additional injections.

No overall differences in safety or effectiveness were observed between elderly subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.