Articaine and Epinephrine Injection

Name: Articaine and Epinephrine Injection

Adverse Reactions

Reactions to articaine are characteristic of those associated with other amide-type local anesthetics. Adverse reactions to this group of drugs may also result from excessive plasma levels (which may be due to overdosage, unintentional intravascular injection, or slow metabolic degradation), injection technique, volume of injection, or hypersensitivity or they may be idiosyncratic.

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The reported adverse reactions are derived from clinical trials in the United States and the United Kingdom. Table 2 displays the adverse reactions reported in clinical trials where 882 individuals were exposed to Articaine HCl and Epinephrine containing epinephrine 1:100,000. Table 3 displays the adverse reactions reported in clinical trials where 182 individuals were exposed to Articaine HCl and Epinephrine containing epinephrine 1:100,000 and 179 individuals were exposed to Articaine HCl and Epinephrine containing epinephrine 1:200,000. 

Adverse reactions observed in at least 1% of patients:

Table 2: Adverse Reactions in Controlled Trials with an Incidence of 1% or Greater in Patients Administered Articaine HCl and Epinephrine containing Epinephrine 1:100,000
Body System/Reaction Articaine HCl and Epinephrine containing epinephrine 1:100,000 (N=882) Incidence
Body as a whole
Face Edema 13 (1%)
Headache 31 (4%)
Infection 10 (1%)
Pain 114 (13%)
Digestive system
Gingivitis 13 (1%)
Nervous system
Paresthesia 11 (1%)
Table 3: Adverse Reactions in Controlled Trials with an Incidence of 1% or Greater in Patients Administered Articaine HCl and Epinephrine containing Epinephrine 1:200,000 and Articaine HCl and Epinephrine containing Epinephrine 1:100,000
Reaction Articaine HCl and epinephrine 1:200,000
(N=179)
Incidence
Articaine HCl and epinephrine 1:100,000
(N=182)
Incidence
Any adverse reaction 33 (18%) 35 (19%)
Pain 11 (6.1%) 14 (7.6%)
Headache 9 (5%) 6 (3.2%)
Positive blood aspiration into syringe 3 (1.6%) 6 (3.2%)
Swelling 3 (1.6%) 5 (2.7%)
Trismus 1 (0.5%) 3 (1.6%)
Nausea and emesis 3 (1.6%) 0 (0%)
Sleepiness 2 (1.1%) 1 (0.5%)
Numbness and tingling 1 (0.5%) 2 (1%)
Palpitation 0 (0%) 2 (1.%)
Ear symptoms (earache, otitis media) 1 (0.5%) 2 (1%)
Cough, persistent cough 0 (0%) 2 (1%)

Adverse reactions observed in less than 1% of patients:

Table 4: Adverse Reactions in Controlled Trials with an Incidence of Less than 1% but Considered Clinically Relevant in Patients Administered Articaine HCl and Epinephrine
Body System Reactions
Body as a Whole Asthenia; back pain; injection site pain; burning sensation above injection site; malaise; neck pain
Cardiovascular System Hemorrhage; migraine; syncope; tachycardia; elevated blood pressure
Digestive System Dyspepsia; glossitis; gum hemorrhage; mouth ulceration; nausea; stomatitis; tongue edemas; tooth disorder; vomiting
Hemic and Lymphatic System Ecchymosis; lymphadenopathy
Metabolic and Nutritional System Edema; thirst
Musculoskeletal System Arthralgia; myalgia; osteomyelitis
Nervous System Dizziness; dry mouth; facial paralysis; hyperesthesia; increased salivation; nervousness; neuropathy; paresthesia; somnolence; exacerbation of Kearns-Sayre Syndrome
Respiratory System Pharyngitis; rhinitis; sinus pain; sinus congestion
Skin and Appendages Pruritus; skin disorder
Special Senses Ear pain; taste perversion

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Articaine HCl and Epinephrine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a casual relationship to drug exposure.

Persistent paresthesias of the lips, tongue, and oral tissues have been reported with use of articaine hydrochloride, with slow, incomplete, or no recovery. These postmarketing events have been reported chiefly following nerve blocks in the mandible and have involved the trigeminal nerve and its branches.

Hypoesthesia has been reported with use of articaine, especially in pediatric age groups, which is usually reversible. Prolonged numbness can result in soft tissue injuries such as that of the lips and tongue in these age groups.

Ischemic injury and necrosis have been described following use of articaine with epinephrine and have been postulated to be due to vascular spasm of terminal arterial branches.

Paralysis of ocular muscles has been reported, especially after posterior, superior alveolar injections of articaine during dental anesthesia. Symptoms include diplopia, mydriasis, ptosis, and difficulty in abduction of the affected eye. These symptoms have been described as developing immediately after injection of the anesthetic solution and persisting one minute to several hours, with generally complete recovery.

Overdosage

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 [see Warnings and Precautions (5.1, 5.2)].

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 (1-800-222-1222).

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies to evaluate the carcinogenic potential of articaine HCl in animals have not been conducted. Five standard mutagenicity tests, including three in vitro tests (the nonmammalian Ames test, the mammalian Chinese hamster ovary chromosomal aberration test, and a mammalian gene mutation test with articaine HCl) and two in vivo mouse micronucleus tests (one with articaine and epinephrine 1:100,000 and one with articaine HCl alone) showed no mutagenic effects.

No effects on male or female fertility were observed in rats for articaine and epinephrine 1:100,000 administered subcutaneously in doses up to 80 mg/kg/day (approximately 2 times the MRHD based on body surface area).

How Supplied/Storage and Handling


Articaine HCl and Epinephrine Injection is available in 1.7 mL single use glass cartridges, packaged in boxes of 50 cartridges in the following two strengths:

  • Articaine HCl and Epinephrine containing articaine HCl 4% (40 mg/mL) and epinephrine 1:200,000 (as epinephrine bitartrate 0.009 mg/mL) (NDC 0404-6625-05)
  • Articaine HCl and Epinephrine containing articaine HCl 4% (40 mg/mL) and epinephrine 1:100,000 (as epinephrine bitartrate 0.018 mg/mL) (NDC 0404-6620-05)

Articaine HCl 4% and Epinephrine, 1:100,000 with Monoject Disposable Dental Injector (Articaine Hydrochloride and Epinephrine) Injection Solution is available in cardbord boxes containing 30 disposable single use injectors, each
containing a single 1.7 mL cartridge (NDC 0404-6620-30)

Storage and Handling

Store at controlled room temperature 25°C (77°F) with brief excursions permitted between 15° and 30°C (59°F-86°F) [see USP Controlled Room Temperature]. Protect from light. Do Not Freeze.

Limited only to cartridges when sold without dental injector: For chemical disinfection of the carpule, either isopropyl alcohol (91%) or ethyl alcohol (70%) is recommended. Many commercially available brands of isopropyl (rubbing) alcohol, as well as solutions of ethyl alcohol not of U.S.P. grade, contain denaturants that are injurious to rubber and therefore are not to be used.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Patient Counseling Information

Loss of Sensation and Muscle Function:

  • Inform patients in advance of the possibility of temporary loss of sensation and muscle function following infiltration and nerve block injections [see Adverse Reactions (6.2)].
  • Instruct patients not to eat or drink until normal sensation returns.

Manufactured by Novocol Pharmaceutical of Canada, Inc.
Cambridge, Ontario, Canada N1R 6X3


Principal Display Panel - Carton

HENRY SCHEIN®

NDC 0404-6620-30

Articaine HCl 4% and Epinephrine 1:100,000
with Monoject™ Disposable Dental Injector
(Articaine Hydrochloride and Epinephrine) Injection Solution

For Single Patient Use Only

Intraoral Submucosal Injection
Contains Sodium Metabisulfite
For Infiltration and Nerve Block Anesthesia

30 single-patient use
disposable injectors

ARTICAINE HYDROCHLORIDE AND EPINEPHRINE 
articaine hydrochloride and epinephrine injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0404-6620
Route of Administration SUBCUTANEOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Articaine Hydrochloride (Articaine) Articaine Hydrochloride 40 mg  in 1 mL
Epinephrine Bitartrate (Epinephrine) Epinephrine 0.01 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
Sodium chloride 1.6 mg  in 1 mL
Sodium metabisulfite 0.5 mg  in 1 mL
Water  
Sodium Hydroxide  
Packaging
# Item Code Package Description
1 NDC:0404-6620-30 30 SYRINGE in 1 CARTON
1 1 CARTRIDGE in 1 SYRINGE
1 1.7 mL in 1 CARTRIDGE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA020971 12/12/2016
Labeler - Henry Schein (012430880)
Registrant - Novocol Pharmaceutical of Canada, Inc. (201719960)
Establishment
Name Address ID/FEI Operations
Novocol Pharmaceutical of Canada, Inc. 201719960 MANUFACTURE(0404-6620)
Revised: 12/2016   Henry Schein
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