Zorcaine

Zorcaine is a brand name medication included in the following groups of medications: Adrenergic and dopaminergic agents, Inhaled alpha and beta adrenoreceptor agonists, Local hemostatics, Other agents for local oral treatment, Sympathomimetics in glaucoma therapy, Sympathomimetics, plain, Amides. For more information about Zorcaine see its generics Articaine, Epinephrine

Use Zorcaine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Your doctor will give this medicine.
• It is given as a shot into the gums.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

• If you need to store Zorcaine at home, talk with your doctor, nurse, or pharmacist about how to store it.

ZurcaineTM, an amide local anesthetic containing a vasoconstrictor, is indicated for local, infiltrative, or conductive anesthesia in both simple and complex dental procedures.

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 ZorcaineTM containing epinephrine 1:100,000. Table 3 displays the adverse reactions reported in clinical trials where 182 individuals were exposed to ZorcaineTM containing epinephrine 1:100,000 and 179 individuals were exposed to articaine hydrochloride 4% containing epinephrine 1:200,000. containing epinephrine 1:200,000.

Adverse reactions observed in at least 1% of patients.

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 Zorcaine containing Epinephrine 1:100,000

Body System/Reaction	Zorcaine 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 hydrochloride 4% containing Epinephrine 1:200,000 and Zorcaine containing Epinephrine 1:100,000

Reaction	articaine hydrochloride 4% with epinephrine 1:200,000 (N=179) Incidence	Zorcaine with 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 Zorcaine

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 ZorcaineTM. 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.

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).

Three randomized, double-blind, active-controlled studies were designed to evaluate effectiveness of Zorcaine™ containing epinephrine 1:100,000 as a dental anesthetic. Patients ranging in age from 4 years to over 65 years old underwent simple dental procedures such as single uncomplicated extractions, routine operative procedures, single apical resections, and single crown procedures, or complex dental procedures such as multiple extractions, multiple crowns and/or bridge procedures, multiple apical resections, alveolectomies, muco-gingival operations, and other surgical procedures on the bone. Zorcaine™ containing epinephrine 1:100,000 was administered as submucosal infiltration and/or nerve block. Efficacy was measured immediately following the procedure by having the patient and investigator rate the patient’s procedural pain using a 10 cm visual analog scale (VAS), in which a score of zero represented no pain and a score of 10 represented the worst pain imaginable. Mean patient and investigator VAS pain scores were 0.3-0.4 cm for simple procedures and 0.5-0.6 cm for complex procedures.
Four randomized, double-blind, active-controlled studies were performed comparing Zorcaine™ containing epinephrine 1:100,000 versus articaine hydrochloride 4% containing epinephrine 1:200,000. The first two studies used electric pulp testers (EPT) to evaluate the success rate (maximum EPT value within 10 minutes), onset, and duration of Zorcaine™ containing epinephrine 1:100,000 versus articaine hydrochloride 4% containing epinephrine 1:200,000 and articaine solution without epinephrine in healthy adults between 18 and 65 years old. Results indicated that the anesthetic characteristics of the 1:100,000 and 1:200,000 formulations are not significantly different.
A third study compared the difference in visualization of the surgical field after administration of Zorcaine™ containing epinephrine 1:100,000 versus articaine hydrochloride 4% containing epinephrine 1:200,000 during bilateral maxillary periodontal surgeries in patients ranging from 21 to 65 years old. Zorcaine™ containing epinephrine 1:100,000 provided better visualization of the surgical field and less blood loss during the procedures. In a fourth study, designed to assess and compare cardiovascular safety, when the maximum dose of each formulation was administered, no clinically relevant differences in blood pressure or heart rate between formulations were observed.

Kaplan, EL, editor. Cardiovascular disease in dental practice. Dallas; American Heart Association; 1986.

NDC 31382-830-50

Cook-Waite

ZorcaineTM (articaine HCl and epinephrine ) Injection

Articaine hydrochloride 4% and epinephrine 1:100,000

FOR INFILTRATION AND NERVE BLOCK ANESTHESIA

Rx only

50 Cartridges • 1.7 mL each

Warning: Contains sodium metabisulfite. See warnings section of insert for detailes.

See warnings section of insert for details

Marketed by Carestream Dental a division of Carestream Health, Inc.

Cook-Waite and Zorcaine are trademarks of Creamstream Health, Inc.

For more information, call 1-800-933-8031 (U.s / Canada)

Manufactured for CARESTREAM HEALTH INC by Novocol Pharmaceutical of Canada Inc.

Cambridge, Ontario, Canada N1R 6X3

Zorcaine  articaine hydrochloride and epinephrine bitartrate injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:31382-830 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 Bitartrate 0.018 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:31382-830-50 50 CARTRIDGE (CARTRIDGE) in 1 CARTON 1 1.7 mL in 1 CARTRIDGE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020971 09/01/2011

Labeler - Carestream Health, Inc. (793169512)

Registrant - Novocol Pharmaceutical of Canada, Inc. (201719960)

Establishment
Name	Address	ID/FEI	Operations
Novocol Pharmaceutical of Canada, Inc.		201719960	MANUFACTURE

Revised: 08/2011   Carestream Health, Inc.