SCANDONEST PLAIN- mepivacaine hydrochloride injection, solution 
SCANDONEST L- mepivacaine hydrochloride and levonordefrin injection, solution 
Septodont, Inc.

----------

SCANDONEST® 3% PLAIN
(Mepivacaine hydrochloride injection, USP)
SCANDONEST® 2% L
(WITH LEVONORDEFRIN 1:20,000)
(Mepivacaine hydrochloride and Levonordefrin injection, USP)

Rx only

THESE SOLUTIONS ARE INTENDED FOR DENTAL USE ONLY.

Description

Mepivacaine hydrochloride, a tertiary amide used as a local anesthetic, is 1-methyl-2', 6'-pipecoloxylidide monohydrochloride with the following structural formula :

Image from Drug Label Content

C15 H22 N2O. HCL                                                                        M.W. 282.81

It is a white, crystalline, odorless powder soluble in water, but very resistant to both acid and alkaline hydrolysis.

Levonordefrin, a sympathomimetic amine used as a vasoconstrictor in local anesthetic solutions, is (-)-a-(1- Aminoethyl)- 3, 4-dihydroxybenzyl alcohol with the following structural formula :

Image from Drug Label Content

C9 H13 NO3                                                                                 M.W. 183.21

It is a white or buff-colored crystalline solid, freely soluble in aqueous solutions of mineral acids, but practically insoluble in water;

DENTAL CARTRIDGES MAY NOT BE AUTOCLAVED.

SCANDONEST 3% PLAIN (mepivacaine hydrochloride injection 3%) and SCANDONEST 2% L (mepivacaine hydrochloride 2% with levonordefrin 1:20,000 injection) are sterile solutions for injection.

Composition

Cartridge
Each mL contains :2%3%
Mepivacaine hydrochloride20     mg30 mg
Levonordefrin0.05 mg-
Sodium chloride4      mg  6 mg
Potassium metabisulfite1.2   mg
Edetate disodium0.25 mg
Sodium hydroxide q.s. ad pH
Hydrochloric acid
0.5   mg
Water for injections q.s. ad1      mL  1 mL

The pH of the 2% cartridge solution is adjusted between 3.3 and 5.5 with NaOH.

The pH of the 3% cartridge solution is adjusted between 4.5 and 6.8 with NaOH.

Clinical Pharmacology

SCANDONEST stabilizes the neuronal membrane and prevents the initiation and transmission of nerve impulses, thereby effecting local anesthesia.

SCANDONEST is rapidly metabolized, with only a small percentage of the anesthetic (5 to 10 percent) being excreted unchanged in the urine. SCANDONEST, because of its amide structure, is not detoxified by the circulating plasma esterases. The liver is the principal site of metabolism, with over 50 percent of the administered dose being excreted into the bile as metabolites. Most of the metabolized mepivacaine is probably resorbed in the intestine and then excreted into the urine since only a small percentage is found in the feces. The principal route of excretion is via the kidney. Most of the anesthetic and its metabolites are eliminated within 30 hours. It has been shown that hydroxylation and N-demethylation, which are detoxification reactions, play important roles in the metabolism of the anesthetic. Three metabolites of mepivacaine have been identified from adult humans : two phenols, which are excreted almost exclusively as their glucuronide conjugates, and the N-demethylated compound (2', 6'-pipecoloxylidide).

The onset of action is rapid (30 to 120 seconds in the upper jaw ; 1 to 4 minutes in the lower jaw) and SCANDONEST 3% PLAIN will ordinarily provide operating anesthesia of 20 minutes in the upper jaw and 40 minutes in the lower jaw.

SCANDONEST 2% L with levonordefrin 1:20,000 provides anesthesia of longer duration for more prolonged procedures, 1 hour to 2.5 hours in the upper jaw and 2.5 hours to 5.5 hours in the lower jaw.

SCANDONEST does not ordinarily produce irritation or tissue damage.

Levonordefrin is a sympathomimetic amine used as a vasoconstrictor in local anesthetic solutions. It has pharmacologic activity similar to that of epinephrine but it is more stable than epinephrine. In equal concentrations, levonordefrin is less potent than epinephrine in raising blood pressure, and as a vasoconstrictor.

Indications and usage

SCANDONEST is indicated for production of local anesthesia for dental procedures by infiltration or nerve block in adults and children.

Contraindications

Mepivacaine is contraindicated in patients with a known hypersensitivity to amide-type local anesthetics.

Warnings

RESUSCITATIVE EQUIPMENT AND DRUGS SHOULD BE IMMEDIATELY AVAILABLE. (See ADVERSE REACTIONS).

Reactions resulting in fatality have occurred on rare occasions with the use of local anesthetics, even in the absence of a history of hypersensitivity.

Fatalities may occur with use of local anesthetics in the head and neck region as the result of retrograde arterial flow to vital CNS areas even when maximum recommended doses are observed. The practitioner should be alert to early evidences of alteration in sensorium or vital signs.

The solution which contains a vasoconstrictor (SCANDONEST 2% L) should be used with extreme caution for patients whose medical history and physical evaluation suggest the existence of hypertension, arteriosclerotic heart disease, cerebral vascular insufficiency, heart block, thyrotoxicosis and diabetes. etc.

The solution which contains a vasoconstrictor (SCANDONEST 2% L) also contains potassium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

SCANDONEST 3% PLAIN is sulfite free.

Precautions

The safety and effectiveness of mepivacaine depend upon proper dosage, correct technique, adequate precautions, and readiness for emergencies.

The lowest dose that results in effective anesthesia should be used to avoid high plasma levels and possible adverse effects. Injection of repeated doses of mepivacaine may cause significant increase in blood levels with each repeated dose due to slow accumulation of the drug or its metabolites, or due to slower metabolic degradation than normal.

Tolerance varies with the status of the patient. Debilitated, elderly patients, acutely ill patients, and children should be given reduced doses commensurate with their weight and physical status.

Mepivacaine should be used with caution in patients with a history of severe disturbances of cardiac rhythm or heart block.

INJECTIONS SHOULD ALWAYS BE MADE SLOWLY WITH ASPIRATION TO AVOID INTRAVASCULAR INJECTION AND THEREFORE SYSTEMIC REACTION TO BOTH LOCAL ANESTHETIC AND VASOCONSTRICTOR.

If sedatives are employed to reduce patient apprehension, use reduced doses, since local anesthetic agents, like sedatives, are central nervous system depressants which in combination may have an additive effect. Young children should be given minimal doses of each agent.

Changes in sensorium such as excitation, disorientation, drowsiness, may be early indications of a high blood level of the drug and may occur following inadvertent intravascular administration or rapid absorption of mepivacaine.

Local anesthetic procedures should be used with caution when there is inflammation and/or sepsis in the region of the proposed injection.

Information for Patients

The patient should be cautioned against loss of sensation and possibility of biting trauma should the patient attempt to eat or chew gum prior to return of sensation.

Clinically Significant Drug Interactions

The administration of local anesthetic solutions containing vasopressors, such as levonordefrin, epinephrine or norepinephrine, to patients receiving tricyclic antidepressants or monoamine oxidase inhibitors may produce severe prolonged hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential. Concurrent administration of vasopressor drugs and of ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents.

Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine.

Solutions containing a vasoconstrictor should be used cautiously in the presence of diseases which may adversely affect the patient's cardiovascular system. Serious cardiac arrhythmias may occur if preparations containing a vasoconstrictor are employed in patients during or following the administration of potent inhalation anesthetics.

Mepivacaine SHOULD BE USED WITH CAUTION IN PATIENTS WITH KNOWN DRUG ALLERGIES AND SENSITIVITIES. A thorough history of the patient's prior experience with mepivacaine or other local anesthetics as well as concomitant or recent drug use should be taken (see CONTRAINDICATIONS). Patients allergic to methylparaben or paraaminobenzoic acid derivatives (procaine, tetracaine, benzocaine, ect.) have not shown cross-sensitivity to agents of the amide type such as mepivacaine. Since mepivacaine is metabolized in the liver and excreted by the kidneys, it should be used cautiously in patients with liver and renal disease.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies of mepivacaine hydrochloride in animals to evaluate the carcinogenic and mutagenic potential or the effect on fertility have not been conducted.

Pregnancy

Teratogenic effects

Pregnancy Category C

Animal reproduction studies have not been conducted with this solution. It is also not known whether this solution can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. This solution should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when this solution, is administered to a nursing woman.

Pediatric Use

Great care must be exercised in adhering to safe concentrations and dosages for pedodontic administration (see DOSAGE AND ADMINISTRATION).

Adverse reactions

Systemic adverse reactions involving the central nervous system and the cardiovascular system usually result from high plasma levels due to excessive dosage, rapid absorption, or inadvertent intravascular injection.

A small number of reactions may result from hypersensitivity, idiosyncrasy or diminished tolerance to normal dosage on the part of the patient.

Reactions involving the central nervous system are characterized by excitation and/or depression. Nervousness, dizziness, blurred vision, or tremors may occur followed by drowsiness, convulsions, unconsciousness, and possibly respiratory arrest. Since excitement may be transient or absent, the first manifestations may be drowsiness merging into unconsciousness and respiratory arrest.

Cardiovascular reactions are depressant. They may be the result of direct drug effect or more commonly in dental practice, the result of vasovagal reaction, particularly if the patient is in the sitting position. Failure to recognize premonitory signs such as sweating, feeling of faintness, changes in pulse or sensorium may result in progressive cerebral hypoxia and seizure or serious cardiovascular catastrophe. Management consists of placing the patient in the recumbent position and administration of oxygen. Vasoactive drugs such as ephedrine or methoxamine may be administered intravenously.

Allergic reactions are rare and may occur as a result of sensitivity to the local anesthetic and are characterized by cutaneous lesions of delayed onset or urticaria, edema and other manifestations of allergy. The detection of sensitivity by skin testing is of limited value. As with other local anesthetics, anaphylactoid reactions to mepivacaine have occurred rarely. The reactions may be abrupt and severe and are not usually dose related. Localized puffiness and swelling may occur.

Overdosage

Treatment of a patient with toxic manifestations consists of assuring and maintaining a patent airway and supporting ventilation (respiration) as required. This usually will be sufficient in the management of most reactions. Should a convulsion persist despite ventilatory therapy, small increments of anticonvulsive agents may be given intravenously, such as benzodiazepine (e.g . diazepam) or ultrashort-acting barbiturates (e.g. thiopental, or thiamylal) or short-acting barbiturates (e.g. pentobarbital or secobarbital). Cardiovascular depression may require circulatory assistance with intravenous fluids and/or vasopressor (e.g. ephedrine) as dictated by the clinical situation. Allergic reactions should be managed by conventional means.

Intravenous and subcutaneous LD50's in mice for mepivacaine hydrochloride 3% are 33 and 258 mg/kg, respectively. The acute IV and SC LD50's in mice for mepivacaine hydrochloride 2% with levonordefrin 1:20,000 are 30 and 184 mg/kg, respectively.

Dosage and administration

As with all local anesthetics the dose varies and depends upon the area to be anesthetized, the vascularity of the tissues, individual tolerance and the technique of anesthesia. The lowest dose needed to provide effective anesthesia should be administered. For specific techniques and procedures refer to standard dental manuals and textbooks.

For infiltration and block injections in the upper or lower jaw, the average dose of 1 cartridge will usually suffice.

Each cartridge contains 1.7 mL (34 mg of 2% or 51 mg of 3%).

5.3 cartridges (180 mg of the 2% solution or 270 mg of the 3% solution) are usually adequate to effect anesthesia of the entire oral cavity. Whenever a larger dose seems to be necessary for an extensive procedure, the maximum dose should be calculated accordlng to the patient's weight. A dose of up to 3 mg per pound of body weight may be administered. At any single dental sitting the total dose for all injected sites should not exceed 400 mg in adults.

The maximum pediatric dose should be carefully calculated :

Maxlmum Dose for pediatric population =
Child's Weight ( lbs )× Maximum Recommended Dose
          150                          For Adults (400 mg)

The following table, approximating these calculations, may also be used as a guide. This table is based upon a recommended maximum for larger pediatric population of 5.3 cartridges (the maximum recommended adult dose) during any single dental sitting, regardless of the child's weight or (for 2 % mepivacaine) calculated maximum amount of drug :

Maximum Allowable Dosage
3% Mepivacaine
(Plain)
2% Mepivacaine
1:20,000 Levonordefrin
3 mg/lb
(270 mg max)
3 mg/lb
(180 mg max)
Weight
(lbs)
mgNumber of CartridgesmgNumber of Cartridges
  20  601.2  601.8
  30  901.8  902.6
  401202.31203.5
  501502.91504.4
  601803.51805.3
  802404.71805.3
1002705.31805.3
1202705.31805.3

Adapted from Malamed, Stanley F : Handbook of medical emergencies in the dental office, ed. 2, St Louis, 1982. The C V Mosby Co.

When using SCANDONEST for infiltration or regional block anesthesia, injection should always be made slowly and with frequent aspiration.

Any unused portion of a cartridge should be discarded.

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

Disinfection of cartridges

As in the case of any cartridge, the diaphragm should be disinfected before needle puncture. The diaphragm should be thoroughly swabbed with either pure 91% isopropyl alcohol or 70% ethyl alcohol, USP just prior to use. Many commercially available alcohol solutions contain ingredients which are injurious to container components, and therefore, should not be used. Cartridges should not be immersed in any solution.

How supplied

- SCANDONEST 2% L (Mepivacaine Hydrochoride and Levonordefrin injection, USP), is available in cardboard boxes containing 5 blisters of 10 × 1.7 mL dental cartridges, 50 per cartons (NDC 12862-1097-8).

- SCANDONEST 3%Plain (Mepivacaine hydrochoride injection, USP), is available in cardboard boxes containing 5 blisters of 10 × 1.7 mL dental cartridges, 50 per cartons (NDC 12862-1098-9).

Store at room temperature, below 25°C (77°F). Protect from light. Do not permit to freeze.

CANS : For protection from light, retain in can until time of use. Once opened, the can should be reclosed using the plastic cap.

BOXES : For protection from light, retain in box until time of use. Once opened, the box should be reclosed by closing the top flap.

SCANDONEST 2%L should not be use if color is pinkish or darker than slightly yellow or if it contains a precipitate.

Cartridge warmers should not be used with SCANDONEST products.

10/04 (1)

Distributed in the U.S.A. by :
Septodont, Inc.
245 Quigley Boulevard - Suite C
NEW CASTLE, Delaware 19720 - U.S.A.

Made in France by :
SEPTODONT

® 05 14 117 90 00

SCANDONEST PLAIN 
mepivacaine hydrochloride injection, solution
Product Information
Product TypeHUMAN PRESCRIPTION DRUG LABELItem Code (Source)NDC:12862-1098
Route of AdministrationSUBCUTANEOUSDEA Schedule    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
Mepivacaine Hydrochloride (Mepivacaine) 30 mg  in 1 mL
Inactive Ingredients
Ingredient NameStrength
Sodium Chloride6 mg  in 1 mL
Sodium hydroxide 
Water 
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:12862-1098-95 in 1 CARTON
110 in 1 BLISTER PACK
11.7 mL in 1 CARTRIDGE
SCANDONEST L 
mepivcaine hydrochloride and levonordefrin injection, solution
Product Information
Product TypeHUMAN PRESCRIPTION DRUG LABELItem Code (Source)NDC:12862-1097
Route of AdministrationSUBCUTANEOUSDEA Schedule    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
Mepivacaine Hydrochloride (Mepivacaine) 20 mg  in 1 mL
Levonordefrin (Levonordefrin) 0.05 mg  in 1 mL
Inactive Ingredients
Ingredient NameStrength
Sodium Chloride4 mg  in 1 mL
Potassium metabisulfite1.2 mg  in 1 mL
Edetate disodium0.25 mg  in 1 mL
Hydrochloric acid0.5 mg  in 1 mL
Sodium hydroxide 
Water 
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:12862-1097-85 in 1 CARTON
110 in 1 BLISTER PACK
11.7 mL in 1 CARTRIDGE
Labeler - Septodont, Inc.

Revised: 6/2006
Document Id: 2816D9CB-8709-C70B-00F7-37C4F03E0A8D
Set id: 2C5DCA54-8D86-411D-A195-4C954D4EBE8F
Version: 1
Effective Time: 20060608
 
Septodont, Inc.