Isocaine

ISOCAINE- mepivacaine hydrochloride injection, solution
ISOCAINE WITH LEVONORDEFRIN- mepivacaine hydrochloride and levonordefrin injection, solution
Septodont Inc

CAUTION: FEDERAL LAW PROHIBITS DISPENSING WITHOUT PRESCRIPTION.

THESE SOLUTIONS ARE INTENDED FOR DENTAL USE ONLY.

DESCRIPTION

ISOCAINE (Mepivacaine Hydrochloride), a tertiary amine used as a local anesthetic, is 1-methyl-2′, 6′ — pipecoloxylidide monohydrochloride with the following structural formula:

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 solution, is (-)-a-(1-Aminoethyl)-3, 4-dihydroxybenzyl alcohol with the following structural formula:

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.

ISOCAINE 3% Injection and ISOCAINE 2% with Levonordefrin 1:20,000 Injection are sterile solutions for injection.

COMPOSITION	CARTRIDGE
Each mL contains:	2%	3%
Mepivacaine Hydrochloride	20 mg	30 mg
Levonordefrin (as the base)	0.05 mg	–
Sodium Chloride	4 mg	3 mg
Sodium Bisulfite	1 mg	–
Water For Injection, qs. ad.	1 mL	1 mL
The pH of the 2% cartridge solution is adjusted between 3.3 and 5.5 with NaOH or HCI.
The pH of the 3% cartridge solution is adjusted between 4.5 and 6.8 with NaOH or HCI.

CLINICAL PHARMACOLOGY

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

ISOCAINE is rapidly metabolized, with only a small percentage of the anesthetic (5 to 10 percent) being excreted unchanged in the urine. Mepivacaine 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 ISOCAINE 3% without vasoconstrictor will ordinarily provide operating anesthesia of 20 minutes in the upper jaw and 40 minutes in the lower jaw.

ISOCAINE 2% 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.

ISOCAINE 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.

Isocaine Indications and Usage

ISOCAINE is indicated for production of local anesthesia for dental procedures by infiltration or nerve block in adults and pediatric patients.

CONTRAINDICATIONS

ISOCAINE 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 hyper- sensitivity.

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 evidence of alteration in sensorium or vital signs.

The solution which contains a vasoconstrictor 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.

Isocaine 2% with Levonordefrin 1:20,000 injection (Mepivacaine Hydrochloride and Levonordefrin Injection, USP) contains sodium bisulfite, 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 non-asthmatic people. Isocaine 3% injection (Mepivacaine Hydrochloride Injection USP 3%) 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 increases 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 pediatric patients 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 pediatric patients should be given minimal doses of each agent.

Changes in sensorium such as excitation, disorientation or 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 disease 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 para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) 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.