Scandonest

Dosage Form: 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 :

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 :

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 hydrochloride	20     mg	30 mg
Levonordefrin	0.05 mg	-
Sodium chloride	4      mg	6 mg
Potassium metabisulfite	1.2   mg
Edetate disodium	0.25 mg
Sodium hydroxide q.s. ad pH Hydrochloric acid	0.5   mg
Water for injections q.s. ad	1      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)	mg	Number of Cartridges	mg	Number of Cartridges
20	60	1.2	60	1.8
30	90	1.8	90	2.6
40	120	2.3	120	3.5
50	150	2.9	150	4.4
60	180	3.5	180	5.3
80	240	4.7	180	5.3
100	270	5.3	180	5.3
120	270	5.3	180	5.3

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 Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 12862-1098 Route of Administration SUBCUTANEOUS DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Mepivacaine Hydrochloride (Mepivacaine) Active 30 MILLIGRAM  In 1 MILLILITER Sodium Chloride Inactive 6 MILLIGRAM  In 1 MILLILITER Sodium hydroxide Inactive   Water Inactive

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 12862-1098-9 5 BLISTER PACK In 1 CARTON contains a BLISTER PACK 1 10 CARTRIDGE In 1 BLISTER PACK This package is contained within the CARTON (12862-1098-9) and contains a CARTRIDGE 1 1.7 mL (MILLILITER) In 1 CARTRIDGE This package is contained within a BLISTER PACK and a CARTON (12862-1098-9)

Scandonest L  mepivcaine hydrochloride and levonordefrin  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 12862-1097 Route of Administration SUBCUTANEOUS DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Mepivacaine Hydrochloride (Mepivacaine) Active 20 MILLIGRAM  In 1 MILLILITER Levonordefrin (Levonordefrin) Active 0.05 MILLIGRAM  In 1 MILLILITER Sodium Chloride Inactive 4 MILLIGRAM  In 1 MILLILITER Potassium metabisulfite Inactive 1.2 MILLIGRAM  In 1 MILLILITER Edetate disodium Inactive 0.25 MILLIGRAM  In 1 MILLILITER Hydrochloric acid Inactive 0.5 MILLIGRAM  In 1 MILLILITER Sodium hydroxide Inactive   Water Inactive

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 12862-1097-8 5 BLISTER PACK In 1 CARTON contains a BLISTER PACK 1 10 CARTRIDGE In 1 BLISTER PACK This package is contained within the CARTON (12862-1097-8) and contains a CARTRIDGE 1 1.7 mL (MILLILITER) In 1 CARTRIDGE This package is contained within a BLISTER PACK and a CARTON (12862-1097-8)

Revised: 06/2006Septodont, Inc.

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Zymar

gatifloxacin

Dosage Form: ophthalmic solution
Zymar®

(gatifloxacin ophthalmic solution) 0.3%

sterile

Zymar Description

Zymar® (gatifloxacin ophthalmic solution) 0.3% is a sterile ophthalmic solution. It is an 8-methoxy fluoroquinolone anti-infective for topical ophthalmic use.

Structure and Empirical Formula:

Chemical Name: (±) - 1 - Cyclopropyl - 6 - fluoro - 1,4 - dihydro - 8 - methoxy - 7 - (3 - methyl - 1 - piperazinyl) - 4 - oxo - 3 - quinolinecarboxylic acid, sesquihydrate

Contains: Active: gatifloxacin 0.3% (3 mg/mL). Preservative: benzalkonium chloride 0.005%. Inactives: edetate disodium; purified water and sodium chloride. May contain hydrochloric acid and/or sodium hydroxide to adjust pH to approximately 6.

Zymar® is a sterile, clear, pale yellow colored isotonic unbuffered solution. It has an osmolality of 260-330 mOsm/kg.

Zymar - Clinical Pharmacology

Pharmacokinetics: Gatifloxacin ophthalmic solution 0.3% or 0.5% was administered to one eye of 6 healthy male subjects each in an escalated dosing regimen starting with a single 2-drop dose, then 2 drops 4 times daily for 7 days and finally 2 drops 8 times daily for 3 days. At all time points, serum gatifloxacin levels were below the lower limit of quantification (5 ng/mL) in all subjects.

Microbiology: Gatifloxacin is an 8-methoxyfluoroquinolone with a 3-methylpiperazinyl substituent at C7. The antibacterial action of gatifloxacin results from inhibition of DNA gyrase and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription and repair of bacterial DNA.

Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division.

The mechanism of action of fluoroquinolones including gatifloxacin is different from that of aminoglycoside, macrolide, and tetracycline antibiotics. Therefore, gatifloxacin may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to gatifloxacin. There is no cross-resistance between gatifloxacin and the aforementioned classes of antibiotics. Cross resistance has been observed between systemic gatifloxacin and some other fluoroquinolones.

Resistance to gatifloxacin in vitro develops via multiple-step mutations. Resistance to gatifloxacin in vitro occurs at a general frequency of between 1 x 10-7 to 10-10.

Gatifloxacin has been shown to be active against most strains of the following organisms both in vitro and clinically, in conjunctival infections as described in the INDICATIONS AND USAGE section.

Aerobes, Gram-Positive:

Corynebacterium propinquum*

Staphylococcus aureus

Staphylococcus epidermidis

Streptococcus mitis*

Streptococcus pneumoniae

Aerobes, Gram-Negative:

Haemophilus influenzae

* Efficacy for this organism was studied in fewer than 10 infections.

The following in vitro data are available, but their clinical significance in ophthalmic infections is unknown. The safety and effectiveness of Zymar® in treating ophthalmic infections due to the following organisms have not been established in adequate and well-controlled clinical trials.

The following organisms are considered susceptible when evaluated using systemic breakpoints. However, a correlation between the in vitro systemic breakpoint and ophthalmological efficacy has not been established.

The following list of organisms is provided as guidance only in assessing the potential treatment of conjunctival infections. Gatifloxacin exhibits in vitro minimal inhibitory concentrations (MICs) of 2 μg/mL or less (systemic susceptible breakpoint) against most (≥ 90%) strains of the following ocular pathogens.

Aerobes, Gram-Positive:

Listeria monocytogenes

Staphylococcus saprophyticus

Streptococcus agalactiae

Streptococcus pyogenes

Streptococcus viridans Group

Streptococcus Groups C, F, G

Aerobes, Gram-Negative:

Acinetobacter lwoffii

Enterobacter aerogenes

Enterobacter cloacae

Escherichia coli

Citrobacter freundii

Citrobacter koseri

Haemophilus parainfluenzae

Klebsiella oxytoca

Klebsiella pneumoniae

Moraxella catarrhalis

Morganella morganii

Neisseria gonorrhoeae

Neisseria meningitidis

Proteus mirabilis

Proteus vulgaris

Serratia marcescens

Vibrio cholerae

Yersinia enterocolitica

Other Microorganisms:

Chlamydia pneumoniae

Legionella pneumophila

Mycobacterium marinum

Mycobacterium fortuitum

Mycoplasma pneumoniae

Anaerobic Microorganisms:

Bacteroides fragilis

Clostridium perfringens

Clinical Studies: In a randomized, double-masked, multicenter clinical trial, where patients were dosed for 5 days, Zymar® solution was superior to its vehicle on day 5-7 in patients with conjunctivitis and positive conjunctival cultures. Clinical outcomes for the trial demonstrated clinical cure of 77% (40/52) for the gatifloxacin-treated group versus 58% (28/48) for the placebo-treated group. Microbiological outcomes for the same clinical trial demonstrated a statistically superior eradication rate for causative pathogens of 92% (48/52) for gatifloxacin vs. 72% (34/48) for placebo. Please note that microbiological eradication does not always correlate with clinical outcome in anti-infective trials.

Indications and Usage for Zymar

Zymar® solution is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms:

Aerobic Gram-Positive Bacteria:

Corynebacterium propinquum*

Staphylococcus aureus

Staphylococcus epidermidis

Streptococcus mitis*

Streptococcus pneumoniae

Aerobic Gram-Negative Bacteria:

Haemophilus influenzae

* Efficacy for this organism was studied in fewer than 10 infections.

Contraindications

Zymar® solution is contraindicated in patients with a history of hypersensitivity to gatifloxacin, to other quinolones, or to any of the components in this medication.

Warnings

NOT FOR INJECTION.

Zymar® solution should not be injected subconjunctivally, nor should it be introduced directly into the anterior chamber of the eye.

In patients receiving systemic quinolones, including gatifloxacin, serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching. If an allergic reaction to gatifloxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management should be administered as clinically indicated.

Precautions

General: As with other anti-infectives, prolonged use may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, discontinue use and institute alternative therapy. Whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining.

Patients should be advised not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis.

Information for Patients: Avoid contaminating the applicator tip with material from the eye, fingers or other source.

Systemic quinolones, including gatifloxacin, have been associated with hypersensitivity reactions, even following a single dose. Discontinue use immediately and contact your physician at the first sign of a rash or allergic reaction.

Drug Interactions: Specific drug interaction studies have not been conducted with Zymar® ophthalmic solution. However, the systemic administration of some quinolones has been shown to elevate plasma concentrations of theophylline, interfere with the metabolism of caffeine, and enhance the effects of the oral anticoagulant warfarin and its derivatives, and has been associated with transient elevations in serum creatinine in patients receiving systemic cyclosporine concomitantly.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

There was no increase in neoplasms among B6C3F1 mice given gatifloxacin in the diet for 18 months at doses averaging 81 mg/kg/day in males and 90 mg/kg/day in females. These doses are approximately 2000-fold higher than the maximum recommended ophthalmic dose of 0.04 mg/kg/day in a 50 kg human.

There was no increase in neoplasms among Fischer 344 rats given gatifloxacin in the diet for 2 years at doses averaging 47 mg/kg/day in males and 139 mg/kg/day in females (1000 and 3000-fold higher, respectively, than the maximum recommended ophthalmic dose). A statistically significant increase in the incidence of large granular lymphocyte (LGL) leukemia was seen in males treated with a high dose of approximately 2000-fold higher than the maximum recommended ophthalmic dose. Fischer 344 rats have a high spontaneous background rate of LGL leukemia and the incidence in high-dose males only slightly exceeded the historical control range established for this strain.

In genetic toxicity tests, gatifloxacin was positive in 1 of 5 strains used in bacterial reverse mutation assays; Salmonella strain TA102. Gatifloxacin was positive in in vitro mammalian cell mutation and chromosome aberration assays. Gatifloxacin was positive in in vitro unscheduled DNA synthesis in rat hepatocytes but not human leukocytes. Gatifloxacin was negative in in vivo micronucleus tests in mice, cytogenetics test in rats, and DNA repair test in rats. The findings may be due to the inhibitory effects of high concentrations on eukaryotic type II DNA topoisomerase.

There were no adverse effects on fertility or reproduction in rats given gatifloxacin orally at doses up to 200 mg/kg/day (approximately 4500-fold higher than the maximum recommended ophthalmic dose for Zymar®).

Pregnancy: Teratogenic Effects. Pregnancy Category C:

There were no teratogenic effects observed in rats or rabbits following oral gatifloxacin doses up to 50 mg/kg/day (approximately 1000-fold higher than the maximum recommended ophthalmic dose). However, skeletal/craniofacial malformations or delayed ossification, atrial enlargement, and reduced fetal weight were observed in fetuses from rats given ≥150 mg/kg/day (approximately 3000-fold higher than the maximum recommended ophthalmic dose). In a perinatal/postnatal study, increased late post-implantation loss and neonatal/perinatal mortalities were observed at 200 mg/kg/day (approximately 4500 times the maximum recommended ophthalmic dose).

Because there are no adequate and well-controlled studies in pregnant women, Zymar® solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: Gatifloxacin is excreted in the breast milk of rats. 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 gatifloxacin is administered to a nursing woman.

Pediatric Use: Safety and effectiveness in infants below the age of one year have not been established.

Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Adverse Reactions

Ophthalmic Use: The most frequently reported adverse events in the overall study population were conjunctival irritation, increased lacrimation, keratitis, and papillary conjunctivitis. These events occurred in approximately 5-10% of patients. Other reported reactions occurring in 1-4% of patients were chemosis, conjunctival hemorrhage, dry eye, eye discharge, eye irritation, eye pain, eyelid edema, headache, red eye, reduced visual acuity and taste disturbance.

Zymar Dosage and Administration

The recommended dosage regimen for the treatment of bacterial conjunctivitis is:

Days 1 and 2: Instill one drop every two hours in the affected eye(s) while awake, up to 8 times daily.

Days 3 through 7: Instill one drop up to four times daily while awake.

How is Zymar Supplied

Zymar® (gatifloxacin ophthalmic solution) 0.3% is supplied sterile in a white, low density polyethylene (LDPE) bottle with a controlled dropper tip and a tan, high impact polystyrene (HIPS) cap in the following size:

              5 mL in 10 mL bottle - NDC 0023-9218-05

Note: Store at 15°-25°C (59°-77°F). Protect from freezing.

Animal Pharmacology

Quinolone antibacterials have been shown to cause bone or cartilage changes in immature animals. There was no evidence of bone cartilage changes following ocular administration of gatifloxacin in rabbits or dogs.

Rx only

Revised: 01/2010

© 2010 Allergan, Inc.

Irvine, CA 92612, U.S.A.

® marks owned by Allergan, Inc.

Licensed from Kyorin Pharmaceuticals Co., Ltd.

U.S. Patents 5,880,283 and 6,333,045

Made in the U.S.A.

71706US13B

Bottle Label – 5 mL

ALLERGAN

NDC 0023-9218-05 Rx Only

Zymar®

(gatifloxacin ophthalmic solution) 0.3%

5 mL sterile

Carton Label – 5 mL

NDC 0023-9218-05

Zymar®

(gatifloxacin ophthalmic solution) 0.3%

5 mL

Rx only sterile

ALLERGAN

Zymar  gatifloxacin  solution/ drops

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0023-9218 Route of Administration OPHTHALMIC DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength gatifloxacin (gatifloxacin) gatifloxacin 3 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength edetate disodium   water   sodium chloride   benzalkonium chloride   hydrochloric acid   sodium hydroxide

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0023-9218-05 1 BOTTLE In 1 CARTON contains a BOTTLE, DROPPER 1 5 mL In 1 BOTTLE, DROPPER This package is contained within the CARTON (0023-9218-05)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA021493	04/11/2003

Labeler - Allergan, Inc. (144796497)

Establishment
Name	Address	ID/FEI	Operations
Allergan, Inc.		362898611	MANUFACTURE

Revised: 02/2011Allergan, Inc.

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Mexitil

Generic Name: Mexiletine Hydrochloride
Class: Class Ib Antiarrhythmics
VA Class: CV300
Chemical Name: 1-(2,6-Dimethylphenoxy)-2-propanamine hydrochloride
Molecular Formula: C₁₁H₁₇NO•HCl
CAS Number: 5370-01-4

Introduction

Antiarrhythmic agent; a local anesthetic-type, class 1B agent.^{1 8 10 11 12 24 34}

Uses for Mexitil

Ventricular Arrhythmias

Treatment of documented life-threatening ventricular arrhythmias (e.g., sustained ventricular tachycardia).^{1 20 34} Use for less severe arrhythmias is notrecommended.^{1 34 44}

Can reduce ventricular premature contractions (VPCs)†, paired VPCs†, and nonsustained ventricular tachycardia† and can suppress the recurrence of ventricular tachycardia and/or fibrillation in patients with ventricular tachycardia and/or fibrillation†.^{1 10 12 13 14 15 16 17 18 19 20 34} Avoid treatment of asymptomatic VPCs.^{1 34}

Has been effective in some patients for the treatment of ventricular arrhythmias unresponsive to other antiarrhythmic agents†.^{10 11 12 13 16 19 20} However, not a recommended or alternative agent for the management of arrhythmias in ACLS.⁴³

Diabetic Neuropathy

Has been used with equivocal results in the management of painful diabetic neuropathy†;^{26 27 28 29 30 31 32 39 45 46} pending further accumulation of data from well-designed studies, use only in patients who do not respond to or cannot tolerate more established therapies.^{32 39}

Mexitil Dosage and Administration

General

Ventricular Arrhythmias

• 
  

  Individualize dosage carefully according to individual response, tolerance, general condition, and cardiovascular status.^{1 12 17 34 44 46}

  
  


• 
  

  Clinical and ECG evaluation (e.g., Holter monitoring) is recommended to determine whether the desired antiarrhythmic effect has been achieved and to guide dosage titration and adjustment.^{1 12 14 17 18 34 44}

  
  


• 
  

  Initiate therapy in a hospital.^{1 34} Patients at high risk for developing life-threatening arrhythmias after discontinuance of existing antiarrhythmic therapy should be hospitalized.^{1 34}

  
  

Administration

Oral Administration

Administer orally, generally every 8 hours.^{1 10 12 15}

Administer with food or antacids to minimize adverse GI effects.^{1 10 11 12 34 44 46}

Dosage

Available as mexiletine hydrochloride; dosage expressed in terms of the salt.¹

Adults

Ventricular Arrhythmias

Oral

If rapid control of arrhythmia is essential, 400-mg loading dose followed by 200 mg in 8 hours.^{1 12 13 15 34} If rapid control of arrhythmia is not essential, initial dosage of 200 mg every 8 hours.^{1 17 20 34}

If necessary, adjust dosage at intervals of at least 2–3 days in increments or decrements of 50 or 100 mg.^{1 13 34} 200–300 mg every 8 hours usually results in satisfactory control of arrhythmias.^{1 10 17 34} If satisfactory control is not achieved and patient tolerates 300 mg every 8 hours, increase dosage to 400 mg every 8 hours.^{1 11 17 34}

If adequate control of arrhythmia has been achieved at doses ≤300 mg every 8 hours, total dosage may be administered twice daily (every 12 hours) with close monitoring of degree of ventricular ectopy suppression.^{1 34}

Switching from Another Class I Antiarrhythmic Agent

Oral

200 mg as a single dose, administered 6–12 hours after last dose of quinidine sulfate or disopyramide, 3–6 hours after last dose of procainamide, or 8–12 hours after last dose of tocainide.^{1 34} Adjust subsequent doses according to individual requirements.^{1 34}

When switching to mexiletine from IV lidocaine, discontinue lidocaine infusion at the time of administration of the first dose of mexiletine; however, keep infusion line open until arrhythmia appears to be satisfactorily suppressed.^{1 34} Closely monitor patient.^{1 34}

Diabetic Neuropathy†

Oral

Initial dosage of 200 mg once daily has been used;^{31 32 39 44 46} dosage increased at 2-day intervals to 200 mg twice daily and then 200 mg 3 times daily.^{32 39 46}

Prescribing Limits

Adults

Ventricular Arrhythmias

Oral

Maximum 400 mg every 8 hours^{1 11 17 34} (1.2 g daily).^{1 13 34 46}

If given twice daily, maximum 450 mg every 12 hours.^{1 34}

Diabetic Neuropathy†

Oral

Dosage generally should not exceed 1.2 g daily.^{32 39 46}

Special Populations

Hepatic Impairment

Consider dosage reduction in patients with hepatic impairment (including those with hepatic dysfunction secondary to CHF).^{1 8 12 34 44}

Renal Impairment

Dosage adjustment not required.^{1 8 12 21 34}

Cautions for Mexitil

Contraindications

• 
  

  Second- or third-degree AV block (unless a cardiac pacemaker is in place).^{1 34 46}

  
  


• 
  

  Cardiogenic shock.^{1 34 46}

  
  

Warnings/Precautions

Warnings

Mortality

In CAST study, excessive rate of mortality and nonfatal cardiac arrest reported in patients with asymptomatic, non-life-threatening ventricular arrhythmias and recent MI (>6 days but <2 years previously) who were receiving encainide or flecainide compared with placebo.^{1 2 3 4 5 34}

Limit use of mexiletine in patients with ventricular arrhythmias to those with life-threatening arrhythmias^{1 34} due to mexiletine’s arrhythmogenic potential (see Cardiovascular Effects under Cautions) and the lack of evidence for improved survival for class I antiarrhythmic agents.^{33 34 40 41 42} Use for treatment of less severe arrhythmias currently is not recommended; avoid treatment of asymptomatic VPCs.^{1 34}

Major Toxicities

Cardiovascular Effects

Possible development or exacerbation of arrhythmias; clinical and ECG evaluations are essential prior to and during therapy.^{1 34} Initiate therapy in a hospital.^{1 34}

Use with caution in patients with preexisting first-degree AV block, sinus node dysfunction, or intraventricular conduction disturbances.^{1 34} Continuous monitoring recommended for patients with second- or third-degree AV block and an operative ventricular pacemaker.^{1 34} (See Contraindications under Cautions.)

Possible exacerbation of hypotension and CHF; use with caution in patients with these conditions.^{1 34}

Hepatic Effects

Possible abnormal liver function test results (AST elevations ≥3 times the ULN),^{1 34 44} especially during initial weeks of therapy in patients with CHF or AMI and/or patients who have received blood transfusions or other drug therapies.^{1 34} Discontinuance of therapy usually is not required.^{1 34} Severe hepatic injury, including hepatic necrosis, reported rarely.^{1 34}

Carefully evaluate patients who develop elevated serum concentrations of hepatic enzymes and those with signs or symptoms suggestive of liver dysfunction; consider discontinuance of therapy if enzyme elevations are persistent or increasing.^{1 34}

Hematologic Effects

Possible leukopenia, agranulocytosis, and thrombocytopenia, ^{1 34} especially in severely ill patients receiving concurrent therapy with drugs known to cause adverse hematologic effects (e.g., procainamide, vinblastine).^{1 34}

Carefully evaluate patients in whom substantial hematologic changes occur; consider discontinuing therapy.^{1 34} Blood cell counts generally return to normal within 1 month following discontinuance.^{1 34}

General Precautions

Seizures

Seizures reported rarely; discontinuance of therapy may be necessary.^{1 34} Use with caution in patients with a history of seizure disorder.^{1 34}

Effects on Urinary Excretion

Substantial changes in urinary pH may affect urinary excretion of mexiletine; avoid concomitant drug therapy or dietary regimens that may markedly affect urinary pH.^{1 11 12 21 34}

Specific Populations

Pregnancy

Category C.¹

Lactation

Distributed into milk.^{1 21 34} Discontinue nursing or the drug.^{1 34}

Pediatric Use

Safety and efficacy not established.^{1 34 44 47}

Hepatic Impairment

Possible prolonged elimination.^{1 8 9 12 13 34} Careful monitoring recommended (including in those with hepatic impairment secondary to CHF).^{1 8 9 34} Consider dosage reduction.^{1 8 12 34 44}

Common Adverse Effects

Nausea,^{1 14 18 19 20 34} vomiting,^{1 18 19 20 34} heartburn,^{1 14 20 34} dizziness^{1 5 18 19 34} or lightheadedness,^{1 34} tremor,^{1 18 20 34} nervousness,^{1 34} chest pain, ^{1 34} coordination difficulties,^{1 34} headache,^{1 15 34} blurred vision/visual disturbances.^{1 20 34}

Interactions for Mexitil

Metabolized by various CYP isoenzymes,^{1 9} principally by CYP2D and CYP1A2.³⁹

Drugs Affecting Hepatic Microsomal Enzymes

Hepatic enzyme inducers: Potential pharmacokinetic interaction (decreased plasma mexiletine concentrations).^{1 8 9 10 11 12 13 21 25 34}

Hepatic enzyme inhibitors: Potential pharmacokinetic interaction (decreased mexiletine clearance).^{1 49 50}

Drugs Affecting Gastric Emptying

Drugs that delay gastric emptying may reduce rate of mexiletine absorption^{1 34} (since mexiletine is absorbed in the small intestine^{1 11 12 13 21 34} ); conversely, drugs that accelerate gastric emptying may increase rate of mexiletine absorption.^{1 10 11 21 34}

Drugs Affecting Urinary pH

Drugs that markedly alter urinary pH may affect elimination of mexiletine; urinary acidification accelerates elimination; alkalinization slows elimination.¹ Avoid concomitant drug therapy that markedly affects urinary pH.^{1 11 12 21 34}

Specific Drugs

Drug	Interaction	Comments
Antacids (aluminum- and magnesium-containing)	Possible decreased rate of absorption of mexiletine1 10 11 21 34
Antianginal agents	Adverse pharmacokinetic interactions not reported1 34
Antiarrhythmic agents (e.g., quinidine, propranolol)	Possible improved control of ventricular ectopy;1 34 prolongation of PR and QT intervals or QRS complex not reported with concomitant propranolol use1 10 11 12 34
Anticoagulants	Adverse pharmacokinetic interactions not reported1 34
Antihypertensive agents	Adverse pharmacokinetic interactions not reported1 34
Atropine	Possible decreased rate of absorption of mexiletine1 10 11 21 34
Benzodiazepines	Pharmacokinetic interactions not reported1 34
Cimetidine	Possible increased, decreased, or unchanged plasma mexiletine concentrations1 8 11 12 34	Closely monitor plasma mexiletine concentrations1 34
Digoxin	Prolongation of PR and QT intervals or QRS complex not reported1 10 11 12 34
Diuretics	Prolongation of PR and QT intervals or QRS complex not reported1 10 11 12 34
Fluvoxamine	Reduced mexiletine clearance49 50	Monitor patient closely and monitor serum mexiletine concentrations 49 50
Lidocaine	Potential additive adverse effects1 34	Close monitoring recommended when patients are switched from IV lidocaine to mexiletine1 34
Methylxanthines (caffeine, theophylline)	Possible decreased methylxanthine clearance and increased plasma theophylline concentrations1 34	Monitor plasma theophylline concentrations; adjust theophylline dosage if necessary1 34
Metoclopramide	Possible increased rate of absorption of mexiletine1 10 11 21 34
Opiate agonists	Possible decreased rate of absorption of mexiletine1 10 11 21 34
Phenobarbital	Possible decreased plasma mexiletine concentrations1 8 9 10 11 12 13 21 25 34	Closely monitor plasma mexiletine concentrations1 34
Phenytoin	Possible decreased plasma mexiletine concentrations1 8 9 10 11 12 13 21 25 34	Closely monitor plasma mexiletine concentrations1 34
Propafenone	Possible increased plasma mexiletine concentrationsa b
Rifampin and rifapentine	Possible decreased plasma mexiletine concentrations1 8 9 10 11 12 13 21 25 34	Closely monitor plasma mexiletine concentrations1 34

Mexitil Pharmacokinetics

Absorption

Bioavailability

About 90% absorbed following oral administration, with peak plasma concentrations attained in 2–3 hours.¹ Undergoes low first-pass metabolism.^{1 34}

Onset

Onset of action is usually within 30–120 minutes.^{1 34}

Plasma Concentrations

Plasma mexilitine concentrations of ≥0.5 mcg/mL generally required to suppress ventricular arrhythmias; concentrations >2 mcg/mL associated with adverse CNS effects.¹

Special Populations

Decreased rate of absorption in patients with AMI or other conditions that delay gastric emptying.¹

Distribution

Plasma Protein Binding

50–60%.¹

Elimination

Metabolism

Extensively metabolized in the liver^{1 9 10 34} by various CYP isoenzymes,⁹ including CYP2D and CYP1A2.³⁹ Pharmacologic activity results principally from the parent drug.^{9 10}

Elimination Route

About 8–15% of a dose is excreted in urine as unchanged drug.^{12 13}

Half-life

10–12 hours.¹

Special Populations

In patients with hepatic impairment, possible decreased metabolism^{1 8 12 34 44} and prolonged elimination.^{1 8 9 12 13 34}

Stability

Storage

Oral

Capsules

20–25°C.¹

ActionsActions

• 
  

  Combines with fast sodium channels within the myocardium and inhibits rapid sodium influx, which decreases the maximal rate of depolarization of phase 0 of the action potential.^{1 8 10 11 12 21 34}

  
  


• 
  

  Inhibits recovery after repolarization in a time- and voltage-dependent manner, which is associated with subsequent dissociation of the drug from the sodium channels.^{35 36 37 39}

  
  


• 
  

  Increases the effective refractory period (ERP) relative to the duration of the action potential (ERP/APD)^{1 8 9 10 12 14 21 34} and reduces ventricular automaticity by raising the threshold for spontaneous firing of ventricular pacemaker cells.¹⁰

  
  


• 
  

  Exhibits electrophysiologic effects characteristic of class IB antiarrhythmic agents,^{8 10 12 35 36 37 38} which rapidly attach to and dissociate from transmembrane sodium channels.^{1 8 9 12 35 36 37}

  
  


• 
  

  Causes little or no prolongation of PR and QT intervals or QRS complex.^{1 8 9 10 12 14 21 34} Has no clinically important effect on heart rate, systemic arterial BP, or myocardial function in healthy individuals or patients with cardiovascular disease.^{1 10 11 12 14 21 34}

  
  

Advice to Patients

• 
  

  Potential for toxicity (e.g., cardiovascular, hepatic).¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 34}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{1 34}

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Mexiletine Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	150 mg*	Mexiletine Hydrochloride Capsules	Roxane, Sandoz, Teva, Watson
			Mexitil (with benzyl alcohol and parabens)	Boehringer Ingelheim
		200 mg*	Mexiletine Hydrochloride Capsules	Roxane, Sandoz, Teva, Watson
			Mexitil (with benzyl alcohol and parabens)	Boehringer Ingelheim
		250 mg*	Mexiletine Hydrochloride Capsules	Roxane, Sandoz, Teva, Watson
			Mexitil (with benzyl alcohol and parabens)	Boehringer Ingelheim

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Mexiletine HCl 150MG Capsules (TEVA PHARMACEUTICALS USA): 90/$45.99 or 270/$109.96

Mexiletine HCl 250MG Capsules (TEVA PHARMACEUTICALS USA): 90/$75.99 or 270/$209.99

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions April 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Mexitil (mexiletine hydrochloride) capsules prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT; 2003 May 30.

2. The Cardiac Arrhythmia Suppression Trial (CAST) investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989; 321:406-12. [IDIS 257848] [PubMed 2473403]

3. Ruskin JN. The Cardiac Arrhythmia Suppression Trial (CAST). N Engl J Med. 1989; 321:386-8. [IDIS 257833] [PubMed 2501683]

4. Echt DC, Liebson PR, Mitchell LB et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo: the Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991; 324:781-8. [IDIS 279004] [PubMed 1900101]

5. Food and Drug Administration. Enkaid and Tambocor use in non-life-threatening arrhythmias halted. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 1989 Apr 25.

6. Department of Health and Human Services. Background statement regarding encainide, flecainide, and moricizine. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; 1989 Apr.

7. The Cardiac Arrhythmia Suppression Trial II investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med. 1992; 327:227-33. [IDIS 299111] [PubMed 1377359]

8. Kowey PR. Pharmacological Effects of Antiarrhythmic Drug: Review and Update. Arch Intern Med. 1998; 158: 325-32. [IDIS 401793] [PubMed 9487229]

9. Kowey PR, Marinchak RA, Rials SJ et al. Classification and pharmacology of antiarrhythmic drugs. Am Heart J. 2000;140: 12-20.

10. . Fenster PE, Comess KA. Pharmacology and clinical use of mexiletine. Pharmacotherapy. 1986; 6:1-9. [IDIS 394809] [PubMed 3513138]

11. Campbell RWF. Mexiletine. N Engl J Med. 1987; 316:29-34. [IDIS 223853] [PubMed 3537793]

12. Monk JP, Brogden RN. Mexiletine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of arrhythmias. Drugs. 1990; 40:374-411. [PubMed 2226221]

13. Mexiletine for arrhythmias. Med Lett Drugs Ther. 1986; 28:65-6.

14. Masotti G, Morettini A, Casolo GC et al. Efficacy of mexiletine in the medium-term treatment of ventricular arrhythmias: a randomized, double-blind, crossover trial against placebo in ambulatory patients. J Int Med Res. 1984; 12:73-80. [PubMed 6202571]

15. Singh JB, Rasul AM, Shah A et al. Efficacy of mexiletine in chronic ventricular arrhythmias compared with quinidine: a single-blind, randomized trial. Am J Cardiol. 1984; 53: 84-7. [IDIS 179626] [PubMed 6362388]

16. Mason JW, for the Electrophysiologic Study versus Electrocardiographic Monitoring Investigators. A comparison of seven antiarrhythmic drugs in patients with ventricular tachyarrhythmias. N Engl J Med. 1993; 329:452-8. [IDIS 318403] [PubMed 8332150]

17. Assey ME, Hudson WM, Hanger KH et al. Comparative study of mexiletine and quinidine in the treatment of ventricular ectopia. South Med J. 1985; 78:565-8. [IDIS 199952] [PubMed 2581322]

18. Frank MJ, Watkins LO, Prisant LM et al. Mexiletine versus quinidine as first-line antiarrhythmia therapy: results from consecutive trials. J Clin Pharmacol. 1991; 31:222-8. [IDIS 279188] [PubMed 2019663]

19. Rutledge JC, Harris F, Amsterdam EA et al. Clinical evaluation of oral mexiletine therapy in the treatment of ventricular arrhythmias. J Am Coll Cardiol. 1985; 6:780-4. [PubMed 4031292]

20. Kerin NZ, Aragon E, Marinescu G et al. Mexiletine: long-term efficacy and side effects in patients with chronic drug-resistant potentially lethal ventricular arrhythmias. Arch Intern Med. 1990; 150:381-4. [IDIS 263330] [PubMed 2302013]

21. Woosley RL, Wang T, Stone W et al. Pharmacology, electrophysiology, and pharmacokinetics of mexiletine. Am Heart J. 1984; 107:1058-65. [IDIS 184957] [PubMed 6326558]

22. Solvay Pharmaceuticals. Luvox (fluvoxamine maleate) tablets prescribing information. Marietta, GA; 2001 Jun.

23. Abbott Laboratories. Norvir (ritonavir) capsules and oral solution prescribing information (dated 2001 Sep). In: Physicians’ desk reference. 57th ed. Montvale, NJ: Medical Economics Company Inc; 2003:482-9.

24. AstraZeneca. EMLA Cream and Anesthetic Disc (lidocaine 2.5% and prilocaine 2.5% cream) prescribing information (dated 2002 Feb). In: Physicians’ desk reference. 57th ed. Montvale, NJ: Medical Economics Company Inc; 2003:599-602.

25. Aventis. Priftin (rifapentine) tablets prescribing information. In: Physicians’ desk reference. 57th ed. Montvale, NJ: Medical Economics Company Inc; 2003:753-6.

26. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Diabetic Neuropathies: the nerve damage of diabetes. From NIDDK website () 2003 Apr 2.

27. Russell D, Stading J. Diabetic Peripheral Neuropathy: minimizing and treating its pain. US Pharmacist. 2002; 27:56-67.

28. Galer BS. Neuropathic pain of peripheral origin: advances in pharmacologic treatment. Neurology. 1995; 45(Suppl 9):S17-25. [IDIS 360673] [PubMed 8538882]

29. Oskarsson P, Ljunggren JG, Lins PE et al. Efficacy and safety of mexiletine in the treatment of painful diabetic neuropathy. Diabetes Care. 1997; 20:1594-7. [IDIS 393128] [PubMed 9314641]

30. Dejgard A, Petersen P, Kastrup J. Mexiletine for treatment of chronic painful diabetic neuropathy. Lancet. 1988; 1:9-11. [IDIS 237595] [PubMed 2891940]

31. Stracke H, Meyer UE, Schumacher HE et al. Mexiletine in the treatment of diabetic neuropathy. Diabetes Care. 1992; 15:1550-5. [PubMed 1468285]

32. Wright JM, Oki JC, Graves L 3rd. Mexiletine in the symptomatic treatment of diabetic peripheral neuropathy. Ann Pharmacother. 1997; 31:116-7. [IDIS 377886] [PubMed 8997478]

33. Hine LK, Laird NM, Hewitt P et al. Meta-analysis of empirical long-term antiarrhythmic therapy after myocardial infarction. JAMA. 1989; 262:3037-40. [IDIS 260965] [PubMed 2509746]

34. Watson. Mexiletine hydrochloride capsules prescribing information. Corona, CA; 2000 May.

35. Vaughan Williams EM. A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol. 1984; 24:129-47. [IDIS 186026] [PubMed 6144698]

36. Harrison DC. Antiarrhythmic drug classification: new science and practical applications. Am J Cardiol. 1985; 56:185-7. [PubMed 2409789]

37. Campbell TJ. Kinetics of onset of rate-dependent effects of class I antiarrhythmic drugs are important in determining their effects on refractoriness in guinea-pig ventricle, and provide a theoretical basis for their subclassification. Cardiovasc Res. 1983; 17:344-52. [PubMed 6883410]

38. Harrison DC. Current classification of antiarrhythmic drugs as a guide to their rational clinical use. Drugs. 1986; 31:93-5. [IDIS 212454] [PubMed 3948737]

39. Jarvis B, Coukell AJ. Mexiletine: a review of its therapeutic use in painful diabetic neuropathy. Drugs. 1998; 56:691-707. [PubMed 9806111]

40. Anon. Drugs for cardiac arrhythmias. Med Lett Drugs Ther. 1989; 31:35-40. [PubMed 2565011]

41. Teo KK, Yusuf S, Furberg CD. Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction. JAMA. 1993; 270:1589-95. [IDIS 320343] [PubMed 8371471]

42. Pratt CM, Moye L. The Cardiac Arrhythmia Suppression Trial: implications for antiarrhythmic drug development. J Clin Pharmacol. 1990; 30:967-74. [IDIS 274583] [PubMed 2122983]

43. The American Heart Association in Collaboration with the International Liaison Committee on Resuscitation. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6: Advanced cardiovascular life support. Circulation. 2000; 102(Suppl I): I-86-171.

44. Reviewers’ comments (personal observations).

45. Vinik AI. Diagnosis and management of diabetic neuropathy. Clin Geriatr Med. 1999; 2:293-320.

46. Guay DRP.Adjunctive agents in the management of chronic pain. Pharmacotherapy. 2001; 9: 1070-81.

47. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT: Personal communication.

49. Barr Laboratories, Inc. Fluvoxamine maleate tablets prescribing information. Pomona, NY; 2005 Jan.

50. Kusumoto M, Ueno K, Oda A et al. Effect of fluvoxamine on the pharmacokinetics of mexiletine in healthy Japanese men. Clin Pharmacol Ther. 2001; 69:104-7. [IDIS 461192] [PubMed 11240973]

a. Libersa C, Caron J, Broly F et al. Interaction of propafenone and mexiletine. J Am Coll Cardiol. 1993; 22:2061. [PubMed 8245368]

b. Yeung-Lai-Wah JA, Murdock CJ, Boone J et al. Propafenone-mexiletine combination for the treatment of sustained ventricular tachycardia. J Am Coll Cardiol. 1992; 20:547-51.

More Mexitil resources

• Mexitil Side Effects (in more detail)
• Mexitil Dosage
• Mexitil Use in Pregnancy & Breastfeeding
• Drug Images
• Mexitil Drug Interactions
• Mexitil Support Group
• 2 Reviews for Mexitil - Add your own review/rating

• Mexitil Prescribing Information (FDA)


• Mexitil MedFacts Consumer Leaflet (Wolters Kluwer)


• Mexitil Concise Consumer Information (Cerner Multum)


• Mexitil Advanced Consumer (Micromedex) - Includes Dosage Information


• Mexiletine Prescribing Information (FDA)

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