Mexiletine

Mexiletine is also used to treat diabetic neuropathy (nerve damage caused by diabetes). Talk to your doctor about the risks of using this medication for your condition.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Mexiletine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• nausea
• vomiting
• heartburn
• changes in appetite
• lightheadedness or dizziness
• shaking of a part of your body that you cannot control
• loss of coordination
• numbness or tingling sensation
• headache
• blurred vision
• nervousness
• difficulty speaking
• swelling of the hands, feet, ankles, or lower legs
• rash

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

• irregular heartbeat
• chest pain
• extreme tiredness
• unusual bleeding or bruising
• lack of energy
• pain in the upper right part of the stomach
• yellowing of the skin or eyes
• flu-like symptoms

Mexiletine may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

Mexiletine is a prescription medication used to treat life-threatening, ventricular arrhythmias (irregular heartbeats).

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Common side effects include:

• nausea
• vomiting
• heartburn
• changes in appetite
• lightheadedness or dizziness
• shaking of a part of your body that you cannot control
• loss of coordination
• numbness or tingling sensation
• headache
• blurred vision
• nervousness
• difficulty speaking
• swelling of the hands, feet, ankles, or lower legs
• rash

This is not a complete list of mexiletine side effects. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Other drugs may interact with mexiletine, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For mexiletine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to mexiletine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Studies on mexiletine have been done only in adult patients, and there is no specific information comparing use of mexiletine in children with use in other age groups.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of mexiletine in the elderly with use in other age groups.

Pregnancy

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking mexiletine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using mexiletine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Levomethadyl
• Vernakalant

Using mexiletine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amiodarone
• Anagrelide
• Bupropion
• Cobicistat
• Dasabuvir
• Disopyramide
• Eltrombopag
• Etravirine
• Lidocaine
• Ombitasvir
• Paritaprevir
• Paroxetine
• Pirfenidone
• Pixantrone
• Prilocaine
• Quinidine
• Simeprevir
• Sotalol
• Theophylline
• Tizanidine

Using mexiletine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Fluvoxamine
• Rifapentine
• Ritonavir

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using mexiletine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use mexiletine, or give you special instructions about the use of food, alcohol, or tobacco.

• Tobacco

Other Medical Problems

The presence of other medical problems may affect the use of mexiletine. Make sure you tell your doctor if you have any other medical problems, especially:

• Congestive heart failure or
• Low blood pressure—Mexiletine may make these conditions worse

• Heart attack (severe) or
• Liver disease—Effects may last longer because of slower removal of mexiletine from the body

• Seizures (history of)—Mexiletine can cause seizures

Take mexiletine exactly as directed by your doctor, even though you may feel well. Do not take more medicine than ordered.

To lessen the possibility of stomach upset, mexiletine should be taken with food or immediately after meals or with milk or an antacid.

mexiletine works best when there is a constant amount in the blood. To help keep this amount constant, do not miss any doses. Also it is best to take the doses at evenly spaced times day and night. For example, if you are to take 3 doses a day, the doses should be spaced about 8 hours apart. If this interferes with your sleep or other daily activities, or if you need help in planning the best times to take your medicine, check with your health care professional.

Dosing

The dose of mexiletine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of mexiletine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  • For irregular heartbeat (arrhythmias):
    • Adults—At first, 200 milligrams (mg) every eight hours. Then, your doctor may raise or lower your dose as needed.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of mexiletine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• Chest pain
• fast or irregular heartbeat
• shortness of breath

• Convulsions (seizures)
• fever or chills
• unusual bleeding or bruising

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Dizziness or lightheadedness
• heartburn
• nausea and vomiting
• nervousness
• trembling or shaking of the hands
• unsteadiness or difficulty in walking

• Blurred vision
• confusion
• constipation or diarrhea
• headache
• numbness or tingling of fingers and toes
• ringing in the ears
• skin rash
• slurred speech
• trouble in sleeping
• unusual tiredness or weakness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Mexiletine hydrochloride capsules are contraindicated in the presence of cardiogenic shock or preexisting second- or third-degree AV block (if no pacemaker is present).

Mexiletine hydrochloride capsules USP, 150 mg are white granular powder in a hard gelatin capsule with an opaque tan cap and an opaque orange body, imprinted with "N" on one side and "739" and "150" on the other in black ink. They are supplied as follows: NDC 0093-8739-01 bottles of 100.

Mexiletine hydrochloride capsules USP, 200 mg are white granular powder in a hard gelatin capsule with an opaque orange cap and an opaque orange body, imprinted with "N" on one side and "740" and "200" on the other in black ink. They are supplied as follows: NDC 0093-8740-01 bottles of 100.

Mexiletine hydrochloride capsules USP, 250 mg are white granular powder in a hard gelatin capsule with an opaque green cap and an opaque orange body, imprinted with "N" on one side and "741" and "250" on the other in black ink. They are supplied as follows: NDC 0093-8741-01 bottles of 100.

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

Manufactured In Canada By:

TEVA CANADA LIMITED

Toronto, Canada M1B 2K9

Manufactured For:

TEVA PHARMACEUTICALS USA, INC.

North Wales, PA 19454

Rev. D 3/2015

Class IB antiarrhythmic, structurally related to lidocaine, which inhibits inward sodium current, decreases rate of rise of phase 0, increases effective refractory period/action potential duration ratio

Absorption

Well absorbed

Distribution

Vd: 5 to7 L/kg

Metabolism

Hepatic via CYP2D6 metabolism to inactive metabolites (~90%) and major metabolites p-hydroxymexiletine, hydroxy-methylmexiletine, and N-hydroxy-mexiletine (minimal antiarrhythmic activity); low first-pass effect

Excretion

Urine (10% as unchanged drug); urinary acidification increases excretion, alkalinization decreases excretion

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification

Agomelatine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Agomelatine. Monitor therapy

Ajmaline: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Alosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Alosetron. Avoid combination

Antihepaciviral Combination Products: May increase the serum concentration of Mexiletine. Monitor therapy

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. Consider therapy modification

Cannabis: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

CloZAPine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Monitor therapy

Cobicistat: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

CYP1A2 Inducers (Moderate): May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Monitor therapy

CYP1A2 Substrates: CYP1A2 Inhibitors (Moderate) may decrease the metabolism of CYP1A2 Substrates. Monitor therapy

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Consider therapy modification

Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

Darunavir: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Deferasirox: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy

Etravirine: May decrease the serum concentration of Mexiletine. Monitor therapy

FluvoxaMINE: May increase the serum concentration of Mexiletine. Monitor therapy

Fosphenytoin: May decrease the serum concentration of Mexiletine. Monitor therapy

Heroin: May decrease the absorption of Mexiletine. Monitor therapy

Imatinib: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Lumefantrine: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Obeticholic Acid: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy

Panobinostat: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Peginterferon Alfa-2b: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy

Perhexiline: CYP2D6 Substrates may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Phenytoin: May decrease the serum concentration of Mexiletine. Monitor therapy

Pirfenidone: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone. Management: Use any such combination with caution and close monitoring for pirfenidone toxicity. Avoid the use of pirfenidone with moderate CYP1A2 inhibitors whenever CYP2C9, 2C19, 2C6, or 2E1 is also inhibited (either by the CYP1A2 inhibitor or by a third drug). Consider therapy modification

QuiNINE: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Rasagiline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Rasagiline. Consider therapy modification

Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Mexiletine. Exceptions: Sertraline. Consider therapy modification

Simeprevir: May increase the serum concentration of Mexiletine. Monitor therapy

Teriflunomide: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

Theophylline Derivatives: Mexiletine may decrease the metabolism of Theophylline Derivatives. Exceptions: Dyphylline. Consider therapy modification

TiZANidine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of TiZANidine. Management: If combined use cannot be avoided, initiate tizanidine in adults at 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Vemurafenib: May increase the serum concentration of CYP1A2 Substrates. Management: Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. Consider therapy modification

>10%:

Cardiovascular: Exacerbation of cardiac arrhythmia (10% to 15%; patients with malignant arrhythmia)

Central nervous system: Dizziness (11% to 25%), ataxia (10% to 20%), nervousness (5% to 10%), unsteady gait

Gastrointestinal: Gastrointestinal distress (41%), nausea (≤40%), vomiting (≤40%)

Neuromuscular & skeletal: Tremor (13%)

1% to 10%:

Cardiovascular: Palpitations (4% to 8%), chest pain (3% to 8%), angina pectoris (2%), ventricular premature contractions (1% to 2%)

Central nervous system: Insomnia (5% to 7%), numbness (fingers or toes: 2% to 4%), depression (2%), paresthesia (2%), confusion, headache

Dermatologic: Skin rash (4%)

Gastrointestinal: Constipation (≤5%), diarrhea (≤5%), xerostomia (3%), abdominal pain (1%)

Neuromuscular & skeletal: Weakness (5%), arthralgia (1%)

Ophthalmic: Blurred vision (5% to 7%), nystagmus (6%)

Otic: Tinnitus (2% to 3%)

Respiratory: Dyspnea (3%)

<1% (Limited to important or life-threatening): Agranulocytosis, alopecia, atrioventricular block, cardiac failure (patients with pre-existing ventricular dysfunction), cardiogenic shock, dysphagia, exfoliative dermatitis, hallucination, hepatic necrosis, hepatitis, hypotension, impotence, leukopenia, lupus-like syndrome (drug-induced), myelofibrosis (patients with pre-existing myeloid abnormalities), pancreatitis (rare), psychosis, pulmonary fibrosis, seizure, sinoatrial arrest, Stevens-Johnson syndrome, syncope, thrombocytopenia, torsades de pointes, upper gastrointestinal hemorrhage, urinary retention, urticaria

Commonly reported side effects of mexiletine include: heartburn, nausea, and vomiting. See below for a comprehensive list of adverse effects.

Substance Name

Mexiletine

CAS Registry Number

31828-71-4

Drug Class

Antiarrhythmics