Drug Interaction:
Antiarrhythmic agents include-
Group I - Moricizine, Qunidine, Procainamide, Disopyramide, Lidocaine, Phenytoin, Tocainide,
Mexiletine, Flecanide, Encainide, Propafenone
Group II- Propranolol, Esmolol, Acebutol
Group III- Bretylium, Amiodarone, Solatol
Group IV- Verapramil, Digoxin, Adenosine
Interacting drugs- summary
+ Mexiletine-
Alumin hydrox / Magnes Hydrox/ Atropine / Narcotics / Hydantoin
Mexiletine absorbtion lowered
Cimetidine
cimetidine increase or decrease mexiletine plasma levels
Hydantoins
increased mexilitine clearance leading to lower steady state plasma
levels occur
Rifampicin
increased mexilitine clearance leading to lower steady-state plasma
levels occur
Metoclopram
Mexiletine absorption accelrated
Urinary alkaniser
in alkaline urine Mexiletine clearance decreased
Urinary acidifier
in acidic urine Mexiletine clearance increased
Mexiletine +
Caffeine
clearance of Caffeine decreased by 50%
Theophylline
serum Theophyllin level may be increased- increased
pharmaocologic and toxic effects
Indication:
Ventricular arrhythmias
Adverse Reaction:
Adverse reactions-
MEXILETINE-
CARDIOVASCULAR - Palpitations 4.3%, Chest pain 2.6% Angina like pain 1.7%
Increased ventricular arrhythmias 1%
CNS Dizziness/lightheadedness 19% Tremor 13% Coordination difficulties 9%
Changes in sleep habits 7.1% Weakness 5% Nervousness 5% Fatigue 4%
Speech difficulties 2.6% Confusion 2.6% Numbness 2.4% Tinnitus 2.4%
Depression 2.4%
GI Nausea/Vomiting/ heartburn 39% Diarrhea 5% Constipation 4%
Changes in appetite 2.6%
MISCELLANEOUS Blurred vision 5% Headache 6% Rash 4% Dyspnea 3% Dry mouth 3% Arthalgia 2% Fever 1%
QUINIDINE-
CARDIOVASCULAR - Palpitations 4.6% Chest pain 4.6% Angina like pain 1.9%
Increased ventricular arrhythmias 2.7%
CNS Dizziness/lightheadedness 14.1% Tremor 2.3 % Coordination difficulties 1.1%
Changes in sleep habits 2.7 % Weakness 5.3% Nervousness 1.9% Fatigue 6%
Numbness 2.3% Tinnitus 1.5% Depression 1.1%
GI Nausea/Vomiting/ heartburn 21% Diarrhea 33%
Changes in appetite 2%
MISCELLANEOUS Blurred vision 3% Headache 7% Rash 4% Dyspnea 3% Dry mouth 2% Arthalgia 2% Fever 3%
PROCIAINAMIDE-
CARDIOVASCULAR - Palpitations 1.3% Chest pain 1.3% Angina like pain 2.6%
Increased ventricular arrhythmias 2.6%
CNS Dizziness/lightheadedness 14.1 Tremor 3.8 % Coordination difficulties 1.3%
Changes in sleep habits 11.5% Weakness 7.7% Nervousness 6.4% Fatigue 5% Confusion 3.8% Numbness 2.6% Depression 1.3%
GI Nausea/Vomiting/ heartburn 33% Diarrhea 2.6% Constipation 6.4%
MISCELLANEOUS Blurred vision 5% Headache 8% Rash 10% Dyspnea 5% Dry mouth 5% Arthalgia 5% Fever 3%
DISPYRAMIDE-
CARDIOVASCULAR - Palpitations 5.8% Chest pain 5.8% Angina like pain 1.4 %
CNS Dizziness/lightheadedness 2.9% Tremor 3.8% Coordination difficulties 1.3%
Changes in sleep habits 8.7% Weakness 2.9% Nervousness 5.8% Fatigue 1% Depression 1.4%
GI Nausea/Vomiting/ heartburn 14% Diarrhea 8% Constipation 11.6%
MISCELLANEOUS Blurred vision 7% Headache 4% Rash 2% Dyspnea 3% Dry mouth 14.5% Arthalgia 2%
In controlled trials, the most frequent adverse reactions were upper GI distress ( 41% ),
tremor ( 12.6 ) lightheadedness ( 10.5% ) and coodrination difficulties ( 10.2 % ).
these reactions were generally serious. these were dose related and were reversible if the
dosage was reduced, if the drug was taken with food or antacids or if it was discontinued.
however they still led to discontinuation in 40%
Lab test abnormalities-
Abnormal liver function tests, positive ANA, thrombocytopenia, leukopenia,
including neutropenia, and agranulocytosis,myelofibrosis
Contra-Indications:
Cardiogenic shock,2nd or 3rd degree AV block.Lactation.
Special precautions:
Cardioivascular effects- if a ventricular pacemaker is operative patients with secondary or third degree heart block may be treated with mexiletine .
Hematologic changes- if significant hematologic changes are observed carefully evaluate the patient and if warranted discontinue mexilitine .
CNS effects- use with caution in patients with a known seizure disorder.
Urinary pH- avoid concurrent drugs or diets which may markedly alter urinary pH . Minor fluctutions in urinary pH associated with normal diet do not affect mexilitine excretion.
Warnings-
Proarrhythmias- mexilitine can worsen arrththmias,it is uncommon in patients with less serious arrhythmias (frequent premature beats or nonsustained ventricular tachycardia)
Survivial - antiarrhthmic drugs have not been shown to enhance survival in patients with ventricular arrhythmias.
Initial therapy- as with other antiarrthythmic initiate therapy in hospitals.
Mortality- it is prudent to consider any antiarrhythmic agent to have a significant risk in patient with structural disease.
Hepatic function impairment- observe caution in patients with hepatic dysfunction secondary to CHF.
Pregnancy- use during pregnancy only if the potential benefits outweigh the potential hazards to the fetus.
Lactation- mexilitine appears in breast milk in concentrations similar to or higher than those in plasma. If mexilitine is essential, consider alternative infant feeding.
Children- safety and efficacy in children have not been established.
Dosages/ Overdosage Etc:
Approved by FDA in December,1985
Indications::
Ventricular arrhythmias
Dosage:
Individualise dose..Administer with food or antacids.
Initial loading dose 400mg followed by 200mg dose every 8 hours.Maximum 450mg every 12
hours.
Overdosage-
Symptoms
Symptoms inlcude- dizziness, drowsiness, nausea,hypotension, sinus bradycardia, paresthesia, seizures intermittant left bundle branch block, and temporary systole.
With massive overdosage, coma and respiratory arrest may occur.
Treatment
1. Usual supportive measures
2. Acidification of urine may be useful
3.Treatment may inlclude the administration of atropine if hypotension or bradycardia occurs
Missed dose-
1. If you miss a dose of this medicine, take it as soon as possible unless the dose is less than 4 hours.
2. However, if you do not remember until later, skip the missed dose and go back to your regular
dosing schedule.
3. Do not double doses.
Patient Information:
MEXILETINE-
1.Take the medicine exactly as directed by the physician
2.To lessen the possibility of stomach upset this medicine should be taken with food or immediately after meals.
3.Do not miss any dose. It is best to take the medicine at evenly spaced time day and night.
4. Allergy- tell your doctor if you ever had any unwanted or unusual raection to mexilitine, lidocaine or locainide Also tell you doctor if you are allergic to any other substances such as food, preservatives or dyes
5. Pregnancy- has no been studied in pregnant women. Studies in animals show that mexiletine cause a decrease in successful pregnancies but no birth defects. Before taking this medicin e make sure that your doctor knows if are pregnant or if you may become pregnant.
6. Breastfeeding- mexilitene pase into breast milk. Because this medicine may cause serious side effects breast feeding is not generally recommended while you are reeiving it. Be sure that you discuss with your doctor.
7. Children- studies done only on adults and there is no specific information comparing use of mexiletine in children with use in other age group.
8. Older adults- nospecific information comparing use of mexiletine in elderly with use in other age groups.
9. Other medicines- tel your doctor if youaretaking anyother prescripton medicines or no prescription OTC products.
10. Other medical problems- tell your doctor if haveany other medical prblems especially- Congestive herat failure or Low blood pressure or Liver dsease - effects may last longer because of slower removal of mexilitene from the body. Seizures - mexiletine can cause seizures
11. Dosing - follow yourdoctors advice and do not change it unlessyourdoctor tells youto do so.
12. Missed dose- If you miss a dose of this medicine take it as soon as possible. However if it is almost time for your next dose skip the missed dose and then go back to your regular dosing schedule. Do not double doses.
13. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places. Keep unwanted or diacarded medicines out of reach of children
Pharmacology/ Pharmacokinetics:
Pharmacology:
Like lidocaine, mexiletine inhibits the inward sodium current, thus reducing the rate of rise of the action potential
Absorption/Distribution: Mexilitine is well absorbed approx 90% from the GI tract. The absorption rate is reduced in clinical situations in which gastric emptying time is increased. Narcotics, atropine and magnesium- alumininium hydroxide may slow absorption; metoclopropramide may increase absorption.
Interaction with Food:
None reported.
Pregnancy and lactation:
Pregnancy:
Use during pregnancy only if the potential benefits outweigh the the potential hazards to the fetus.
Lactation:
Mexilitine appears in breast milk in concentrations higher than those in plasma. If mexilitine is essential, consider alternative infant feeding.
Children-
Safety and efficacy in children have not been established
Manufacturer Details