Antiarrhythmic agents include-

Group I -  Moricizine, Qunidine, Procainamide, Disopyramide, Lidocaine, Phenytoin,  

                Tocainide,             Mexiletine, Flecanide,  Propafenone
Group II- Propranolol, Esmolol, Acebutol
Group III- Bretylium, Amiodarone, Solatol
Group IV- Verapramil, Digoxin, Adenosine

Interacting drugs- summary

+ Moricizine-

Cimetidine  
 increase in moricizine plasma levels, and decrease in            
   clearance Initiate moricizine at low doses (not more than 600mg/day)

Digoxin 
 additive prolongation of the PR interval but not with a significant            
  increase in the rate of second or third degree AV block. Little change 
   in serum digoxin levels or pharmacokinetics    

Propanolol
 small additive increase in PR interval, no change in overal ECG
   intervals

Moricizine +

Theophylline  
 theophylline clearance increased and plasma half-life
  decreased ( conventional and sustained release  theophylline)          
            
 

Ventricular arrhythmias, ventricular tachycardia that are life threatening.

Antiarrhythmic agents include-

Group I -  Moricizine, Qunidine, Procainamide, Disopyramide, Lidocaine, Phenytoin,

                Tocainide, Mexiletine, Flecanide,  Propafenone
Group II- Propranolol, Esmolol, Acebutol
Group III- Bretylium, Amiodarone, Solatol
Group IV- Verapramil, Digoxin, Adenosine

The most serious adverse reaction reported is proarrhyhmias .

In addition in controlled clinical trials and in open studies adverse reactions led to discontinuation of morcize in 7% of 1105 patients with ventricular and supraventricular arrhthmias including nausea  ( 3 % )  ECG abnormalites  ( 1%  prinicipally conduction defects, sinus pause, junctional rhythm or AV block

Other-
Sweating, musculoskeletal pain, dry mouth, blurred vision,  ( 2% to < 5% )
drug fever, hypothemia, temperature intolerance, eye pain, rash, pruritus, dry skin, urticaria,
 swelling of the lips and tongue, periorbital edema.  ( < 2% )

Cardiovascular-
Palpitations,  ( 5 % )sustained ventricular tachycardia, cardiac chest pain, CHF, cardiac
 death,  ( 2% to < 5% ) hypotension, hypertension, syncope, supraventricular arrhythmias, cardiac arrest, bradycardia,  pulmonary embolism, MI, vasodilation, cerebrovascular events,
thrombophelebitis ( < 2% ).

CNS-
Dizziness, ( 15% ) headache, ( 8% )fatigue,( 5 % )  hyperthesias, asthenia, nervousness, sleep disorders,  ( 2% to < 5% ) tremor, anxierty, depressions, euphoria,confusion, somnolence, agitation, seizure,coma, abnormal gait, hallucinations, nysstagmus, diplopia, speech disorder,akasthisia, memory loss, ataxia, abnormal coodrination ,dyskinesia, vertigo, tinnitus ( < 2% )
 
GU-
Urinary retention or frequency, dysuria, urinary incontinuance, kidney pain, impotence, decreased  libido ( < 2% )

Respiratory-
Dyspnea,  ( 5% ) hyperventillation, apnea, asthma, pharyngitis, cough, sinusitis ( < 2% )

GI-
Nausea, abdominal pain, dysphagia, vomiting, diarrhea, anorexia, bitter taste, dysphagia,
 flatluence, ileus. ( < 2% )

Pre-existing second or third degree AV block ; right bundle branch block when associated with left hemiblock (bifascicular block ) unless a pacemaker is present; cardiogenic shock,
hypersensitivity to the drug

Special precautions:
ECG changes/conduction abnormalities- moricizine slows AV nodal and intraventricular
conduction.  In patients with pre-existing conduction abnormalities, initiate therapy
cautiously.

Congestive heart failure-  carefully watch patients with pre-existing heart failure, when therapy is initiated.

Effects on pace-maker threshold- monitor pacing parameters, if moricizine is used.

Drug fever-   Fevers developed, but resolved within 48 hours after discontinuation of moricizine.

Warnings-
Mortality- it is prudent to reserve the use of morcizine for patients with life-threatening ventricular  arrhythmias.

Survival- antiarrhythmic drugs ahve not been proven to favourably affect survival or incidence of  sudden death.

Proarrhythmic effects- like other antiarrhymic drugs moricize can provoke new rhythm disturbances or make existing arrhythmias worse. It is not often possible to distinguish aic effect from the patients  underlying rhythm disorder, therefore consider the occrrence rates that follow approximations.

Electrolyte disturbances- hypokalemia or hypomagnesemia may alter the effects  of Class 1 antiarrhythmic drugs. Correct electrolyte imbalance before administration of morcizine

Renal function impairment- administer with particular care to patients with severe liver disease,  if at all.

Pregnancy- use during pregnancy only if clearly needed.

Lactation- because of te potential for serious adverse  to nursing infants, decide whether to
 discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

Children- safety and efficacy in children < 18 years of age have not been established.

Approved by FDA on June 26, 1990

Indications:
Ventricular arrhythmias, ventricular tachycardia that are life threatening.

Dosage:
Individualise dose- usual adult dose is between 600 and 900mg/day, given every 8 hours in 3 equally divided doses. Wthin the range the dose can be adjusted as tolerated in increments of 150mg/day at 3 day intervals.

Overdosage-    Symptoms                  
                                                     
Emesis, lethargy, coma, syncope, conduction disturbances, exacerbation of CHF, MI, sinus  arrest, arrthythmias (including juntional bradycardia)  ventricular tachycardia, ventricullat fibrillation,  and  asystole) rspiratory failure.        

                                               
Deaths have occurred after accidental or intentional  overdosages of 2250 and 10,000 mg respy. 

Treatment
              
 1. Treatment should be supportive
 2.  Hospitalize patients and monitor for cardiac, respiratory and CNS changes.
 3. Provide advanced life support systems, including an  intracardiac pacing catheter where necessary.
  4. Treat acute overdosage with appropiate gastric   evacuation and with special care to avoid  aspiration

Missed dose-

1. If you miss a dose of this medicine and remember within 2 hours of missed dose take it as soon as  possible.
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.

MORICIZINE

1. Take exactly as prescribed. Dosage changes must be supervised by the physician.

2. Contact physician, if chest pain or discomfort, pounding in the chest (palpitations). irregular heartbeat or fever occur.

3. Hospitalisation is required when starting medication.

4. Allergy- tell your doctor if you ever had any allergic reaction to morcizine or any other substances  such as food,    preservatives or dyes.

5. Pregnancy- not studied in pregnant women. However this medicine has not shown to cause birth  defects  or other problems in animal studies, although it affected  weight gain, in some animals.     Before taking morcizne make sure if you are pregnant or if you may become pregnant

6. Children- studies on this medicine has been done only on adult patients,and there is no specific information comparing use of morcizine  in children with use in other age groups.

7. Older adults- no specifc information comparing use of morcizine in the elderly with the use other  age groups  though  therisk f unwanted effects may be increased

8. Other medicines-  tell your doctor if you are on other prescription drugs or if you are taking any   non-prescription OTC medicines

9. Other medical problems- tell your doctor if you any other medical problems especially-

     Kidney disease or   Liver disease -effects may be incr  because of slower removal of morcizine   from the body.
    
8. Missed dose -
     If you miss a dose of this medicine, take it as soon as possible. however, if it is almost  time   for the next dose, skip the missed dose. Do not double doses.

9. 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.

10. Outdated medicines -
     Do not keep outdated medicine or medicine no longer needed. Be sure that any
     discarded medicine is out of reach of children.

Pharmacology:
Moricizine is classicaI antiarrhythmic agent with  potential  local anesthetic activirty and
myocardial membrane stabilising effects. Moricizine reduces the fast inward current carried by sodium ions

Pharmacokinetics:
Following oral administration, moricizine undergoes significant first-pass metabolism resulting in an absolute bioavailability of about 38%. Peak plasma concentrations are reached within 0.5 to 2 hours. Administration 30 minutes after a meal delays the rate of absorption, resulting in lower peak plasma concentration, but the the extent of absorption is not altered.  Moricizine undergoes extensive biotransformation and less than 1% is excreted in the urine.

 

Administration 30 minutes after a meal delays the rate of absorption, but the extent of absorption is not altered

Pregnancy:
Use during pregnancy only if needed.

Lactation:
Oberve caution while administratering to nursing mother because of potential  for serious adverse reactions to the nursing infants.

Children-
Safety and efficacy in children < 18 years of age have not been established.