Drugs List

Therapeutic Indications

Uses

Control of arrhythmias especially after myocardial infarction
Control of arrhythmias following digitalis/cardiac glycosides
Maintenance of sinus rhythm after conversion of atrial flutter/fibrillation
Paroxysmal supra-ventricular tachyarrhythmias
Persistent atrial extrasystoles
Persistent ventricular extrasystoles
Prevent/control arrhythmias developing during surgical procedures
Wolff-Parkinson-White syndrome

Contraindications

Children under 18 years
Acute porphyria
Bundle branch block with first degree atrioventricular block
Cardiogenic shock
Hepatic impairment
Hereditary fructose intolerance
Long QT syndrome
Non-paced bifascicular block
Non-paced second degree atrioventricular block
Non-paced sinus node dysfunction
Non-paced third degree atrioventricular block
Renal impairment
Severe cardiac failure - unless secondary to arrhythmia
Torsade de pointes

Precautions and Warnings

Cardiac glycoside toxicity
Elderly
Family history of long QT syndrome
Atrial flutter
Atrial tachycardia with atrioventricular block
Benign prostatic hyperplasia
Breastfeeding
Cardiac failure
Cardiomyopathy
Diabetes mellitus
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of torsade de pointes
Malnutrition
Myasthenia gravis
Narrow angle glaucoma
Pregnancy
Structural cardiac disorder

Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Consider need for digitalisation if poor cardiac reserve
Preparation contains sucrose
Perform ECG before and during treatment
Monitor blood glucose
Monitor serum electrolytes
Monitor serum potassium regularly
Review therapy if atrioventricular or bifascicular block occurs
May aggravate/provoke arrhythmias
Discontinue drug if ECG shows QRS or QT interval increased by 25%
Discontinue if hypoglycaemia occurs
Discontinue if hypotension occurs, restart at lower dose and monitor
Discontinue if Torsade de Pointes should occur during treatment
Discontinue if ventricular fibrillation occurs
Discontinue if ventricular tachycardia occurs

There is no evidence that prolonged suppression of ventricular premature contractions with anti arrhythmic drugs prevent sudden death. For this reason, antiarrhythmic drugs should not be prescribed for the treatment of patients with asymptomatic ventricular premature contractions. All antiarrhythmic drugs can produce unwanted effects when used to treat symptomatic but not life threatening arrhythmias.

Use with caution in patients with atrial flutter or atrial tachycardia with block as conversion of a partial AV block to a 1:1 response may occur, leading to potentially more serious tachyarrhythmia.

Patients suffering from cardiac failure may be especially sensitive to the negative inotropic effects of disopyramide. Such patients should be fully digitalised or controlled with other therapy before treatment is commenced.

Pregnancy and Lactation

Pregnancy

Use disopyramide with caution in pregnancy.

Animal testing for teratogenicity have not shown any effects on the developing foetus and no reports of malformations have been found. Disopyramide has been shown to cross the placenta. Maternal toxicity (decreased food consumption and weight gain), embryotoxicity (decreased number of implantation sites) and foetotoxicity (decreased growth and pup survival) were observed in pregnant rats dosed at over 20 times the recommended human dose of 12 mg/kg/day. Disopyramide has been reported to stimulate contractions in the pregnant uterus. Most reviews of antiarrhythmic drug therapy consider disopyramide as probably being safe during pregnancy, but one review does not recommend it for routine therapy and warns of its oxytocic effects (Briggs 2011). Schaefer (2007) recommends that quinidine is the drug of choice of the class 1a antiarrhythmic drugs for pregnant women, and that treatment with disopyramide does not necessitate termination of pregnancy. A detailed ultrasound scan should be offered in the cases of first trimester exposure.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use disopyramide with caution in breastfeeding.

Disopyramide has been found in the plasma of nursing infants at levels of 7.5 to 12.5 % of the mother's levels. The N-monodesalkyldisopyramide metabolite appears in breast milk in levels that are higher than disopyramide and also exhibits greater anticholinergic properties than disopyramide. No reports of adverse effects in the infant have been seen in the cases reported. LactMed state that disopyramide may be used cautiously while breastfeeding if other alternate drugs are deemed unsuitable. The infant should be observed for anticholinergic symptoms and the serum concentrations in the infant should be measured if there is any cause for concern. Schaefer (2007) recommend that quinidine is the preferred class 1a antiarrhythmic agent to disopyramide. However, if treatment has begun with an antiarrhythmic drug not recommended, weaning may not necessarily be required. If possible therapy should be changed to the preferred agent. Disopyramide may theoretically decrease the milk supply.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute hepatic ischaemia
Anorexia
Arrhythmias
Atrioventricular block
Blurred vision
Bradycardia
Bundle branch block
Cardiac conduction disturbances
Cardiac failure
Cardiogenic shock
Cholestatic jaundice
Cognitive impairment
Coma
Constipation
Diarrhoea
Diplopia
Disturbances in accommodation
Dizziness
Dry mouth
Dysuria
Gastro-intestinal symptoms
Glaucoma (closed angle)
Headache
Hypoglycaemia
Hypotension
Impotence
Myocardial depression
Nausea
Neutropenia
Pro-arrhythmic effects
Prolongation of QT interval
Psychiatric disorders
Rash
Renal impairment
Sino-atrial block
Torsades de pointes
Urinary retention
Ventricular fibrillation
Ventricular tachycardia
Vomiting
Widened QRS complex

Presentation

Modified release formulation of disopyramide

Drugs List

Therapeutic Indications

Uses

Control of arrhythmias especially after myocardial infarction
Control of arrhythmias following digitalis/cardiac glycosides
Maintenance of sinus rhythm after conversion of atrial flutter/fibrillation
Paroxysmal supra-ventricular tachyarrhythmias
Persistent atrial extrasystoles
Persistent ventricular extrasystoles
Prevent/control arrhythmias developing during surgical procedures
Wolff-Parkinson-White syndrome

Dosage

Adults

Elderly

Contraindications

Children under 18 years
Acute porphyria
Bundle branch block with first degree atrioventricular block
Cardiogenic shock
Hepatic impairment
Hereditary fructose intolerance
Long QT syndrome
Non-paced bifascicular block
Non-paced second degree atrioventricular block
Non-paced sinus node dysfunction
Non-paced third degree atrioventricular block
Renal impairment
Severe cardiac failure - unless secondary to arrhythmia
Torsade de pointes

Precautions and Warnings

Cardiac glycoside toxicity
Elderly
Family history of long QT syndrome
Atrial flutter
Atrial tachycardia with atrioventricular block
Benign prostatic hyperplasia
Breastfeeding
Cardiac failure
Cardiomyopathy
Diabetes mellitus
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of torsade de pointes
Malnutrition
Myasthenia gravis
Narrow angle glaucoma
Pregnancy
Structural cardiac disorder

Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Consider need for digitalisation if poor cardiac reserve
Preparation contains sucrose
Perform ECG before and during treatment
Monitor blood glucose
Monitor serum electrolytes
Monitor serum potassium regularly
Review therapy if atrioventricular or bifascicular block occurs
May aggravate/provoke arrhythmias
Discontinue drug if ECG shows QRS or QT interval increased by 25%
Discontinue if hypoglycaemia occurs
Discontinue if hypotension occurs, restart at lower dose and monitor
Discontinue if Torsade de Pointes should occur during treatment
Discontinue if ventricular fibrillation occurs
Discontinue if ventricular tachycardia occurs

There is no evidence that prolonged suppression of ventricular premature contractions with anti arrhythmic drugs prevent sudden death. For this reason, antiarrhythmic drugs should not be prescribed for the treatment of patients with asymptomatic ventricular premature contractions. All antiarrhythmic drugs can produce unwanted effects when used to treat symptomatic but not life threatening arrhythmias.

Use with caution in patients with atrial flutter or atrial tachycardia with block as conversion of a partial AV block to a 1:1 response may occur, leading to potentially more serious tachyarrhythmia.

Patients suffering from cardiac failure may be especially sensitive to the negative inotropic effects of disopyramide. Such patients should be fully digitalised or controlled with other therapy before treatment is commenced.

Pregnancy and Lactation

Pregnancy

Use disopyramide with caution in pregnancy.

Animal testing for teratogenicity have not shown any effects on the developing foetus and no reports of malformations have been found. Disopyramide has been shown to cross the placenta. Maternal toxicity (decreased food consumption and weight gain), embryotoxicity (decreased number of implantation sites) and foetotoxicity (decreased growth and pup survival) were observed in pregnant rats dosed at over 20 times the recommended human dose of 12 mg/kg/day. Disopyramide has been reported to stimulate contractions in the pregnant uterus. Most reviews of antiarrhythmic drug therapy consider disopyramide as probably being safe during pregnancy, but one review does not recommend it for routine therapy and warns of its oxytocic effects (Briggs 2011). Schaefer (2007) recommends that quinidine is the drug of choice of the class 1a antiarrhythmic drugs for pregnant women, and that treatment with disopyramide does not necessitate termination of pregnancy. A detailed ultrasound scan should be offered in the cases of first trimester exposure.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use disopyramide with caution in breastfeeding.

Disopyramide has been found in the plasma of nursing infants at levels of 7.5 to 12.5 % of the mother's levels. The N-monodesalkyldisopyramide metabolite appears in breast milk in levels that are higher than disopyramide and also exhibits greater anticholinergic properties than disopyramide. No reports of adverse effects in the infant have been seen in the cases reported. LactMed state that disopyramide may be used cautiously while breastfeeding if other alternate drugs are deemed unsuitable. The infant should be observed for anticholinergic symptoms and the serum concentrations in the infant should be measured if there is any cause for concern. Schaefer (2007) recommend that quinidine is the preferred class 1a antiarrhythmic agent to disopyramide. However, if treatment has begun with an antiarrhythmic drug not recommended, weaning may not necessarily be required. If possible therapy should be changed to the preferred agent. Disopyramide may theoretically decrease the milk supply.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute hepatic ischaemia
Anorexia
Arrhythmias
Atrioventricular block
Blurred vision
Bradycardia
Bundle branch block
Cardiac conduction disturbances
Cardiac failure
Cardiogenic shock
Cholestatic jaundice
Cognitive impairment
Coma
Constipation
Diarrhoea
Diplopia
Disturbances in accommodation
Dizziness
Dry mouth
Dysuria
Gastro-intestinal symptoms
Glaucoma (closed angle)
Headache
Hypoglycaemia
Hypotension
Impotence
Myocardial depression
Nausea
Neutropenia
Pro-arrhythmic effects
Prolongation of QT interval
Psychiatric disorders
Rash
Renal impairment
Sino-atrial block
Torsades de pointes
Urinary retention
Ventricular fibrillation
Ventricular tachycardia
Vomiting
Widened QRS complex

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: January 2016

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press Accessed on 19 January 2016.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Rythmodan Retard. Sanofi. Revised June 2014.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/download.txt
Disopyramide. Last revised: 16 January, 2014
Last accessed: 19 January, 2016