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Disopyramide standard release oral

Presentation

Standard release oral formulation of disopyramide

Drugs List

  • disopyramide 100mg capsules
  • disopyramide 150mg capsules
  • RYTHMODAN 100mg capsules
  • 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

    300 mg to 800 mg daily in divided doses.

    Elderly

    300 mg to 800 mg daily in divided doses.

    Dose reduction may be required in the elderly (especially in non smokers) with renal or hepatic impairment.

    Patients with Renal Impairment

    Reduce the dosage by adjusting the interval between administrations. Patients who have renal impairment should have their plasma levels measured regularly.

    Some of the manufacturers recommend the following doses:
    Creatinine clearance 20 to 60 ml/minute:100 mg every 8 hours or 150 mg every 12 hours.
    Creatinine clearance 8 to 20 ml/minute:100 mg every 12 hours.
    Creatinine clearance less than 8 ml/minute:150 mg every 24 hours.

    The Renal Drug Handbook suggests the following doses:
    Glomerular Filtration Rate (GFR)

    GFR 30 to 40 ml/minute:100 mg every 8 hours.
    GFR 15 to 30 ml/minute:100 mg every 12 hours.
    GFR less than 15 ml/minute:100 mg every 24 hours.

    Patients with Hepatic Impairment

    Reduced dosages may be required, as an increase in plasma half-life of disopyramide may occur.

    Contraindications

    Children under 18 years
    Acute porphyria
    Bundle branch block with first degree atrioventricular block
    Cardiogenic shock
    Galactosaemia
    Long QT syndrome
    Non-paced bifascicular block
    Non-paced second degree atrioventricular block
    Non-paced sinus node dysfunction
    Non-paced third degree atrioventricular block
    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
    Hepatic impairment
    History of torsade de pointes
    Lactose intolerance
    Malnutrition
    Myasthenia gravis
    Narrow angle glaucoma
    Pregnancy
    Renal impairment
    Structural cardiac disorder

    Correct electrolyte disorders before treatment
    Reduce dose in patients with hepatic impairment
    Reduce dose in patients with renal impairment
    Advise ability to drive/operate machinery may be affected by side effects
    Consider need for digitalisation if poor cardiac reserve
    Some formulations contain lactose
    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 death. 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. Consider the need for prior digitalisation in these patients.

    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 anti-arrhythmic 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 6 January 2016.

    Summary of Product Characteristics: Rythmodan Capsules. Sanofi. Revised February 2010.
    Summary of Product Characteristics: Rythmodan 100mg Capsules. Sanofi. Revised August 2013.

    Summary of Product Characteristics: Disopyramide Phosphate 100mg Capsules. Generics (UK) Ltd. Revised March 2015.
    Summary of Product Characteristics: Disopyramide Phosphate 150mg Capsules. Generics (UK) Ltd. Revised March 2015.

    The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
    Disopyramide Last revised: 16 January 2014
    Last accessed: 6 January 2016

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