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2.3 Anti-arrhythmic drugs

Digoxin tablets, elixir, injection
Flecainide tablets, injection
Propafenone tablets
Verapamil tablets, injection
Adenosine injection

 

Drugs acting on supraventricular and ventricular arrhythmias
Amiodarone tablets, injection - see Monitoring guidelines
Dronedarone - see NICE TA 197 - see note below
Disopyramide capsules, MR tablets, injection
Sotalol tablets, injection
Drugs acting on ventricular arrhythmias
Lidocaine injection
Bretylium injection
Phenytoin injection (for digoxin-induced arrhythmias)

Notes:

1. CSM advice: July 1996. Sotalol should be limited to the treatment of ventricular arrhythmias or prophylaxis of supraventricular tachyarrhythmias. It should no longer be used for angina, hypertension, thyrotoxicosis or for secondary prevention after MI. Evidence is lacking that sotalol has a favourable benefit to risk profile in comparison to alternative beta-blockers available for the treatment of these conditions. When stopping sotalol the dose should be reduced gradually.

2. Dronedarone is now only indicated in adult clinically stable patients with paroxysmal or persistent atrial fibrillation for the maintenance of sinus rhythm after successful cardio version. It should be initiated and monitored only under specialist supervision and after other treatment options have been considered. Dronedarone has been associated with an elevated risk of or worsening, or new-onset, heart failure, and liver toxicity including two cases of liver failure requiring transplantation. Pulmonary toxicity has also been described.

For further information, see the Drug Safety Updates from  February 2011 and October 2011

Advice for healthcare professionals

Contraindications:

Dronedarone is now contraindicated in patients with:

  • Unstable haemodynamic conditions
  • History of, or current, heart failure or left ventricular systolic dysfunction
  • Permanent AF (ie, duration ≥6 months or unknown, and attempts to restore sinus rhythm no longer considered by physician).
  • Liver and lung toxicity related to previous use of amiodarone


Cardiovascular monitoring:

  • Patients should receive regular cardiac examinations, including an ECG at least every 6 months, to identify those who revert to AF. Discontinuation of dronedarone should be considered for these patients.

  • Discontinue treatment if the patient develops permanent AF
  • Patients should be carefully evaluated for symptoms of heart failure during treatment
  • Patients should be appropriately anticoagulated as per clinical AF guidelines. International Normalised Ratio (INR) should be closely monitored after initiating dronedarone in patients taking vitamin K antagonists as per the prescribing information for these products.


Hepatic monitoring:

For patients prescribed dronedarone, liver-function tests should be performed:

- before treatment.

- 1 week after starting

- 1 month after starting

- on a monthly basis for 6 months.

- at months 9 and 12, and periodically thereafter.  

  • If alanine transaminase (ALT) levels are elevated to ≥3× upper limit of normal (ULN), levels should be retested within 48–72 hours. If ALT levels are confirmed to be ≥3× ULN after retesting, dronedarone treatment should be withdrawn.

  • Patients should be advised to consult a physician if they develop any of the following symptoms of liver injury: abdominal pain or discomfort; loss of appetite; nausea; vomiting; yellowing of the skin or the whites of the eyes; unusual darkening of the urine; itching; or fatigue (especially in association with other symptoms listed above).

     

Renal monitoring:

  • Plasma creatinine values should be measured before and 7 days after initiation of dronedarone, and renal function should be monitored periodically afterwards. Discontinue treatment in any patients with further elevations of serum creatinine.


Pulmonary monitoring:

  • Cases of interstitial lung disease, including pneumonitis and pulmonary fibrosis, have been reported in association with dronedarone. Onset of dyspnoea or non-productive cough may be related to pulmonary toxicity. If pulmonary toxicity is suspected during treatment, relevant lung examinations should be considered and treatment discontinued if confirmed.


3. Amiodarone Loading

IV-300mg over 20 minutes to 2 hours (typically over one hour) to a maximum of 1200mg/24 Hours. Dilute the solution in 250ml of dextrose 5%. A dose of 900mg/500ml dextrose 5% is then given over 23 hours

Simultaneously orally loading can be started, i.e:

- 200mg tds for one week - then 200mg bd for one week - then 200mg od maintenance (unless adjustment required)

There is no evidence that rapid oral loading (eg 1g stat) is effective.

4. The lowest effective dose of amiodarone should be used for maintenance.

5. Advise patients on amiodarone to protect the skin from light and use a wide spectrum (UVA and UVB) sunscreen

6. Liver function (particularly transaminases) and thyroid function tests should be performed before commencement of amiodarone and then every 6 months thereafter

7. Amiodarone will increase the anticoagulant effect of Warfarin - monitor INR.

8. Amiodarone IV should be infused in Dextrose 5%, preferably into a central line to avoid thrombophlebitis. It should be infused by a volumetric pump, e.g. a Volumed/Baxter Colleague.

 

For link to BNF section: 2.3 Anti-arrhythmic drugs