Antiarrhythmics – Class III

Amiodarone, Dronedarone

  Issues for Surgery

Risk of cardiac arrhythmias if omitted.

Risk of cardiac complications (i.e. bradycardia, hypotension, conduction disturbances and decreased cardiac output) if continued.

Risk of QT-interval prolongation if continued (see Interaction(s) with Common Anaesthetic Agents and Interaction(s) with other Common Medicines used in the Perioperative Period).

  Advice in the Perioperative period

Elective and Emergency Surgery

Continue.

Amiodarone
Ensure Anaesthetist informed on the day of surgery that the patient is taking amiodarone due to drug interactions (including patients who may have stopped treatment within the last few months – see Further Information)¹

Post-operative Advice

Restart post-operatively as soon as next dose is due, but bear in mind potential drug interactions see Interaction(s) with other Common Medicines used in the Perioperative Period and consult current product literature where necessary.

  Interaction(s) with Common Anaesthetic Agents

Bradycardia 

Amiodarone can increase the risk of bradycardia when used concomitantly with the following²: -

• alfentanil, fentanyl or remifentanil
• neostigmine
• propofol
• suxamethonium

Local Anaesthetics

Levobupivacaine and bupivacaine may increase the risk of cardio-depression when given with amiodarone or dronedarone – manufacturer advises monitor².

Opioids

Dronedarone may increase the effect of alfentanil and fentanyl – manufacturer advises monitor for adverse effects (such as excessive sedation, respiratory depression) and adjust dose^{2, 3}_.

Midazolam

Dronedarone may increase the effect of midazolam – manufacturer advises monitor for adverse effects (such as excessive sedation, respiratory depression) and adjust dose^{2, 3.}

QT-Interval Prolongation (see also under Interaction(s) with other Common Medicines used in the Perioperative Period)
Amiodarone and dronedarone prolong the QT-interval^{2, 3}. Co-administration with other medicines known to prolong the QT-interval must be based on careful assessment of the potential risks and benefits for each patient.

Anaesthetic agents that may be used in the perioperative period that are known to, or predicted to, prolong the QT-interval include^{2, 3}: -

• desflurane, isoflurane, sevoflurane - avoid
• thiopental (theoretical)*

*monitor ECG if concurrent use unavoidable; if risk factors for QT-prolongation are also present (increasing age, female sex, cardiac disease, and some metabolic disturbances e.g. hypokalaemia) use greater caution

  Interaction(s) with other Common Medicines used in the Perioperative Period

Hypokalaemia

Dexamethasone and hydrocortisone may cause hypokalaemia (potentially increasing the risk of torsades de pointes) with amiodarone or dronedarone – use with caution^{1, 2, 3, 4}. If hypokalaemia occurs, corrective action should be taken and QT-interval monitored^{1, 4}.

QT-Interval Prolongation (see also under Interaction(s) with Common Anaesthetic Agents)
Amiodarone and dronedarone prolong the QT-interval; co-administration of amiodarone and dronaderone with other medicines known to prolong the QT-interval must be based on a careful assessment of the potential risks and benefits for each patient since the risk of torsade de pointes may increase.

Medicines that may be used in the perioperative period that are known to prolong the QT-interval include^{1, 2, 3, 4}:-

• ciprofloxacin*
• clarithromycin – avoid with dronaderone, for amiodarone*
• domperidone – avoid 
• droperidol – avoid 
• erythromycin – particularly intravenous*
• granisetron*
• haloperidol – avoid 
• loperamide – increased risk with high doses*
• ondansetron – avoid 
• prochlorperazine – only a theoretical risk*

*monitor ECG with concurrent use particularly if risk factors for QT-interval prolongation also present (increasing age, female sex, cardiac disease, and some metabolic disturbances e.g. hypokalaemia)

Metronidazole
There has been an isolated report of QT-interval prolongation and torsades de pointes in a patient given metronidazole and amiodarone. No general conclusions can be drawn from this apparent interaction, but keep this in mind in the event of an unusual case³.

Oxycodone

Dronedarone may increase the effects of oxycodone – manufacturer advises monitor for adverse effects (such as excessive sedation, respiratory depression) and adjust dose^{2, 3}_.

Oxygen

There is potential for an interaction between amiodarone and high concentrations of oxygen. A few cases of adult respiratory distress syndrome, sometimes fatal, most often in the period immediately after surgery, have been observed¹.

  Further Information

Amiodarone has a long half-life; there is potential for drug interactions to occur for several weeks (or even months) after treatment has stopped².

  References

1. Summary of Product Characteristics – Amiodarone 100mg Tablets BP. Accord Healthcare Limited. Accessed via www.medicines.org.uk 4/05/2019 [date of revision of the text May 2017]
2. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 4^th May 2019]
3. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 4^th May 2019]
4. Summary of Product Characteristics – Multaq^® (dronedarone) 400mg tablets. SANOFI. Accessed via www.medicines.org.uk 4/05/2019 [date of revision of the text October 2014]