Issues for surgery
For life-threatening ventricular arrythmias – increased risk of recurrence if omitted.
For myotonia in non-dystrophic myotonic disorders – increased risk of muscle stiffness and pain if omitted.
Advice in the perioperative period
Elective and emergency Surgery
Continue.
Check electrocardiogram (ECG) and electrolytes (potassium, magnesium) pre-operatively (see Further information).
Check FBC pre-operatively (see Further information).
Confirm indication, brand, and dose with patient or carer (see Further information).
For patients who may decide to quit smoking during the perioperative period see Further information.
Post-operative advice
Restart post-operatively, at usual dose, as soon as next dose is due. Absorption of mexiletine may be delayed if there is a delay in gastric emptying post-operatively, i.e., in post-operative ileus, and this should be borne in mind when restarting treatment due to its narrow therapeutic index.
Monitor serum potassium and magnesium levels post-operatively (see Further information).
Monitor FBC post-operatively and seek advice from haematologist if there are any haematological changes (see Further information).
If patients with life-threatening arrhythmias are unable to take their mexiletine orally post-operatively consult Cardiologist for advice.
Interactions with common anaesthetic agents
Opioids
Opioids may reduce absorption of oral mexiletine, possibly by delaying gastric emptying. This interaction is not clinically relevant where patients are already taking maintenance mexiletine treatment but bear in mind if there is clinical concern of lack of efficacy of mexiletine.
Local anaesthetics
Co-administration of lidocaine with mexiletine potentially increases the risk of adverse cardiac reactions, including torsades de pointes, due to the antiarrhythmic action of lidocaine. Manufacturer advises to avoid; however, the interaction is not fully confirmed. The combination should be used with caution and, although it is not known if topical lidocaine interacts, caution is advised with large doses of lidocaine.
Co-administration of mexiletine with lidocaine or ropivacaine may be associated with elevation in plasma concentration of lidocaine/ropivacaine which could prolong the therapeutic effect and/or increase the risk of adverse reactions. Monitor for adverse effects during concomitant use and adjust doses as necessary.
Interactions with other common medicines used in the perioperative period
Gastric emptying
Medicines that delay gastric emptying, such as opioids and antacids, may delay absorption of mexiletine (see Interactions with common anaesthetic agents above).
Medicines that accelerate gastric emptying, such as metoclopramide, may slightly hasten absorption of oral mexiletine, without affecting the extent of absorption; the interaction is unlikely to be of clinical significance.
Antacids
Some antacids (such as aluminium hydroxide and magnesium hydroxide) alkalinise the urine and might affect the levels of mexiletine in some patients. Bear the interaction in mind should there be an altered response to treatment.
Omeprazole
The manufacturers advise that co-administration of mexiletine with omeprazole may theoretically increase the clearance and elimination rate of mexiletine due to increased hepatic metabolism via CYP1A2, resulting in decreased plasma concentrations and half-life of mexiletine. However, further study has demonstrated that omeprazole does not affect mexiletine pharmacokinetics. The combination appears safe but bear potential interaction in mind should there be an altered response to treatment.
Ciprofloxacin
Ciprofloxacin reduces the clearance of mexiletine, due to CYP1A2 inhibition, potentially increasing the risk of adverse reactions to mexiletine. The extent of this reduced clearance is unlikely to be of clinical significance but bear interaction in mind in case of an altered response to treatment.
Further information
Mexiletine licensing
There is variation in the licensing of different formulations of mexiletine. Only Namuscla® is licensed for myotonia in non-dystrophic myotonic disorders; the dose of this product is also expressed as mexiletine base rather than mexiletine hydrochloride, hence it is important to ensure that the correct brand is prescribed.
Electrolyte disturbances
Electrolyte imbalance such as hypokalaemia/hyperkalaemia or hypomagnesaemia may increase the proarrhythmic effects of mexiletine. Electrolyte imbalance needs to be corrected during mexiletine treatment.
Blood dyscrasias
Leukopenia and thrombocytopenia have been reported in clinical studies. Monitoring of FBC is recommended during therapy. If significant haematological changes are observed, patients should be reviewed by a haematologist.
Smoking cessation
Tobacco is known to induce CYP1A2 which is partly involved in the metabolism of mexiletine resulting in reduced half-life (although no effect on its absorption and distribution). Quitting smoking pre-operatively improves surgical outcomes through reducing risk of post-operative complication. If a patient decides to quit smoking during the perioperative period, it must be remembered that smoking cessation can reduce mexiletine clearance and dose reduction may be necessary. Seek advice from a specialist.
References
Mexiletine. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 18th May 2023]
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 21st September 2023]
Summary of Product Characteristics – Namuscla® (mexiletene) 167 mg hard capsules. Lupin Healthcare (UK) Ltd. Accessed via www.medicines.org.uk 21/09/2023 [date of revision of the text January 2019]
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 21st September 2023]
Faculty of Public Health, The Royal College of Surgeons of Edinburgh, The Royal College of Anaesthetists, ash (action on smoking and health). Joint Briefing: Smoking and surgery. April 2016. Available at www.rcoa.ac.uk [Accessed on 21st September 2023]