Published: 5 September 2024

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Medicines may cause or exacerbate myasthenia gravis

Published: 5 September 2024
Prescriber Update 45(3): 63–66
September 2024

Myasthenia gravis

Myasthenia gravis (MG) is a neuromuscular transmission disorder. It is caused by autoantibodies blocking or destroying nicotinic acetylcholine receptors (AChR) or other proteins at the neuromuscular junction of skeletal muscles.^1,2

MG is characterised by fluctuating weakness of the voluntary muscles that control eye movements, facial expression, speaking, swallowing, limb movement and breathing. Symptoms include drooping eyelids, double vision, problems with chewing or swallowing, speech disturbance, limb weakness and shortness of breath.³ Generalised MG involves multiple groups of muscles and ocular MG only affects the eye muscles.¹

People of any age can be affected, but MG typically starts in women aged under 40 years and men aged over 60 years.³

Numerous factors may cause or exacerbate MG, including medicines (described below), stress, tiredness, infections, excess physical activity, warm weather, surgery and changes in immunomodulatory treatments.^3,4

Diagnosis and treatment

MG is typically diagnosed with a detailed neurological examination, laboratory and/or electrodiagnostic testing. Approximately 85% of patients with generalised MG have AchR antibodies, and approximately 40% who are seronegative for AChR antibodies are positive for muscle-specific tyrosine kinase (MuSK) antibodies.¹

Treatment aims to reduce the symptoms and may include:^5,6

• avoiding triggers
• anticholinesterases to improve strength
• immunosuppressants or immunomodulatory treatment to suppress the autoimmune reaction
• surgery to remove the thymus gland (thymectomy).

Medicine-related myasthenia gravis

Many medicines are associated with MG. Immune checkpoint inhibitors, tyrosine kinase inhibitors and statins may cause new-onset (de novo) MG or exacerbate existing MG by causing an autoimmune reaction at the neuromuscular junction.^1,2,7

Other medicines, such as aminoglycosides, antimuscarinics, neuromuscular blockers and benzodiazepines, affect neuromuscular transmission and may exacerbate or unmask MG symptoms.^1,7

Table 1 lists examples of medicines, by class, that may cause or exacerbate MG as listed in the respective data sheets. Note that the list is not exhaustive.

Table 1: Examples of medicines, by class, that may cause or exacerbate myasthenia gravis (list not exhaustive)

Class	Examples*	Class	Examples*
Immune checkpoint inhibitors	Atezolizumab Durvalumab Ipilimumab Nivolumab Pembrolizumab	Neuromuscular blockers	Botulinum toxin type A Atracurium Mivacurium Rocuronium Vecuronium Suxamethonium
Statins	Atorvastatin Pravastatin Rosuvastatin Simvastatin	Benzodiazepines	Clonazepam Diazepam Lorazepam Temazepam
Tyrosine kinase inhibitors	Lenvatinib	Beta-blockers	Propranolol Nadolol
Aminoglycosides	Gentamycin Amikacin Tobramycin	Fluoroquinolones	Norfloxacin Ciprofloxacin Moxifloxacin
Antimuscarinics	Atropine (systemic) Hyoscine (scopolamine) Propantheline	Macrolides	Azithromycin Clarithromycin Erythromycin Roxithromycin

* Refer to the respective data sheets for information about myasthenia gravis. Data sheets are available at: www.medsafe.govt.nz/Medicines/infoSearch.asp

Patients with pre-existing MG

Some medicines may exacerbate MG and so are not recommended or should be used with caution in patients with pre-existing MG.

Refer to the data sheets and clinical guidelines before prescribing medicines that can cause autoimmune reactions or affect neuromuscular transmission to patients with pre-existing MG. Seek specialist advice as appropriate.

Patients with suspected medicine-related MG

Refer to the data sheet and consider stopping the medicine if clinically appropriate. Follow local clinical guidelines for MG diagnosis and treatment.

Statins and MG

Myasthenia gravis was recently identified as an adverse effect associated with statins.³ Medsafe has requested the NZ sponsors of these medicines to update their data sheets to reflect this association.

In a few cases, statins were reported to induce or exacerbate MG or ocular myasthenia, including reports of recurrence when the same or a different statin was administered. The statin should be discontinued if these conditions occur.^8–11

Advise patients who are taking statins to be alert for any new symptoms that could be MG, or for worsening symptoms of pre-existing MG, and to seek medical advice if these occur.³

NZ case reports

As of 30 June 2024, Medsafe and the Centre for Adverse Reactions Monitoring (CARM) had received 5 reports of myasthenia gravis:

• 3 reports where pembrolizumab was the suspect medicine (NZ-Medsafe: 155420, 156395, 156552)
• 2 reports where atorvastatin was the suspect medicine (NZ-Medsafe: 156410, 156483).

References

1. Sheikh S, Alvi U, Soliven B, et al. 2021. Drugs that induce or cause deterioration of myasthenia gravis: an update. Journal of Clinical Medicine 10(7): 1537. DOI: 10.3390/jcm10071537 (accessed 19 June 2024).
2. Gras-Champel V, Masmoudi I, Batteux B, et al. 2020. Statin-associated myasthenia: A case report and literature review. Therapie 75(3): 301-9. DOI: 10.1016/j.therap.2019.07.004 (accessed 20 June 2024).
3. Medicines and Healthcare products Regulatory Agency. 2023. Statins: very infrequent reports of myasthenia gravis 26 September 2023. URL: www.gov.uk/drug-safety-update/statins-very-infrequent-reports-of-myasthenia-gravis (accessed 19 June 2024).
4. Shah A. 2023. Myasthenia gravis updated 5 December 2023. URL: emedicine.medscape.com/article/1171206-overview (accessed 20 June 2024).
5. National Health Service (UK). 2023. Myasthenia gravis 13 September 2023. URL: www.nhs.uk/conditions/myasthenia-gravis/ (accessed 24 June 2024).
6. New Zealand Formulary (NZF). 2024. NZF v144: Drugs that enhance neuromuscular transmission 1 June 2024. URL: nzf.org.nz/nzf_5702 (accessed 24 June 2024).
7. Narayansaswami P, Sanders D, Wolfe G, et al. 2021. International consensus guidance for management of myasthenia gravis. Neurology 96(3): 114-22. DOI: 10.1212/WNL.0000000000011124 (accessed 19 June 2024).
8. A. Menarini New Zealand Pty Ltd. 2024. Crestor New Zealand Data Sheet 8 May 2024. URL: www.medsafe.govt.nz/profs/Datasheet/c/Crestortab.pdf (accessed 4 July 2024).
9. Viatris Ltd. 2024. Lorstat New Zealand Data Sheet 21 June 2024. URL: www.medsafe.govt.nz/profs/Datasheet/l/lorstattab.pdf (accessed 19 August 2024).
10. Clinect NZ Pty Ltd. 2024. Pravastatin New Zealand Data Sheet 9 April 2024. URL: www.medsafe.govt.nz/profs/Datasheet/p/pravastatintab.pdf (accessed 4 July 2024).
11. Viatris Ltd. 2023. Simvastatin Viatris New Zealand Data Sheet 16 November 2023. URL: www.medsafe.govt.nz/profs/Datasheet/s/simvastatinmylantab.pdf (accessed 4 July 2024).