Statins: very infrequent reports of myasthenia gravis

Globally, there has been a very small number of reports of new-onset or aggravation of pre-existing myasthenia gravis with atorvastatin, pravastatin, lovastatin, fluvastatin, simvastatin, rosuvastatin and pitavastatin (single-ingredient and fixed-dose combination products). Advise patients taking statins to be alert to new symptoms for myasthenia gravis, or worsening symptoms of pre-existing myasthenia gravis, and to seek medical advice if these occur.

From:
Medicines and Healthcare products Regulatory Agency
Published
26 September 2023
Therapeutic area:
Cardiovascular disease and lipidology

Advice for healthcare professionals:

  • there have been some suspected reports of new-onset or aggravation of pre-existing myasthenia gravis or ocular myasthenia associated with statin use; the current frequency of these adverse events is not known but given the extensive use of statins in the population, the reports are understood to be very infrequent
  • the majority of UK reports note that the patient recovered after stopping statin treatment, while a minority continued to experience symptoms; recurrence of symptoms has been reported when patients restarted on the same or a different statin
  • refer patients presenting with suspected new-onset myasthenia gravis after starting statin therapy to a neurology specialist – it could be necessary to discontinue statin treatment depending on the assessment of the individual benefits and risks
  • advise patients with pre-existing myasthenia gravis to be alert to aggravation of symptoms while taking a statin (see advice below); it could be necessary to discontinue statin treatment depending on the assessment of the individual benefits and risks
  • report suspected adverse drug reactions associated with statins on a Yellow Card

Advice for healthcare professionals to give to patients and carers:

  • statins are important medicines to lower a person’s risk of having cardiovascular events such as angina, heart attacks and stroke
  • many people who take statins do not experience side effects and, where this does happen, these are typically mild – but it is important to read the Patient Information Leaflet that comes with your medicine and talk to a healthcare professional if you are experiencing problems
  • do not stop your statin treatment without first discussing this with your doctor
  • before taking a statin, inform your doctor if you have history of myasthenia gravis or ocular myasthenia
  • talk to your doctor if you experience weakness in your arms or legs that worsens after periods of activity, double vision or drooping of your eyelids, difficulty swallowing, or shortness of breath
  • seek medical help immediately if you develop severe breathing or swallowing problems

Review of myasthenia gravis associated with statin medicines

Statins are an acceptably safe and effective group of medicines that help lower the level of low-density lipoprotein (LDL) cholesterol in the blood. Statins play an important role in the treatment of atherosclerotic cardiovascular disease (narrowing and hardening of arteries). Currently available statins in the UK are atorvastatin, fluvastatin, pravastatin, rosuvastatin and simvastatin.

A recent European review recommended new warnings on the risk of new onset or aggravation of pre-existing myasthenia gravis with multiple statins.[footnote 1] The findings of this review were considered by the Pharmacovigilance Expert Advisory Committee (PEAG) of the Commission on Human Medicines (CHM), which agreed with the recommendations. The product information of all statins is being updated to list myasthenia gravis and ocular myasthenia gravis as adverse drug reactions with a frequency ‘not known’. New warnings will also be added to the Summaries of Product Characteristics and Patient Information Leaflets.

In reviewing this issue, the PEAG recommended that the MHRA inform healthcare professionals and patients of the newly identified risk. They also noted that existing International Consensus Guidance for Management of Myasthenia Gravis (2020) states that statins may rarely worsen or precipitate myasthenia gravis. [footnote 2]

About myasthenia gravis

Myasthenia gravis is a rare long-term auto-immune neuromuscular disorder 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.

Myasthenia gravis can affect people of any age, generally starting in women under 40 years old and men over 60 years old. Drug treatment can usually help keep the symptoms under control.
Several triggers have been identified for patients with myasthenia gravis that can aggravate symptoms. These include stress, tiredness, infections, excess physical activity, surgery, changes in immunomodulatory treatments, and medicines. Some examples of medicines that have been associated with worsening symptoms include several groups of antibiotics (fluoroquinolones, macrolides, aminoglycosides) and beta-blockers. Reports of worsening myasthenia gravis with medicines are very rare.

UK reports of myasthenia gravis with statins

From 14 June 1995 up to 19 June 2023, the MHRA has received 10 UK Yellow Card reports citing a statin as a suspect medicine for an adverse drug reaction (ADR) involving myasthenia gravis; with reports received for simvastatin, atorvastatin and pravastatin. This is against a background of extensive use of statins. In 2022 alone, more than 9.5 million patients were dispensed a statin in the UK. [footnote 3]

Across the 10 Yellow Card reports the median age of the patients was 66 years (affected patient age groups ranged from 40 to 89 years with the majority of reports concerning those aged over 60 years). Symptoms reported include double vision, difficulty with speech and swallowing, weakness in limbs and shortness of breath. Onset of symptoms started from a few days up to three months after starting statin therapy.

Three of the 10 cases involved the recurrence or exacerbation of symptoms in patients with known myasthenia gravis. There was also one report of positive rechallenge with symptoms recurring on reinitiating statin therapy. While four of the reports indicated that patients were hospitalised, the majority of patients had recovered or were recovering at the time of reporting. No fatal UK reports have been received.

At this time there is insufficient data to conclude whether different statins, different duration of therapy and different dosing levels alter the risk of experiencing myasthenia gravis. It is also unknown whether the development of new-onset myasthenia gravis following statin therapy is a transient or permanent condition.

Report suspected drug reactions on a Yellow Card

Please continue to report suspected adverse drug reactions to the Yellow Card scheme. Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:

When reporting please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset timing, treatment dates, and product brand name.

Article citation: Drug Safety Update volume 17, issue 2: September 2023: 1.

  1. PRAC recommendations on signals: Adopted at the 9-12 January 2023 PRAC meeting (EMA/PRAC/4770/2023). ↩

  2. Narayanaswami P and others. International Consensus Guidance for Management of MG - 2020 Update. International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update. Neurology 2021; issue 96 pages 114 to 122. ↩

  3. Estimated number of UK patients dispensed a statin. The UK estimate was derived from dispensing data for England. The dispensing data was extracted from NHS Business Services Authority (NHSBSA) ePACT2 by MHRA in August 2023. ↩

Updates to this page

Published 26 September 2023
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