cautionary drugs

Cautionary Drugs and Immune Checkpoint Inhibitors in Myasthenia Gravis (MG)

For individuals living with Myasthenia Gravis (MG), understanding the potential impact of medications from a cautionary standpoint is a vital part of disease management. Certain drugs, including immune checkpoint inhibitors (ICIs) used in cancer treatment, can exacerbate MG symptoms or, in rare cases, trigger the onset of the disease.

This comprehensive guide compiled by the Myasthenia Gravis Foundation of America (MGFA) and the International Consensus Guidance for Management of Myasthenia Gravis provides essential information about cautionary drugs and ICIs to help patients and caregivers make informed decisions alongside their healthcare providers.

Cautionary Drugs for MG

Many medications, both prescription and over-the-counter, have been associated with worsening MG symptoms. While these drugs are not necessarily prohibited for individuals with MG, their use should be carefully discussed with a physician to weigh the risks and benefits.

Common Medications to Avoid or Use with Caution

1. Telithromycin

   • Usage: Antibiotic for community-acquired pneumonia.

   • Risk: Strongly associated with worsening MG.

   • FDA Warning: Black box warning; should not be used in MG.

2. Fluoroquinolones (e.g., ciprofloxacin, moxifloxacin, levofloxacin)

   • Usage: Broad-spectrum antibiotics.

   • Risk: Associated with worsening MG.

   • FDA Warning: Black box warning; use cautiously, if at all.

3. Botulinum Toxin

   • Risk: Known to worsen MG.

   • Recommendation: Avoid.

4. D-penicillamine

   • Usage: Treatment for Wilson disease and, rarely, rheumatoid arthritis.

   • Risk: Strongly associated with causing MG.

   • Recommendation: Avoid.

5. Quinine

   • Usage: Occasionally prescribed for leg cramps (prohibited in the U.S. except for malaria).

   • Risk: May worsen MG.

   • Recommendation: Avoid except for malaria treatment.

6. Magnesium

   • Usage: Administered intravenously for conditions like eclampsia or hypomagnesemia.

   • Risk: Potentially dangerous; can worsen MG symptoms.

   • Recommendation: Use only if absolutely necessary, with close physician monitoring.

7. Macrolide Antibiotics (e.g., erythromycin, azithromycin, clarithromycin)

   • Usage: Commonly prescribed for gram-positive bacterial infections.

   • Risk: May worsen MG.

   • Recommendation: Use cautiously, if at all.

8. Aminoglycoside Antibiotics (e.g., gentamicin, neomycin, tobramycin)

   • Usage: Used for gram-negative bacterial infections.

   • Risk: May exacerbate MG.

   • Recommendation: Use cautiously if no alternative is available.

9. Corticosteroids

   • Usage: A standard treatment for MG.

   • Risk: Can cause transient worsening of symptoms during the first two weeks of treatment.

   • Recommendation: Monitor carefully with Physician monitoring during initial and prolonged use.

10. Procainamide

    • Usage: Treatment for irregular heart rhythms.

    • Risk: May worsen MG symptoms.

    • Recommendation: Use with caution.

11. Desferrioxamine

    • Usage: Chelating agent for hemochromatosis.

    • Risk: May exacerbate MG symptoms.

    • Recommendation: Use cautiously.

12. Beta-blockers

    • Usage: Commonly prescribed for hypertension, heart disease, and migraines.

    • Risk: May worsen MG symptoms.

    • Recommendation: Use cautiously.

13. Statins (e.g., atorvastatin, pravastatin, rosuvastatin, simvastatin)

    • Usage: Cholesterol-lowering medications.

    • Risk: May worsen or trigger MG.

    • Recommendation: Use cautiously at the lowest effective dose.

14. Iodinated Radiologic Contrast Agents

    • Usage: Used in imaging procedures.

    • Risk: Older agents have been associated with MG worsening; modern agents are generally safer.

    • Recommendation: Use cautiously and monitor for worsening symptoms.

15. Chloroquine (Aralen)

    • Usage: Treatment for malaria and amoeba infections.

    • Risk: May worsen or precipitate MG symptoms.

    • Recommendation: Use with caution.

16. Hydroxychloroquine (Plaquenil)

    • Usage: Used for malaria, rheumatoid arthritis, and lupus.

    • Risk: May worsen or trigger MG.

    • Recommendation: Use with caution.

Immune Checkpoint Inhibitors (ICIs) and Myasthenia Gravis

Immunotherapy for cancer represents a groundbreaking advancement in oncology, offering new hope for patients. However, ICIs have been associated with rare complications, including the onset or exacerbation of MG.

What Are Immune Checkpoint Inhibitors (ICIs)?

ICIs are a class of drugs that enhance the immune system’s ability to fight cancer by targeting immune checkpoint proteins. These proteins regulate the immune response, and inhibiting them can boost immune activity against cancer cells. However, this heightened immune response can sometimes result in autoimmune side effects, such as MG.

MG and ICIs

ICIs may trigger MG in individuals with no prior history of the disease or worsen symptoms in those with pre-existing MG. Symptoms typically appear within six weeks of starting ICIs, though cases have been reported as early as two weeks and as late as 12 weeks.

Examples of ICIs:

• Pembrolizumab (Keytruda)

• Nivolumab (Opdivo)

• Atezolizumab (Tecentriq)

• Avelumab (Bavencio)

• Durvalumab (Imfinzi)

• Ipilimumab (Yervoy)

Recommendations for Patients and Providers

Patients with MG who are undergoing or considering immunotherapy should consult with both their oncologist and neurologist to discuss potential risks and benefits. Any new-onset weakness or worsening MG symptoms should be reported immediately to a healthcare provider.

Important Considerations

Patients should always inform their healthcare providers about their MG diagnosis before starting any new medication, including over-the-counter preparations. A full list of cautionary drugs can be accessed through the Myasthenia GravisFoundation of America (MGFA) website.

References and Additional Reading:

1. Myasthenia Gravis Foundation of America. (2020). Cautionary Drugs. Retrieved January 13, 2025, from https://myasthenia.org/living-with-mg/mg-emergency-preparedness/cautionary-drugs/

2. Sanders, D. B., Wolfe, G. I., Benatar, M., Evoli, A., Gilhus, N. E., Illa,& Narayanaswami, P. (2016). International consensus guidance for management of myasthenia gravis: Executive summary. Neurology, 87(4), 419–425. https://doi.org/10.1212/wnl.0000000000002790

additional cautionary drug resources from around the world

CLINICAL GUIDELINE: Myasthenia Gravis or Lambert-Eaton Myasthenia Syndrome – Medicines that may affect patients

By NHS Greater Glasgow and Clyde - Scotland

PDF link: https://rightdecisions.scot.nhs.uk/.../myasthenia-gravis

This guideline is intended to assist healthcare professionals in the choice of disease-specific treatments. There are certain medicines that have been reported to worsen or induce Myasthenia Gravis (MG), often by increasing muscular weakness, and should be used with caution in patients with this condition.

The list of medicines in table 1 has been compiled to assist prescribers in the decision-making process when prescribing medicines for patients with Myasthenia Gravis.

The medicines in this list have been classed according to those which should be:

• Absolutely contraindicated

• Avoided

• Used with caution

• Probably safe with patient monitoring.

Document info:

• Version Number: 2

• Date Approved: 16 th March 2022

• Lead Author: Laura Stobo

References and additional reading

1. https://www.nn.nhs.scot/smn/professionals/guidelines/myasthenia-gravis-2/