When Jonni Sutton was six months pregnant with her son, who's now 3, she experienced chest pains and went to the emergency department near her home in Columbia, MO. After an examination, the doctor thought she might have bacterial pneumonia and prepared to start her on an intravenous drip of an antibiotic.
But Sutton, who's now 43 and was diagnosed with myasthenia gravis (MG) in college, knew that many drugs—including certain antibiotics, heart medications, and magnesium—could worsen her symptoms or cause a flare-up. It could also cause an MG crisis—extreme muscle weakness, especially of the diaphragm and chest muscles involved in breathing. After refusing the IV drip, Sutton was given a cup filled with what the doctor called his “GI cocktail.” As soon as Sutton took a sip, she started gasping. “When I asked what was in it and he told me lidocaine and magnesium, I asked if he was trying to put me on a ventilator,” says Sutton, who insisted that the doctor call her neurologist before giving her anything else. “I always tell people they need to ask their doctors about any drugs they might be prescribed.”
MG is a chronic autoimmune disorder in which antibodies disrupt the communication between nerves and muscles. It affects more than 70,000 Americans, according to the Myasthenia Gravis Foundation of America, and causes varying and fluctuating weakness of voluntary muscle groups, like those that control the eyes and eyelids, facial expressions, swallowing and speaking, and arm and leg movements. And some drugs can harm people with the disorder or even trigger the disease. Certain immune therapies used in cancer treatment can unmask myasthenia gravis symptoms such as weakness in people who have not been diagnosed, says Kourosh Rezania, MD, professor of neurology at the University of Chicago, who specializes in MG and other neuromuscular diseases.
Several common medications interfere with neuromuscular transmission—the process by which information gets sent from a motor nerve ending to a muscle fiber, producing voluntary movement. In most people, neuromuscular transmission works even under significant physiological stress. In people with MG, neuromuscular transmission is damaged, so any drug that impairs transmission will exacerbate symptoms.
Drugs to Avoid
Various classes of antibiotics should be used with caution in people with MG. They include macrolide antibiotics, such as erythromycin, azithromycin, and clarithromycin, which are prescribed for gram-positive bacterial infections like staphylococcus and streptococcus (typically less resistant to antibiotics and easier to treat); fluoroquinolones, such as ciprofloxacin and levofloxacin, which have a black box warning on their labels regarding MG; and aminoglycosides, such as gentamycin, neomycin, and tobramycin, which are used to treat gram-negative bacterial infections like pneumonia, meningitis, and bloodstream or wound infections (usually more resistant to antibiotics and harder to kill).
Other medications that can aggravate MG include certain cardiovascular drugs like beta-blockers, calcium channel blockers, statins, and corticosteroids. “Corticosteroids are used to treat MG, but if given in high doses acutely, they can actually cause deterioration, even an MG crisis,” Dr. Rezania says. “People with MG should not be started on high-dose steroids unless there is an urgent reason to do so. In that case, they must be observed very closely. In most instances, we start with low doses and escalate gradually.” The negative effects of statins and beta-blockers are rarer, so they may be used at the lowest effective dose in people whose disease is well controlled, says Dr. Rexania. “Patients should be monitored closely, especially when they first start treatment.”
Medications that can cause more severe reactions in people with MG include botulinum toxin (Botox); antimalarial drugs such as quinine, chloroquine, and hydroxychloroquine; and magnesium, particularly when given intravenously, such as for the treatment of eclampsia in late pregnancy. Dr. Rezania advises using them with extreme caution.
MG-Triggering Medications
In some cases, treatment with one or more of these drugs can reveal previously undiagnosed MG. When Christina Ramirez, an intensive care unit nurse from Rogers, AR, was given a course of antibiotics that included clarithromycin and amoxicillin for a serious gastrointestinal infection in July 2017, she had never had any symptoms associated with MG other than years of persistent, unexplained fatigue. “I was always more tired than everyone around me, but I chalked it up to the pressures of college, or being a new mom, or being a nurse,” she says.
In September 2017, she began having trouble swallowing, and food would get stuck in her throat. By the end of the month, she could no longer swallow liquids without coughing. A GI specialist found nothing abnormal and referred Ramirez to a neurologist, who diagnosed her with double antibody-negative MG and told her she probably had had underlying MG for years and the antibiotics triggered more overt symptoms by interfering with neuromuscular transmission.
“That's pretty common,” says Ramirez, who now volunteers as an educator for other people with MG, as she has been on disability for her illness since 2019. “I just spoke with someone yesterday who had been hospitalized for an asthma attack and went into respiratory failure after receiving IV magnesium. That was how she was first diagnosed with MG. It is so important for patients to be fully informed about their disease so they can ensure their safety and better advocate for themselves.”
A few immunotherapy medications called immune checkpoint inhibitors used to treat cancer can cause MG. The complication is rare but real: A study published in Cureus in 2019 found that 14 of 5,898 patients (0.24 percent) who received treatment with immune checkpoint inhibitors developed MG, with symptoms appearing on average four weeks after treatment. About two-thirds of those patients developed severe muscle weakness, and 45 percent of them had breathing problems that required mechanical support. Almost all patients were hospitalized. The more severe symptoms may be because patients receiving cancer immunotherapies are usually older than the average patient with MG and have more underlying health conditions.
“People with any known underlying immune-mediated condition such as lupus or rheumatoid arthritis are more likely to develop MG as a result of checkpoint inhibitors, so doctors need to be extraordinarily cautious in prescribing these drugs to those patients,” says Gil Wolfe, MD, FAAN, co-chair of the panel that developed the International Consensus Guidance for Management of Myasthenia Gravis. Published in Neurology in 2021, the guideline has an extensive table of drugs to avoid or use with caution in patients with MG. “But even patients without any known predisposition can develop MG after being given these drugs, which can turn the immune system against the body.”
The mortality rate for people who develop MG under these circumstances can be up to 50 percent, says Dr. Rezania. “If there is any reason to suspect that someone who needs an immune checkpoint inhibitor for cancer might have an underlying immune condition, they should be treated in advance with immune globulin or plasma exchange. If a person in the hospital for cancer treatment develops symptoms like double vision and swallowing problems, that is my first question: Have you been treated with one of these immunotherapy medications?”
D-penicillamine, which is sometimes used to treat autoimmune disorders such as rheumatoid arthritis, primary biliary cirrhosis, scleroderma, and Wilson's disease, a rare genetic condition that causes copper buildup in vital organs, also has been found to cause MG in 1 to 7 percent of patients who take it. In about two-thirds of the cases, the disease goes into remission after the drug is discontinued.
Safety Measures
In most practices, physicians are alerted about potential harmful effects when prescribing contraindicated drugs for people with MG, but studies have found that these alerts are often overridden. “We get so many alerts that we have become numb to them, and they are often ignored,” Dr. Wolfe acknowledges. “I still see patients coming in with worsening symptoms because a doctor gave them ciprofloxacin or levofloxacin. Many primary care doctors are unaware of these contraindications for people with MG.”
To be safe, patients should keep a list of risky medications with them at all times, he says. “I still rely on plain old paper; I hand my patients a list, and as I give it to them, I circle the ones that are the biggest problems.” The Myasthenia Gravis Foundation of America maintains a printable list of cautionary drugs, and the MyMG mobile app has a warning section about these drugs, he says.
Jonni Sutton, who runs a support group for people with MG, uses a personal health app called Guava and carries a card with a QR code for emergency personnel, which explains that she has MG and won't be able to communicate in a crisis situation. It also says that any respiratory problems she may have may be caused by diaphragmatic weakness, which won't be reflected in her oxygen levels. It then refers emergency personnel to the Myasthenia Gravis Foundation of America website for the list of risky drugs.
Sometimes a risky drug is necessary, says Dr. Rezania. For example, immunomodulating treatments are commonly prescribed for MG, which can put patients at increased risk of infection, necessitating antibiotics—and sometimes the most appropriate antibiotic is contraindicated. Sutton once had a resistant skin infection that didn't respond to trimethoprim/sulfamethoxazole (Bactrim) or amoxicillin (Moxatag). Her doctor then prescribed ciprofloxacin (Cipro), which worked. “Ciprofloxacin is definitely contraindicated, but we had to get rid of that infection,” says Sutton. “I always work closely with my MG specialist to weigh my options in a situation like that.”
Infections and the stress associated with them can lead to MG exacerbations, says Dr. Rezania. “You have to weigh the pros and cons. For outpatient treatment, you should be particularly cautious about the ‘Z-pack’ antibiotics and fluoroquinolones like ciprofloxacin,” he says. “If you have to use one of these antibiotics, your doctor should monitor you closely and tell you what symptoms might warrant a trip to the emergency department.”
Over time, Sutton has had enough experiences with the health care system to know when she needs to be particularly cautious. “If a health care person is passive or dismissive when I tell them about my disease, I know I need to be very wary,” she says. “Make sure all necessary information is in a safe place, both on your person and in your home, and that someone can access it easily if you're unable to communicate. And never be afraid to ask questions and challenge medical personnel. Being knowledgeable about your disease is the most important thing you can do to save your life.”
