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Drugs causing or worsening MG

Penicillamine: Rarely, about 1-2% of individuals treated long term with penicillamine develop MG and/or have low concentrations of antibodies to AChR. Their MG is often mild and predominantly ocular MA, involves antibodies directed at AChR in about 80% of the cases, becomes evident usually 6–7 months (range one month to 8 years) after starting the drug), and goes into complete remission in 70% of the cases within 6–10 months after discontinuation of the drug.

Botulinum toxin A: Botulinum toxin A (sold under the brand name Botox, Jeuveau, and Xeomin) blocks transmission at neuromuscular junctions to paralyze the muscles into which it is injected. Local botulinum toxin A injection for cosmetic purposes has on occasion resulted in weaknesses in distant muscles, symptoms resembling ocular or generalized MG in individuals with subclinical MG and exacerbations of previously controlled MG. Botulinum toxin A has also been used to treat Spasmodic torticollis (i.e., involuntarily neck turning), blepharospasm (involuntary contraction of the eye lids), and other uncontrolled facial muscle spasms in MG patients without side effects or with only short-lived dysphagia or diplopia. Botulinum toxin A treatment, it is suggested, is best avoided in MG patients but may be offered with caution to patients with mild or stable MG using gradual increases in its dosages close monitoring.

Immune checkpoint inhibitors: Immune checkpoint inhibitors promote certain types of autoimmune responses by blocking checkpoint pathways that inhibit these responses. The checkpoint inhibitors include pembrolizumab, nivolumab, ipilimumab, avelumab, atezolizumab, and durvalumab. From a total 5,898 patients who received these drugs, 52 developed new onset MG and 11 had a flare of their preexisting MG. The symptoms of MG developed with 6 days to 16 weeks (median time 4 weeks). Their MG was often sever with 29 patients developing respiratory failure that required mechanical ventilation. Other studies have have also reported that these checkpoint inhibitors often produce life-threatening complications resulting in respiratory failure in 45% and fatality in 25–40% of patients.

Statins: Statins are drugs that lower blood cholesterol levels. In a review of 169 patients who taking a statin (i.e., Simvastatin, atorvastatin, rosuvastatin, pravastatin, lovastatin, or fluvastatin), 136 developed generalized MG, 18 had an exasperation of their MG, and 13 developed ocular MG. Following discontinuance of the statin and treatment of their disease, 63 patients had fully recovered, 27 patients were recovering, 19 patients had not yet recovered, 5 patients recovered but had ongoing symptoms, 1 patient had died, and there was no follow-up data for 54 patients. Among these cases, 56% were considered to be serious. Non-statin lipid lowering drugs (e.g., niacin, bile acid sequestrants (cholestyramine, colestipol, colesevelam, alirocumab, evolocumab have been used in MG patients and not been reported to cause worsening of MG symptoms.

Antibiotics: In the macrolide family of antibiotics, azithromycin, telithromycin (which is no longer available in the US market), and erythromycin, have been reported to exacerbate MG. In the fluoroquinolone antibiotic family ciprofloxacin, norfloxacin, ofloxacin, moxifloxacin, and moxifloxacin have been reported to exacerbate MG. In the aminoglycoside family of antibiotics, gentamicin, streptomycin, and neomycin have been reported to exacerbate MG. The aminoglycoside tobramycin has not been reported to exacerbate MG and may be used in patients that require aminoglycoside treatment. Because of the rarity or absent reports on their exacerbation of MG, the following antibiotics are considered safe to use in MG patients: the cephalosporin class of drugs, sulfa drugs, the tetracycline group of drugs, clindamycin, polymyxin B and nitrofurantoin.

Ia antiarrhythmic agents: A type Ia antiarrhythmic agent (see Vaughan Williams classification), i.e., procainamide, which is used to treat cardiac arrhythmias has caused respiratory failure in MG patients who, prior to being treated with it, did not have respiratory symptoms. Furthermore, this drug has caused MG-like symptoms in patients who have kidney failure but do not have MG. And, procainamide worsened muscle dysfunction in a rat model of human MG. These studies suggest that procainamide as well as other Type Ia antiarrhythmic agent should be avoided or used with extreme caution in MG patients.

Depolarizing neuromuscular blockers: Depolarizing neuromuscular blockers suppress the neurons' signaling at the neuromuscular junction thereby reducing or blocking the affected skeletal muscles contractibility. They are used as muscle relaxants in patients undergoing surgery. Succinylcholine is the only depolarizing neuromuscular blocker available in the US market. Its ability to induce or worsen MG is unclear. Succinylcholine has also been suggested to cause life-threatening side effects such as [[rhabdomyolysis, myotonia, and hyperkalemia in patients with muscle disease although the role of succinylcholine in causing these side effects also remain unclear. Until more evidence on these unclear issues becomes available and the availability of other neuromuscular blocking agents without these deleterious side effects, the use of succinylcholine in MG (and other neuromuscular disorders) should probably be avoided where feasible.

Inhalation anesthetics: Inhalation anesthetics are general anesthetics that are delivered by inhalation generally for patients undergoing surgery. MG patients undergoing surgery with inhaled anesthetics have an increased incidence of developing a life-threatening myasthenia crisis which must be treated by prolonged mechanical ventilation. In a study of 759 MG patients undergoing surgical removal to their thymus under general anesthesia,. sugammadex, a medication that reverses neuromuscular blockade, significantly reduced the development of this crisis.