Is propranolol an okay choice for a beta blocker when the patient has myasthenia gravis? Or, is there a better beta blocker choice?

Comment by InpharmD Researcher

Current evidence is insufficient to recommend propranolol over other beta-blockers, or to identify a preferred beta-blocker for patients with myasthenia gravis (MG). Available societal guidelines caution that beta-blockers may worsen MG and should be used with caution, but neither distinguishes among individual agents. Available evidence consists primarily of case reports, small clinical studies, pharmacovigilance data, and expert opinion, with conflicting findings regarding the effects of propranolol and other beta-blockers on neuromuscular transmission. Although cardioselective beta-blockers have been proposed to carry less theoretical risk, comparative clinical data are lacking, and no agent has been shown to be safer than another. Beta-blockers are not considered absolutely contraindicated when clinically indicated, and treatment should be individualized based on the anticipated benefits and potential risks, using the lowest effective dose with close monitoring for worsening MG symptoms, particularly during treatment initiation or dose escalation.
Background

The 2020 International Consensus Guidance for Management of Myasthenia Gravis and the Myasthenia Gravis Foundation of America (MGFA) Cautionary Drugs List both identify beta-blockers as medications that may worsen myasthenia gravis (MG) and recommend that they be used with caution. Both resources note that beta-blockers are commonly prescribed for conditions such as hypertension, cardiovascular disease, and migraine but may exacerbate MG symptoms. The 2020 International Consensus Guidance further emphasizes that although many medications have been associated with worsening MG, these reports do not necessarily mean such agents should never be prescribed. Reported associations are often rare or may represent coincidental findings, and treatment decisions should be individualized based on clinical judgment and an assessment of the potential risks and benefits. The guideline also notes that the medications included in its cautionary list represent those with the strongest evidence for worsening MG. Neither guideline distinguishes among individual beta-blockers or identifies a preferred agent within the class for patients with MG. [1], [2]

Additionally, available review articles suggest that the relationship between beta-blockers and MG remains uncertain, with evidence consisting largely of case reports, small clinical studies, and expert opinion rather than high-quality comparative data. A 2017 letter to editor noted that while at least three cases of beta-blockers precipitating or worsening myasthenic syndromes had been reported, propranolol was administered safely in a small study, and the effects of more cardioselective beta-blockers (e.g., atenolol and metoprolol) on neuromuscular transmission had not been studied. The authors suggested that, from a pharmacodynamic perspective, there may be less theoretical concern with selective agents, although they concluded that a preferred beta-blocker for patients with MG could not be identified. A review of congenital myasthenic syndromes similarly lists beta-blockers among medications that may impair neuromuscular transmission but notes that they are not absolutely contraindicated and may be used with caution. Likewise, a 2021 review on drugs that induce or cause deterioration of MG concluded that the effects of beta-blockers on neuromuscular transmission remain unclear. Although transient MG exacerbations have been reported, a small study of 10 patients found no significant overall change in compound muscle action potential decrement after intravenous propranolol, and a crossover study found no detrimental effect of oral or intravenous propranolol on muscle strength or repetitive nerve stimulation compared with placebo. A retrospective study also observed a higher frequency of exacerbations among patients receiving beta-blockers, although these events were not temporally associated with beta-blocker initiation, suggesting that underlying comorbidities may have contributed. The authors concluded that patients with stable or well-controlled MG who require beta-blocker therapy may generally receive treatment at the lowest effective dose with close monitoring, particularly during treatment initiation. [3], [4], [5]

Background References: [1] Narayanaswami P, Sanders DB, Wolfe G, et al. International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update. Neurology. 2021;96(3):114-122. doi:10.1212/WNL.0000000000011124
[2] Myasthenia Gravis Foundation of America. Cautionary drug list. Accessed July 9, 2026. https://myasthenia.org/wp-content/uploads/2024/09/MGFA-Cautionary-Drug-List.pdf
[3] Miranda S, Reid DK, John CS. Myasthenia Gravis. N Engl J Med. 2017;376(13):e25. doi:10.1056/NEJMc1701027
[4] Abicht A, Müller JS, Lochmüller H. Congenital Myasthenic Syndromes Overview. 2003 May 9 [Updated 2021 Dec 23]. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1168/
[5] Sheikh S, Alvi U, Soliven B, Rezania K. Drugs That Induce or Cause Deterioration of Myasthenia Gravis: An Update. J Clin Med. 2021;10(7):1537. Published 2021 Apr 6. doi:10.3390/jcm10071537
Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

Is propranolol an okay choice for a beta blocker when the patient has myasthenia gravis? Or, is there a better beta blocker choice?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-5 for your response.

The risk of worsening of myasthenia by cardiovascular medication as reflected by reporting frequency
Design

Retrospective analysis using the World Health Organization pharmacovigilance database

N= 79 drugs with a total number of adverse drug reaction (ADRs) >5000 included in the analysis
Objective To assess the risk of worsening myasthenia gravis by cardiovascular medications using reporting frequency from a pharmacovigilance database
Study Groups Not applicable (analysis based on drug classes rather than patient groups)
Inclusion Criteria Drugs with a total number of ADRs >5000 from the WHO pharmacovigilance database
Exclusion Criteria Drugs with a total number of ADRs <5000
Methods Data were retrieved from the WHO pharmacovigilance database for various cardiovascular drugs and related drugs. The reporting odds ratio (ROR) was calculated to assess the risk of myasthenia-related ADRs. A 95% confidence interval of reporting odds ratio (ROR) >1 indicated a higher risk, while ROR <1 indicated a lower risk. The analysis included 79 drugs with more than 5000 ADRs each.
Duration Data retrieval date: March 31, 2021
Outcome Measures ROR for myasthenia-related ADRs 
Baseline Characteristics Not applicable
Results   ROR
Tizanidine 11

Alpha-blockers

Doxazosin

Tamsulosin

Terazosin

 

10

2.4

6.4

All Beta-blockers drugs

Atenolol

Metoprolol

Propranolol

Sotalol

Timolol

3.2

5.4

2.1

2.5

5.3

4.3
Ca antagonists 1.7
Angiotensin receptor inhibitors 0.37
Anticoagulants 0.52
Thrombocytic function inhibitors 0.46
Adverse Events Signals for increased risk were noted for tizanidine, alpha-blocking drugs, beta-blocking drugs, and Ca antagonists. Lower-than-average risk was indicated for salbutamol, angiotensin receptor antagonists, oral anticoagulants, thrombocytic function inhibitors, and heparins
Study Author Conclusions Angiotensin receptor antagonists, ACE inhibitors, and diuretics appear safe for antihypertensive therapy in myasthenia patients. Alpha receptor-blocking drugs may carry a risk of myasthenia worsening, requiring further confirmation. Amiodarone seems to be a safe alternative for antiarrhythmic therapy
Critique The study provides valuable insights into the risk of myasthenia worsening by cardiovascular drugs using a large pharmacovigilance database. However, the reliance on spontaneous reporting may introduce biases, and the findings require further confirmation through case reports and clinical studies. The analysis is limited by the exclusion of drugs with fewer than 5000 ADRs, which may overlook some relevant drugs.
Table 1 References:
[6] Trillenberg P, Katalinic A, Thern J, Graf T. The risk of worsening of myasthenia by cardiovascular medication as reflected by reporting frequency. Eur J Neurol. 2021;28(9):2965-2970. doi:10.1111/ene.14996

Acute Effects of Intravenous Injection of Beta-Adrenoreceptor- and Calcium Channel Antagonists and Agonists in Myasthenia Gravis
Design

Clinical study with repetitive nerve stimulation and clinical tests

N= 10
Objective

To investigate the acute effects of intravenous injection of beta-adrenoreceptor and calcium channel blocking agents on neuromuscular transmission in patients with myasthenia gravis and to assess if these effects can be mitigated by edrophonium or their natural antidotes
Study Groups

All patients (n= 10)
Inclusion Criteria

Patients with mild to moderate myasthenia gravis symptoms, no asthma or cardiovascular diseases, including A-V conduction disturbances
Exclusion Criteria

Patients with asthma or cardiovascular diseases, including A-V conduction disturbances
Methods

Patients were seated relaxed for 30 minutes before each experiment. Repetitive nerve stimulation (RNS) was performed at 3 Hz in both a proximal muscle, the deltoid, and a distal muscle, the abductor digiti minimi (ADM). Baseline decrement was calculated as the mean of 3 RNS measurements before any injections. Muscle function testing included peak expiratory flow (PEF), repetitive hand-grip strength, and, when eye symptoms were present, diplopia or ptosis testing during gaze fixation. During the β-adrenoreceptor experiment, propranolol 0.1 mg/kg IV was administered at 1 mg/min, followed by RNS at 0, 5, 10, and 15 minutes. Muscle function tests were then repeated. Edrophonium 0.1 mg/kg IV was administered, with RNS 1 to 2 minutes later, followed by muscle function tests and another RNS 7 minutes after edrophonium. Terbutaline 0.01 mg/kg IV was then administered at 0.1 mg/min, followed by RNS at 0, 5, 10, and 15 minutes and muscle function testing. The verapamil/calcium experiment used the same procedure, with verapamil 0.1 mg/kg IV at 1 mg/min instead of propranolol and calcium glubionate 1 mg/kg IV at 9 mg/min instead of terbutaline.
Duration

Not specified
Outcome Measures

Changes in neuromuscular transmission as measured by decrement in RNS; clinical muscle function tests
Baseline Characteristics  

All patients (n= 10)
Age, years

27 to 71

Gender

 3 males, 7 females

Thymus histology

 Hyperplasia (H), Normal (N), Thymoma (T)

Anti-AChE daily dose

 Varied among patients

Osserman-Oosterhuis classification

 2A to 2B
Results

Intravenous propranolol did not significantly worsen neuromuscular transmission, with mean deltoid decrement changing from 31% before injection to 27% at 15 minutes after injection.

At the individual level, deltoid decrement increased in 3 patients, was unchanged in 2 patients, and slightly improved in 5 patients 15 minutes after propranolol administration; no significant decrement changes were observed in either the deltoid or abductor digiti minimi muscles were observed overall.

Clinical muscle function testing, including peak expiratory flow, hand-grip strength, and eye testing when applicable, showed only minor fluctuations and no significant changes after propranolol.

Edrophonium administered after propranolol significantly improved deltoid decrement (p= 0.006), and terbutaline administered after propranolol also significantly improved deltoid decrement across all post-injection time points (p= 0.012, 0.017, 0.014, and 0.017).
Adverse Events

One patient experienced breathing difficulties after edrophonium and a pressure feeling under the larynx after terbutaline. No significant changes in clinical muscle function tests were observed.
Study Author Conclusions

When indicated, propranolol as well as verapamil may be given intravenously without deterioration of neuromuscular transmission. Both terbutaline and calcium improve neuromuscular transmission. In cardiovascular emergencies, propranolol and verapamil may be utilized without danger, especially when their natural antidotes lessen the possible negative effects. The effect of long-term oral treatment with these drugs on myasthenic neuromuscular transmission remains to be investigated.
Critique

This study directly evaluated acute IV propranolol exposure in patients with mild to moderate MG using both neurophysiologic testing and clinical muscle function assessments, which makes it relevant to the question of short-term propranolol safety. However, the study was small, uncontrolled, limited to acute IV administration, and did not compare propranolol with other beta blockers; therefore, it does not establish whether propranolol is preferable to another beta blocker or whether chronic oral propranolol is safe in MG.
Table 2 References:
[7] Jonkers I, Swerup C, Pirskanen R, Bjelak S, Matell G. Acute effects of intravenous injection of beta-adrenoreceptor- and calcium channel at antagonists and agonists in myasthenia gravis. Muscle Nerve. 1996;19(8):959-965. doi:10.1002/(SICI)1097-4598(199608)19:8<959::AID-MUS4>3.0.CO;2-7

 

Effect of the Administration of Cautionary Drugs on the Risk of Worsening Myasthenia Gravis: A Retrospective Matched Case-Control Study
Design

Retrospective matched case-control study

N= 440 
Objective To investigate whether the risk of clinical worsening of myasthenia gravis (MG) increases after administering cautionary drugs in patients with MG
Study Groups

Exposed group (n= 220)

Non-exposed group (n= 220)
Inclusion Criteria Patients diagnosed with MG between 2007 and 2020 at Severance Hospital, classified based on exposure to cautionary drugs
Exclusion Criteria Patients with AChR Ab-negative MG not tested for MuSK Ab; follow-up less than 6 months; discrepancy in disease severity between matched pairs
Methods Retrospective review of medical records for patients with MG. Patients were classified into exposed and non-exposed groups based on exposure to cautionary drugs. Matching was done for sex, age, thymoma, and autoantibodies. The risk period was defined as 6 months from the first exposure to cautionary drugs. Clinical worsening was defined by an increase in MG Activities of Daily Living (MG-ADL) score by 2 or more from baseline
Duration 2007 to 2020
Outcome Measures Incidence of clinical worsening of MG
Baseline Characteristics   Exposed (n=220) Non-exposed (n=220) p-value
Male 74 (33.6%) 74 (33.6%) >0.999

Age, years

≤20

21–40

41–60

61–80

 

11 (4.6%)

87 (36.1%)

106 (44.0%)

37 (15.4%)

 

11 (4.6%)

87 (36.1%)

106 (44.0%)

37 (15.4%)

 >0.999    

Autoantibody

AChR Ab-positive

MuSK Ab-positive

Double seronegative

 

197 (89.5%)

4 (1.8%)

19 (8.6%)

 

197 (89.5%)

4 (1.8%)

19 (8.6%)

 >0.999   

Thymus

Thymomatous

Non-thymomatous

 

72 (32.7%)

148 (67.3%)

 

72 (32.7%)

148 (67.3%)

 >0.999  

MGFA classification at exposure or hypothetical exposure

No symptoms

Class I

Class II

Class III

 

27 (12.3%)

88 (40.0%)

90 (40.9%)

15 (6.8%)

 

31 (14.1%)

84 (38.2%)

90 (40.9%)

15 (6.8%)

 0.617    

Treatment

Prednisolone

Azathioprine

Cyclosporine

Tacrolimus

Mycophenolate mofetil

Maximum prednisolone dose, mg

  

126 (57.3%)

45 (20.5%)

28 (12.7%)

27 (12.3)

5 (2.3%)

20 [0–50]

  

141 (64.1%)

45 (20.5%)

20 (9.1%)

21 (9.5%)

2 (0.9%)

25 [0–60]

  

0.172

>0.9990

0.2800

0.4400

0.453

0.093
Results   Exposed (n=220) Non-exposed (n=220) p-value
Clinical worsening observed 31 (14.1%) 8 (3.6%) <0.001
Odds ratio 4.09  
95% confidence interval 1.88–8.90  
Beta blockers were prescribed to 32.0% of patients and accounted for the greatest cumulative exposure among cautionary drugs (66,123 person-days), exceeding magnesium salts (15,748 person-days), calcium channel blockers (7,535 person-days), and antibiotics (5,554 person-days). Although neuromuscular blocking agents (58.0%), antibiotics (52.2%), and magnesium salts (49.0%) were prescribed to a greater proportion of patients, concurrent exposure to more than one cautionary drug was uncommon (12.9%).
Adverse Events See Results
Study Author Conclusions The administration of cautionary drugs increased the risk of clinical worsening in patients with MG. Clinicians should be aware of this risk when cautionary drugs need to be administered.
Critique The study provides valuable insights into the risk of MG worsening due to cautionary drugs, supported by a well-matched case-control design. However, it is limited by its retrospective nature and single-center data, which may not capture all prescriptions. Potential confounding factors like infections or surgeries were not fully accounted for, and the effect of individual drugs was not separately analyzed.
Table 3 References:
[8] Han HJ, Kim SW, Lee M, Kim HR, Roh YH, Shin HY. Effect of the Administration of Cautionary Drugs on the Risk of Worsening Myasthenia Gravis: A Retrospective Matched Case-Control Study. Yonsei Med J. 2025;66(4):218-225. doi:10.3349/ymj.2024.0017

Evaluation of Medication Exposure on Exacerbation of Disease in Patients With Myasthenia Gravis
Design

Retrospective chart review

N= 38 unique adult patients across 55 hospital encounters, including 70 medication administration events
Objective

To determine the incidence of myasthenic exacerbations following medication exposure after override of a clinical decision support tool
Study Groups

All included hospital encounters (n= 55)

Medication administration events (n= 70)
Inclusion Criteria

Adult patients (≥18 years) with myasthenia gravis (MG) admitted to Massachusetts General Hospital or Brigham and Women’s Hospital between November 2019 and November 2021 who received a medication following override of the clinical decision support tool
Exclusion Criteria

Exacerbation present at admission, stabilized on medication at baseline, or receiving mechanical ventilatory support prior to medication administration
Methods

This retrospective chart review evaluated adult patients with MG who received potentially exacerbating medications after provider override of a clinical decision support alert. Screened medications included oral and IV macrolides, fluoroquinolones, aminoglycosides, aminoquinolines, β-blockers, class 1a antiarrhythmics, non-dihydropyridine calcium channel blockers, and magnesium sulfate. Medication administration events were reviewed for myasthenic exacerbation after administration. Exacerbation was defined as escalation of respiratory support after administration, initiation of intravenous immunoglobulin (IVIG) or plasma exchange for acute MG exacerbation within 96 hours, NIF <20 cm H₂O, and/or VC <1 L after administration. Respiratory status, negative inspiratory force (NIF), and vital capacity (VC) were assessed the day before, day of, day after, and 2 days after administration. Motor strength scores were assessed within 48 hours before and after medication administration when documented. For encounters meeting the primary outcome, the Naranjo Adverse Drug Reaction Probability Scale was used to assess likelihood of drug-induced exacerbation.
Duration

November 2019 to November 2021
Outcome Measures

Primary: Incidence of myasthenic exacerbations

Secondary: Changes in motor strength, length of stay, discharge disposition, unplanned level-of-care escalations, changes to immunosuppressant therapy
Baseline Characteristics

 

 n= 55

Age, years (IQR)

 72 (65 to 78)

Male

 33 (60%)

Weight, kg (IQR)

 76.9 (67.6 to 95.0)

Admitting diagnosis

Infectious diseases

Cardiovascular

Pulmonary

 

19 (34.5%)

16 (29.1%)

6 (10.9%)

Baseline disease-modifying therapy

Pyridostigmine

Corticosteroid

 

26 (47.3%)

18 (32.7%)

Antibody status

AcH Receptor positive

Double negative

 

24 (43.6%)

12 (21.8%)

Taking at least 1 exacerbating medication prior to admission

 33 (60%)

Abbreviations: IQR, interquartile range.
Results

 

 N= 55

Escalation of respiratory support

 7 (12.7%)

IV Magnesium sulfate (n= 38)

 6 (15.8%)

Pre-administration median extremity motor strength score (IQR)

 4 (3-5)

Post-administration median extremity motor strength score (IQR)

 4 (4-5)

Decreased motor strength by ≥1 point in ≥1 extremity

 4 (7.3%)

Increased dose or new initiation of immunosuppressants for MG

 6 (10.9%)

Exacerbation after any β-blocker

 1 (5.0%)

Exacerbation after IV labetalol

 1 (14.3%)

The study reported that median extremity motor strength scores were available for 36 medication administrations within 48 hours before and after high-risk medication use.

Median extremity motor strength was unchanged from pre- to post-administration, with a pre-administration score of 4 (IQR 3-5) and post-administration score of 4 (IQR 4-5).

Decreased motor strength by at least 1 point in at least 1 extremity occurred in 4 encounters (7.3%), and 1 of these instances corresponded with an exacerbation following IV magnesium use.

Increased doses or new initiation of immunosuppressant therapy for MG occurred in 6 encounters (10.9%), including 1 encounter with an exacerbation, and no unplanned inpatient level-of-care escalations were observed.

Among encounters with versus without exacerbation, median hospital length of stay was 8 days (IQR 4-57) versus 16 days (IQR 7-34), median ICU length of stay was 8 days (IQR 3-39) versus 7.5 days (IQR 4-30), skilled nursing or long-term care facility discharge occurred in 5 encounters (71.4%) versus 7 encounters (14.6%), and death before discharge occurred in 2 encounters (28.6%) versus 1 encounter (2.1%), respectively.
Adverse Events

Exacerbation of disease occurred in 12.7% of encounters, primarily after IV magnesium sulfate or IV labetalol administration. All exacerbations involved escalation of respiratory support.
Study Author Conclusions

Of the medications reported to potentially worsen MG, intravenous labetalol and intravenous magnesium were the 2 agents associated with myasthenic exacerbations with a higher incidence in patients harboring additional risk factors.
Critique

This study provides clinically relevant inpatient data on β-blocker exposure in patients with MG, but it does not directly evaluate propranolol. Among β-blockers administered, exacerbation occurred only after IV labetalol, while no exacerbations were reported with metoprolol exposures; however, the small sample size, retrospective design, incomplete respiratory/motor documentation, and frequent presence of additional exacerbation risk factors limit comparative conclusions regarding a preferred β-blocker.
Table 4 References:
[9] Petrucelli N, Barra ME, Koehl JL. Evaluation of Medication Exposure on Exacerbation of Disease in Patients With Myasthenia Gravis. Neurohospitalist. 2024;14(1):52-57. doi:10.1177/19418744231206256

Propranolol-Induced Myasthenia Gravis In A Patient With Graves’ Disease: A Case Report

Design

 Case report

Case presentation

A 27-year-old male with thyroid enlargement was diagnosed with Graves’ disease and started on propranolol for thyrotoxicosis-related tachycardia and tremors. Within 1 week of propranolol initiation, he developed progressive fatigability, ptosis, and difficulty chewing, with symptoms worsening in the evening.

Neurologic examination demonstrated bilateral asymmetric ptosis, mild dysarthria, and proximal limb weakness; ptosis improved with the ice pack test. Repetitive nerve stimulation showed a decremental response, and serologic testing revealed elevated anti–acetylcholine receptor antibodies, confirming autoimmune myasthenia gravis.

A diagnosis of propranolol-triggered myasthenia gravis was made; propranolol was discontinued, pyridostigmine led to significant clinical improvement, and a corticosteroid-sparing immunosuppressive regimen was initiated. Imaging showed no thymoma.

Study Author Conclusions

Propranolol, a commonly prescribed medication for thyrotoxicosis, may unmask or exacerbate underlying MG Clinicians should maintain a high index of suspicion.
Table 5 References:
[10] Anshu P, Bhoi K, Jaiswal D, Thomas J. Propranolol-induced myasthenia gravis in a patient with Graves’ disease: A case report. Journal of the Neurological Sciences. 2025;480:125392. doi:10.1016/j.jns.2025.125392