Can amiodarone cause muscle weakness?

October 13, 2025 •

5 min read

Neuromyopathy, a condition that can cause muscle weakness, is a recognized but relatively rare side effect of the antiarrhythmic drug amiodarone, with a reported incidence of 3%–30% in some series. Although affecting a small percentage of patients, it is a significant consideration, and anyone with concerns about whether can amiodarone cause muscle weakness should seek medical advice.

Quick Summary

Amiodarone can cause neuromyopathy, a rare side effect presenting as muscle weakness and peripheral neuropathy, often affecting the legs. Symptoms typically develop over months to years but can be reversible upon discontinuation.

Key Points

Rare, but Serious: Amiodarone can cause muscle weakness as part of a rare condition called neuromyopathy, with incidence rates varying.
Neuropathy and Myopathy: The weakness results from toxicity affecting both the peripheral nerves and the muscles, leading to cellular damage.
Lower Limbs Affected: Muscle weakness often begins in the lower extremities and can be accompanied by pain and sensory loss.
Long-Term Exposure: The risk of developing neuromyopathy increases with the duration of amiodarone therapy.
Diagnosis is Key: Diagnostic tools like EMG are crucial, as standard lab tests like creatine kinase can be normal.
Reversible Upon Discontinuation: In many cases, stopping amiodarone leads to gradual improvement, though full recovery can take months due to the long half-life.
Concomitant Risks: Concurrent use of amiodarone with other myotoxic drugs like statins can increase the risk of muscle problems.

Amiodarone is a powerful and effective antiarrhythmic medication used to treat various cardiac rhythm disturbances, including atrial fibrillation and life-threatening ventricular arrhythmias. While its cardiac benefits are well-established, amiodarone is also known for its extensive side effect profile, which can involve nearly every organ system. Among these, neuromuscular complications are a significant, though less common, concern. Patients or caregivers experiencing unexplained fatigue, pain, or weakness often question: Can amiodarone cause muscle weakness?

The Link Between Amiodarone and Muscle Weakness

The muscle weakness sometimes associated with amiodarone is typically part of a broader condition known as neuromyopathy. This term signifies that both the nerves (neuropathy) and the muscles (myopathy) can be affected. While it is a rare complication, it is a well-documented adverse effect, particularly with long-term therapy. The condition is thought to be a form of toxicity stemming from the drug's unique chemical properties.

The Mechanisms Behind the Weakness

Amiodarone is a highly lipophilic drug, meaning it readily dissolves in and accumulates in fatty tissues, including those in the nervous system and muscles. It is also an amphiphilic compound, which allows it to interfere with normal cellular processes, specifically disrupting the lysosomes within cells. Lysosomes are responsible for waste removal, and their dysfunction leads to the accumulation of lipid complexes and cellular debris, a phenomenon known as phospholipidosis. This toxic buildup ultimately damages the cells:

Nerve Damage (Neuropathy): The accumulation of toxic substances in nerve tissue, especially the peripheral nerves, can lead to damage and impaired nerve function. This often manifests as a symmetrical sensorimotor polyneuropathy, where both sensation and motor function are affected, often starting in the legs.
Muscle Damage (Myopathy): In some cases, amiodarone also causes direct damage to muscle fibers, leading to a true myopathy. Muscle biopsies in affected patients have revealed vacuolar changes and lipid inclusions. The drug's metabolite, desethyl-amiodarone, can also accumulate in muscle tissue, contributing to toxicity.

Symptoms of Amiodarone Neuromyopathy

Recognizing the signs of this condition is crucial for prompt intervention. Symptoms can vary but often include:

Proximal and Distal Weakness: Significant muscle weakness can occur in both the limbs closer to the body (proximal, e.g., hips and shoulders) and further away (distal, e.g., hands and feet).
Leg Pain and Weakness: The lower extremities are typically more affected than the upper limbs. Patients may experience leg pain and progressive weakness that can impact mobility and function.
Sensory Changes: Loss of distal sensation, such as numbness or tingling in a "glove-and-stocking" pattern, is common.
Diminished Reflexes: A decrease in deep tendon reflexes is a typical finding on neurological examination.
Ataxia and Gait Disturbances: Difficulty with coordination and walking can result from a combination of nerve and muscle dysfunction.
Dysphagia: Difficulty swallowing has been reported in some cases of myopathy.
Tremor: A dose-related tremor is one of the more frequent neurotoxic effects of amiodarone.

Key Factors and Diagnosis

Several factors can influence the likelihood of developing amiodarone-induced neuromyopathy, though it is not always possible to predict who will be affected. Diagnosis can be challenging, as symptoms may be vague and mimic other conditions.

Duration and Dosage: The risk increases with longer durations of treatment, and while most cases involve moderate to high doses over months or years, it can occur at lower doses.
Age: Case reports highlight the potential for increased susceptibility in geriatric patients, possibly due to changes in drug metabolism.
Other Medications: Concomitant use of drugs like statins can potentiate the risk of myotoxicity.
Diagnosis: A comprehensive evaluation is necessary, including a full clinical examination, electromyography (EMG), and nerve conduction studies (NCS). A key diagnostic point is that creatine kinase (CK) levels, a common marker for muscle damage, may remain normal in amiodarone neuromyopathy, particularly when the nerve damage component is significant. This can lead to underdiagnosis if clinicians rely solely on lab values.

Management and Reversibility

The cornerstone of managing amiodarone-induced neuromyopathy is discontinuing or significantly reducing the amiodarone dose. Recovery is often a gradual process, which is to be expected given the drug's exceptionally long half-life, which can be up to 100 days.

Slow Recovery: Patients may start to see improvement in muscle strength within a few weeks, but full recovery can take up to six months or more.
Rehabilitation: Active rehabilitation, including strength training and physical therapy, can help restore function and mobility.
Potential Irreversibility: While often reversible, some neurological complications may persist even after the drug is stopped. This underscores the importance of early detection and intervention.

Comparison: Amiodarone Neuromyopathy vs. Statin Myopathy


Feature	Amiodarone-Induced Neuromyopathy	Statin-Induced Myopathy
Mechanism	Disrupts lysosomes, causing cellular toxicity in nerves and muscles.	Interferes with HMG-CoA reductase and cholesterol synthesis in muscle cells.
Prevalence	Rare side effect, though incidence estimates vary.	More commonly reported, especially muscle pain, but severe myopathy is rare.
Typical Onset	Typically occurs with long-term use, over months to years.	Can occur at any time, but risk may increase with duration.
Key Symptoms	Proximal and distal muscle weakness (often in legs), sensory loss, ataxia, tremor, diminished reflexes.	Muscle pain, aches, tenderness, and weakness, primarily affecting large muscles.
Creatine Kinase (CK)	Often normal, but can be elevated.	Elevated CK levels are common, especially with more severe myopathy.
Neuropathy Presence	Frequently involves a component of peripheral neuropathy.	Typically does not cause a clinically significant peripheral neuropathy.
Prognosis After Drug Stop	Gradual improvement expected, though it can take months due to amiodarone's long half-life.	Symptoms usually resolve after discontinuation or dose change; may take weeks.
Drug Interactions	Concomitant use of statins can increase myotoxicity.	Amiodarone can increase statin levels, elevating myotoxicity risk.

Conclusion

In summary, the answer to the question "Can amiodarone cause muscle weakness?" is yes, although it is a rare complication. The weakness is typically a manifestation of amiodarone-induced neuromyopathy, affecting both the nerves and muscles over time. This side effect is often linked to the duration of treatment, with a higher incidence observed with longer exposure. Early diagnosis is vital and depends on a thorough neurological evaluation, including electrodiagnostic studies, as common lab markers like creatine kinase may not be elevated. For patients experiencing these symptoms, stopping amiodarone is the primary management strategy, which often leads to significant, though slow, recovery. Because of its long half-life, improvement can take several months. Awareness of this potential side effect is crucial for healthcare providers and patients on long-term amiodarone therapy. For further information on managing amiodarone side effects, a useful resource can be found via the National Institutes of Health.

For Patients and Caregivers

If you are on amiodarone and experience new or worsening muscle weakness, pain, or numbness, it is essential to contact your doctor immediately. Do not stop taking your medication on your own. Your doctor can assess your symptoms, consider other potential causes, and determine the appropriate course of action, which may involve reducing the dose or switching to a different medication. Early reporting can lead to a quicker diagnosis and better outcome.

Frequently Asked Questions

Yes, amiodarone can cause muscle pain, also known as myalgia, especially as part of amiodarone-induced neuromyopathy. This pain is often accompanied by muscle weakness and other neurological symptoms.

Amiodarone-induced muscle weakness is a rare complication. While some older studies reported neurotoxic effects in a higher percentage of patients, more recent data suggests a much lower incidence, possibly due to lower maintenance doses. However, the exact rate can be difficult to determine due to variations in dosage, duration, and patient factors.

Symptoms can include proximal and distal muscle weakness, particularly in the lower limbs, leg pain, distal sensory loss (numbness or tingling), diminished reflexes, gait ataxia, and tremor.

Improvement is typically gradual after discontinuing the drug. Due to amiodarone's long half-life, it can take several weeks for symptoms to begin resolving and up to six months or longer for full recovery of muscle strength.

Yes, amiodarone can interact with other drugs that cause myotoxicity, such as statins. Amiodarone inhibits an enzyme system that metabolizes statins, which can increase the concentration of statins in the body and potentiate their myotoxic effects.

While amiodarone-induced neuromyopathy is often reversible upon drug discontinuation, some cases of neurological complications may not fully resolve. Early detection and intervention are therefore important for maximizing the potential for recovery.

Diagnosis relies heavily on a clinical evaluation of symptoms. Electromyography (EMG) and nerve conduction studies (NCS) are key tools for confirming nerve and muscle involvement. Unlike many other forms of myopathy, serum creatine kinase (CK) levels may be normal in amiodarone-induced cases.

As an amphiphilic drug, amiodarone and its metabolite accumulate in cell lysosomes. This leads to a build-up of lipid complexes and cellular debris, a process known as phospholipidosis, which is toxic to the muscle cells and nerves.