Does Hydroxychloroquine (Plaquenil) cause peripheral neuropathy?

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Last updated: May 21, 2025View editorial policy

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From the FDA Drug Label

Skeletal muscle myopathy or neuropathy leading to progressive weakness and atrophy of proximal muscle groups, depressed tendon reflexes, and abnormal nerve conduction, have been reported. Inform the patient that muscle weakness and atrophy has been reported with hydroxychloroquine sulfate use.

Yes, hydroxychloroquine (also known by its brand name Plaquenil) can cause peripheral neuropathy.

  • The drug label warns of skeletal muscle myopathy or neuropathy as a potential side effect.
  • Patients on long-term therapy with hydroxychloroquine sulfate should be assessed for muscle strength and deep tendon reflexes periodically.
  • If muscle or nerve toxicity is suspected or demonstrated by tissue biopsy, the drug should be discontinued 1.

From the Research

Plaquenil (hydroxychloroquine) can cause peripheral neuropathy, though it is considered a relatively uncommon side effect. This medication-induced neuropathy typically presents as sensory symptoms including numbness, tingling, burning sensations, or pain in the extremities, particularly in the hands and feet. The risk of developing peripheral neuropathy from Plaquenil appears to be related to both the daily dose and the duration of treatment, with higher doses and longer treatment periods increasing the risk, as suggested by a study on drug-induced peripheral neuropathy 2. Patients who have been taking Plaquenil for several years, especially at doses exceeding 5 mg/kg/day, may be at greater risk.

Some key points to consider:

  • The mechanism behind hydroxychloroquine-induced neuropathy likely involves the medication's ability to accumulate in peripheral nerves and disrupt normal nerve function.
  • If a patient taking Plaquenil experiences symptoms of peripheral neuropathy, they should promptly report these to their healthcare provider, as early detection and medication adjustment can help prevent permanent nerve damage.
  • In some cases, the neuropathy may improve after discontinuation of the medication, though recovery can be slow and sometimes incomplete, as noted in a case report on hydroxychloroquine neuromyotoxicity 3.
  • A study on the association of methotrexate, sulfasalazine, and hydroxychloroquine use with fracture in postmenopausal women with rheumatoid arthritis found no significant association between hydroxychloroquine use and incident fractures 4.
  • Real-world outcomes associated with methotrexate, sulfasalazine, and hydroxychloroquine triple therapy versus tumor necrosis factor inhibitor/methotrexate combination therapy in patients with rheumatoid arthritis showed that drug persistence and clinical effectiveness outcomes were less favorable in triple therapy patients compared to TNFi/MTX therapy patients, but did not specifically address peripheral neuropathy 5.

Overall, while Plaquenil can cause peripheral neuropathy, the risk is relatively low, and patients should be monitored for symptoms and adjusted as needed to minimize the risk of permanent nerve damage, based on the most recent and highest quality study available 2.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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