What medications can cause peripheral neuropathy?

Medications That Cause Peripheral Neuropathy

The most common medication classes causing peripheral neuropathy are chemotherapeutic agents (particularly platinum compounds, taxanes, vinca alkaloids, bortezomib, and thalidomide), antiretroviral medications (especially stavudine and didanosine), and among these, vincristine is the single most notorious agent for causing neuropathy as its primary side effect. 1, 2

Chemotherapeutic Agents

Vinca Alkaloids

• Vincristine is the chemotherapeutic agent most commonly associated with peripheral neuropathy, presenting with a "glove and stocking" distribution pattern, mechanical allodynia, sensory/tactile disorders, and numbness in hands and feet 1
• Autonomic manifestations are common with vincristine, including pain, constipation, postural hypotension, bladder disturbances, and reduced heart rate variability 1
• Pre-existing neuropathy significantly increases both incidence and severity of vincristine-induced neuropathy, and advanced age (>65-75 years) is associated with more severe neuropathy 1

Platinum Compounds

• Platinum-containing agents cause dose-related axonal polyneuropathy with predominantly sensory or sensory-motor symptoms 2, 3
• Oxaliplatin causes acute neuropathy with cold sensitivity, throat discomfort, difficulty swallowing cold liquids, and muscle cramps beginning during infusion and peaking 2-3 days after each dose 4
• Oxaliplatin also causes chronic/cumulative neuropathy that is more severe in upper limbs than lower limbs and exhibits a "coasting phenomenon" where symptoms worsen for 2-3 months after therapy completion before improving 4

Taxanes

• Taxanes cause dose-dependent peripheral neuropathy with sensory symptoms predominating 2, 3
• Paclitaxel causes an acute pain syndrome occurring days after each dose, primarily in truncal/hip distribution, peaking approximately 2-3 days after each dose 4

Proteasome Inhibitors and Immunomodulatory Drugs

• Bortezomib and thalidomide cause peripheral neuropathy that has become a leading cause of iatrogenic neurotoxicity in multiple myeloma patients 5
• Thalidomide induces dose-dependent sensory-motor length-dependent axonal neuropathy 6

Antiretroviral Medications

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

• Stavudine causes peripheral neuropathy manifested by numbness, tingling, or pain in hands or feet, which can be common and severe, occurring more frequently in patients with advanced HIV-1 disease or history of peripheral neuropathy 7
• Didanosine causes peripheral neuropathy with numbness, tingling, or pain in hands or feet, occurring more frequently in patients with advanced HIV disease, history of neuropathy, or when combined with other neurotoxic drugs including stavudine 8
• The combination of didanosine and stavudine should be avoided due to additive peripheral neuropathy risk 5, 8
• Zidovudine should be avoided due to myelosuppression rather than neuropathy 5

Other Medication Classes

Antimicrobials

• Metronidazole, dapsone, and nitrofurantoin have been reported to cause peripheral neuropathy, though cases are rare 6

Immunosuppressants

• Tacrolimus has been reported to cause neuropathy in some cases 6

Other Agents

• Alpha-interferon and statins have been reported to cause neuropathy within the past years, though these etiologies are rare 6
• Colchicin can cause peripheral neuropathy 6

Risk Factors for Drug-Induced Neuropathy

• Pre-existing conditions that predispose to neuropathy include diabetes mellitus, renal insufficiency, hypothyroidism, vitamin deficiencies, HIV infection, autoimmune rheumatological conditions, and alcohol abuse 1
• Risk factors for chemotherapy-induced neuropathy include dose per cycle, cumulative dose, treatment schedule, duration of infusion, administration of other neurotoxic agents, comorbidity, and pre-existing peripheral neuropathy 2
• Co-administration with other neurotoxic agents significantly increases neuropathy risk and should be avoided when possible 1
• Smoking has been associated with increased risk of long-term prevalent paresthesias 1

Clinical Characteristics

• Drug-induced peripheral neuropathy typically presents with symmetric, distal, length-dependent "glove and stocking" distribution, with primarily sensory symptoms rather than motor symptoms 4
• Patients experience positive symptoms (pain, paresthesias) or negative symptoms (numbness) in distal extremities 3
• Motor weakness and autonomic involvement are less prominent but can occur 3
• Symptoms may continue, worsen, or temporarily worsen after stopping the offending medication 7

Management Principles

• Baseline neurological evaluation is recommended before initiating neurotoxic medications, with monitoring of neurological symptoms before each treatment cycle 1
• Dose adjustment or treatment discontinuation should be considered in patients with pre-existing neuropathy or significant risk factors 1, 4
• Duloxetine is the only treatment with strong evidence of benefit for chemotherapy-induced peripheral neuropathy 1, 4
• For established painful neuropathy, gabapentin or pregabalin serve as alternatives for neuropathic pain 1