What classes of drugs can cause foot pain?

Drug Classes That Cause Foot Pain

Multiple drug classes can cause foot pain, primarily through peripheral neuropathy or myopathy, with chemotherapeutic agents being the most consistent offenders, followed by antimicrobials, cardiovascular drugs (especially statins), and psychotropic medications.

Chemotherapeutic Agents

Chemotherapy drugs are the most reliable cause of drug-induced foot pain through peripheral neuropathy:

• Vinca alkaloids (vincristine) cause dose-dependent peripheral neuropathy with a predictable sequence: initial sensory impairment and paresthesias, followed by neuritic pain, then motor difficulties including foot drop and ataxia 1
• Vincristine commonly causes jaw pain, pharyngeal pain, bone pain, back pain, and limb pain that may be severe 1
• Paclitaxel causes dose-related peripheral neuropathy affecting 46-87% of patients, with severe symptoms in 1-21% depending on dose and schedule 2
• Paclitaxel also causes myalgia/arthralgia in 21-96% of patients, with severe symptoms in 1-16% 2

Statins (Cardiovascular Drugs)

Statins cause both peripheral neuropathy and focal myopathy affecting the feet:

• Statins cause peripheral polyneuropathy in approximately 1 in 10,000 patients treated for one year, presenting with sensory impairment, decreased reflexes, and sometimes marked reduction in muscle strength 3
• Bilateral foot myopathy is an unusual but documented presentation of statin toxicity, causing foot pain, weakness, and soreness severe enough to affect ambulation 4
• Both atorvastatin and rosuvastatin have been documented to cause isolated bilateral foot myopathy 4
• Renal failure and diabetes increase the risk of statin-induced neuropathy 3

Antimicrobials

Several antimicrobial classes cause peripheral neuropathy that can manifest as foot pain:

• Isoniazid, ethambutol, ethionamide (anti-tuberculosis agents) 5
• Nitrofurantoin and metronidazole 5
• These typically cause sensory or mixed sensorimotor neuropathy 6, 5

Psychotropic and Anticonvulsant Medications

These drug classes can cause peripheral neuropathy affecting the feet:

• Anticonvulsants, particularly phenytoin 5
• Hypnotics and psychotropics, notably methaqualone 5
• These cause sensory or mixed sensorimotor neuropathy 6

Other Cardiovascular Drugs

Beyond statins, other cardiovascular medications cause neuropathy:

• Perhexiline and hydralazine 5
• These cause peripheral neuropathy through various mechanisms 6

Antirheumatics

Drugs used for rheumatic conditions can cause neuropathy:

• Gold, indomethacin, and chloroquine 5
• These cause sensory or mixed sensorimotor neuropathy 5

Other Notable Agents

Additional drugs that cause peripheral neuropathy affecting the feet:

• Disulfiram and calcium carbimide (alcohol deterrents) 5
• Dapsone 5
• These cause sensory or mixed sensorimotor neuropathy 6, 5

Clinical Recognition and Management

Key points for identifying and managing drug-induced foot pain:

• Drug-induced peripheral neuropathy is almost always due to dose-dependent primary axonal degeneration 7
• Patients with preexisting neuropathy, diabetes, renal failure, hepatic failure, or malnutrition are at higher risk 6, 7
• Patients complaining of paresthesias, pain, muscle cramps, or abnormal sensations while on these medications should undergo neurological examination and nerve conduction studies 5
• For statin-induced symptoms, withdrawal often leads to clinical improvement after ruling out other causes 3
• For chemotherapy-induced neuropathy, gabapentinoids, SNRIs, tricyclic antidepressants, and sodium channel blockers are recommended for pain management 8
• Prophylactic vitamins may allow continuation of necessary treatments in some cases 7
• When drug-induced neuropathy is identified, the offending drug should be stopped if possible, with generally good prognosis for recovery 7