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Peripheral Neuropathy: Pharmacologic Interventions

for Health Care Providers

Table 1. Pharmacologic Interventions

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Discontinuation of offending drug (eg, switching from dNRTIs, avoiding combinations with additive neurotoxicity)
  • Differentiate DSP and ARV toxic neuropathy by timing of symptom onset.
  • Prompt discontinuation of a neurotoxic medication may prevent progression of symptoms, and may allow reversal of symptoms.
  • Before discontinuing an offending drug, carefully weigh risks and potential benefits.
  • Consider dosage reduction of d4T, if discontinuation is not possible.
  • With ARV toxic neuropathy caused by a dNRTI, symptoms often improve within 3 months (though they may be permanent).
Initiation of ART
  • Avoid dNRTIs
  • Initiation of ART can improve non-ARV-associated DSP for patients with advanced HIV who have uncontrolled viremia and low CD4 counts.
(for dosages and additional information, see Pain Medications)
Mild analgesics
  • Acetaminophen
  • NSAIDs
  • Use as first-line therapy for mild symptoms.
  • Can use in combination with tricyclic antidepressants (TCAs), anticonvulsants, and topical adjuncts.
  • Avoid use or limit dosages for patients with underlying liver or renal disease.
  • Gabapentin
  • Pregabalin
  • Lamotrigine
  • Gabapentin: considered first-line for its tolerability.
  • Pregabalin: sometimes better tolerated than gabapentin. Little evidence of efficacy for HIV-SN.
  • Lamotrigine: has shown the greatest efficacy in clinical trials for HIV-SN.
  • Data for other anticonvulsants, such as topiramate, are lacking; may be useful for selected patients with close monitoring.
  • To discontinue these agents, taper slowly over course of ≥7 days.
Antidepressants: TCAs and SNRIs
  • TCAs: amitriptyline and nortriptyline
  • SNRIs: venlafaxine and duloxetine; these are inadequately studied in people with HIV infection
  • Consider SNRIs for patients with comorbid depression.
  • Small studies have shown limited or negative results with TCAs.
  • TCAs may cause sedation.
  • Monitor serum TCA levels and EKG to avoid cardiotoxicity at higher dosage levels.
Potential ARV Interactions
  • Drug interactions: RTV and other PIs may increase the level of TCAs; start at low dosage, increase slowly.
Topical anesthetics
  • Capsaicin patch or cream
  • Lidocaine patch
  • A single capsaicin patch application can provide some degree of pain relief for up to 12 weeks.
  • Topical lidocaine has not shown significant benefit over placebo, and is expensive. Consider brief trial for patients with incomplete pain relief on other therapies.
Opiate analgesics
  • Long-acting narcotics preferred:
    • Transdermal fentanyl
    • Long-acting morphine
    • Methadone
    • Long-acting oxycodone
  • For moderate to severe HIV-SN with an inadequate response to the therapies listed above.
  • Titrate carefully. (For more information, see Pain Medications.)
  • Methadone: acts on NMDA receptors; may give adjunctive benefit. Caution: start at low dosage and titrate slowly because of its long half-life; consult with pharmacist.
  • Transdermal fentanyl is appropriate only for patients already on stable dosage of other opiates: start at equianalgesic (or lower) dosage.

From Peripheral Neuropathy
Primary Care of Veterans with HIV
Office of Clinical Public Health Programs
Veterans Health Administration, 2009