Pharmacologic agents for the treatment of HIV-DSPN

Medication	Dosage and administration in adults	Avoid or use caution in:	Common adverse effects
Preferred agents for most patients
Gabapentin*	IR: Start with 100 to 300 mg orally 1 to 3 times daily. Can increase gradually to 800 mg 3 times daily (2400 mg daily in 2 or 3 divided doses). ER: Start with 300 mg orally once daily at bedtime. Can increase gradually to 900 mg to 2400 mg once daily.	Older adults: Initiate at lowest dose and titrate more gradually History of substance use	Neurologic: Dizziness, drowsiness, ataxia, confusion. Gastrointestinal: Nausea, diarrhea. Other: Weight gain, peripheral edema, risk for misuse and addiction.
Pregabalin*	IR: Start with 25 to 75 mg orally twice daily. Can increase gradually to 75 to 150 mg orally twice daily. ER: Start with 165 mg orally once daily. Can increase gradually to 330 mg orally once daily.	Older adults: Initiate at lowest dose and titrate more gradually History of substance use	Neurologic: Dizziness, drowsiness, ataxia, confusion. Gastrointestinal: Nausea, diarrhea. Other: Weight gain, peripheral edema, risk for misuse and addiction.
Duloxetine	Start with 30 mg orally once daily for one week. Can increase to 120 mg orally once daily thereafter.	Hepatic impairment or severe kidney impairment Angle-closure glaucoma	Neurologic: Insomnia, dizziness, fatigue. Gastrointestinal: Nausea, dry mouth, constipation. Other: Sexual dysfunction.
Tricyclic antidepressants (amitriptyline; nortriptyline)^¶	Start with 10 to 25 mg orally daily at bedtime. Can increase gradually to 75 to 100 mg orally once daily at bedtime.	Older adults: Typically avoided; if used, initiate at lowest dose and titrate more gradually Cardiovascular disease, conduction abnormalities Autonomic dysfunction Seizures Glaucoma	Antihistaminic: Dizziness, drowsiness, confusion, increased appetite. Anticholinergic: Dry mouth, constipation, urinary retention, blurred vision. Cardiovascular: Orthostatic hypotension, prolonged QT interval, cardiac arrhythmias. Other: Sexual dysfunction, dangerous in overdose.
Alternative agents for patients who would like to avoid oral medications^Δ
Capsaicin patch 8% NOTE: Administered by health care provider in a clinical setting and monitored for up to 2 hours after treatment	Apply patch to most painful areas of the feet for 30 minutes. Up to 4 patches may be applied in a single application. Treatment may be repeated every 3 months as needed for return of pain (do not apply more frequently than every 3 months). Area should be pretreated with a topical anesthetic prior to patch application.	Sensitive skin or chronic skin disorders Do not use on abraded skin	Application site burning, pain, erythema, pruritus. Local pain and irritation may be intolerable.
Lidocaine patch 5%	Apply 1 to 3 patches to most painful areas of the feet for 12 hours. Remove for a period of 12 hours before reapplication.	Sensitive skin or chronic skin disorders Do not use on abraded skin	Mild to moderate irritation at application site.
Other alternative agents
Tramadol	Start with 37.5 mg orally every 6 hours, as needed for breakthrough pain.	History or risk of substance use Older adults Frail patients who are at risk of falls Kidney or hepatic impairment Seizures	Side-effects are similar to other opioids including risks of overdose and opioid use disorder. Added risk of seizures due to drug interactions.

Preferred oral agents for HIV-DSPN symptom management are initiated at a low dose to minimize adverse effects and titrated in small increments over several weeks based upon efficacy and tolerability. When stopping therapy, dose should be tapered over 1 week or more to reduce the risk of withdrawal symptoms.

HIV-DSPN: human immunodeficiency virus-associated distal symmetric polyneuropathy; IR: immediate release; ER: extended release.

* Requires dose adjustment in kidney impairment; refer to Lexicomp monographs.

¶ Nortriptyline is less sedating and has fewer anticholinergic side effects than amitriptyline.

Δ Also used in combination with oral therapies for reducing medication load or as an alternative for patients with contraindications to systemic therapies.

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Pharmacologic agents for the treatment of HIV-DSPN