Inclusion Criteria

Concurrent Medication:

Allowed:

• Aspirin and acetaminophen.
• Nonsteroidal anti-inflammatory agents.
• Opiates.
• Pyridoxine (only if accompanied by isoniazid).
• ddI, ddC, d4T, and 3TC if on a stable dose.
• AZT.
• Cimetidine if on a stable dose.

NOTE:

• Per 3/16/95 amendment, Lactaid may be taken by lactose-intolerant patients for effects of lactose in placebo capsules.

Concurrent Treatment:

Allowed:

• Acupuncture.

Patients must have:

• Documented HIV infection.
• Painful peripheral neuropathy.

NOTE:

• Patients in ACTG blinded studies of dideoxynucleosides such as ddI, ddC, and d4T are encouraged to enroll in this study.

Prior Medication:

Allowed:

• Prior ddI, ddC, d4T, or 3TC, if on a stable dose for at least 8 weeks prior to study entry.
• Prior cimetidine if on a stable dose for at least 2 weeks prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Diabetes mellitus.
• Neurological disease of sufficient severity to confound the evaluation of peripheral neuropathy, such as myelopathy without neuropathy. (NOTE: Patients with both myelopathy AND painful peripheral neuropathy are eligible.)
• Electrocardiogram (EKG) indicating malignant arrhythmia or cardiac conduction disturbances (such as second or third degree AV block, anterior hemi-block, or prolonged QT interval).
• Suicidal thoughts of sufficient severity to require treatment with antidepressant medication.

Concurrent Medication:

Excluded:

• Phenytoin or carbamazepine (unless on stable dose for 8 weeks prior to study entry).
• Capsaicin.
• Any MAO inhibitor antidepressants, any tricyclic or tetracyclic antidepressants, certain serotonin re-uptake inhibitors (fluoxetine, paroxetine, and venlafaxine), or mexiletine (except as dispensed for this study).
• Disopyramide.
• Procainamide.
• Quinidine.
• Tocainide.
• Flecainide acetate.
• Encainide.
• Lidocaine.
• Cisplatin.
• Vincristine.
• Chloramphenicol, disulfiram, ethionamide glutethimide, gold, hydralazine, iodoquinol, metronidazole, nitrofurantoin, or ribavirin (only in patients in whom the onset or clear worsening of painful peripheral neuropathy was attributed to previously taking these drugs).
• Any investigational drugs other than 3TC (except with permission of the protocol team).
• Terfenadine (if concurrent with ketoconazole).

Patients with the following prior conditions are excluded:

• Documented history of cardiac disease.
• History of allergy to, or intolerance of, tricyclic antidepressants, mexiletine, or benztropine.

Prior Medication:

Excluded:

• Prior disopyramide.
• Prior procainamide.
• Prior quinidine.
• Prior tocainide.
• Prior flecainide acetate.
• Prior encainide.
• Prior lidocaine.
• Cisplatin or vincristine within 8 weeks prior to study entry.
• Chloramphenicol, disulfiram, ethionamide glutethimide, gold, hydralazine, iodoquinol, metronidazole, nitrofurantoin, or ribavirin within 8 weeks prior to study entry (only in patients in whom the onset or clear worsening of painful peripheral neuropathy was attributed to taking these drugs).
• Any MAO inhibitor antidepressants, any tricyclic or tetracyclic antidepressants, certain serotonin re-uptake inhibitors (fluoxetine, paroxetine, and venlafaxine), or mexiletine, within 4 weeks prior to study entry.
• More than 50 percent change in the weekly dosage of any pain control medications within 2 weeks prior to study entry.

Per 3/16/95 amendment:

• ddI, ddC, d4T, or 3TC within 8 weeks prior to study entry ONLY IF dideoxynucleoside dosing was suspended or permanently discontinued.

Risk Behavior:

Excluded:

• Active drug or alcohol abuse.