1-Important Administration Instructions

Averopreg is given orally with or without food.

When discontinuing Averopreg, taper gradually over a minimum of 1 week [see Warnings and Precautions].

Because Averopreg is eliminated primarily by renal excretion, adjust the dose in adult patients with reduced renal function.

2- Neuropathic Pain Associated with Diabetic Peripheral Neuropathy in Adults

The maximum recommended dose of Averopreg is 100 mg three times a day (300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Begin dosing at 50 mg three times a day (150 mg/day). The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability.

Although Averopreg was also studied at 600 mg/day, there is no evidence that this dose confers additional significant benefit and this dose was less well tolerated.

In view of the dose -dependent adverse reactions, treatment with doses above 300 mg/day is not recommended [see Adverse Reactions].

3- Postherpetic Neuralgia in Adults

The recommended dose of Averopreg is 75 to 150 mg two times a day, or 50 to 100 mg three times a day (150 to 300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Begin dosing at 75 mg two times a day, or 50 mg three times a day (150 mg/day). The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability.

Patients who do not experience sufficient pain relief following 2 to 4 weeks of treatment with 300 mg/day, and who are able to tolerate Averopreg, may be treated with up to 300 mg two times a day, or 200 mg three times a day (600 mg/day). In view of the dose-dependent adverse reactions and the higher rate of treatment discontinuation due to adverse reactions, reserve dosing above 300 mg/day for those patients who have on-going pain and are tolerating 300 mg daily

4- Adjunctive Therapy for Partial-Onset Seizures in Patients 1 Month of Age and Older

The recommended dosages for adults and pediatric patients 1 month of age and older are included in Table 1. Administer the total daily dosage orally in two or three divided doses as indicated in Table 1. In pediatric patients, the recommended dosing regimen is dependent upon body weight. Based on clinical response and tolerability, dosage may be increased, approximately weekly.

Table 1. Recommended Dosage for Adults and Pediatric Patients 1 Month and Older

Both the efficacy and adverse event profiles of Averopreg have been shown to be dose-related.

The effect of dose escalation rate on the tolerability of Averopreg has not been formally studied.

The efficacy of adjunctive Averopreg in patients taking gabapentin has not been evaluated in controlled trials. Consequently, dosing recommendations for the use of Averopreg with gabapentin cannot be offered.

5-Management of Fibromyalgia in Adults

The recommended dose of Averopreg for fibromyalgia is 300 to 450 mg/day. Begin dosing at 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient benefit with 300 mg/day may be further increased to 225 mg two times a day (450 mg/day). Although Averopreg was also studied at 600 mg/day, there is no evidence that this dose confers additional benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 450 mg/day is not recommended

6- Neuropathic Pain Associated with Spinal Cord Injury in Adults

The recommended dose range of Averopreg for the treatment of neuropathic pain associated with spinal cord injury is 150 to 600 mg/day. The recommended starting dose is 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient pain relief after 2 to 3 weeks of treatment with 150 mg two times a day and who tolerate Averopreg may be treated with up to 300 mg two times a day.